Clinical research

Recent research suggests that romantic love may be literally addictive. Although the exact nature of the relationship between love and addiction has been described in inconsistent terms throughout the literature, we offer a framework that distinguishes between a narrow view and a broad view of love addiction. The narrow view counts only the most extreme, harmful forms of love or love-related behaviors as being potentially addictive in nature. The broad view, by contrast, counts even basic social attachment as being on a spectrum of addictive motivations, underwritten by similar neurochemical processes as more conventional addictions. We argue that on either understanding of love-as-addiction, treatment decisions should hinge on considerations of harm and well-being rather than on definitions of disease. Implications for the ethical use of anti-love biotechnology are considered.

As the use of qualitative inquiry increases within the field of social work, researchers must consider the issue of establishing rigor in qualitative research. This article presents research procedures used in a study of autoethnographies that were written regarding the experience of being Jewish. In this project, the researchers utilized reflexivity, audit trail, triangulation by observer, peer debriefing, member check and prolonged engagement in order to manage the threats to trustworthiness as discussed by Padgett (1998). Implications of the project suggest that research procedures utilized by qualitative researchers to establish rigor are an important way to increase our confidence that the voice of the participants is heard, therefore fitting the mission of the social work profession.

With sincere satisfaction and pride, I present this first editorial of
the Journal of Histology and Histopathology edited by myself.
I know this is a very challenging task, assuming the editorial
coordination of this journal, targeted to enhance the work
of so many esteemed international experts as well as dear
colleagues, who work on morphological research. A special
thanks goes to our current editorial team (Sherif M Karam,
Xueyong Zhu, Gjumrakch Aliev, Khin Thway, Han-Seung yoon,
Paul Evans, George Perry and Khush Mittal) and the publishing
group (Herbert Publications) that, day after day, thanks to
their valuable contribution, make possible the growth of
this journal. Reviewing a manuscript is time-consuming and
unpaid, and often reviewers are bombarded with requests to
review simultaneously from several journals. I hope to increase
the number of editors of the editorial board members (with
different geographical origin), to assure a rapid publication.
My aim and that of all the other editors is that this journal will
constitute a valuable tool, of both learning and research, to
understand how modern histology and histopathology can
be a fundamental bridge between molecular and anatomicalphysiological
disciplines and how the structural organization
of cells in tissues is inextricably linked to the functions that
the pathological and normal tissues must perform. These
concepts must constitute a significant part of imprinting training,
necessary to help researchers to work in a more guided way,
increasingly interested in a cellular approach to diseases and
their related treatments. Finally, conscious of the fact that this
journal can be considered a “system” subjected to the laws
of evolution, we welcome criticism and suggestions for its
improvement in the future. The purpose of this editorial was
to explain my view on histology and histopathology of today,
providing a brief overview from the past to the future.

The Centers for Disease Control and Prevention (CDC) has announced a set of provisional guidelines concerning male circumcision, in which they suggest that the benefits of the surgery outweigh the risks. In this brief comment, I highlight a few of the key scientific and ethical issues worth considering in interpreting the CDC recommendations.

According to Brian Morris (2013), “Science supports infant circumcision” and “so should skeptics.” It would be more accurate to say that ‘Brian Morris supports infant circumcision,’ and that skeptics can think for themselves. In this paper, we critically assess the arguments and evidence presented by Morris in his recent article, and draw some general lessons for the ongoing debate about the science and ethics of infant male circumcision.

a b s t r a c t a r t i c l e i n f o Social aggression is an escalating hazard for individuals and society. It is most frequently observed as impulsive-reactive aggression in antisocial personality disorder (APD), but in psychopathic aggressive personalities instrumental social aggression is more prominent. However, the psychobiological mechanisms underlying human social aggression are still poorly understood. Here we propose a psychobiological mechanism that may explain human social aggression wherein the steroid hormones cortisol and testosterone play a critical role. High levels of testosterone and low levels of cortisol have been associated with social aggression in several species but it seems that in those individuals wherein these hormonal markers combine social aggression is most violent. In this review we discuss fundamental and clinical research which underscores the potential of the testosterone-cortisol ratio as a possible marker for criminal aggressive tendencies.

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

The complexity of chronic pain has represented a major dilemma for clinical researchers interested in the reliable and valid assessment of the problem and the evaluation of treatment approaches. The West Haven-Yale Multidimensional Pain Inventory (WHYMPI) was ...

In this article, we summarize the definition, etiology, assessment, and treatment of sexual dysfunctions in women. Although the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV-TR) is our guiding framework for classifying and defining women's sexual dysfunctions, we draw special attention to recent discussion in the literature criticizing the DSM-IV-TR diagnostic criteria and their underlying assumptions. Our review of clinical research on sexual dysfunction summarizes psychosocial and biomedical management approaches, with a critical examination of the empirical support for commonly prescribed therapies and limitations of recent clinical trials.

This paper describes a number of historical breaches of research ethics. Typically the victims of such breaches belong to vulnerable populations, such as prisoners, mentally disabled people, women and people in developing countries. This article provides a brief introduction to the main ethical approaches in bioethics. Subsequently it looks at a number of currently discussed ethical issues in clinical research ethics, notably the ethics standards of clinical trials in developing countries, the use of prisoners and incompetent people in clinical research, and the modus operandi of research ethics committees. 7

Review Soft tissue changes following extraction vs. nonextraction orthodontic fixed appliance treatment: a systematic review and meta-analysis Konstantonis D, Vasileiou D, Papageorgiou SN, Eliades T. Soft tissue changes following extraction vs. nonextraction orthodontic fixed appliance treatment: a systematic review and meta-analysis. Eur J Oral Sci 2018; 00: 1–13. © 2018 Eur J Oral Sci The aim of this systematic review was to assess the effect of systematic extraction protocols during orthodontic fixed appliance treatment on the soft tissue profile of human patients. Nine databases were searched until December 2016 for controlled clinical studies including premolar extraction or nonextraction treatment. After elimination of duplicate studies, data extraction, and risk-of-bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MD) or standardized mean differences (SMD) and their 95% CIs were performed, followed by subgroup, meta-regression, and sensitivity analyses. Extraction treatment was associated with increased lower lip retraction (24 studies; 1,456 patients; MD = 1.96 mm), upper lip retraction (21 studies; 1,149 patients; MD = 1.26 mm), nasolabial angle (21 studies; 1,089 patients; MD = 4.21°), soft-tissue profile convex-ity (six studies; 408 patients; MD = 1.24°), and profile pleasantness (three studies; 249 patients; SMD = 0.41). Patient age, extraction protocol, and amount of upper incisor retraction during treatment were significantly associated with the observed extraction effects, while the quality of evidence was very low in all cases due to risk of bias, baseline confounding, inconsistency, and imprecision. Although tooth extractions seem to affect patient profile, existing studies are heterogenous and no consistent predictions of profile response can be made.

The goal of this project is to develop and utilize a microfluidic device to isolate and enrich tumor cells circulating in peripheral blood. Circulating tumor cells (CTCs) have been used as biomarkers for cancer diagnostics and prognosis. However, the rarity of these cells (roughly 1 in a billion) poses a technological challenge to sort and concentrate them. CTCs hold potential sources for early detection, characterization, monitoring of cancers, and development of personalized treatment. The project is currently funded by the US National Cancer Institute (NCI) of the National Institutes of Health (NIH).

After studying this article, participants should be better able to do the following: 1. Understand the difference between criminal investigative analysis and forensic psychology. 2. Consider ethical considerations when offering forensic psychological opinions. 3. Implement Daubert factors when evaluating the appropriateness of forensic testimony.

Ações em saúde indígena amazônica E lá no Alto do Rio Juruá, vez por vezes imaginei o Alto Rio Negro! Relembrei o vivido há 30-40 anos atrás, tempos de uma cidade mais calma, dos paralelepípedos, do urbano mais limpo, do silêncio noturno precoce. Percorri São Paulo dentro e nos contornos dos bairros da Mooca [onde nasci], Perdizes [Rua Apinagés, onde cresci], Butantan [aonde vim trabalhar]. Na cidade de São Paulo, índios não há, mas o Tupi-Guarani segue inscrito: Mooca -é o construir, o pouso; Apinagés -uma das várias tribos extintas no Brasil; Butantan -é a terra firme, dura... Visitei novamente a São Paulo do avô Augusto Esteves [1891-1966] desenhista, que ilustrou várias obras científicas que, até os anos 1950 escrevia, surpreendam-se, poesia caipira com o pseudônimo de Mané Coivara...; cidade do avô Oswaldo Sant´Anna [1901-1976], bancário, que consertava tudo, que, pasmem, esculpia madeira e criava brinquedos...; terra adotiva do meu bisavô Mineiro da Campanha, o cientista Vital Brazil [1865-1950] que no Instituto Butantan descreveu pela primeira vez a especificidade dos sistemas biológicos através dos estudos que conduziram à obtenção dos soros anti-ofídicos. Dessa São Paulo, há exatos 80 anos, partiu para a Amazônia o paulistano Mário de Andrade [1893-1945] intelectual genial que anunciou Macunaíma, entidade divina para os indígenas do Alto Rio Branco, e que descreveria sua Viagem Etnográfica pelo país, como... Viagem pelo Amazonas até o Peru, pelo Madeira até a Bolívia, e pelo Marajó até dizer chega. Como Mário, o filósofo-antropólogo belga Claude Lévi-Strauss quando professor da Universidade de São Paulo viajou pela Amazônia em fins da década de 30. Ambos embebedaram-se da floresta tropical, apaixonaramse pelos povos honestos de sinceridade assustadora. Imagino que essas características foram determinantes de sua vulnerabilidade ante o homem branco.

Screening of Generalized Anxiety Disorder (GAD), which is often undetected and untreated, could be improved by quick and easy web-based data collection. This paper aims to validate the web-based self-rated 7-item GAD-7, its shortened 2-item GAD-2 and a single item from the GAD-7 scale (GAD-SI) to screen for GAD. Of a total of 502 subjects aged 18-80 who rated the web-based GAD-7, Center for Epidemiological Studies Depression scale (CES-D) and Hospital Anxiety and Depression Scale (HADS), 157 (31%) subjects had a WHO Composite International Diagnostic Interview for DSM-IV-disorders by telephone. The GAD-7 had good reliability. Subjects with a GADdiagnosis had significantly higher means on GAD-2, GAD-SI and GAD-7 than subjects without a GAD-diagnosis. The AUC (Area Under the Curve) of the GAD-SI and GAD-2 was accurate and not significantly different to the GAD-7 AUC. The web-based GAD-SI, GAD-2 and GAD-7 are reliable, valid tools to quickly screen for GAD in busy mental health settings and clinical research. More research is needed to validate the GAD-SI 'Do you have trouble relaxing' to see if its screening properties approach those of the GAD-7.

Multidisciplinary teams (MDTs) are conventionally recommended in mental health
care literature as an important way to offer holistic treatment provision to patients. This
study aims to explore multidisciplinary teamwork in contemporary mental health
settings, particularly what aids and hinders the process of multidisciplinary teamworking,
and the social work contribution in such teams. In order to attain an in-depth
exploration of these phenomena, a single case study design was employed. Within this
design, data were generated through semi-structured interviews and structured
observation of a mental health MDT in Ireland. These data were analysed using
interpretative phenomenological analysis. The research highlights how the concept of
mental illness is contested within this MDT, with the medical model dominant within
an environment of fluid working arrangements. Professional role blurring and
stereotyping were found to impact the division of labour on this team, with role
negotiation found to be an integral part of retaining a professional’s practice identity.
This research raises concerns for social work’s capacity to function within mental
health MDTs in Ireland, and highlights ways in which social work educators might
respond in order to empower Irish social workers to meet the challenges of mental
health multidisciplinary teamworking.

This review provides an updated overview of the neurophysiological rationale, basic and clinical research literature, and current methods of practice pertaining to clinical neurofeedback. It is based on documented findings, rational theory, and the research and clinical experience of the authors. While considering general issues of physiology, learning principles, and methodology, it focuses on the treatment of epilepsy with sensorimotor rhythm (SMR) training, arguably the best established clinical application of EEG operant conditioning. The basic research literature provides ample data to support a very detailed model of the neural generation of SMR, as well as the most likely candidate mechanism underlying its efficacy in clinical treatment. Further, while more controlled clinical trials would be desirable, a respectable literature supports the clinical utility of this alternative treatment for epilepsy. However, the skilled practice of clinical neurofeedback requires a solid understanding of the neurophysiology underlying EEG oscillation, operant learning principles and mechanisms, as well as an in-depth appreciation of the ins and outs of the various hardware/software equipment options open to the practitioner. It is suggested that the best clinical practice includes the systematic mapping of quantitative multi-electrode EEG measures against a normative database before and after treatment to guide the choice of treatment strategy and document progress towards EEG normalization. We conclude that the research literature reviewed in this article justifies the assertion that neurofeedback treatment of epilepsy/seizure disorders constitutes a well-founded and viable alternative to anticonvulsant pharmacotherapy.

This review on autism spectrum disorder (ASD) focusses on recent insights in the clinical picture, such as continuity of the phenotype and the concept of broader phenotype, on epidemiology and on clinical issues relevant to physicians, including new methods for early screening and diagnosis, psychiatric and somatic co-morbidity, and the expansion of so-called complementary and alternative treatments. ASD is a disorder with mainly genetic causes and recent insights show that a variety of genetic mechanisms may be involved, i.e. single gene disorders, copy number variations and polygenic mechanisms. Technological advances in genetics have lead to a number of promising findings, which, together with other lines of fundamental research, suggest that ASD may be a disorder of connectivity in the brain, at least in a subgroup of patients. It is possible that part of the genetic load in autism actually reflects geneenvironment interaction, but there is no evidence for purely environmental causes in a substantial number of cases. Clinical research suggests that ASD may be a multi-system disorder in at least a subgroup of subjects, affecting the gastro-intestinal (GI) tract, the immune system and perhaps other systems. Behavioural treatments remain the cornerstone of management, and are mainly aimed at stimulation of the domains of impaired development and reducing secondary behaviours. These treatments are constantly being refined, but the main progress in this area may be the increase of research on effectiveness.

Schizophrenia is a chronic, severe, and disabling brain disease. About one-third of all patients with schizophrenia do not respond adequately to drug treatment. Advances in neuroscience and clinical research have led to the introduction of a novel generation of compounds with neuroprotective properties. Despite numerous animal studies with promising neuroprotective agents, no successful strategy for neuroprotection from functional psychoses has been successfully demonstrated. There are two main targets for neuroprotective therapy: (1) neurodegenerative processes in schizophrenia (e.g. apoptosis, excitotoxicity, oxidative stress, stress sensitization, and alteration of neurosteroids); and (2) phenotypic presentations of illness including psychopathological symptoms, significant decline in cognition, psychosocial functioning and in health related quality of life (HRQL). In this chapter substantial information about clinical trials with neurosteroids, vitamins, and some herbal supplements with neuroprotective properties in schizophrenia is presented. Neurosteroids such as pregnenolone (PREG), dehydroepiandrosterone (DHEA) and their sulfates (PREGS and DHEAS) are reported to have a modulatory effect on neuronal excitability and synaptic plasticity. In addition, vitamins and herbal supplements are important for regular cell function, growth and development. As a rule, vitamins promote the activity of enzymes to improve their efficiency and in this role they are called coenzymes. The herbal supplements are active antioxidants with neuroptective properties. The authors hope that neuroprotective strategies will pave the way to the next generation of antipsychotic, sedative and mood stabilizer medications. The clinical effects of neuroprotective agents clearly merit further clinical trials for the treatment of mental disorders.

W HAT MAKES RESEARCH INvolving human subjects ethical? Informed consent is the answer most US researchers, bioethicists, and institutional review board (IRB) members would probably offer. This response reflects the preponderance of existing guidance on the ethical conduct of research and the near obsession with autonomy in US bioethics. 1-4 While informed consent is necessary in most but not all cases, in no case is it sufficient for ethical clinical research. 5-8 Indeed, some of the most contentious contemporary ethical controversies in clinical research, such as clinical research in developing countries, 9-13 the use of placebos, 14-16 phase 1 research, 17-19 protection for communities, 20-24 and involvement of children, 25-29 raise questions not of informed consent, but of the ethics of subject selection, appropriate risk-benefit ratios, and the value of research to society. Since obtaining informed consent does not ensure ethical research, it is imperative to have a systematic and coherent framework for evaluating clinical studies that incorporates all relevant ethical considerations.

Waning interest in urinary tract infection (UTI) research has limited clinical advances during the past two decades. Although care has improved for some specific UTI syndromes, there is limited evidence for most of the decisions made each day in the management of these infections. Additional clinical research is necessary to improve UTI prevention and care strategies. : S 0 9 2 4 -8 5 7 9 ( 0 1 ) 0 0 3 0 3 -X

This article describes the rationale, development, and validation of the Scale for Suicide Ideation (SSI), a 19-item clinical research instrument designed to quantify and assess suicidal intention. The scale was found to have high internal consistency and moderately high correlations with clinical ratings of suicidal risk and self-administered measures of self-harm. Furthermore, it was sensitive to changes in levels of depression and hopelessness over time. Its construct validity was supported by two studies by different investigators testing the relationship between hopelessness, depression, and suicidal ideation and by a study demonstrating a significant relationship between high level of suicidal ideation and "dichotomous" attitudes about life and related concepts on a semantic differential test. Factor analysis yielded three meaningful factors: active suicidal desire, specific plans for suicide, and passive suicidal desire.

Abstract
Engineering of craniofacial tissues would have a profound impact on various treatment strategies in dentistry. The role of
mesenchymal stem cells in the formation of all craniofacial and dental structures has been well demonstrated. Stem cells from
various craniofacial structures like dental epithelium, dental follicle, apical papilla, exfoliated deciduous teeth, periodontal
ligament and dental pulp are readily accessible and have immense potential in craniofacial research for regenerative and tissue
engineering applications. Various signalling molecules that pattern the morphogenesis of craniofacial tissues have been explored.
This review article epitomises how dentistry should evolve and highlights the need for close partnerships between basic and
clinical scientists.
Keywords: Tissue engineering, dentistry, stem cell, dental papilla, dental follicle, dental pulp stem cells

Efek samping parkinsonisme merupakan suatu bagian dari sindrom ekstrapiramidal yang muncul akibat penggunaan antipsikotik. Skizofrenia merupakan gangguan jiwa berat yang ditandai oleh dua atau lebih tanda tanda halusinasi, pembicaraan tidak teratur, sikap katakonik, emosi negatif seperti kehilangan ekspresi emosi. Gangguan di jaras nigrostriatal oleh penggunaan antipsikotik dapat mencetus timbulnya efek samping parkinsonisme pada pasien skizofrenia. Pola penggunaan antipsikotik, antipsikotik tipikal ataupun antipsikotik yang melebihi dosis dapat menimbulkan efek samping parkinonisme. Tujuan dari penelitian ini adalah untuk mengetahui hubungan antara pola pemberian obat antipsikotik terhadap efek samping parkinsonisme pada pasien skizofrenia di Badan Layanan Umum Daerah Rumah Sakit Jiwa Aceh tahun 2015. Pengambilan sampel menggunakan teknik accidental sampling dengan jumlah sampel 501 pasien yang terdiri atas 222 pasien dengan pola pengobatan monoterapi dan 279 pasien dengan pola pengobatan polifarmaka. Pengumpulan data dilakukan melalui rekam medik pasien. Hasil penelitian menunjukkan jumlah pasien dengan efek samping parkinsonisme adalah 258 orang (51,5%). Jenis antipsikotik yang paling banyak diberikan adalah kombinasi antipsikotik atipikal berjumlah 108 (37,3%). Pola pengobatan yang mendominasi pasien dengan efek samping parkinsonisme adalah polifarmaka sebanyak 152 (59%). Jenis kelamin pasien dengan efek samping parkinsonisme paling banyak ditemukan adalah laki laki dengan jumlah 204 pasien (79%). Kelompok usia yang paling banyak ditemukan pada pasien dengan efek samping parkinsonisme adalah 25-45 tahun dengan jumlah 179 pasien (69,4%). Hasil analisis dengan metode chi-square menunjukkan adanya hubungan pola pemberian obat antipsikotik terhadap efek samping parkinsonisme pada pasien skizofrenia dengan nilai signifikansi 0,010 (p <0,05).



xii
ABSTRACT
Drug induced-parkinsonism (DIP) is part of extrapyramidal syndrome which is caused by the use of antipsychotic. Schizophrenia is a severe mental condition signified by two or more signs of hallucination dissociated conversation, catatonic, and negative emotions such as loss of expression. Disturbance in nigrostriatal pathway by antipsychotic usage may cause DIP on schizophrenic patients. Antipsychotic usage  pattern, typical antipsychotic, or overdosing of antipsychotic may cause DIP. The  purpose of this research is to analyze the association between antipsychotic usage  pattern and DIP on schizophrenic patients in General Regional Service Unit of Aceh  Mental Health Hospital on 2015. Samples were obtained by using accidental sampling method with total sample of 501 patients analyzed of which 222 patients using monotherapy antipsychotic usage pattern and 279 patients using polypharmacy antipsychotic usage pattern. Data was obtained via medical record. The result of this research shows the total of patient with DIP was 258 patients (51,5%). Most given type of antipsychotic is atypical with total of 108 (37,3%). Antipsychotic usage pattern which is dominating the patients with DIP was polypharmacy with total of 152 (59%). Most  found gender in patients with DIP was male with total of 204 patients (79%). Most  patients were in age group of 25-45 with total of 179 patients (69,4%). Analysis with chi-square shows that there is association between antipsychotic usage pattern with  DIP on schizophrenic patients with significance value of 0,010 (p <0,05)

Very often patients, suffering from renal calculi are reluctant to surgery unless there is much trouble. They look for medical management whether allopathic, homeopathic or ayurvedic, to get rid of it. Literatures show effectiveness of homeopathic medicines in expulsion of moderate to big sized renal stones. This case reported here is such an example which again proves the importance of individualization and thus efficacy of homeopathic medicines in addressing the underlying cause and expulsion of renal stone. Phosphorus, a homoeopathic remedy has acted nicely and helped to clear the renal stone.

Science has caught wind of mysticism once again. Operationalising metrics from the writings of perennial philosophers, psychopharmacologists are using psychedelics in a laboratory context to reliably induce ‘mystical experiences’. These experiences are scored along such dimensions as unity, noesis, transcendence of space–time and ineffability. How are we to read this moment? I draw on data from an ethnography of psychedelic science and take cue from Walter Benjamin’s treatment of the threshold in Convolute O of The Arcades Project, to identify apophatic narratives of trickery that contrast with the positive knowledge prominent in the sciencing of the mystical experience. Read as apophatic labour, psychedelic trip reports reveal how the significance of the mystical encounter lies not in its point-like efficacy in transforming the subject, but in precisely the doubts, contradictions and aporias involved in the writing out of their experiences.

É importante que o profissional médico desenvolva uma boa avaliação crítica sobre a utilização de procedimentos voltados à detecção, seguimento e prevenção de estados patológicos. Com essa finalidade, inúmeros marcadores de lesão endotelial têm sido pesquisados e suas análises parecem produzir orientações úteis que melhoram a eficácia do tratamento, otimizando resultados e favorecendo o custo global dos cuidados à saúde.

There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor gamma, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness.

OBJECTIVE. To design a brief cognitive screener with acceptable sensitivity and speci- ficity for identifying subjects with cognitive impairment DESIGN. Cohort one is assembled from a community-based survey coupled with a second-stage diagnostic evaluation using for- mal diagnostic criteria for dementia. Cohort two is assembled from referrals to a specialty clinic for dementing disorders that completed the same diagnostic evaluation.

Clinical trial adaptation refers to any adjustment of the trial protocol after the onset of the trial. The main goal is to make the process of introducing new medical interventions to patients more efficient by reducing the cost and the time associated with evaluating their safety and efficacy. The principal question is how should adaptation be performed so as to minimize the chance of distorting the outcome of the trial. We propose a novel method for achieving this. Unlike previous work our approach focuses on trial adaptation by sample size adjustment. We adopt a recently proposed stratification framework based on collected auxiliary data and show that this information together with the primary measured variables can be used to make a probabilistically informed choice of the particular sub-group a sample should be removed from. Experiments on simulated data are used to illustrate the effectiveness of our method and its application in practice.

Clinical trial adaptation refers to any adjustment of the trial protocol after the onset of the trial. Such adjustment may take on various forms, including the change in the dose of administered medicines, the frequency of administering an intervention, the number of trial participants, or the duration of the trial, to name just some possibilities. The main goal is to make the process of introducing new medical interventions to patients more efficient, either by reducing the cost or the time associated with evaluating their safety and efficacy. The principal challenge, which is an outstanding research problem, is to be found in the question of how adaptation should be performed so as to minimize the chance of distorting the outcome of the trial. In this paper we propose a novel method for achieving this. Unlike most of the previously published work, our approach focuses on trial adaptation by sample size adjustment i.e.\ by reducing the number of trial participants in a statistically informed manner. We adopt a stratification framework recently proposed for the analysis of trial outcomes in the presence of imperfect blinding and based on the administration of a generic auxiliary questionnaire that allows the participants to express their belief concerning the assigned intervention (treatment or control). We show that this data, together with the primary measured variables, can be used to make the probabilistically optimal choice of the particular sub-group a participant should be removed from if trial size reduction is desired. Extensive experiments on a series of simulated trials are used to illustrate the effectiveness of our method.

A set of Good Clinical Laboratory Practice (GCLP) standards that embraces both the research and clinical aspects of GLP were developed utilizing a variety of collected regulatory and guidance material. We describe eleven core elements that constitute the GCLP standards with the objective of filling a gap for laboratory guidance, based on IND sponsor requirements, for conducting laboratory testing using specimens from human clinical trials. These GCLP standards provide guidance on implementing GLP requirements that are critical for laboratory operations, such as performance of protocol-mandated safety assays, peripheral blood mononuclear cell processing and immunological or endpoint assays from biological interventions on IND-registered clinical trials. The expectation is that compliance with the GCLP standards, monitored annually by external audits, will allow research and development laboratories to maintain data integrity and to provide immunogenicity, safety, and product efficacy data that is repeatable, reliable, auditable and that can be easily reconstructed in a research setting.

Clinical research usually involves patients with a certain disease or a condition. The generalizability of clinical research findings is based on multiple factors related to the internal and external validity of the research methods. The main methodological issue that influences the generalizability of clinical research findings is the sampling method. In this educational article, we are explaining the different sampling methods in clinical research .

This six-part research series is aimed at clinicians who wish to develop research skills, or who have a particular clinical problem that they think could be addressed through research. The series aims to provide insight into the decisions that researchers make in the course of their work, and to also provide a foundation for decisions that nurses may make in applying the findings of a study to practice in their own Unit or Department. The series emphasises the practical issues encountered when undertaking research in critical care settings; readers are encouraged to source research methodology textbooks for more detailed guidance on specific aspects of the research process.