Editorial on the Research TopicCurrent and future role of artificial intelligence in cardiac imaging, volume IIHeart imaging without the need for invasive procedures plays a crucial role in various aspects of cardiology, including diagnosis, risk evaluation, treatment decisions, medical and invasive therapies, prognosis, and ongoing monitoring. As a key component in the pursuit of precision medicine, cardiac imaging enables a personalized approach to healthcare. Cardiac imaging is essential for a comprehensive understanding of cardiovascular conditions, intricate physiology, and the implications of imaging results for managing cardiovascular health and disease. Consequently, the demand for cardiac imaging continues to grow.Artificial Intelligence (AI) methods are increasingly needed for improving imaging exams, to optimize workflow, reduce waiting times, improve accuracy and precision, reduce costs and benefit patient outcomes. The special issue on “Current and Future Role of Artificial Intelligence in Cardiac Imaging” in 2020 provided 10 comprehensive reviews of a wide range of AI applications in cardiovascular imaging, from efficient image acquisition and fast reconstruction, to structure and function analysis, to statistical atlases and imaging-genetics synergies. In the meantime the field has been advancing rapidly. The second volume of this topic focuses on original research articles which showcase new methods and applications. Applications were invited for all topics and forms of cardiac imaging, and the resulting published papers reflect a range of modalities and applications which have a common goal of improving patient outcomes through extraction of more detailed and precise information than has previously been possible.Abdulkareem et al., Alabed et al., Beetz et al., Campello et al., Chen et al., Hampe et al., Li et al., Lin et al., Lin et al., Puyol-Antón et al., Suinesiaputra et al., Szabo et al., Zhai et al., Zhao et al. and Zhao et al.). The special issue attracted a greater number of submissions than the first edition, with 15 papers eventually published , followed closely by CT  and echocardiography . One paper provided a guide to trustworthy and responsible AI in all imaging modalities . Although not an imaging method, ECG processing is an important topic in cardiovascular disease, and can give anatomical information such as hypertrophy, which was the focus of one paper . In terms of application area, the most common was structural analysis  , followed by image motion analysis [in echo  and CT ]. These reflect the ongoing development of methods for quantifying anatomy and function in cardiac images, which are extremely important for diagnosis and prognosis. Two papers were concerned with synthesis of images or anatomy, using generative adversarial networks  and variational auto encoders  respectively. This is an exciting area of research with the promise to synthesise large numbers of datasets with different pathology and characteristics, which can be used to understand the influence of disease processes on structure and function. Two papers discussed learning contrast-enhanced information from non-contrast scans, applied to late gadolinium enhancement CMR  and calcium scoring CT  respectively. These highlight the ability of AI methods to leverage information present in standard scans to provide additional information, which would normally require an extra scan and administration of a contrast agent. The papers on AI fairness , and trustworthiness , illustrate another promising area of research into methods for improving AI methods, mitigating bias in the training data and explaining how inferences are made in complex networks. These were identified in the first special issue as topics of high importance. Another important topic highlighted by the first special issue is the reporting of AI methods to foster reproducibility and generalization, and this is the focus of the review article .Imaging modality was varied with CMR being the most common (AI methods are becoming ubiquitous in all areas of cardiac imaging. This is driven by the increasing role of imaging in guidelines for patient treatment, as well as the wealth of data generated by large cohort imaging studies such as the UK Biobank and the Multi-Ethnic Study of Atherosclerosis. The recent advent of widely available large language models which link imaging and videos with text such as GPT-4 highlight the rapidly advancing technology which will transform medical imaging in general and cardiovascular imaging in particular. The ability to generate reports from images and to combine images and reports into structured datasets will enable large amounts of data already residing in hospital databases to be reused for new applications. Generative models will enable new understanding of the ways in which longitudinal changes between imaging exams can be more precisely quantified, by comparing predicted follow-up images with the actual scans and highlighting any anomalies. Physics-based networks and neural implicit functions are also on the horizon which will enable super-resolution in fluid flow imaging, and computation of physical entities such as pressure and stiffness from imaging data. The linking of digital twins with imaging methods will enable surrogate AI-based methods to simulate growth and remodeling in health and disease, to estimate physiological parameters from non-invasive imaging. In summary, this second issue on AI in cardiac imaging illustrates important areas which are rapidly developing. However the next advances in this area are only limited by the imaginations of the researchers in the community. At present, there is no AI solution for this!


Ren et al. contribute to this Research Topic by identifying a novel sulfur dioxide probe that inhibits high glucose-induced senescence in umbilical vascular endothelial cells by inducing the degradation of lipid droplets . Senescence is also induced after adjuvant therapy (chemotherapy and radiotherapy) by inducing DNA damage. In their study, Jiang et al. demonstrated that the small GTPases RagC and Rheb are required for the activation of mTOR to promote chemoresistance in chemotherapy-induced senescence in HepG2 cells . Moreover, the regulatory role of E3 ubiquitin ligases is discussed in response to DNA damage, as reviewed by Lu et al..This Research Topic of Frontiers in Physiology includes important studies on senescence and some of the various physiopathological events that play an important role in the process. The article by Zhang et al. points out that polo-like kinase 1 activity delays senescence formation of nucleus pulposus cells and mediates the reduction of intervertebral disc degeneration and thus the prevention of back pain . Apart fIn conclusion, recent reports of this Research Topic fill an important gap in the physiopathological events in which senescent takes place.


The loss of muscle mass is a common adaptation to some physiological situations , but also to many diseases , which is due to an imbalance between protein synthesis and protein degradation . Muscle Depending on the catabolic situation, different signaling pathways controlling the main proteolytic pathways and protein synthesis can be implicated in the development of muscle atrophy, which implies a large panel of potential therapeutical targets for fighting against muscle atrophy . NumerouInternational Journal of Molecular Sciences entitled “Muscle atrophy: from bench to bedside” includes a total of six contributions  providing new information in the field of skeletal muscle atrophy, with a special focus on key actors controlling muscle proteostasis.The Special Issue of the Cussonneau et al.  addresseDowling et al.  addresseValdebenito-Maturana et al.  addresseVan de Haterd et al.  reviewedWinzer et al.  addresseYoshihara et al.  provide


Cerebral small vessel disease (CSVD) is a common chronic and progressive disease that can lead to mental and cognitive impairment. Damage to brain structure and function may play an important role in the neuropsychiatric disorders of patients with CSVD. Increasing evidence suggests that functional changes are accompanied by structural changes in corresponding brain regions. Thus, normal structure–function coupling is essential for optimal brain performance, and disrupted structure–function coupling can be found in many neurological and psychiatric disorders. To date, most studies on patients with CSVD have focused on separate structures or functions, including reductions in white matter volume and blood flow, which lead to cognitive dysfunction. However, there are few studies on brain structure–function coupling in patients with CSVD. In recent years, with the rapid development of multilevel  brain structure–functional coupling analysis methods based on multimodal magnetic resonance imaging (MRI), new evidence has been provided to reveal the correlation between brain function and structural abnormalities and cognitive impairment. Therefore, studying brain structure–function coupling has a potential significance in the exploration and elucidation of the neurobiological mechanism of cognitive impairment in patients with CSVD. This article mainly describes the currently popular brain structure–function coupling analysis technology based on multimodal MRI and the important research progress of these coupling technologies on CSVD and cognitive impairment to provide a perspective for the study of the pathogenesis and early diagnosis of CSVD. Cerebral small vessel disease (CSVD) is a general term for intracranial vascular  diseases based on a variety of pathological and neurological processes and refers to syndromes with different clinical manifestations and neuroimaging features caused by structural changes in blood vessels and brain parenchyma  is a tight regional and temporal coupling in the brain, which means that brain regions with stronger connectivity tend to have more frequent neuronal activity and more energy expenditure, resulting in increased cerebral blood flow (CBF)  parameters and gray matter (GM) morphological parameters, and the other is the coupling of rs-fMRI parameters and diffusion tensor imaging (DTI)-based white matter (WM) microstructural parameters.In the first approach, Kang et al.  combinedIn the second approach, Tan et al. combined DTI and rs-fMRI and found that patients with classical trigeminal neuralgia had high fractional anisotropy (FA) and low ReHo in the right hippocampus, and the ReHo and FA values were positively correlated with the Montreal Cognitive Assessment scale score. This indicated that there is a clear correlation between cognitive dysfunction and hippocampal functional and structural dysfunction in classical trigeminal neuralgia patients. Strong evidence has been provided showing that pain depends on the activation of mechanisms in higher brain centers that control emotions and generate emotional recognition   or functional connectivity (FC) (Shah et al., Studies have shown significantly altered SC and FC between hippocampal cognitive and emotional subregions and cortical areas in patients with cognitive impairment, which is manifested as an increase in the early stage of the disease, possibly due to compensatory mechanisms (Liang et al., The tight coupling between neuronal activity and CBF is called NVC (Li L. et al., There is increasing evidence that impaired NVC is present in many patients with CSVD. Increased microvascular damage and a decrease in the number of microvessels in the hippocampus and neocortex can cause a decrease in vasodilator reserve, leading to impaired NVC function, which is associated with cognitive decline (Phillips et al., As an important anatomical structure, the hippocampus is of great significance in the pathogenesis of neuropsychiatric diseases. Neuropsychiatric disorders caused by CSVD can lead to structural and functional damage to the hippocampus in many ways. Indeed, hippocampal neuronal loss and atrophy, regional cerebral blood volume reduction, and hippocampal microinfarction have been observed in patients with CSVD (Perosa et al., At present, structure–function coupling analysis methods and research specific to the hippocampal region are developing continuously. Recently, Bayrak et al. isolated the hippocampus and investigated its structure–function coupling using the twin setup of the Human Connectome Project with multimodal neuroimaging (Bayrak et al., In summary, the above structure–function coupling methods, including voxel-wise structure–function coupling, SC-FC coupling, and NVC, are of great significance for CSVD, but the current research is not perfect, and most of them only focus on independent structural or functional aspects. In addition, although multimodal MRI has been widely used in studies of CSVD, some issues remain. For instance, the mechanisms leading to cognitive impairment are complex and may be the result of a combination of factors other than CSVD alone (Lawrence et al., In addition, advances in machine learning have led to the development of artificial intelligence algorithms that can aid in the diagnosis of diseases based on MRI for detection at the preclinical stage. Using machine learning techniques, Uysal and Ozturk, successfully differentiated patients with cognitive impairment, patients with Alzheimer's disease, and normal subjects by hippocampal volume information (Uysal and Ozturk, Therefore, with the continuous development of multimodal MRI fusion analysis technology, brain structure–function coupling will become a hot spot in the study of CSVD in the future.NW and CL wrote the main manuscript text. XZ, CS, and YG prepared the imaging data. LG and HW revised the main manuscript text. All authors reviewed the manuscript. All authors contributed to the article and approved the submitted version.


No man is an island, entire of itself;Every man is a piece of the continent, a part of the main……!—John Donne's (1572–1631) in Devotions upon Emergent Occasions.Those lines penned by John in 1624 succinctly captured the challenges and opportunities facing not only mental health (MH) professionals but also other health experts worldwide. Like other horrifying pandemics of the past, the COVID-19 was a wake-up call that reminded all health professionals to seriously think of humanity as “a whole greater than the sum of its parts,” borrowing from the wisdom and research work of Gestalt psychologists who followed his steps. As clinicians who tirelessly work to ease the suffering of people with mental and physical disorders, we are often plagued by the nagging question at the back of our minds/psyche, “is this all I can do?” given the interconnected and multisectoral web of challenging predisposing, precipitating, and perpetuating factors in terms of biopsychosocial, epigenetic, and spiritual spanning the entire macrocosm often beyond our reach, as also evident in World Health Organization report , “Hope. It is the quintessential human delusion, simultaneously the source of (y) our greatest strength, and greatest weakness.” Born of this delusional—like hope, this Research Topic on “Tian et al., on the effort-reward imbalance in ER physicians, the review on MH interventions at the workplace by Pandya et al. and the impact of welfare schemes and programs offering fringe benefits to urban and rural employees by Luo et al. span the multiple areas of occupational MH.The research by Hu J et al., in their study on MH literacy, sleep and depressive symptoms. A worldwide online survey of 65 countries on stigma of medical students toward psychiatric patients by Babicki et al., shows that more needs and efforts to be done and address this pernicious attitude.The MH of students and young adults is captured by Tang et al., and the MH of Trans women and its association with sexual myths by Uyar et al., explore issues in marginalized and minority populations.The MH of female domestic workers and their relation to social networks by Wu J et al., in their study of mindfulness exercise guided by a Smartphone application. Gatto et al., have presented positive results concerning an online brief emotional training program for emerging adults, and Kim et al., have developed an online-coaching blended couple-oriented intervention for adults. At the same time, the negative effects of technology on MH have been explored by Zhang et al., on smartphone addiction, sleep, academic stress, and depression.Technology-driven MH promotion is presented with positive results by Sun et al., investigated the factors influencing the attitudes of patients living in the community toward long-acting depot antipsychotics, while the risk factors of violent behavior in schizophrenic psychosis is presented by Huang et al., in a 2-year follow-up study. Interestingly, wisdom as a protective factor for psychotic-like experiences in the general population are reported by Wu Z et al. Sexuality in people with ultra-high risk such as late adolescents and early adulthood, genetic vulnerability and attenuated psychotic symptoms and first-episode psychosis is systematically reviewed by Ciocca et al..Promoting the adherence to treatment in chronic and severe mental disorders, Li W et al.; chronic low back pain and depression by Hu Y et al.; body image concerns in hemodialysis by Nia et al.; social support and quality of life in female systemic lupus erythromatosis sufferers by Gao et al.; the impact of maternal depression on neonatal outcomes by Li H et al.; psychological factors affecting treatment adherence in patients with tuberculosis by Pradhan et al.; and finally a review of the impact of MH on outcome in tuberculosis by Agbeko et al., are presented in this issue.In the area of liaison psychiatry, depression, type 2 diabetes mellitus, and coronary atherosclerotic heart disease by Chen et al., on the restorative effect of rooftop gardens in urban settings needs special mention. Similarly, Zhou et al., have demonstrated that childhood neighborhood cohesion has a significant impact on neurocognitive functions in later life. Also a protocol for assessing the feasibility of psychological or MH first aid training of front-line healthcare workers in the provision of MH care during emergencies is presented by Wang L et al..Novel studies including the research by Yang et al., in their study on the impact of volunteering services in older adults and Wang J et al., in their research paper related to social participation in community activities in middle age and elderly residents.The role of community services on positive MH is highlighted by Moro et al., and the review of telemental health use during COVID-19 pandemic by Abraham et al., find place in this Research Topic.Finally, the impact of the COVID-19 pandemic on the MH of healthcare workers in Italy during the reopening phase after lockdown by To summarize, we are sure this issue does justice to MH Promotion and Protection, as we coordinate our resources, influence policy makers, engage with the community, and strive to make this World a better place for our future generations. We tentatively suggest the next topic of greatest interest: “Traumatic events in infants and adolescents and its psychiatric trajectories in future life.”All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


With a growing aging population around the world , frailtyThis Special Issue contains fourteen papers. Three studies were conducted in Japan. The study by Tsujishita et al.  aimed to“How to Make Primary Healthcare More Popular” is the title of the study by Fu et al. . These rTasioudi et al.  identifiThis Special Issue also includes a systematic review and meta-analysis by To et al.  who aimeTwo papers describe studies conducted in the Netherlands. One of these studies examined the opinions of nurses on frailty  . The nurThe deterioration of cognitive and psychophysical ability associated with aging has an effect on road safety, especially in the driving of vehicles. Mirabet et al.  evaluateIn conclusion, this Special Issue offers a wide range of papers that all contribute to our knowledge about frailty in older people. This knowledge is much needed given the increasing global number of frail community-dwelling older people and helps ensure that their quality of life is not diminished.


Editorial on the Research TopicInsights in orthopedic surgery: 2021Zhou et al. all topics that constituted background noise at the turn of the 21st century. In this context, we thought it would be informative to open up a topic with an open editorial agenda; we asked our thinkers to provide us with a glimpse of orthopaedics today.When we opened up this topic in just past 2020, orthopaedic surgery was moving at a pace and in ways that we could not have predicted even a few decades ago. Certainly, the way we examine, evaluate and investigate our thoughts, behaviors and results continues to change year to year, even month to months. Some of our most spirated debates now incorporate psychosocial nuances of care, honest solutions around preventing opioid-induced deaths and…artificial intelligence Wan et al. shoulder dysfunction from rotator cuff tears Zhou et al. and Jin et al. hip fractures and frailty of our older family members Yu et al. and our never ending dance with our microbial co-habitants Kankilic et al. But besides the new knowledge and skills gained over time, the way we analyze what we have done continues to make progress in ways difficult to predict. In addtion to the standard clinical study methodologies, systematic review and meta-analyses, our compendium now includes modalities such as the aforementioned artificial intelligence and modern ways of conceptualizing our research trends and attention through bibliometric analysis, be it for ankle fractures, patellar instability or rotator cuff disease Zeng et al., Zheng et al. and Jin et al.What we found was that some issues that have plagued our patients continue to do so although some of the ways we evaluate and treat them have changed dramatically over the years: back pain and symptoms from lumbar disc herniation As we progress through this decade and beyond, what will we see? AI assembled meta-analyses and registry reports? A dashboard that provides live bibliometric data on-demand? A decision aid phone app that is up-to-the-second current on the literature? Wiil the lines between “research” and data-driven patient care blur? What kind of “knowledge” will we be reporting on in 2050? Bone glue that supports weight-bearing, adaptive surgical implants that guide tissue healing, a cell-programming biologic that requires no surgery at all? I am excited to not only find out but to participate and contribute; and hope that you are too.


To critically appraise the literature to determine availability and identify the cultural responsiveness of infant resuscitation education for Aboriginal and Torres Strait Islander populations.Despite overall reductions in infant mortality in the last two decades, Aboriginal people have some of the highest rates of infant mortality of any developed nation. One of the key factors that has attributed to improvements in infant mortality rates is parent and carer education around risk factors and actions of first responders. Identifying gaps in the current basic first-aid initiatives available to Aboriginal communities may contribute to developing resources to contribute to reductions in Aboriginal neonatal mortality rates.The review used key terms and Boolean operators across an 11-month time frame searching for research articles utilising the databases of CINAHL, Scopus, Ovid Emcare, Informit, Pubmed and Proquest. After review, 39 articles met the inclusion criteria, 25 articles were discarded due to irrelevant material and 14 articles were included in the structured literature review. The search process was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Articles were assessed for validity and inclusion using the Critical Appraisal Skills Program checklist.Research literature relating to First Nation community-based CPR and first-aid education programmes in Canada, USA, India, UK and Europe, Asia and Africa were identified; however, none pertaining specifically to CPR and first-aid education in Australian Aboriginal communities were found.Despite the lack of research evidence relating to infant cardiopulmonary resuscitation (CPR) education for Australian Aboriginal populations, the reviewed studies noted the importance of culturally responsive education designed in collaboration with First Nation peoples, using novel ways of teaching CPR, that align with the language, culture and needs of the communities it is intended for.Further research is required to create a framework for the delivery of culturally responsive infant resuscitation education for Australian Aboriginal parents and communities. The importance of providing culturally responsive education to Aboriginal communities, which are co-designed and community-specific.Review of novel ways for infant resuscitation education for parents.What does this paper add to the wider global clinical community?Note: for conciseness the term Aboriginal will be used to refer to both Aboriginal and Torres Strait Islander peoples with no disrespect intended.et al., et al., Aboriginal and Torres Strait Islander people have some of the highest rates of infant death in Australia, including sudden unexpected death in infancy (SUDI) and sudden infant death syndrome (SIDS). In 2018, data from the Australian Mothers and Babies Report  guidelines, the review was conducted between the end of November 2020 and the end of September 2021 utilising the databases CINAHL, Scopus, Ovid Emcare, Informit, Pubmed and Proquest. The search strategy involved the use of the following Boolean operators ‘Resus* OR CPR * OR Cardiopulmonary Resuscitation* OR Infant resus* OR first aid OR basic life support’ AND ‘Infant* OR baby OR Neonate* OR Newborn’ AND ‘education OR training OR cultural programs’ AND ‘Aboriginal parents OR Aboriginal mothers OR Indigenous Parents OR Indigenous Mothers OR Aboriginal carers or Indigenous carers OR Aboriginal communities OR Indigenous communities’. Boolean operators were used to make the search more precise whilst still remaining broad enough to capture the required data.A total of 550 articles were initially found using the search strategy criteria, and 18 others were found from additional sources during sequel searches. After an initial review and the removal of duplicates, a total of 160 articles remained. These first pool articles were reviewed, and a further 121 articles were further excluded for not meeting criteria  checklists. Specific CASP study design checklists were used for the differing study designs, and the results against the appraisal criterion are presented in Table A total of 14 studies were included in the review. Several study types were noted which included one retrospective case study (7%), one retrospective observational analysis (10%), five surveys/questionnaires 35%), two prospective cohort studies (15%) and three community-based participatory research methods (22%), one randomised trial (7%) and one focus group (7%). The studies were conducted in Australia (7%), Ireland (14%), Singapore (7%), America (36%), Canada (22%), Sweden (7%) and South Sudan (7%). Outcomes ranged from the diagnosis and need for high-dependency transport (7%) to knowledge and attitudes to learning infant CPR (36%), teaching high-risk populations first aid (14%), rural medical issues (21%) and native language training (21%). In those studies that utilised an infant CPR education kit, outcomes ranged from knowledge levels pre- and post-kit use and satisfaction with the kit (50%) to confidence in skills and ability to perform resuscitation skills (17%). Of the four studies that reviewed infant CPR education kits, 75% used the CPR Anytime™ training Kit and 25% used the pillow CPR kit and e-learning programme. Further information, including aims and limitations of the studies, are included in Table 5%, two pet al., et al., A retrospective study conducted in Australia reviewing the need for aeromedical high-dependency transport described the cohort of 789 cases as being predominantly Aboriginal . The most common causes of transport were respiratory, with bronchiolitis and pneumonia at 31%, and the mean age range for transportation with bronchiolitis was 0.7 years (0.1–6.8) . The researchers noted that the majority of transport cases were newborns, which included preterm infants occurring in higher rates amongst the Aboriginal population. The increased risks and needs for high-dependency intervention amongst Aboriginal infants suggest a need for education for Aboriginal caregivers surrounding infant CPR. Another study was conducted in the USA  also looked at the specific challenges faced by First Nation peoples living a traditional life in the remote wilderness. Using a community-based participatory research approach, 20 Sachigo Lake First Nation people were involved in the SLWEREI training course mentioned previously. The irrelevance of generic first-aid courses in remote settings which focus on patient stabalisation while awaiting almost immediate assistance and transporation were highlighted. The findings identified the need for relevant remote medical emergency training to increase the community’s confidence to provide care that could lead to improved outcomes for remote populations. Similar issues were identified in a study conducted with 10 Nishnawbe Aski Nation health leaders and 33 other stakeholders, to review their emergency response systems  explored the management of medical emeregencies in remote First Nation communities. The findings identified that remote communities often lacked an established coordinated response system, and that there was a need to create education that was culturally specific and sustainable for the individual community and the region it was to be used in  in the USA. One study conducted by Yip et al.  in Seatt et al., . The stuTo determine parent’s knowledge, attitudes and perceptions of infant basic life support, Chia and Lian  recruiteet al.  enrolled 311 participants including 238 parents of premature infants and 73 parents of infants with congenital heart disease and aimed to assess the usefulness and parent comfort associated with the infant CPR Anytime™ kit. This is a particularly high-risk group of infants more likely to need infant CPR. It was noted that 75% of participants had received prior CPR education before receiving the kit (Pierick et al., et al., et al., et al., Pierick et al.  enrolledet al.  enrolledet al.  enrolledet al.  enrolledet al., et al., et al., et al., Knight, Wintch, Nichols, Arnolde and Schroeder provided the infant CPR Anytime™ kit to 117 parents of high-risk infants prior to discharge from the hospital, who were then contacted at one, three and six months to assess retention of knowledge and skills and comfort with using the kit (Knight Barry  enrolledet al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., The main purpose of this structured review was to critically appraise the literature to determine availability and identify the cultural responsiveness of infant resuscitation education for Australian Aboriginal populations. Despite an extensive literature search, only one non-research focused case study was found addressing a community-based first-aid programme in an Australian Aboriginal community (Anderson, et al., et al., et al., et al., et al., et al., et al., et al., et al., Many of the reported OHCAs that occurred in homes involved infants, and bystander CPR has been shown to increase the odds of survival two to three times, supporting the idea that teaching parents CPR could save lives (Knight Providing infant CPR education to parents will likely lead to the development of appropriate skills, improved confidence and decreased levels of anxiety to act as first responders. Bystander CPR is a critical step to ensure survival with good neurological outcomes, and there can be a delay in commencing CPR if bystanders need to be instructed by dispatchers. The use of self-instructional infant CPR kits provide education at a time that is beneficial to parents. The paucity in the literature regarding Aboriginal parents’ perceptions of infant CPR and the lack of availability of culturally specific infant CPR training programmes in Australia supports the need for collaborative and consultative research into these areas. Utilising these methods and engaging and collaborating with Australian Aboriginal communities to develop a framework for infant resuscitation education that is culturally responsive to Aboriginal parents’ needs and adaptable to a variety of settings could save lives and provide parents, carers and communities with important skills. Evaluation should also be conducted on the provision of such culturally sensitive infant CPR education to determine its effectiveness and if such education impacts on infant mortality and morbidity rates, particularly in remote communities.


Journal of Medical Internet Research titled, “Addiction Symptom Network of Young Internet Users: Network Analysis” by Lu et al [We read with great interest the article published in the Lu et al . With thLu et al  used theThe study stated that participants were recruited from 2 universities in Jiangsu, China, via advertisement. We do not know the exact environment of the 2 universities that the participants were recruited from. Environmental factors are known to play a great role in the development of IA . It may The authors should clarify the process and describe the implications of using advertisements as the method of recruitment. Participants in studies are often motivated by different factors, which could result in biases . It shouIn conclusion, we believe addressing the above points can help clarify the interpretation of the results. Lu et al  touch up


The ocular surface is a unique sensory ecosystem consisting of the cornea, conjunctiva, and adnexal elements, which are coated by a thin layer of the pre-ocular tear film . There iSingh et al.; Ramos et al.; Chen et al.; Li et al.). Recent developments in regenerative medicine have opened the door to the use of novel therapeutics with encouraging outcomes. This includes ocular surface regeneration using limbal tissues, cultured cells, and biomaterials. The approach of stem cell-based therapy has been spectacularly successful in the management of blinding chronic sequelae of chemical injuries . Once c et al.; . Besides et al.; .Now the horizon for application of cell therapy is being expanded to corneal opacification due to scarring using mesenchymal stem cells . This isChen et al.; (Singh et al.; (There is also great interest in regenerative approaches for the lacrimal and meibomian glands, that are important adnexal elements and critical to the health of the ocular surface . Damage et al.; . Three m et al.; . These g et al.; ].The ocular surface is exceptional in terms of the range of research that is being done for developing regenerative approaches for each individual element be it the cornea, the conjunctiva, or the lacrimal glands. These developments are exciting and could pave the way for disruptive new therapies in the future. Once of the challenges would be to achieve the right balance between efficacy, safety, and affordability. As researchers we must not lose sight of those who are most desperately in need of these new therapies. Therefore, an equal emphasis must be placed on developing low-cost products that are easy to deliver . DespiteThe author confirms being the sole contributor of this work and has approved it for publication.


Editorial on the Research TopicAnticoagulation in cardiovascular diseases: evolving role, unmet needs and grey areasThrombosis is a key pathophysiological mechanism for many serious cardiovascular diseases, including deep vein thrombosis (DVT), pulmonary embolism (PE), acute coronary syndrome (ACS), and ischemic stroke.Thrombi consist of aggregated platelets, fibrin, and trapped cells, with the distribution of these components differing substantially between arterial and venous thrombi . The maiFor several decades, vitamin K antagonists (VKAs) have been the treatment of choice for long-term oral anticoagulation. Unfortunately, VKAs have many disadvantages that limit their use in the real world. Almost all the limitations of VKAs have been overcome by DOACs, which are at least as effective as VKAs in preventing thrombotic events in patients with non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE), with the advantage of being safer in terms of bleeding risk  and easier to use . This haHard to believe until a while ago, DOACs—which have been called “novel anticoagulants” for many years—might become “older” very soon. This is because strategies that target coagulation factors XI and XII (FXI and FXII) might soon hit the market. These newer medications promise to have the ability to limit thrombosis growth with an impact on hemostasis that is lower than that of DOACs . Very rePastori et al. on the use of DOACs in patients with antiphospholipid syndrome (APS). This is indeed a delicate issue, with controversial recommendations among the different international guidelines. For instance, the European Society of Cardiology (ESC) recommends against the use of DOACs in APS patients. However, the authors correctly argue that these recommendations do not make any distinction between single-, double-, and triple-positive APS patients, between patients who only had venous thrombotic events and those who had arterial events, nor between different DOACs. This is despite the fact that these recommendations are exclusively based on the results of the Trial on Rivaroxaban in AntiPhospholipid Syndrome (TRAPS)  , which h (TRAPS) –15. AccoFu et al., which compared the relative risk of embolism and major bleeding between apixaban and warfarin in patients with NVAF and compromised kidney function, was also highly viewed. The use of DOACs in subjects with severe chronic kidney disease (CKD), i.e., hemodialysis patients, was the focus of a meta-analysis by Elfar et al. This contribution is of interest because hemodialysis patients have been excluded from clinical trials on DOACs, and therefore, the evidence of their efficacy and safety is weak in this cohort.The research paper by Parsi et al., Liu et al., Zeng et al., Gao et al. These articles are important because they reflect the need for physicians to better understand how to treat frail older adults in real life.Many contributions to our Research Topic consisted of articles on anticoagulation in frail subjects, including those with cancer, dementia, and increased risk of falling Gottsäter, which focused on the rationale for recommendations on dual antiplatelet and anticoagulant treatment in subjects with peripheral artery disease (PAD), the original cross-sectional study by Suo et al. on the evolution of antithrombotic treatments for patients with AF and coronary syndromes in China, and the mini-review by Hardy et al. on the possible importance of DOAC level for an uninterrupted DOAC approach for catheter ablation in AF.Other contributions that merit mention are the review by Wu et al. on the association between the use of anticoagulants and bone fractures, Mirijello et al. on pulmonary artery stump thrombosis, Prouse et al. on the possibility of using the SOFA Score to identify subjects at high risk for VTE among those affected by SARS-CoV-2, Li et al. on a nomogram to predict left atrial thrombus in patients with AF, Liu et al. on the reappraisal of DOACs in AF patients, Lin et al. on the differences in the presentation of arterial thrombotic events between patients with a history of VTE or AF, Liu et al. on intraocular bleeding in patients with AF treated with different anticoagulants, Meihandoest et al. on a heparin-calibrated anti-Xa assay, Liu et al. on the evidence available on DOACs vs. VKA in Latin American patients with AF, Liu et al. on the risk of diabetes in patients with AF treated with DOACs compared to VKA, Cao et al. on anticoagulation in AF patients who have bioprosthetic heart valves, Li ei al. on the clinical characteristics and prognosis of patients with left ventricular thrombus in China, and Gao et al. on the use of sodium alginate hydrogel coatings on extracorporeal membrane oxygenation for anticoagulation.In this Research Topic, there were also contributions on anticoagulation during cardiac surgery. Other contributions were from


A number of previous reviews of the literature have shown the prevalence of mental disorders in prisons is considerably higher than in the general population –3. This In regard to the treatment of prisoners with mental disorders, a policy document from the WHO “Good governance for prison health in the twenty first century”  recommenWhere studies have been undertaken they have indicated the needs for treatment of prisoners for mental health disorders have often not been identified and treatment needs have not been met , 11. FewSimpson et al. conducted a systematic review of publications investigating mental health services in the correctional framework. In regard to those passing through the correctional system, they found no evidence for standardized assessment approaches, some evidence to support specific psychosocial interventions and relatively weak evidence to support reintegration methods back into the community.Yesuf et al. looked at the prevalence of mental illness among inmates in north-western Ethiopia. They found around 75% of inmates had some form of mental disorder with symptoms including feeling unhappy and finding it difficult to play an important role in life. However, those that took part in rehabilitation activities had an improved outcome. The authors concluded that this was an area for further research and development that could lead to better outcomes for those with symptoms of mental disorder.Other contributors to our topic have added to what is known. Linked to the theme of the effectiveness of interventions for those passing through the criminal justice system, Stawinska-Witoszynska et al. found a high level of generalized anxiety disorders (GAD) in the population of inmates detained in one of the largest penitentiary units in north-eastern Poland. They found a three times higher prevalence of GAD among inmates detained in a closed type prison compared with those in an open prison. They made the case for increased availability of psychological therapies for prisoners.McIntosh et al. conducted a mental health needs assessment for Scotland's prison population. They concluded that existing provision to support the mental health needs of people in prison in Scotland was inadequate. This was partly due to a lack of integrated care between the justice, health and social work systems resulting in prisoners not receiving the support they needed both during and following imprisonment.Another theme of this topic is whether care is sufficiently integrated between the criminal justice system and community based services. Sekiguchi et al. looked at treatment options for persistent methamphetamine associated psychosis and how this should be distinguished from schizophrenia spectrum disorder. They found benefits from using a lower dose antipsychotic to treat methamphetamine associated psychosis. Naidoo et al. in a study based on a women's correctional center in South Africa emphasized the need to educate, support and manage those infected with HIV which has a high prevalence in South Africa. In Canadian based studies, Moghimi, Knyahnytska, Zhu et al. explored the mental health needs of correctional workers and found, Moghimi, Knyahnytska, Omrani et al. digital mental health care interventions could help meet these needs. Shafti, Steeg et al. and Shafti, Taylor et al. explored the relationship between aggressive behaviors and self-harm and implications for managing such behavior in correctional settings.In line with another topic theme some research has been undertaken on treatment options for different mental health conditions seen in prisons in various countries. Skipworth et al. a study in New Zealand indicated that there has been an increasingly poor outcome in terms of imprisonment following discharge from a mental health unit over a ten-year period and concluded that models of community based mental health care may be increasingly reliant on the criminal justice system to manage aggressive and dangerous behavior among those with mental illness. There have been reports of similar trends in other countries including the UK.In terms of other themes of this Research Topic such as whether an individual's needs for treatment and care are successfully handed over to community-based services and the impact of the quality of care on the likelihood of recidivism more research is needed. As noted by NM: Writing—original draft. AF: Writing—review and editing.


Karystianis et al.; Popovic et al.; Yu et al.) and a systematic review .Machine learning (ML) as a modern form of statistical analysis is becoming more and more common in psychiatric research. The possibilities of ML to analyze complex relationships and potentially build predictive models seem particularly appealing regarding multifactorial yet poorly understood phenomena like violence and offending. This Research Topic aimed to gather evidence in this area to further promote the application of ML in forensic psychiatry. The contributing works comprise three original articles , data analysis, and creation of predictive models to anticipate events relevant to forensic psychiatry. With ML becoming more widespread, an increase in studies with similar methodology can be well-expected. However, it is essential to ensure that the application and evaluation of the calculated models would be done on different patient populations—ideally international ones. Only then, generally valid predictors can be identified, and a robust generalizable model can be built and applied in clinical practice.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Michael James is remembered. Michael James12, and the first protein structures having recently been determined in Cambridge. Michael’s thesis project was to determine structures of antibiotic peptides. While there, he was exposed to protein crystallography through the work going on at the same time to determine the 3D structure of insulin.Michael James was born in Vancouver and grew up in Winnipeg, Manitoba on the Canadian prairies. After high school, he studied chemistry at the local University of Manitoba, where he was excited to learn that it was possible to see the 3D structures of molecules using X-ray crystallography. Aiming to get the best possible background for a future working in this area, he applied to do a DPhil at Oxford with Dorothy Hodgkin in 1963. It was a time of great advances in crystallography, with Dorothy about to win the Nobel Prize for her ground-breaking structures of penicillin and vitamin BStreptomyces griseus protease B, a serine protease) in 1974 (Delbaere et al., 1975After completing his DPhil in 1966, Michael took a postdoctoral position determining small-molecule structures in the Department of Chemistry at the University of Alberta in Edmonton, Canada. He remained at the University of Alberta for the rest of his life. However, his career took a quick turn when he learned that the Biochemistry Department was seeking to set up a protein crystallography laboratory. With his move to Biochemistry he became the first protein crystallographer in Canada, determining the first 3D protein structure (that of et al., 1979In his research, Michael brought the same expectations of high precision to proteins that he had learned in small-molecule crystallography, and his group became known for the quality of the structures it produced, becoming early adopters of least-squares refinement (Sielecki et al., 1979et al., 1982et al., 1977et al., 1989Initially, Michael concentrated his group’s efforts on understanding the structure and function of proteases, an area that remained important to him through the rest of his career. The group worked on a variety of serine proteases and their complexes with both small molecules (Brayer et al., 1994et al., 1997et al., 1999Eventually, the James laboratory turned its interest to the proteolytic enzymes from picornaviruses. Members of the laboratory determined the structures of the 3C proteinases from hepatitis A virus (Allaire et al., 2004Prior to 2004, five families of proteolytic enzymes were known. A sixth family, the glutamic peptidases, was discovered in a collaboration between the James laboratory and Professor Kohei Oda of Kyoto, Japan (Fujinaga et al., 1994et al., 1996et al., 2003et al., 2006et al., 2013Branching out into other areas, Michael’s group carried out structural studies of a variety of biochemically and medically important proteins. The structure of troponin-C (Herzberg & James, 1985et al., 2003In collaboration with the Canadian company ViroChem Pharma, members of the James laboratory determined the structures of allosteric inhibitors of NS5B, the RNA-dependent RNA polymerase from hepatitis C virus (Wang et al., 2022His last published paper, on a protease from a virus that causes porcine epidemic diarrhoea, was special in having his daughter Michelle as a coauthor (Shamsi Michael received many honours during his long and distinguished career. He was elected as a Fellow of the Royal Society of Canada in 1985 and as a Fellow of the Royal Society of London in 1989. He was presented the Martin Buerger Award of the American Crystallographic Association in 2009. In 2010, he received an honorary doctorate of science from his undergraduate alma mater, the University of Manitoba. In June of 2023, the month before he died, he was appointed an Officer of the Order of Canada, one of Canada’s highest honours.In his approach to science, Michael’s passion was always to move closer to the truth. As a consequence, he took as much pleasure in the scientific advances of others in the MRC Group and the Department of Biochemistry as he did in his own group’s breakthroughs. He wanted to contribute and to understand, but was always unassuming; he could laugh at himself and never dominated or inflated his ego at the expense of others. Beloved by members of his laboratory, Michael was an inspirational friend and mentor to his students, postdoctoral associates and colleagues, and a joyous companion to those lucky enough to know him.Michael James died on the 24 July 2023 after a short admission to the University of Alberta Hospital. He is survived by his three children, Daphne and Marcus from his first marriage to Pat, and Michelle from his third marriage to Deborah.


Mixed-species groups of birds, fishes and mammals have traditionally been described in taxa-specific journals. However, mixed-species systems are actually more widely found when one includes aggregative (non-moving) systems, such as those common in amphibians and invertebrates. The objective of this special issue is to dispel the idea that mixed-species phenomena are a ‘niche topic’ to ecology and instead explore how taking a mixed-species perspective can change our conception of important ecological patterns and processes. A mixed-species perspective starts by understanding the relative abundance and positioning of individuals of different species and their behavioural synchrony; it is enriched by understanding differences between species in their vulnerability/attractiveness to predators, their potential for competing with other group participants and their use as a source of public information. Contributions to the special issue show how the mixed-species perspective can change our ideas about invasion ecology, island biogeography, keystone species, mimicry, predator eavesdropping and more. Rather than seeking synthesis, the special issue celebrates the taxonomic and conceptual breadth of the field of mixed-species groups, with detailed descriptions of many distinctive systems.This article is part of the theme issue ‘Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes’. These groups and aggregations include flocks of birds that can reach up to 60 species and 100 individuals , and groMixed-species group phenomena have historically been described separately within taxonomic boundaries, with little cross-talk between these streams of research. Reports about moving groups have traditionally been in three clusters: birds , social Philosophical Transactions of the Royal Society, B, entitled ‘Collective behaviour through time’ (edited by Christos Ioannou and Kate Laskowski) will also cover some exciting mixed-species systems.Our special issue is representative of the historical development of the field, as we include a large range of bird flock studies , two mammal studies, one fish study and two papers that aim to be applicable to multiple taxa. We also include aggregation systems: one each for amphibians, birds, insects, and a system of fishes and pelagic mammals. In bringing the studies on aggregations into the fold with moving systems, our hope is to show that a range of ‘mixed-species’ questions—shown perhaps best in the bird literature—can be applied to a much wider range of other taxa. Indeed, some of the issues of how groups of species in close proximity interact might be relevant to the burgeoning research field focused on plant communication and behaviour ,20. We w (i)how many and which species are present in a group, how do they differ in their relative abundance, and how stable are these characteristics over time and space? (ii)what is the spatial organization of individuals in these groups? How far are individuals typically apart from each other? Is the spacing between individuals different for conspecifics and heterospecifics? (iii)if the whole system moves together, which species lead and which species follow? Is this consistent across different contexts and different group compositions? If the whole system is stationary, which species initiate aggregation at a location and which arrive subsequently? (iv)how synchronous or asynchronous is individual behaviour, for both conspecifics and heterospecifics? This could include movements, foraging activities or communicative signals; (v)how does information flow through the group? Is it unidirectional or multidirectional? Is it mutualistic or does it typically include aspects of eavesdropping/parasitism? (vi)how does predation influence these groups? Does predation pressure increase group formation? Do group participants share the same level of vulnerability to the same predators or does this vary across species? Are some species in these groups preferred by predators and therefore each species benefits differently in both degree and type of benefits they receive in the group? (vii)how does competition influence group structure (composition and organization) and how does this relate to an individual's proximity to resources? How do dominance hierarchies influence group structure? (viii)how does a specific species composition affect a group's functioning, and how can we effectively experimentally remove or add individuals of different species or simulate their absence/presence to investigate this question? (ix)how does the environment (e.g. gradients and habitat structure) affect, or even dictate, local group structure? (x)how does the grouping phenomenon itself affect the composition of the whole community, as well as how that community uses resources? and (xi)how does the grouping phenomenon affect the participants' responses to human disturbance and how can this information be used to improve conservation approaches?What then are the common themes across all this diversity? First, we are talking about groups of animals (and possibly microorganisms) in mobile life stages that are of the same trophic level. Basic ‘mixed-species’ questions that can be asked of these groups include:With the inclusion of aggregations, it is clear that mixed-species phenomena are ubiquitous. Further, the breadth of these kinds of questions, from those that focus on the behaviour of individuals, to those that probe questions of community assembly, suggest that mixed-species issues are not a niche, but rather a core topic of ecological study. Below we argue further that thinking about the differences among participants in mixed-species groups can fundamentally alter the way we think about ecological patterns and processes.. 2et al. [et al. [et al. [et al. [et al. [In the last section of Goodale et al.  the authet al.  review t [et al.  examine  [et al.  explore  [et al.  revisit  [et al.  study pret al. [et al. [et al. [et al. [et al. [et al. [The second section is behavioural in focus, with the unifying concept being the comparison between intraspecific and interspecific sociality. We start with several papers that chronicle in depth the proximity of species to each other and their behavioural synchrony in a fascinating set of different contexts: captive South American monkeys by Daoudi-Simison et al. , groups et al. , and pel [et al. . This se [et al.  provide  [et al.  describe [et al.  use a la [et al.  use a miet al. [et al. [et al. [et al. [The third section asks what effects mixed-species systems have at the community level. Here the unifying concept is exploring how behavioural interactions between species influence species distributions and community composition across abiotic or biotic gradients. Charabidze & Aubernon  chroniclet al.  examine  [et al.  review t [et al.  examine  [et al.  investig [et al.  use an i [et al.  describe. 3One final storyline for this special issue is also social in nature, but focused on human sociality, for this special issue developed out of an online symposium in June 2021. For Kathryn Sieving and Eben Goodale, this was the third such mixed-species group symposium in a decade, after a 2011 meeting sponsored by the Field Ornithology Group of Sri Lanka, and one in 2015 at Ecosummit in Montpellier, France, that was the first to attempt to mix researchers who work on different animal taxa. The topic of bird sociality and interspecific information flow has also been the focus of symposia before . Anne passed away unexpectedly towards the end of the preparation of this special issue. She was an active member of our team, handling five of these manuscripts, and we are deeply grateful for her contribution, as well as saddened by losing her. Her passion for mixed-species systems and her beloved fish shoals shines forth in these pages.


R2 value (0.9680) and small root mean square error (RMSE) value (2.6409) compared to APCS-MLR model. Meanwhile from the sensitivity analysis, fertilizer waste acts as the dominant pollutant contributor (59.82%) to the basin studied followed by anthropogenic input (22.48%), surface runoff (13.42%), erosion (2.33%) and lastly chemical and mineral changes (1.95%). Thus, this study concluded that receptor modeling of APCS-ANN can be used to solve various constraints in environmental problem that exist between water distribution variables toward appropriate water quality management.Recent techniques in the management of surface river water have been expanding the demand on the method that can provide more representative of multivariate data set. A proper technique of the architecture of artificial neural network (ANN) model and multiple linear regression (MLR) provides an advance tool for surface water modeling and forecasting. The development of receptor model was applied in order to determine the major sources of pollutants at Kuantan River Basin, Malaysia. Thirteen water quality parameters were used in principal component analysis (PCA) and new variables of fertilizer waste, surface runoff, anthropogenic input, chemical and mineral changes and erosion are successfully developed for modeling purposes. Two models were compared in terms of efficiency and goodness-of-fit for water quality index (WQI) prediction. The results show that APCS-ANN model gives better performance with high  In addition, surface waters are most susceptible due to easy accessibility for wastewater  and antet al.,); sewageet al.,) and urbMonitoring programs often worked out with frequent water samplings at many sampling sites all over the world and determination of physiochemical parameters can provide a representative and dependable estimation of the surface water quality. In Malaysia, Department of Environment (DOE) has been conducting unstoppable monitoring activities since 1978 resulting to large data matrix collection and desperately requires remarkable statistical tools such as multivariate and artificial intelligent for exceptional data illustration.in-situ measurements of the river water quality. According to the DOE’s Environmental Quality Report in 2007, 158 river basins are involved in this program to monitor river quality changes on a continuous basis . Even tWater quality is referring to the characteristics of water whether in its physical, chemical or biological character. Based on the water quality data, the water quality index (WQI) was developed to evaluate the water quality status and river classification in Malaysia. WQI provides a useful way to predict changes and trends in the water quality by considering multiple parameters. WQI is formed by six selected water quality variables, namely dissolved oxygen (DO), BOD, chemical oxygen demand (COD), SS, AN and pH . WQI vaet al., [et al., [et al., [Continuous monitoring of river water quality reveals the chemical and physico-chemical parameters for the interpretation of large data set with many variables; therefore environmetric approach need to be constructed to comprehend the variation on the data since it is not entirely convincing. In this study, the large data matrix obtained from monitoring programme conducted by DOE, Malaysia from year 2003 to 2007 was introduced to receptor models techniques that involved varimax factor from principal components analysis (PCA) with two different data based on multiple linear regression (MLR) and artificial neural network (ANN) models. These approaches were conducted in many fields such as prediction of ozone concentrations , foreca[et al., ), predic[et al., ), predic[et al., ) howeveret al., [Source apportionment techniques were applied in the data set by combining PCA with MLR and PCA with ANN. The aim of this study is to discover the major pollution sources that significantly change the WQI values in Kuantan River Basin from the varimax factors produced for MLR and ANN models. The uncorrelated new variables that account much of the original data will be used as input variables for the models; other than combining statistical and an artificial intelligent techniques which has been received great spotlight in environmental pattern recognition study . Moreovet al., [et al., [et al., [et al., [et al., [et al., [et al., [et al., [et al., [Generally, MLR may lead to incorrect identification of most the predictor due to collinearity between the input variables . Many s[et al., ; Chaloul[et al., ; Bandyop[et al., ; Sousa e[et al., ; Jahandi[et al., ; Gutierr[et al., ; Rossel [et al., ; Wu et a[et al., ). ANNs a[et al., ) and hav[et al., . MLR als[et al., ). Althou[et al., ).The objectives of this study are to predict WQI values as well as to estimate the main contributor using MLR and ANN model from the varimax factors generated by PCA. This study will provide comprehensive understanding on goodness and weakness for both models and consequently finalised the correct model for WQI prediction in the Kuantan River Basin.2 catchment area which started from forest reserved area in Mukim Ulu Kuantan through agricultural areas, Kuantan town  towards the South China Sea. Kuantan River Basin consists of several important tributaries and these rivers drain the major rural, agricultural, urban and industrial areas of Kuantan District and discharge into South China Sea.Kuantan River Basin is in the district of Kuantan at the north eastern end of Pahang State in Peninsular Malaysia Figure . It is oKuantan River basin which is in Kuantan District area has six administrative mukims . In terms of land use, the main types of land use in this district are forest and agriculture that cover approximately 56% and 32% respectively, from the whole area of Kuantan District. Majority of the forested areas are at the west of Kuantan District or in upstream of the basin. Besides that, there is an ex-tin mining land in Sungai Lembing or at upstream or low sub basin area. The mining activities was started in 1906 and stopped in 1986 due to economic recession in our country.In term of land use utilisation, agriculture is considered to be one of the main economic activities in this river basin where it covers about 70,128 hectares of the area . Accordet al., [There are three palm oil mills which are the major agro-based industries in the middle of the basin and might be contributed to deterioration of Kuantan river water quality . Recentet al., ). Since et al., ).3), chloride (Cl-), phosphate (PO4-), Escherichia coli (E. coli) and coliform. According to DOE [The water quality data were collected in 2003 to 2007 from eleven monitoring stations provided by DOE. However, some of the stations are inconsistently sampling thus leading to the missing data. Thirty water quality parameters are selected by DOE in order to represent the water quality in the river. Unfortunately only 13 parameters are consistently sampled along 2003 to 2007 therefore a total of 275 observations were used for source apportionment and modeling techniques. The thirteen water quality parameters are selected for analysis in this study are: pH, dissolve oxygen (DO), biological oxygen demand (BOD), chemical oxygen demand (COD), suspended solid (SS), ammoniacal nitrogen (AN), dissolved solids (DS), total solids (TS), nitrate .et al., [et al., [et al., [et al., [The data were initially arranged according to the stations and year of monitoring. Variables that are not have been detected (below detection limit) were set to half of its detection limit in order to ensure that there is no missing data in the dataset. Normality test were performed using the Anderson-Darling test since the multivariate statistical techniques requires the variables to be normally distributed . Data t[et al., ). Log sc[et al., ). Statis[et al., ).et al., [et al., [et al., [et al., [et al., [The most powerful technique for pattern recognition that attempts to explain the variance of a large set of inter-correlated variables and transforming it into smaller set of independent (uncorrelated) variables . PCA aims to uncover a more underlying set of factors that accounts for the major pattern across all the original variables . Moreov[et al., ). This t[et al., ; Helena [et al., ; Wunderl[et al., ). PCA is[et al., ). Hence,z is the component loading, y is the component score, x is the measured value of a variable, a is the component number, b is the sample number, and m is the total number of variables. PCA was performed on correlation matrix of rearranged data which explains the structure of the underlying dataset. The correlation coefficient matrix measures the variance of each constituent explained by relationship with each others. PCA of the normalized variables were then performed to extract the significant PCs and reduce the variables with minor significance. These PCs were subjected to varimax rotation (raw) generating VFs as it sometimes not readily interpreted thus performing varimax rotation is recommended to reduce the dimensionality of the data and identify most significant new variables. Varimax factor (VF) coefficient having a correlation >0.75 are regarded as strong significant factor loading . Meanwhet al., [et al., [Receptor modeling application based on APCS-MLR is a commonly apply statistical technique for source apportionment of environmental contaminants in air pollution studies . It hasZbc is the normalized concentration of contaminant (variable), Qab refers to the factor loadings, the coefficient matrix of the components relates with pollution sources and their elemental concentrations; and Rbc the factors cores in Eq. (2). Qab is dimensionless. Since, Zbc in Eq. (2) is normalized value of variables, it cannot be used directly for computation of quantitative source contributions, the normalized factor scores determined in Eq. (2) were converted to unnormalized APCS following the method reported elsewhere . The coMbc is the contaminant’s concentration; da0 is the average contribution of the bth contaminant from sources not determined by PCA/FA, Dab is the linear regression coefficient for the ath contaminant and the bth factor, and (APCS)bc the absolute factor score for the bth factor with the cth measurement. The values for Mbc, da0 and Dab have the dimensions of the original concentration measurements. After determining the number and identity of possible sources influencing the river water quality by PCA/FA, source contributions were computed through APCS-MLR technique. Quantitative contributions from each source for individual parameter or contaminant were compared with their measured values.Where et al., [Several studies on water quality model have been developed in order to manage and protect the water quality in many countries. Most of the models demand many inputs for model development and eventually lead to time consuming and high priced. ANN models are defined by topology, node characteristics and training or learning rules. It is an inter-related set of weights that composed of the knowledge generated by the model. An ANN contains large number of simple processing units, each interconnecting with others via excitatory or inhibitory connections. The most unique features of ANN model is the non-linear modeling capability, ability dealing with large sets amount of data and robustness to noisy data . The di3, Cl-, PO4, E. coli and coliform).(i) An input layer which is connecting the input information to the network. In this assessment thirteen input nodes representing the thirteen water quality parameters were applied  Hidden layer which is acting as the intermediate computational layer. Multi-layer feed forward network formed by only one hidden layer. ANN models consist of the following set of equations: P represents the scaled input vector and M is output vector of the neurons contain in the hidden layer. The bias is set equal to 1.(iii) Output layer is producing the desired output which is in this case the WQI following this equation: Pab and Pbc in the summation, which are usually referred as the weights, are the fitting coefficients of the neural model.The coefficients Many studies already emphasized the use of linear regression in apportionment of sources toward the dependable variables in their studies. Nonetheless, ANN application was yet to be explored. The aim of this method is to minimize the effect of multicollinearity and achieve better prediction model with minimum residual errors. The small number of input variables from APCS was combined with the ANN model to obtain high interpretability as the irrelevant and superfluous variables were excluded Figure .The PCA showed that the two main PCs accounted for 45.13% of the total variance  for the overall observations. The larger variability graph for factor loading 1 and factor loading 2 were plotted to explain the variance. The 13 variables were well represented on the plane.et al., [The five VFs were generated after varimax rotation based on eigenvalues >1 , Figur. Eigenvaet al., ). PCA afet al., [PCA aims to exclude redundant information from the original raw dataset by obtaining a small number of variables. This is comprehensible especially for detailed analysis such as modeling. Source apportioning are well known especially for air pollution and water quality data as it integrated with WQI although it is less documented in tropical regions. In air pollution studies, PCA and environmetric techniques are used extensively to determine possible natural and anthropogenic contributions in the determination of total mass and concentration . Therefet al., [et al., [et al., [R2) is commonly used to evaluate model performance . Therefet al., ). Other [et al., ). MLR ar[et al., ). SourcePearson, ); howeve et al., ). Table Figure Figure Figure et al., [et al., [et al., [APCS-ANN is a comparatively new concept driven in river water quality modeling to allow non-linear relationships between variables to be ‘learnt’ through repeated presentation of input–output data sets. The use of numerical models such as ANN provides powerful tools to stimulate complex natural resources management problems . Curren[et al., ). Althou[et al., ).Figure Figure et al., [et al., [Classical process-based modeling approaches can provide good evaluations of water quality variables however the approach is too common to be applied directly without a lengthy data calibration process . Since [et al., ).R2 values .et al., [3-NL, DS, TS, NO3, Cl-, PO4, E.coli, coliform) with 275 observations to identify the pollution sources. PCA is able to describe the relationship between analytical variables than single analytical variable alone. VF1  represents 21.40% of the total variability in one axis (VF1) comprising DO, AN and PO4. VF1 represents moderate loading matrix of coliform and E. coli. while DO was negatively correlated to AN and PO4 owing to the decrease of DO values in the increasing AN and PO4 inputs in the water body at Kuantan River. VF2 explain DS, TS and Cl in new variable with strong factor loadings.Based on Figure et al., ). PCA wa4 were strongly correlated to VF1 (32.409% of variance) and a new variable termed as fertilizer waste which explains that NH4 likely to comes from the vicinity of animal farm and agricultural nonpoint source . Modera-. While for VF3 (9.605% of variance)  Figure  was stro et al., ). VF4 . MoreovR2 value for APCS-MLR model in this study is 0.87 and the model indicates that 87% variability of WQI explained by the five independent variables used in the model. While for adjusted R2 it is always less than R2 and increases only if the new term improve the model . Mean SR2 and adjusted R2 values closet to unity  and Schwarz Bayesian Criteria (SBC) values and  et al., ). In genBased on Figure R2 value, 0.9680 (Table APCS-ANN (WQI) was developed to investigate which pollution patterns contribute most to the Kuantan River Basin. Previously five VFs were generated from PCA after varimax rotation and the VFs were used as input parameter for ANN model. The five input parameters were fertilizer waste, surface runoff, and anthropogenic input, chemical and mineral changes and erosion and WQI as output. Based on Figure R2 is (0.9680) and low RMSE (2.6409) as compared to other models. From the sensitivity analysis, the highest pollutant that contributed to Kuantan River Basin (WQI variation) was identified. Fertilizer waste (L-FW) accounted as the main pollution contributor  due to the exclusion of the parameters results in reduction of R2 (0.8115) and high RMSE (6.9275) which signify the model. Anthropogenic input (L-AI) was identified as the second pollution contributor , R2 (0.9092) and RMSE (4.549) followed by surface runoff (L-SR), erosion (L-E) and lastly chemical and mineral changes (L-CMC) which were the least contributors as the inputs influencing the APCS-ANN model performance.As shown in Figure et al., [APCS-MLR in apportionment of sources affecting water quality reveals that industrial discharge contributed the highest pollutant of ammonia observed . Howeve4 inputs that reflects to DO reading from year 2003–2007, were due to the oil palm, rubber and forestry areas along the river. This also leads to chemical mineral changes to the field areas. From the results stated above, it is shown that ANN gives better accuracy as compared to MLR technique for WQI forecasting. Moreover ANN also capable to stimulate the complex relationship between the data set and consequently is able to justify the water quality puzzles. By using PCA, main pollution contributors to the basin were justified without eliminating any data and parameters. Moreover due to non-linearities of dependent variables in this study and the intricate associations between water quality parameters and WQI values, APCS-ANN model is able to justify and predict the WQI values at Kuantan River Basin. In this sense, APCS methods proved constitute recommended tools for more comprehensible of large volume data sets especially in environmental monitoring studies. Thus, the prediction of WQI values using APCS-ANN model can be used for environmental monitoring agencies in Malaysia to reduce the monitoring and chemical analysis cost as only significant parameters  will further used for monitoring purposes. The model gives efficient computational judgments.As a conclusion, agricultural practices and minimum contribution of anthropogenic human activities were among the responsible sources for surface water pollution in Kuantan River Basin, Malaysia. A main AN and POThe authors declare that they have no competing interests.Nasir MFM, carried out the environmental modeling studies, assisting in the writing, data analyzing, drafted and submission of the manuscript. Zali AM, carried out the environmental modeling studies, assisting in the writing, data analyzing and drafted the manuscript. Juahir H, carried out the environmental modeling studies, participated in sequence alignment and reviewing the manuscript. Hussain H, contributed in the data and landuse map of the manuscript. Zain SM, participated in the reviewing of the manuscript. Ramli N., contributed in the water quality data for the manuscript. All authors read and approved the final manuscript.


In Response: We welcome the critiques of Nasci, et al. (The underlying data were obtained with an ELISA specific to severe fever with thrombocytopenia syndrome virus (SFTSV). The conclusion was based on our knowledge, at the time our manuscript was submitted, that in North America no other known phleboviruses of this expanded Uukuniemi group that contains SFTSV and HLV were reported to be cross-reactive with SFTSV. When tested by using our reagent, SFTSV was not cross-reactive with Rift Valley fever virus. Related phleboviruses of this group  have not been reported in North America  are distantly related and have ≈11% amino acid sequence homology to SFTSV. The recently characterized Lone Star virus appears to be the closest relative to SFTSV and HLV and may cross-react with SFTSV and HLV, as also suggested by Nasci et al., but this virus is apparently known only from 1 isolate obtained in 1967 (


As one of the phylogenetically and ontogenetically oldest neurotransmitters, the monoamine serotonin (5-HT) is derived from tryptophan in neurons within the raphe nuclei, and innervates various parts of the nervous system (Jacobs and Azmitia, Although the serotonergic system has been studied for many years, an integrative account of its underlying functions remains elusive. This could be partly attributed to the high variability and heterogeneity in terms of neuronal properties and receptor subtypes, and its extensive connections with other brain regions. Indeed, it has been claimed that serotonin is in involved “in virtually everything, but responsible for nothing” (Jacobs and Fornal, in vitro and in vivo conditions.At the receptor and cellular levels, Maejima et al.  discusseAt the neuronal circuit level, Celada et al., Besides the cortex, serotonin is also known to modulate important subcortical brain regions. Using a mathematical model of multiple brain regions, Reed et al.  demonstrIt has been proposed that reinforcement learning models can be used as a platform for studying neurological and neuropsychiatric disorders (Maia and Frank, We hope that this issue will provide a comprehensive review of the diverse and complex functions and computations of serotonergic and related systems at multiple scales of investigation. We wish that this will motivate and inspire a more integrative research approach from cellular to systems level toward understanding neuromodulatory systems.


Anxiety is arguably an emotion that predates the evolution of man. Its ubiquity in humans, and its presence in a range of anxiety disorders, makes it an important clinical focus. Developments in nosology, epidemiology and psychobiology have led to significant advancement in our understanding of the anxiety disorders in recent years. Advances in pharmacotherapy and psychotherapy of these disorders have brought realistic hope for relief of symptoms and improvement in functioning to patients. Neurotic disorders are basically related to stress, reaction to stress  and individual proneness to anxiety. Interestingly, both stress and coping have a close association with socio-cultural factors. Culture can effect symptom presentation, explanation of the illness and help-seeking. Importance given to the symptoms and meaning assigned by the physician according to their cultural background also differs across culture. In this way culture can effect epidemiology, phenomenology as well as treatment outcome of psychiatric illness especially anxiety disorders. In this review an attempt has been made to discuss such differences, as well as to reflect the important areas in which Indian studies are lacking. An attempt has been made to include most Indian studies, especially those published in Indian Journal of Psychiatry. Anxiety is arguably an emotion that predates the evolution of man. Its ubiquity in humans, and its presence in a range of anxiety disorders, makes it an important clinical focus. Developments in nosology, epidemiology and psychobiology have significantly advanced our understanding of the anxiety disorders in recent years. Advances in pharmacotherapy and psychotherapy of these disorders have brought realistic hope for relief of symptoms and improvement in functioning to patients.The word anxiety is derived from the Latin “anxietas”  and encompasses behavioral, affective and cognitive responses to the perception of danger. Anxiety is a normal human emotion. In moderation, anxiety stimulates an anticipatory and adaptive response to challenging or stressful events. In excess, anxiety destabilizes the individual and dysfunctional state results. Anxiety is considered excessive or pathological when it arises in the absence of challenge or stress, when it is out of proportion to the challenge or stress in duration or severity, when it results in significant distress, and when it results in psychological, social, occupational, biological, and other impairment.The DSM-IV (American Psychiatric Association) includesNeurotic disorders are basically related to stress, reaction to stress  and individual proneness to anxiety. Interestingly, both stress and coping have close association with socio-cultural factors. Culture can affect symptom presentation, explanation of the illness and help-seeking. Importance given to the symptoms and meaning assigned by the physician according to their cultural background also differ across culture. In this way culture can affect epidemiology, phenomenology as well as treatment outcome of psychiatric illness especially anxiety disorders. In this review an attempt has been made to highlight on any such difference if there, as well as this review will also reflect the important areas, in which Indian studies are lacking.This review will summarize most Indian studies pertaining to anxiety disorders published in Indian Journal of Psychiatry as well as found in other journals too.P < 0.5) were significantly higher  in urban communities than rural, and all neurotic disorders were significantly high among females . Though meta-analysis has its own limitations, this was the first attempt to analyze the epidemiological studies.To the author’s knowledge there are three meta-analyses of Indian epidemiological studies of psychiatric disorders. A meta-analysis of 13 psychiatric epidemiological studies (Reddy and Chandrashekhara) with a tIt has been seen that rural epidemiological studies are more difficult to conduct as compared to urban ones, due to ignorance, stigma and lack of resources. Disorders like obsessive compulsive disorder often go unaccounted due to ignorance and attribution of such issues to personality factors. This canGanguli analyzedMadhav, in an anDelineation of the sample and initial contact with subjects including collection of background demographic data.Identification of suspected cases, usually on the basis of interviews and questionnaire by non-psychiatric personnel like social workers and sometimes by psychological tests. Physical examination of suspected cases by medical personnel was part of this phase.Psychiatric examination and clinical diagnosis and classification of suspected cases were the third stage.Epidemiological data of anxiety disorder in special population like pediatric and elderly are scant. To the best of the author’s knowledge, one population-based study on geriatric population was reported by Tiwari and Srivastava. These auet al.)[et al.[et al.[A prevalence rate of psychiatric morbidity among pediatric population has been reported since very early 9 but theet al.) observed.)[et al. found nel.[et al. found thl.[et al. reportedIn an another epidemiological study conducted by Manchanda and Manchanda, a total et al.)[In another epidemiological study of possession syndrome  conducteet al.)[Recently a community-based study was conducted by ICMR in Lucknow  and Banget al.) in childet al.).[Most of the epidemiological studies done in India neglected anxiety disorders. The use of poor sensitive screening instruments, single informant and systematic under- reporting has added to the discrepancy in the prevalence rate. The prevalence of mental disorders reported in epidemiological surveys can be considered lower estimates rather than accurate reflections of the true prevalence in the population .et al.).[Most of the Indian epidemiological studies analyzed here have surveyed a population less than 6000. This raises a query whether the findings can be generalized to even one State of India. Mental health care priorities need to be shifted from psychotic disorders to common mental disorders like depression, anxiety disorders, somatoform disorder, etc., which are also associated with high disability in all measures .In children and adolescents, review of literature shows that common disorders seen are dissociative convulsions and stupor.–29 Sympt30262628The phenomenology of panic disorder has been studied widely in the West but rarely in India. Srinivasan and Neerakal studied Social Anxiety Disorder (SAD) is a chronic, disabling and treatable disorder with common onset in adolescence. There is only one study conducted by Mehtalia and Vanker to find PTSD has a global significance, and its impact in countries that have been experiencing repeated disaster and social unrest for many years could be a large public health problem. Despite having a global significance, its prevalence has been best studied in industrialized societies only particularly in USA. It is unThe very first paper published in Indian Journal of Psychiatry, in 1951, was authored by Dr. P.K. Ray, titled “Common Obsession –compulsive symptoms in India”. In this et al.[Akthar et al.54 tried et al.[et al.),[Khanna et al. tried toet al. and compet al. which ha[et al.), T hey de[et al.),.Understanding the biology of various psychiatric disorders has taken the front seat in psychiatric research. Indian studies particularly on this area of anxiety disorders are very less .et al.[et al.[Only a few studies have assessed neuro-cognitive domains in anxiety disorders. A study by Tarafder et al. on 20 pal.[et al. on 30 paBhatti and Channabasavanna studied Sharma and Ram carried et al.),[et al.)[Studies based on treatment of anxiety states or disorders are being published in Indian Journal of Psychiatry since 1959. The initial few published studies have been - Effect on anxiety states of carbon dioxide Jetley, and Guaiet al.), Trial ofet al.), double bet al.), clinicalet al.), and stud,[et al.)et al.[The first Indian study on the effect of Benzodiazepines in anxiety disorders was conducted by Master and Kajaria. This douet al. and lateet al.et al.[Khanna et al. studied et al.[Shah et al. conducteet al.81 More pet al.[Shah et al. evaluateet al.[et al.,[Sahasi et al. ascertai.[et al., found siet al.[Vahia et al. conducteet al.[et al.).[Andrade et al. conducte[et al.). India isStatus of anxiety disorder research from India in relation to epidemiology, phenomenology, course, outcome and management are lacking. Research areas like family studies, genetics, and neurobiology are not touched adequately. Most of the studies have tried to replicate the findings from the West. Despite rapid advancement in the field of psychopharmacology, the researches in the field of anti-anxiety and antidepressant drugs are dismally low from India. Furthermore research is lacking in the areas of non-pharmacological management like relaxation therapies, yoga, other meditation techniques and psychotherapies despite India being the birth place of many such techniques. Most of the research is done by tertiary centers involving limited sample which may not provide the real picture.


Antipsychotic as a class of medications became available for treatment of various psychiatric disorders in the early 1950’s. Over the last 60 years many antipsychotics have become available. In line with the west, Indian researchers have evaluated the efficacy of antipsychotics in various conditions. Additionally, researchers have also evaluated the important safety and tolerability issues. Here, we review data originating from India in the form of drug trials, effectiveness, usefulness, safety and tolerability of antipsychotics. Additionally, data with respect to other important treatment related issues is discussed. When one looks at the history of psychiatric treatments, prior to availability of electroconvulsive therapy (ECT), measures like magic, restraints, blood letting, emetics, purgatives, surgical operations on various organs, removal of foci of infections, vaccines and endocrines were tried as treatment options for schizophrenia. Therapies like insulin coma and electroconvulsive therapy became available. However,India, as a country was not isolated from all these developments. Over the years many classes of antipsychotics have become available in India, some of which have stood the test of time and are still in use and some are no more marketed or are no more favorite of the clinicians. Research focusing on the usefulness of psychotics in India has more or less followed the trends in the West; however, some of the newer antipsychotic drugs which are currently marketed have not been evaluated as thoroughly as others. The pharmaceutical industry and the policy of the government have ensured that these medications are available at a reasonable price.This review focuses on research done on various anti psychotics in India. For this a thorough internet search was done using key words like India, antipsychotics, name of each antipsychotic, efficacy, effectiveness, usefulness, tolerability, side effects, metabolic syndrome, weight gain, prescription, cost in various combinations. Various search engines like PUBMED, GOOGLE SCHOLAR, SCIENCEDIRECT, SEARCH MEDICA, SCOPUS, and MEDKNOW were used. In addition, a through search of all the issues of Indian Journal of Psychiatry available online was done. Hand search of some of the missing issues was also attempted and this yielded a few more articles. We have excluded review articles which we felt did not reflect the Indian scenario to a large extent or did not cover the available Indian data. Data from the animal studies that originated in the form of case reports and studies published only as abstract have not been included.Twenty eight studies which have evaluated the efficacy of first generation oral antipsychotics in schizophrenia have been published.–29 Of thExcept for some of the trials in the 1960s and early 1970s, the efficacy and side effects were measured on some rating scales. All these trials have not used the dropouts in their final analysis of data. Data from all these trials can be summarized as: Typical antipsychotics are useful for treatment of schizophrenia, typical antipsychotics are more efficacious than placebo in the treatment of schizophrenia, improvement is seen more in paranoid and catatonic symptoms, aggression and less so in depressive symptoms; addition of trihexyphenidyl doesn’t reduce the efficacy of antipsychotic like trifluperazine and extrapyramidal symptoms are common with typical antipsychotics.et al.[Nine trials have evaluated the efficacy of depot antipsychotics in schizophrenia.–38 Some et al. that comThirteen studies have compared typical antipsychotics with either electroconvulsive therapy (ECT) alone or a combination of ECT and typical antipsychotic medication.39–50 AllCentbutindole was developed by Central Drug Research Institute, Lucknow; it has been evaluated in four trials and has been compared with trifluperazine, haloperidol and risperidone . Another multicentric trial, which included subjects from India too, showed that both risperidone and haloperidol were better than placebo; however, there was no difference in the efficacy of risperidone and haloperidol.[P < 0.01). At 12 weeks, the response rate was maintained in almost all subjects who responded at three weeks and additionally more than 80% of the subjects who did not respond  to risperidone or haloperidol at three weeks but continued the medications responded at 12 weeks.However, in the recent trials, atypical antipsychotics have been evaluated in large samples in double blind placebo control trials and the outcomes have been measured using standard instruments. In the study by Khanna et al. risperidoperidol. At threeet al.[Four studies have reported the efficacy of antipsychotics in the management of acute psychosis, of which three have specified that the trials included subjects with acute and transient psychosis,7477 whil74Studies in 1970s and 1980s evaluated the efficacy of low dose haloperidol, flupenthet al.[et al.[Two studies have evaluated the role of antipsychotic in violent and agitated subjects attending the psychiatry emergency settings. In a randomized controlled trial, Alexander et al. comparedl.[et al. comparedOnly a small case series of seven cases reported that risperidone is effective in the management of delirium and it is well tolerated by these subjects.et al.[Good response to antipsychotics like trifluperazine, haloperidol and chlorpromazine was reported in cases of delusional parasitosis. In theiret al. found thSeven studies have evaluated the efficacy of various antipsychotics in childhood disorders or childhood/adolescent onset disorders. Studies done in 1960s and early 70s evaluated the role of antipsychotics primarily in the behavioral problems in children with epilepsy/epilepsy and mental retardation and have shown that trifluperazine, prothipendyl and trifluperidol are useful but fluphenazine is ineffective. One small study evaluated the usefulness of clozapine in childhood onset schizophrenia. A study et al.[P = 0.03) and schizophrenia (P = 0.04), but the association was rendered insignificant after corrections for multiple comparisons. Vijayan et al.(2007)[et al.[et al.[With increasing interest in the role of genetic factors in treatment response and side effects of medications, studies from India have tried to address the genetic links of tardive dyskinesia, treatment response and severity of psychopathology.–96 Howevet al. evaluateal.(2007) studied 7)[et al. reportedA study reported that subjects, who showed initial dysphoric response to a test dose of neuroleptic, later respond poorly to the neuroleptics.et al.[et al.[et al.[et al.[A few studies have evaluated the antipsychotic prescription patterns from India. In one of the early studies, Khanna et al. evaluatel.[et al. reportedl.[et al. evaluatel.[et al. evaluateIn a recently conducted survey, Grover and Avasthi found thet al.[et al.[et al.[et al.[et al.[Khanna et al. reportedl.[et al. reportedl.[et al. studied l.[et al. evaluatel.[et al. reportedl.[et al. reportedA recently published study, which compared three groups of community dwelling subjects with schizophrenia, showed that mean disability scores remain virtually unchanged in those who remained untreated, but showed a significant decline (indicating decrement in disability) in those who continued to receive antipsychotics and in those in whom antipsychotic treatment was initiated. The proportion of patients classified as ‘disabled’ declined significantly in the treated group, but remained the same in the untreated group.et al.[et al.[A few studies have evaluated the cost of antipsychotics per se and cost of management of schizophrenia. Girish et al. found thet al. showed tl.[et al. found thl.[et al. In anothl.[et al. reportedet al.[Besides the efficacy or usefulness studies, some studies have specifically evaluated the side effects and tolerability issues with antipsychotics.–136 In o118124et al.–133 wheret al.130 Studiet al. and amonet al.Reasonably good amount of data on the efficacy of antipsychotics in schizophrenia is available from India. In addition, studies also suggest usefulness of antipsychotics in mania, acute and transient psychosis, delusional disorders and agitation and violence. Older studies also suggest that typical antipsychotics have usefulness in anxiety states. Many of the recent studies followed double blind randomized controlled design and had a reasonable sample size. Further, many studies have been carried out at multiple sites throughout the country. To some extent, data is also available with regards to the tolerability of antipsychotics and it shows that extrapyramidal symptoms and NMS are more common with typical antipsychotics and weight gain is more common with antipsychotics like olanzapine and risperidone.However, the major limitation of the research is that there are not many studies on the treatment of schizophrenia in elderly, in subjects with comorbid physical illnesses and in cases with comorbid substance abuse. Data on long term efficacy of antipsychotics is also meager. There is still a need to conduct long term comparative multicentric studies to evaluate the efficacy, effectiveness, tolerability and side effects of antipsychotics.