Impaired Glucose Metabolism among Those with and without Diagnosed Diabetes and Mortality: A Cohort Study Using Health Survey for England Data.

The extent that controlled diabetes impacts upon mortality, compared with uncontrolled diabetes, and how pre-diabetes alters mortality risk remain issues requiring clarification

Influence of Tap Water Quality and Household Water Use Activities on Indoor Air and Internal Dose Levels of Trihalomethanes

Individual exposure to trihalomethanes (THMs) in tap water can occur through ingestion, inhalation, or dermal exposure. Studies indicate that activities associated with inhaled or dermal exposure routes result in a greater increase in blood THM concentration than does ingestion. We measured blood and exhaled air concentrations of THM as biomarkers of exposure to participants conducting 14 common household water use activities, including ingestion of hot and cold tap water beverages, showering, clothes washing, hand washing, bathing, dish washing, and indirect shower exposure. We conducted our study at a single residence in each of two water utility service areas, one with relatively high and the other low total THM in the residence tap water. To maintain a consistent exposure environment for seven participants, we controlled water use activities, exposure time, air exchange, water flow and temperature, and nonstudy THM sources to the indoor air. We collected reference samples for water supply and air (pre–water use activity), as well as tap water and ambient air samples. We collected blood samples before and after each activity and exhaled breath samples at baseline and postactivity. All hot water use activities yielded a 2-fold increase in blood or breath THM concentrations for at least one individual. The greatest observed increase in blood and exhaled breath THM concentration in any participant was due to showering (direct and indirect), bathing, and hand dishwashing. Average increase in blood THM concentration ranged from 57 to 358 pg/mL due to these activities. More research is needed to determine whether acute and frequent exposures to THM at these concentrations have public health implications. Further research is also needed in designing epidemiologic studies that minimize data collection burden yet maximize accuracy in classification of dermal and inhalation THM exposure during hot water use activities

Spectroscopic analysis of finite size effects around a Kondo quantum dot

We consider a simple setup in which a small quantum dot is strongly connected to a finite size box. This box can be either a metallic box or a finite size quantum wire.The formation of the Kondo screening cloud in the box strongly depends on the ratio between the Kondo temperature and the box level spacing. By weakly connecting two metallic reservoirs to the quantum dot, a detailed spectroscopic analysis can be performed. Since the transport channels and the screening channels are almost decoupled, such a setup allows an easier access to the measure of finite-size effects associated with the finite extension of the Kondo cloud.Comment: contribution to Les Houches proceeding, ``Quantum magnetism'' 200

An in vivo platform to select and evolve aggregation-resistant proteins

Protein biopharmaceuticals are highly successful, but their utility is compromised by their propensity to aggregate during manufacture and storage. As aggregation can be triggered by non-native states, whose population is not necessarily related to thermodynamic stability, prediction of poorly-behaving biologics is difficult, and searching for sequences with desired properties is labour-intensive and time-consuming. Here we show that an assay in the periplasm of E. coli linking aggregation directly to antibiotic resistance acts as a sensor for the innate (un-accelerated) aggregation of antibody fragments. Using this assay as a directed evolution screen, we demonstrate the generation of aggregation resistant scFv sequences when reformatted as IgGs. This powerful tool can thus screen and evolve ‘manufacturable’ biopharmaceuticals early in industrial development. By comparing the mutational profiles of three different immunoglobulin scaffolds, we show the applicability of this method to investigate protein aggregation mechanisms important to both industrial manufacture and amyloid disease

Antimicrobial resistance in commensal opportunistic pathogens isolated from non-sterile sites can be an effective proxy for surveillance in bloodstream infections

Antimicrobial resistance (AMR) surveillance in bloodstream infections (BSIs) is challenging in low/middle-income countries (LMICs) given limited laboratory capacity. Other specimens are easier to collect and process and are more likely to be culture-positive. In 8102 E. coli BSIs, 322,087 E. coli urinary tract infections, 6952 S. aureus BSIs and 112,074 S. aureus non-sterile site cultures from Oxfordshire (1998–2018), and other (55,296 isolates) rarer commensal opportunistic pathogens, antibiotic resistance trends over time in blood were strongly associated with those in other specimens (maximum cross-correlation per drug 0.51–0.99). Resistance prevalence was congruent across drug-years for each species (276/312 (88%) species-drug-years with prevalence within ± 10% between blood/other isolates). Results were similar across multiple countries in high/middle/low income-settings in the independent ATLAS dataset (103,559 isolates, 2004–2017) and three further LMIC hospitals/programmes (6154 isolates, 2008–2019). AMR in commensal opportunistic pathogens cultured from BSIs is strongly associated with AMR in commensal opportunistic pathogens cultured from non-sterile sites over calendar time, suggesting the latter could be used as an effective proxy for AMR surveillance in BSIs

Quantum phase transition in a single-molecule quantum dot

Quantum criticality is the intriguing possibility offered by the laws of quantum mechanics when the wave function of a many-particle physical system is forced to evolve continuously between two distinct, competing ground states. This phenomenon, often related to a zero-temperature magnetic phase transition, can be observed in several strongly correlated materials such as heavy fermion compounds or possibly high-temperature superconductors, and is believed to govern many of their fascinating, yet still unexplained properties. In contrast to these bulk materials with very complex electronic structure, artificial nanoscale devices could offer a new and simpler vista to the comprehension of quantum phase transitions. This long-sought possibility is demonstrated by our work in a fullerene molecular junction, where gate voltage induces a crossing of singlet and triplet spin states at zero magnetic field. Electronic tunneling from metallic contacts into the $\rm{C_{60}}$ quantum dot provides here the necessary many-body correlations to observe a true quantum critical behavior.Comment: 8 pages, 5 figure

International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: Rationale and protocol

Background: Clinically useful treatment moderators of Major Depressive Disorder (MDD) have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators.Methods/Design: The International Study to Predict Optimized Treatment - in Depression (iSPOT-D) is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65) from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls). Study-eligible patients are antidepressant medication (ADM) naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary) and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary). Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm.Discussion: First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide.Trial registration: International Study to Predict Optimised Treatment - in Depression (iSPOT-D) ClinicalTrials.gov Identifier: NCT00693849. URL: http://clinicaltrials.gov/ct2/show/NCT00693849?term=International+Study+to+Predict+Optimized+Treatment+for+Depression&rank=1. © 2011 Williams et al; licensee BioMed Central Ltd

Universal newborn eye screening: a systematic review of the literature and review of international guidelines.

Background: This systematic review assessed the effectiveness of universal screening for newborn eye abnormalities compared with no screening in improving infant vision and health outcomes. Methods: We searched CENTRAL (Cochrane Library), MEDLINE, Embase, Global Health, Global Index Medicus, clinical trials databases, and bibliographies of relevant articles. We included randomized and observational studies of all newborns, regardless of illness or risk factors, that compared universal screening for any eye abnormality by eight weeks of age with no universal screening. Two authors independently selected studies, extracted data, and evaluated the risk of bias. We used GRADE to assess the certainty of evidence. We also reviewed available recommendations on newborn eye screening. Results: Fourteen studies were identified but only three compared universal red reflex screening with no screening. Findings suggest that universal red reflex testing in maternity wards (MWs) may increase the number of newborns with congenital cataracts referred for eye care from MWs or well-baby clinics (WBCs) in the first year of life (risk ratio (RR) = 9.83, 95% confidence interval (CI) = 1.36-71.20; low certainty evidence). However, the effect of screening in WBC is uncertain (RR = 6.62, 95% CI = 0.87-50.09). The effect of MW or WBC screening on referral from any health care facility (MWs, WBCs, paediatrician clinic, other) in the first year is uncertain (MW screening: RR = 1.22, 95% CI = 0.63-2.39; WBC screening: RR = 0.97, 95% CI = 0.46-2.05). However, referral or surgery by 6 weeks of age may be higher with universal MW screening (early referral: RR = 4.61, 95% CI = 1.12-19.01; early surgery: RR = 8.23, 95% CI = 1.13-59.80; low certainty evidence). The effect of WBC screening on early referral and surgery is uncertain (early referral: RR = 1.98, 95% CI = 0.43-9.19; early surgery: RR = 3.97, 95% CI = 0.50-31.33; very low certainty evidence). Universal red reflex testing may increase clinical conjunctivitis (OR = 1.22, 95% CI = 1.01-1.47; low certainty evidence) but the effect on confirmed bacterial conjunctivitis is uncertain (OR = 1.20, 95% CI = 0.76-1.90; very low-certainty evidence). Nine guidelines recommended universal newborn eye screening using red reflex testing. Conclusions: Evidence supports the role of red reflex testing shortly after birth to increase early identification, referral, and surgery for congenital cataracts

Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al

MRSA model of learning and adaptation: a qualitative study among the general public

<p>Abstract</p> <p>Background</p> <p>More people in the US now die from Methicillin Resistant <it>Staphylococcus aureus </it>(MRSA) infections than from HIV/AIDS. Often acquired in healthcare facilities or during healthcare procedures, the extremely high incidence of MRSA infections and the dangerously low levels of literacy regarding antibiotic resistance in the general public are on a collision course. Traditional medical approaches to infection control and the conventional attitude healthcare practitioners adopt toward public education are no longer adequate to avoid this collision. This study helps us understand how people acquire and process new information and then adapt behaviours based on learning.</p> <p>Methods</p> <p>Using constructivist theory, semi-structured face-to-face and phone interviews were conducted to gather pertinent data. This allowed participants to tell their stories so their experiences could deepen our understanding of this crucial health issue. Interview transcripts were analysed using grounded theory and sensitizing concepts.</p> <p>Results</p> <p>Our findings were classified into two main categories, each of which in turn included three subthemes. First, in the category of <it>Learning</it>, we identified how individuals used their <it>Experiences with MRSA</it>, to answer the questions: <it>What was learned? </it>and, <it>How did learning occur? </it>The second category, <it>Adaptation </it>gave us insights into <it>Self-reliance, Reliance on others</it>, and <it>Reflections on the MRSA journey</it>.</p> <p>Conclusions</p> <p>This study underscores the critical importance of educational programs for patients, and improved continuing education for healthcare providers. Five specific results of this study can reduce the vacuum that currently exists between the knowledge and information available to healthcare professionals, and how that information is conveyed to the public. These points include: 1) a common model of MRSA learning and adaptation; 2) the self-directed nature of adult learning; 3) the focus on general MRSA information, care and prevention, and antibiotic resistance; 4) the interconnected nature of adaptation; and, 5) the need for a consistent step by step plan to deal with MRSA provided at the time of diagnosis.</p