A forward-backward fragment assembling algorithm for the identification of genomic amplification and deletion breakpoints using high-density single nucleotide polymorphism (SNP) array

<p>Abstract</p> <p>Background</p> <p>DNA copy number aberration (CNA) is one of the key characteristics of cancer cells. Recent studies demonstrated the feasibility of utilizing high density single nucleotide polymorphism (SNP) genotyping arrays to detect CNA. Compared with the two-color array-based comparative genomic hybridization (array-CGH), the SNP arrays offer much higher probe density and lower signal-to-noise ratio at the single SNP level. To accurately identify small segments of CNA from SNP array data, segmentation methods that are sensitive to CNA while resistant to noise are required.</p> <p>Results</p> <p>We have developed a highly sensitive algorithm for the edge detection of copy number data which is especially suitable for the SNP array-based copy number data. The method consists of an over-sensitive edge-detection step and a test-based forward-backward edge selection step.</p> <p>Conclusion</p> <p>Using simulations constructed from real experimental data, the method shows high sensitivity and specificity in detecting small copy number changes in focused regions. The method is implemented in an R package FASeg, which includes data processing and visualization utilities, as well as libraries for processing Affymetrix SNP array data.</p

Awareness and acceptability of human papillomavirus vaccine: an application of the instrumental variables bivariate probit model

<p>Abstract</p> <p>Background</p> <p>Although lower uptake rates of the human papillomavirus (HPV) vaccine among socioeconomically disadvantaged populations have been documented, less is known about the relationships between awareness and acceptability, and other factors affecting HPV vaccine uptake.</p> <p>The current study aimed to estimate the potential effectiveness of increased HPV vaccine awareness on the acceptability of HPV vaccination in a nationally representative sample of women, using a methodology that controlled for potential non-random selection.</p> <p>Methods</p> <p>This study used a population-based sample from the 2007 Health Information National Trends Survey, a cross-sectional study of the US population aged 18 years or older, and focused on the subsample of 742 women who have any female children under the age of 18 years in the household. An instrumental variables bivariate probit model was used to jointly estimate HPV vaccine awareness and acceptability.</p> <p>Results</p> <p>The proportion of HPV vaccine acceptability among the previously aware and non-aware groups was 58% and 47%, respectively. Results from the instrumental variables bivariate probit model showed that the estimated marginal effect of awareness on acceptability was 46 percentage points, an effect that was even greater than observed.</p> <p>Conclusions</p> <p>Among populations who are not currently aware of the HPV vaccine, the potential impact of raising awareness on acceptability of HPV vaccination is substantial. This finding provides additional support to strengthening public health programs that increase awareness and policy efforts that address barriers to HPV vaccination.</p

Serum IgE Reactivity Profiling in an Asthma Affected Cohort

BACKGROUND: Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear. METHODS: We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema. RESULTS: Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09). An artificial neural network (ANN)-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations. CONCLUSIONS: These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile

Mechanical Work as an Indirect Measure of Subjective Costs Influencing Human Movement

To descend a flight of stairs, would you rather walk or fall? Falling seems to have some obvious disadvantages such as the risk of pain or injury. But the preferred strategy of walking also entails a cost for the use of active muscles to perform negative work. The amount and distribution of work a person chooses to perform may, therefore, reflect a subjective valuation of the trade-offs between active muscle effort and other costs, such as pain. Here we use a simple jump landing experiment to quantify the work humans prefer to perform to dissipate the energy of landing. We found that healthy normal subjects (N = 8) preferred a strategy that involved performing 37% more negative work than minimally necessary (P<0.001) across a range of landing heights. This then required additional positive work to return to standing rest posture, highlighting the cost of this preference. Subjects were also able to modulate the amount of landing work, and its distribution between active and passive tissues. When instructed to land softly, they performed 76% more work than necessary (P<0.001), with a higher proportion from active muscles (89% vs. 84%, P<0.001). Stiff-legged landings, performed by one subject for demonstration, exhibited close to the minimum of work, with more of it performed passively through soft tissue deformations (at least 30% in stiff landings vs. 16% preferred). During jump landings, humans appear not to minimize muscle work, but instead choose to perform a consistent amount of extra work, presumably to avoid other subjective costs. The degree to which work is not minimized may indirectly quantify the relative valuation of costs that are otherwise difficult to measure

Pharmacological adjuncts to stop bleeding: options and effectiveness

Severe trauma and massive haemorrhage represent the leading cause of death and disability in patients under the age of 45 years in the developed world. Even though much advancement has been made in our understanding of the pathophysiology and management of trauma, outcomes from massive haemorrhage remain poor. This can be partially explained by the development of coagulopathy, acidosis and hypothermia, a pathological process collectively known as the “lethal triad” of trauma. A number of pharmacological adjuncts have been utilised to stop bleeding, with a wide variation in the safety and efficacy profiles. Antifibrinolytic agents in particular, act by inhibiting the conversion of plasminogen to plasmin, therefore decreasing the degree of fibrinolysis. Tranexamic acid, the most commonly used antifibrinolytic agent, has been successfully incorporated into most trauma management protocols effectively reducing mortality and morbidity following trauma. In this review, we discuss the current literature with regard to the management of haemorrhage following trauma, with a special reference to the use of pharmacological adjuncts. Novel insights, concepts and treatment modalities are also discussed

The do's, don't and don't knows of supporting transition to more independent practice

Introduction: Transitions are traditionally viewed as challenging for clinicians. Throughout medical career pathways, clinicians need to successfully navigate successive transitions as they become progressively more independent practitioners. In these guidelines, we aim to synthesize the evidence from the literature to provide guidance for supporting clinicians in their development of independence, and highlight areas for further research. Methods: Drawing upon D3 method guidance, four key themes universal to medical career transitions and progressive independence were identified by all authors through discussion and consensus from our own experience and expertise: workplace learning, independence and responsibility, mentoring and coaching, and patient perspectives. A scoping review of the literature was conducted using Medline database searches in addition to the authors’ personal archives and reference snowballing searches. Results: 387 articles were identified and screened. 210 were excluded as not relevant to medical transitions (50 at title screen; 160 at abstract screen). 177 full-text articles were assessed for eligibility; a further 107 were rejected (97 did not include career transitions in their study design; 10 were review articles; the primary references of these were screened for inclusion). 70 articles were included of which 60 provided extractable data for the final qualitative synthesis. Across the four key themes, seven do’s, two don’ts and seven don’t knows were identified, and the strength of evidence was graded for each of these recommendations. Conclusion: The two strongest messages arising from current literature are first, transitions should not be viewed as one moment in time: career trajectories are a continuum with valuable opportunities for personal and professional development throughout. Second, learning needs to be embedded in practice and learners provided with authentic and meaningful learning opportunities. In this paper, we propose evidence-based guidelines aimed at facilitating such transitions through the fostering of progressive independence

Using video-reflexive ethnography to capture the complexity of leadership enactment in the healthcare workplace

This research was part of LG’s Ph.D. research which was generously funded by NHS Education for Scotland through SMERC.Current theoretical thinking asserts that leadership should be distributed across many levels of healthcare organisations to improve the patient experience and staff morale. However, much healthcare leadership education focusses on the training and competence of individuals and little attention is paid to the interprofessional workplace and how its inherent complexities might contribute to the emergence of leadership. Underpinned by complexity theory, this research aimed to explore how interprofessional healthcare teams enact leadership at a micro-level through influential acts of organising. A whole (interprofessional) team workplace-based study utilising video-reflexive ethnography occurred in two UK clinical sites. Thematic framework analyses of the video data (video-observation and video-reflexivity sessions) were undertaken, followed by in-depth analyses of human–human and human–material interactions. Data analysis revealed a complex interprofessional environment where leadership is a dynamic process, negotiated and renegotiated in various ways throughout interactions (both formal and informal). Being able to “see” themselves at work gave participants the opportunity to discuss and analyse their everyday leadership practices and challenge some of their sometimes deeply entrenched values, beliefs, practices and assumptions about healthcare leadership. These study findings therefore indicate a need to redefine the way that medical and healthcare educators facilitate leadership development and argue for new approaches to research which shifts the focus from leaders to leadership.Publisher PDFPeer reviewe

Situational awareness within objective structured clinical examination stations in undergraduate medical training - a literature search

Background: Medical students may not be able to identify the essential elements of situational awareness (SA) necessary for clinical reasoning. Recent studies suggest that students have little insight into cognitive processing and SA in clinical scenarios. Objective Structured Clinical Examinations (OSCEs) could be used to assess certain elements of situational awareness. The purpose of this paper is to review the literature with a view to identifying whether levels of SA based on Endsley's model can be assessed utilising OSCEs during undergraduate medical training. Methods: A systematic search was performed pertaining to SA and OSCEs, to identify studies published between January 1975 (first paper describing an OSCE) and February 2017, in peer reviewed international journals published in English. PUBMED, EMBASE, PsycINFO Ovid and SCOPUS were searched for papers that described the assessment of SA using OSCEs among undergraduate medical students. Key search terms included "objective structured clinical examination", "objective structured clinical assessment" or "OSCE" and "non-technical skills", "sense-making", "clinical reasoning", "perception", "comprehension", "projection", "situation awareness", "situational awareness" and "situation assessment". Boolean operators (AND, OR) were used as conjunctions to narrow the search strategy, resulting in the limitation of papers relevant to the research interest. Areas of interest were elements of SA that can be assessed by these examinations. Results: The initial search of the literature retrieved 1127 publications. Upon removal of duplicates and papers relating to nursing, paramedical disciplines, pharmacy and veterinary education by title, abstract or full text, 11 articles were eligible for inclusion as related to the assessment of elements of SA in undergraduate medical students. Discussion: Review of the literature suggests that whole-task OSCEs enable the evaluation of SA associated with clinical reasoning skills. If they address the levels of SA, these OSCEs can provide supportive feedback and strengthen educational measures associated with higher diagnostic accuracy and reasoning abilities. Conclusion: Based on the findings, the early exposure of medical students to SA is recommended, utilising OSCEs to evaluate and facilitate SA in dynamic environment