A Guide to the Human Genome Project: Technologies, People, and Institutions

There are many scientific reports and full-length books dealing with the Human Genome Project in all its facets; this simple, concise guide is intended for those who need a broad overview and a quick reference. The information presented here is drawn from such journals as Cell, FASEB Journal, and Science; from official publications, in particular Human Genome News, the Office of Technology Assessment\u27s Mapping Our Genes, and the Department of Energy\u27s program reports; and from several secondary sources, including the prepublication draft of Gene Quest, by Robert Mullan Cook-Deegan, an insider\u27s historical account, and the exploration of techniques in Exons, Introns, and Talking Genes, by Christopher Wills. The report focuses almost entirely on the genome project in the United States. We have shortened and simplified whenever possibly, providing citations and a bibliography for those who would like more detailed information. We begin by exploring the origins of the genome project and the questions and criticisms it has provoked in the scientific community. Then we explore important techniques; the isntitutions connected with the prokect, including designated genome centers, important suppliers of resources, and corporations; systems of communication; and the ethical, legal, and social issues raised by the project. After two appendixes—lists of key personnel and of the disease associated with each chromosome—the report closes with a bibliography, a glossary (including a list of acronyms), and a timeline

Achieving Prudent Dementia Care (Palliare): An International Policy and Practice Imperative

This paper examines the provision of integrated advanced dementia care within seven European countries and critically reviews the potential contribution of the Prudent Healthcare perspective as a starting point for reform. Progressive efforts to innovate, promote quality and integrate care are tempered with the reality of resource constraints. Some policy makers in Europe and North America have turned their attention to the principles of Prudent Healthcare as a potential mechanism to maximise benefits for patients within available resources. As dementia progresses, living well requires increasing levels of support and care, people living with advanced dementia have complex health and social care needs, are highly dependent on others but are not yet at the terminal end stage of the condition. People with advanced dementia can benefit from a dementia specific palliative approach to care (Palliare), that helps them to live the best life possible for the months and often years they live with advanced dementia. It is also highly desirable to align policy innovations with integrated palliative care practice models and the education of the dementia workforce to accelerate informed improvements in advanced dementia care. There may be some coherence, at least superficially between Prudent Healthcare and integrated palliative care models such as Palliare. It is argued that for successful implementation, both require practitioners to be equipped with knowledge and skills and be empowered to deliver high quality care often within impoverished care environments. Adoption of the prudent perspective will however require development of a repertoire of approaches to hear the voice or proxy voice of people living with advanced dementia and to commit to the development and implementation of new evidence for advanced dementia practice. Evidence informing this policy debate draws upon contemporary literature and policy and the findings from research activities undertaken by the Palliare project supported through the Erasmus+ K2 Strategic Partnerships funding programme.info:eu-repo/semantics/publishedVersio

Mapping Review of Fieldwork Education Literature

Fieldwork is an integral phase of occupational therapy education, bolstered by a small but growing evidence base. A broad understanding of the state of that evidence base is necessary to inform the directions for future growth. The purpose of this work was to establish the current state of occupational therapy fieldwork literature, map that literature to recognized criteria for educational research, and identify gaps in the existing literature. Authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct a mapping review of articles with a primary focus on fieldwork education of occupational therapy (OT) or occupational therapy assistant (OTA) students in United States (Accreditation for Occupational Therapy Education)-based programs. Mapping criteria included level of education [OT, OTA], level of fieldwork [Level I, Level II], and categories of the AOTA Education Research Agenda - Revised (2018). Sources included four databases (Academic Search Premier, CINAHL, ERIC, PubMed) and one additional journal (Journal of Occupational Therapy Education). A total of 1,619 articles were identified, with 67 articles meeting inclusion criteria. The 67 included articles disproportionately focused on Level II OT fieldwork (53%, n=36), with sparse representation of Level I OTA fieldwork (1.5%, n=1), and addressed only two categories of the Education Research Agenda (2018; 80%, n=54). Level I fieldwork, occupational therapy assistant programs, and large swaths of the association’s Education Research Agenda (2018) were dramatically (or completely) underrepresented in fieldwork education research, suggesting important priorities for the immediate future of occupational therapy fieldwork education

Brukarens roll i välfärdsforskning och utvecklingsarbete

Tekstene er fra forelesninger samt fra doktorantkurset "Brukarmedverkan i forskning och utvecklingsarbete inom hälso- och sjukvård, socialt arbete och omsorg". Kurset ble avholdt våren 2009.Fra omslag: På 1980-talet blev ”brukare” ett modeord i offentlig förvaltning och förvaltningsforskning. Termen betecknar den som använder sig av välfärdsservice (jfr. engelskans service user), eller ”slutmottagare” av offentlig nyttighet eller åtgärd. Brukare av välfärdstjänster vet hur hjälp och service fungerar i praktiken och kan därför ge synnerligen viktig återkoppling enligt devisen: ”Den som har skorna på fötterna vet var de skaver”. Välfärdsorganisationer har all anledning att involvera brukare i planering och policyarbete i syfte att utveckla förmågan att göra rätt saker. Det finns inte mycket dokumentation och forskning kring brukarmedverkan i utvecklingsarbete och forskning på välfärdsområdet. I synnerhet saknas kunskap om hur välfärdstjänster tas emot och realiseras i brukarens livssammanhang. En ambition i doktorandkursen ”brukarmedverkan i forskning och utvecklingsarbete inom hälso- och sjukvård, socialt arbete och omsorg” var att samla och presentera kunskaper på området. Kursen genomfördes våren 2009 i ett unikt samarbete mellan Karlstads Universitet, Sheffield University i England, Högskolan i Hedmark i Norge, Hälsohögskolan i Jönköping och Högskolan i Borås/FoU Sjuhärad Välfärd. Texterna i denna bok härrör från kursens föreläsningar och paperarbeten. De ger många exempel på hur brukare kan involveras i forskning och utvecklingsarbete, och presenterar en rad praktiska metoder för brukarsamverkan. Boken rekommenderas till välfärdens politiker och yrkespersoner, till studenter som förbereder sig för välfärdens yrken liksom till forskare och utvecklingsarbetare som vill utveckla samarbete med brukare och brukarorganisationer. Den vänder sig givetvis även till brukare och brukarorganisationer som vill engagera sig i forskning och utvecklingsarbete

Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years

To compare the prevalence of cognitive, neurological, and behavioral outcomes at 10 years of age in 428 girls and 446 boys who were born extremely preterm (EP)

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities

IMPORTANCE The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI). OBJECTIVES To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD. DESIGN, SETTING, AND PARTICIPANTS This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives. MAIN OUTCOMES AND MEASURES Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data. RESULTS Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P 100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies. CONCLUSIONS AND RELEVANCE The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre