VizWiz

The lack of access to visual information like text labels, icons,and colors can cause frustration and decrease independence for blind people. Current access technology uses automatic approaches to address some problems in this space, but the technology is error-prone, limited in scope, and quite expensive. In this paper, we introduce VizWiz, a talking application for mobile phones that offers a new alternative to answering visual questions in nearly real-time—asking multiple people on the web. To support answering questions quickly, we introduce a general approach for intelligently recruiting human workers in advance called quikTurkit so that workers are available when new questions arrive. A field deployment with 11 blind participants illustrates that blind people can effectively use VizWiz to cheaply answer questions in their everyday lives, highlighting issues that automatic approaches will need to address to be useful. Finally, we illustrate the potential of using VizWiz as part of the participatory design of advanced tools by using it to build and evaluate VizWiz::LocateIt, an interactive mobile tool that helps blind people solve general visual search problems

The Virome of Cerebrospinal Fluid: Viruses Where We Once Thought There Were None.

Traditionally, medicine has held that some human body sites are sterile and that the introduction of microbes to these sites results in infections. This paradigm shifted significantly with the discovery of the human microbiome and acceptance of these commensal microbes living across the body. However, the central nervous system (CNS) is still believed by many to be sterile in healthy people. Using culture-independent methods, we examined the virome of cerebrospinal fluid (CSF) from a cohort of mostly healthy human subjects. We identified a community of DNA viruses, most of which were identified as bacteriophages. Compared to other human specimen types, CSF viromes were not ecologically distinct. There was a high alpha diversity cluster that included feces, saliva, and urine, and a low alpha diversity cluster that included CSF, body fluids, plasma, and breast milk. The high diversity cluster included specimens known to have many bacteria, while other specimens traditionally assumed to be sterile formed the low diversity cluster. There was an abundance of viruses shared among CSF, breast milk, plasma, and body fluids, while each generally shared less with urine, feces, and saliva. These shared viruses ranged across different virus families, indicating that similarities between these viromes represent more than just a single shared virus family. By identifying a virome in the CSF of mostly healthy individuals, it is now less likely that any human body site is devoid of microbes, which further highlights the need to decipher the role that viral communities may play in human health

Implementing a 48 h EWTD-compliant rota for junior doctors in the UK does not compromise patients’ safety : assessor-blind pilot comparison

Background: There are currently no field data about the effect of implementing European Working Time Directive (EWTD)-compliant rotas in a medical setting. Surveys of doctors’ subjective opinions on shift work have not provided reliable objective data with which to evaluate its efficacy. Aim: We therefore studied the effects on patient's safety and doctors’ work-sleep patterns of implementing an EWTD-compliant 48 h work week in a single-blind intervention study carried out over a 12-week period at the University Hospitals Coventry & Warwickshire NHS Trust. We hypothesized that medical error rates would be reduced following the new rota. Methods: Nineteen junior doctors, nine studied while working an intervention schedule of <48 h per week and 10 studied while working traditional weeks of <56 h scheduled hours in medical wards. Work hours and sleep duration were recorded daily. Rate of medical errors (per 1000 patient-days), identified using an established active surveillance methodology, were compared for the Intervention and Traditional wards. Two senior physicians blinded to rota independently rated all suspected errors. Results: Average scheduled work hours were significantly lower on the intervention schedule [43.2 (SD 7.7) (range 26.0–60.0) vs. 52.4 (11.2) (30.0–77.0) h/week; P < 0.001], and there was a non-significant trend for increased total sleep time per day [7.26 (0.36) vs. 6.75 (0.40) h; P = 0.095]. During a total of 4782 patient-days involving 481 admissions, 32.7% fewer total medical errors occurred during the intervention than during the traditional rota (27.6 vs. 41.0 per 1000 patient-days, P = 0.006), including 82.6% fewer intercepted potential adverse events (1.2 vs. 6.9 per 1000 patient-days, P = 0.002) and 31.4% fewer non-intercepted potential adverse events (16.6 vs. 24.2 per 1000 patient-days, P = 0.067). Doctors reported worse educational opportunities on the intervention rota. Conclusions: Whilst concerns remain regarding reduced educational opportunities, our study supports the hypothesis that a 48 h work week coupled with targeted efforts to improve sleep hygiene improves patient safety

Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination

RAG1 binding to TCR gene elements is dictated by transcriptional control elements and by transcription itself; these findings provide direct confirmation of the long-held accessibility model

p63 is an alternative p53 repressor in melanoma that confers chemoresistance and a poor prognosis.

The role of apoptosis in melanoma pathogenesis and chemoresistance is poorly characterized. Mutations in TP53 occur infrequently, yet the TP53 apoptotic pathway is often abrogated. This may result from alterations in TP53 family members, including the TP53 homologue TP63. Here we demonstrate that TP63 has an antiapoptotic role in melanoma and is responsible for mediating chemoresistance. Although p63 was not expressed in primary melanocytes, up-regulation of p63 mRNA and protein was observed in melanoma cell lines and clinical samples, providing the first evidence of significant p63 expression in this lineage. Upon genotoxic stress, endogenous p63 isoforms were stabilized in both nuclear and mitochondrial subcellular compartments. Our data provide evidence of a physiological interaction between p63 with p53 whereby translocation of p63 to the mitochondria occurred through a codependent process with p53, whereas accumulation of p53 in the nucleus was prevented by p63. Using RNA interference technology, both isoforms of p63 (TA and ΔNp63) were demonstrated to confer chemoresistance, revealing a novel oncogenic role for p63 in melanoma cells. Furthermore, expression of p63 in both primary and metastatic melanoma clinical samples significantly correlated with melanoma-specific deaths in these patients. Ultimately, these observations provide a possible explanation for abrogation of the p53-mediated apoptotic pathway in melanoma, implicating novel approaches aimed at sensitizing melanoma to therapeutic agents

HIV Infection Is Associated with a Lower Incidence of Constriction in Presumed Tuberculous Pericarditis: A Prospective Observational Study

The original publication is available at http:/www.plosone.orgBackground: Pericardial constriction is a serious complication of tuberculous pericardial effusion that occurs in up to a quarter of patients despite anti-tuberculosis chemotheraphy. The impact of human immunodeficiency virus (HIV) infection on the incidence of constrictive pericarditis following tuberculous pericardial effusion is unknown. Methods and Results: We conducted a prospective observational study to determine the association between HIV infection and the incidence of constrictive pericarditis among 185 patients (median age 33 years) with suspected tuberculous pericardial effusion. These patients were recruited consecutively between March and October 2004 on commencement of anti-tuberculosis treatment, from 15 hospitals in Cameroon, Nigeria and South Africa. Surviving patients (N = 119) were assessed for clinical evidence of constrictive pericarditis at 3 and 6 months of follow-up. Clinical features of HIV infection were present in 42 (35.2%) of the 119 patients at enrolment into the study.66 of the 119 (56.9%) patients consented to HIV testing at enrolment. During the 6 months of follow-up, a clinical diagnosis of constrictive pericarditis was made in 13 of the 119 patients (10.9%, 95% confidence interval [CI] 5.9-18%). Patients with clinical features of HIV infection appear less likely to develop constriction than those without (4.8% versus 14.3%; P = 0.08). None of the 33 HIV seropositive patients developed constriction, but 8 (24.2%, 95%CI 11.1-42.3%)of the 33 HIV seronegative patients did (P = 0.005). In a multivariate logistic regression model adjusting simultaneously for several baseline characteristics, only clinical signs of HIV infection were significantly associated with a lower risk of constriction (odd ratio 0.14, 95% CI 0.02-0.87, P = 0.035). Conclusions: These data suggest that HIV infection is associated with a lower incidence of pericardial constriction in patients with presumed tuberculous pericarditis. © 2008 Ntsekhe et al.This study was funded, in part, through research grants from the University of Cape Town, the Medical Scholarships for South African Blacks (MESAB), the Medical Research Council of South Africa, the National Research Foundation of South Africa.Publishers' versio

Investigation of 2 Models to Set and Evaluate Quality Targets for Hb A1c: Biological Variation and Sigma-Metrics

BACKGROUND: A major objective of the IFCC Task Force on Implementation of HbA1c Standardization is to develop a model to define quality targets for glycated hemoglobin (Hb A1c). METHODS: Two generic models, biological variation and sigma-metrics, are investigated. We selected variables in the models for Hb A1c and used data of external quality assurance/proficiency testing programs to evaluate the suitability of the models to set and evaluate quality targets within and between laboratories. RESULTS: In the biological variation model, 48% of individual laboratories and none of the 26 instrument groups met the minimum performance criterion. In the sigma-metrics model, with a total allowable error (TAE) set at 5 mmol/mol (0.46% NGSP), 77% of the individual laboratories and 12 of 26 instrument groups met the 2σ criterion. CONCLUSIONS: The biological variation and sigma-metrics models were demonstrated to be suitable for setting and evaluating quality targets within and between laboratories. The sigma-metrics model is more flexible, as both the TAE and the risk of failure can be adjusted to the situation—for example, requirements related to diagnosis/monitoring or international authorities. With the aim of reaching (inter)national consensus on advice regarding quality targets for Hb A1c, the Task Force suggests the sigma-metrics model as the model of choice, with default values of 5 mmol/mol (0.46%) for TAE and risk levels of 2σ and 4σ for routine laboratories and laboratories performing clinical trials, respectively. These goals should serve as a starting point for discussion with international stakeholders in the field of diabetes

A non-imaging high throughput approach to chemical library screening at the unmodified adenosine-A3 receptor in living cells

Recent advances in fluorescent ligand technology have enabled the study of G protein-coupled receptors in their native environment without the need for genetic modification such as addition of N-terminal fluorescent or bioluminescent tags. Here, we have used a non-imaging plate reader (PHERAstar FS) to monitor the binding of fluorescent ligands to the human adenosine-A3 receptor (A3AR; CA200645 and AV039), stably expressed in CHO-K1 cells. To verify that this method was suitable for the study of other GPCRs, assays at the human adenosine-A1 receptor, and β1 and β2 adrenoceptors (β1AR and β2AR; BODIPY-TMR-CGP-12177) were also carried out. Affinity values determined for the binding of the fluorescent ligands CA200645 and AV039 to A3AR for a range of classical adenosine receptor antagonists were consistent with A3AR pharmacology and correlated well (R2 = 0.94) with equivalent data obtained using a confocal imaging plate reader (ImageXpress Ultra). The binding of BODIPY-TMR-CGP-12177 to the β1AR was potently inhibited by low concentrations of the β1-selective antagonist CGP 20712A (pKi 9.68) but not by the β2-selective antagonist ICI 118551(pKi 7.40). Furthermore, in experiments conducted in CHO K1 cells expressing the β2AR this affinity order was reversed with ICI 118551 showing the highest affinity (pKi 8.73) and CGP20712A (pKi 5.68) the lowest affinity. To determine whether the faster data acquisition of the non-imaging plate reader (∼3 min per 96-well plate) was suitable for high throughput screening (HTS), we screened the LOPAC library for inhibitors of the binding of CA200645 to the A3AR. From the initial 1,263 compounds evaluated, 67 hits (defined as those that inhibited the total binding of 25 nM CA200645 by ≥40%) were identified. All compounds within the library that had medium to high affinity for the A3AR (pKi ≥6) were successfully identified. We found three novel compounds in the library that displayed unexpected sub-micromolar affinity for the A3AR. These were K114 (pKi 6.43), retinoic acid p-hydroxyanilide (pKi 6.13) and SU 6556 (pKi 6.17). Molecular docking of these latter three LOPAC library members provided a plausible set of binding poses within the vicinity of the established orthosteric A3AR binding pocket. A plate reader based library screening using an untagged receptor is therefore possible using fluorescent ligand opening the possibility of its use in compound screening at natively expressed receptors

Atherosclerosis of the descending aorta predicts cardiovascular events: a transesophageal echocardiography study

PURPOSE: Previous studies have shown that atherosclerosis of the descending aorta detected by transesophageal echocardiography (TEE) is a good marker of coexisting coronary artery disease. The aim of our study was to evaluate whether the presence of atherosclerosis on the descending aorta during TEE has any prognostic impact in predicting cardiovascular events. MATERIAL AND METHODS: The study group consisted of 238 consecutive in-hospital patients referred for TEE testing (135 males, 103 females, mean age 58 +/- 11 years) with a follow up of 24 months. The atherosclerotic lesions of the descending aorta were scored from 0 (no atherosclerosis) to 3 (plaque >5 mm and/or "complex" plaque with ulcerated or mobile parts). RESULTS: Atherosclerosis was observed in 102 patients, (grade 3 in 16, and grade 2 in 86 patients) whereas 136 patients only had an intimal thickening or normal intimal surface. There were 57 cardiovascular events in the follow-up period. The number of events was higher in the 102 patients with (n = 34) than in the 136 patients without atherosclerosis (n = 23, p < 0.01). The frequency of events was in close correlation with the severity of the atherosclerosis of the descending aorta. Fifty percent of the patients with grade 3 experienced cardiovascular events. Excluding patients with subsequent revascularization, the multivariate analysis only left ventricular function with EF < 40% (HR 3.0, CI 1.3–7.1) and TEE atherosclerotic plaque >=2 (HR 2.4, CI 1.0–5.5) predicted hard cardiovascular events. CONCLUSION: Atherosclerosis of the descending aorta observed during transesophageal echocardiography is a useful predictor of cardiovascular events