Genome-wide detection of segmental duplications and potential assembly errors in the human genome sequence

BACKGROUND: Previous studies have suggested that recent segmental duplications, which are often involved in chromosome rearrangements underlying genomic disease, account for some 5% of the human genome. We have developed rapid computational heuristics based on BLAST analysis to detect segmental duplications, as well as regions containing potential sequence misassignments in the human genome assemblies. RESULTS: Our analysis of the June 2002 public human genome assembly revealed that 107.4 of 3,043.1 megabases (Mb) (3.53%) of sequence contained segmental duplications, each with size equal or more than 5 kb and 90% identity. We have also detected that 38.9 Mb (1.28%) of sequence within this assembly is likely to be involved in sequence misassignment errors. Furthermore, we have identified a significant subset (199,965 of 2,327,473 or 8.6%) of single-nucleotide polymorphisms (SNPs) in the public databases that are not true SNPs but are potential paralogous sequence variants. CONCLUSION: Using two distinct computational approaches, we have identified most of the sequences in the human genome that have undergone recent segmental duplications. Near-identical segmental duplications present a major challenge to the completion of the human genome sequence. Potential sequence misassignments detected in this study would require additional efforts to resolve

N-of-1 randomized trials for psychological and health behavior outcomes: a systematic review protocol

Background Randomized controlled trials are the sine qua non of causal inference; however, heterogeneity of treatment effects for many chronic conditions and for many symptoms often limits their utility. Single-patient studies in which patients select a treatment after trying a randomized sequence of treatments (i.e., multiple crossover trials) offer an alternative to traditional randomized controlled trials by providing scientifically valid results in a practical manner that can be used by patients and their providers to decide upon their personally optimal treatment. Although N-of-1 trials have been used in the medical literature, their use for interventions that consist of psychological or health behavior outcomes is unknown. This systematic review thus aims to describe the interventions and outcomes and assess the quality of N-of-1 trials for psychological or health behavior outcomes. Methods/Design Electronic databases (Ovid MEDLINE, EMBASE, CINAHL, PsycINFO, and the six databases in the Cochrane Library) will be searched using all relevant subject headings and free-text terms to represent N-of-1 trials and psychological or behavioral interventions. Full text review and bibliography searching will be conducted. Unpublished studies will be sought by searching trial registries and contacting authors of included studies. Eligibility criteria are the following: population, all human participants for whom N-of-1 trials with psychological or health behavior outcomes have been conducted; interventions, all interventions for which N-of-1 trials have been conducted; comparison, placebo or active treatment control; and outcome, psychological and health behavior outcomes including self-perceived disease severity and psychological phenomena such as mood and affect. Studies that do not contain sufficient trial detail, describe only design or statistical analytic issues in N-of-1 trials without presentation of an N-of-1 trial itself, and/or are not written in the English language are ineligible. Screening, data extraction, and quality assessment will be conducted by two independent reviewers with disagreements resolved through discussion. Discussion This systematic review will describe the interventions and outcomes and assess the quality of N-of-1 trials for psychological or health behavior outcomes. The results will clarify the use of this research methodology in the health psychology and behavioral medicine literature and may pave the way for additional N-of-1 trials to be conducted

Effects of a Structured Exercise Programme on Functional Balance in Visually Impaired Elderly Living in a Residential Setting

AbstractOne major priority for health care professionals is to minimize the risk of fall in the elderly population. While the quality of life of an individual is affected by fall accidents, management of post-fall disability in the elderly could be a huge economic burden to the society. Visually impaired elderly are at a higher risk of fall, because “vision”, an important component contributing to balance, is disturbed. The aim of this study was to examine the effects of an exercise programme, which focused on improvement of the functional balance of visually impaired elderly. Visually impaired elderly residents were randomly assigned to either the exercise training or control group. A multidimensional, individually tailored exercise programme was introduced by physiotherapists to the exercise group for 12 weeks. Functional balance status reflected by the Berg Balance Scale, chair stand test, and timed up-and-go test assessed before and after the 12-week training programme was compared between the two groups. Results demonstrated a significant improvement in balance outcomes in the exercise group (p < 0.05) but not in the control group. The results of this study suggest that a physiotherapist-designed strengthening and balance-training programme can improve the functional balance status of visually impaired elderly

Quantum dot-doped porous silicon metal–semiconductor metal photodetector

In this paper, we report on the enhancement of spectral photoresponsivity of porous silicon metal–semiconductor metal (PS-MSM) photodetector embedded with colloidal quantum dots (QDs) inside the pore layer. The detection efficiency of QDs/PS hybrid-MSM photodetector was enhanced by five times larger than that of the undoped PS-MSM photodetector. The bandgap alignment between PS (approximately 1.77 eV) and QDs (approximately 1.91 eV) facilitates the photoinduced electron transfer from QDs to PS whereby enhancing the photoresponsivity. We also showed that the photoresponsitivity of QD/PS hybrid-MSM photodetector depends on the number of layer coatings of QDs and the pore sizes of PS.Published versio

Zee model and phenomenology of lepton sector

The virtual effects of the Zee charged scalar boson on the lepton-family-number (LFN) violating processes are studied. We obtain the constraints on the individual Yukawa coupling constants of the Zee boson to leptons. Using these constraints, we predict the upper bounds on the muonium-antimuonium conversion probability, the branching fractions of the LFN violating decays such as $\tau \to e\gamma$, $\tau \to \mu\gamma$, $\tau^- \to \mu^+e^-e^-$ and $\tau \to e^+\mu^-\mu^-$. The contribution of the Zee boson to the muon anomalous magnetic moment is also consideredComment: 13pages, 2figures, Latex; Notes added, two references adde

Physical inactivity is a strong risk factor for stroke in the oldest old: Findings from a multi-ethnic population (the Northern Manhattan Study)

Background The fastest growing segment of the population is those age ≥80 who have the highest stroke incidence. Risk factor management is complicated by polypharmacy-related adverse events. Aims To characterize the impact of physical inactivity for stroke by age in a multi-ethnic prospective cohort study (NOMAS, n = 3298). Methods Leisure time physical activity was assessed by a validated questionnaire and our primary exposure was physical inactivity (PI). Participants were followed annually for incident stroke. We fit Cox-proportional hazard models to calculate hazard ratios and 95% confidence intervals (HR 95% CI) for the association of PI and other risk factors with risk of stroke including two-way interaction terms between the primary exposures and age (<80 vs. ≥80). Results The mean age was 69 ± 10.3 years and 562 (17%) were ≥80 at enrolment. PI was common in the cohort (40.8%). Over a median of 14 years, we found 391 strokes. We found a significant interaction of age ≥80 on the risk of stroke with PI (p = 0.03). In stratified models, PI versus any activity (adjusted HR 1.60, 95%CI 1.05–2.42) was associated with an increased risk of stroke among those ≥80. Conclusion Physical inactivity is a treatable risk factor for stroke among those older than age 80. Improving activity may reduce the risk of stroke in this segment of the population

Quality assessment of phase I dose-finding cancer trials: proposal of a checklist

Qualitative checklists for phase III trials have been proposed, to improve the reporting of such trials and to assess the validity of their results

Creatinine- versus cystatin C-based renal function assessment in the Northern Manhattan Study

Background Accurate glomerular filtration rate estimation informs drug dosing and risk stratification. Body composition heterogeneity influences creatinine production and the precision of creatinine-based estimated glomerular filtration rate (eGFRcr) in the elderly. We compared chronic kidney disease (CKD) categorization using eGFRcr and cystatin C-based estimated GFR (eGFRcys) in an elderly, racially/ethnically diverse cohort to determine their concordance. Methods The Northern Manhattan Study (NOMAS) is a predominantly elderly, multi-ethnic cohort with a primary aim to study cardiovascular disease epidemiology. We included participants with concurrently measured creatinine and cystatin C. eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equation. Logistic regression was used to estimate odds ratios and 95% confidence intervals of factors associated with reclassification from eGFRcr≥60ml/min/1.73m2 to eGFRcys<60ml/min/1.73m2. Results Participants (n = 2988, mean age 69±10yrs) were predominantly Hispanic, female, and overweight/obese. eGFRcys was lower than eGFRcr by mean 23mL/min/1.73m2. 51% of participants’ CKD status was discordant, and only 28% maintained the same CKD stage by both measures. Most participants (78%) had eGFRcr≥60mL/min/1.73m2; among these, 64% had eGFRcys65 years, obesity, current smoking, white race, and female sex. Conclusions In a large, multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr. Determining the optimal method to estimate GFR in elderly populations needs urgent further study to improve risk stratification and drug dosing

A comparison of nurses’ and physicians’ perception of cancer treatment burden based on reported adverse events

Background Cancer treatments are associated with a multitude of adverse events (AEs). While both nurses and physicians are involved in patient care delivery and AE assessment, very few studies have examined the differences between nurses’ and physicians’ reporting and perception of AEs. An approach was recently proposed to assess treatment burden based on reported AEs from the physician’s perspective. In this paper, we use this approach to evaluate nurses’ perception of burden, and compare nurses’ and physicians’ assessment of the overall and relative burden of AEs. Methods AE records for 334 cancer patients from a randomized clinical trial conducted by the SWOG Cancer Research Network were evaluated by 14 nurses at Columbia University Medical Center. Two nurses were randomly selected to assign a burden score from 0 to 10 based on their impression of the global burden of the captured AEs. These nurses did not interact directly with the patients. Scores were compared to previously obtained physicians scores using paired T-test and Kappa statistic. Severity scores for individual AEs were obtained using mixed-effects models with nurses assessments, and were qualitatively compared to physicians’. Results Given the same AEs, nurses’ and physicians’ perception of the burden of AEs differed. While nurses generally perceived the overall burden of AEs to be only slightly worse compared to physicians (mean average VAS score of 5.44 versus 5.14), there was poor agreement in the perception of AEs that were in mild to severe range. The percent agreement for a moderate or worse AE was 64% with a Kappa of 0.34. Nurses also assigned higher severity scores to symptomatic AEs compared to physicians (p < 0.05), such as gastrointestinal (4.77 versus 4.14), hemorrhage (5.07 versus 4.14), and pain (5.17 versus 4.14). Conclusions These differences in the perception of burden of AEs can lead to different treatment decisions and symptom management strategies. Thus, having provider consistency, training, or a collaborative approach in follow-up care between nurses and physicians is important to ensure continuity in care delivery. Moreover, estimating overall burden from both physicians’ and nurses’ perspective, and comparing them may be useful for deciding when collaborations are warranted