Characteristics of service users and provider organisations associated with experience of out of hours general practitioner care in England: population based cross sectional postal questionnaire survey.

OBJECTIVE: To investigate the experience of users of out of hours general practitioner services in England, UK. DESIGN: Population based cross sectional postal questionnaire survey. SETTING: General Practice Patient Survey 2012-13. MAIN OUTCOME MEASURES: Potential associations between sociodemographic factors (including ethnicity and ability to take time away from work during working hours to attend a healthcare consultation) and provider organisation type (not for profit, NHS, or commercial) and service users' experience of out of hours care (timeliness, confidence and trust in the out of hours clinician, and overall experience of the service), rated on a scale of 0-100. Which sociodemographic/provider characteristics were associated with service users' experience, the extent to which any observed differences could be because of clustering of service users of a particular sociodemographic group within poorer scoring providers, and the extent to which observed differences in experience varied across types of provider. RESULTS: The overall response rate was 35%; 971,232/2,750,000 patients returned surveys. Data from 902,170 individual service users were mapped through their registered practice to one of 86 providers of out of hours GP care with known organisation type. Commercial providers of out of hours GP care were associated with poorer reports of overall experience of care, with a mean difference of -3.13 (95% confidence interval -4.96 to -1.30) compared with not for profit providers. Asian service users reported lower scores for all three experience outcomes than white service users (mean difference for overall experience of care -3.62, -4.36 to -2.89), as did service users who were unable to take time away from work compared with service users who did not work (mean difference for overall experience of care -4.73, -5.29 to -4.17). CONCLUSIONS: Commercial providers of out of hours GP care were associated with poorer experience of care. Targeted interventions aimed at improving experience for patients from ethnic minorities and patients who are unable to take time away from work might be warranted

PSYCHOSOCIAL IMPACT OF COVID-19 ON STUDENTS AT INSTITUTIONS OF HIGHER LEARNING

Students at higher institutions of learning are more susceptible to psychosocial problems compared to the general public. These may further be exacerbated by the measures put in place to curb the spread of COVID-19. This mixed methods study examined the factors associated with the psychosocial impact of COVID-19 on students’ financial stability, interpersonal relationships and worries related to achieving academic milestones. Data comprised of a series of closed and open-ended questions collected via Qualtrics from students in the United States and Africa (Central and West). The quantitative data were analyzed using frequency counts, percentages and chi-square, while the qualitative data was analyzed using thematic content analysis. More than 90% of the students resided in the United States, 72.5% were females and 78.4% were undergraduates. Financial hardship was experienced by 26.4% of the students, 55.8% indicated that COVID-19 negatively affected their relationship with friends and over 40% worried over delays in achieving academic milestones. Continent of residence, employment status and financial hardship were significantly associated with the negative impact of COVID-19 on one or more of the students’ relationships and with worries about achieving academic milestones. Qualitative data support the findings that financial hardship contributed to experience of psychological distress by students. It also revealed negative (compromised relationships – broken or fractured relationships and loneliness) and positive (bonding) impact of COVID-19 on interpersonal relationships. School administrators should provide students with resources to access economic relief packages and tele-counseling services to help meet their financial and psychosocial support needs amidst COVID-19.  Article visualizations

Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance.

Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance

Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance

Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

The anterior temporal lobes support residual comprehension in Wernicke’s aphasia

Wernicke’s aphasia occurs following a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke’s aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used fMRI to investigate the neural basis of written word and picture semantic processing in Wernicke’s aphasia, with the wider aim of examining how the semantic system is altered following damage to the classical comprehension regions. Twelve participants with Wernicke’s aphasia and twelve control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and ROI analysis in Wernicke’s aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke’s aphasia group displayed an “over-activation” in comparison to control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke’s aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results concord with models which indicate that the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions

Effects of an attention demanding task on dynamic stability during treadmill walking

<p>Abstract</p> <p>Background</p> <p>People exhibit increased difficulty balancing when they perform secondary attention-distracting tasks while walking. However, a previous study by Grabiner and Troy (<it>J. Neuroengineering Rehabil</it>., 2005) found that young healthy subjects performing a concurrent Stroop task while walking on a motorized treadmill exhibited <it>decreased </it>step width variability. However, measures of variability do not directly quantify how a system responds to perturbations. This study re-analyzed data from Grabiner and Troy 2005 to determine if performing the concurrent Stroop task directly affected the dynamic stability of walking in these same subjects.</p> <p>Methods</p> <p>Thirteen healthy volunteers walked on a motorized treadmill at their self-selected constant speed for 10 minutes both while performing the Stroop test and during undisturbed walking. This Stroop test consisted of projecting images of the name of one color, printed in text of a different color, onto a wall and asking subjects to verbally identify the color of the text. Three-dimensional motions of a marker attached to the base of the neck (C5/T1) were recorded. Marker velocities were calculated over 3 equal intervals of 200 sec each in each direction. Mean variability was calculated for each time series as the average standard deviation across all strides. Both "local" and "orbital" dynamic stability were quantified for each time series using previously established methods. These measures directly quantify how quickly small perturbations grow or decay, either continuously in real time (local) or discretely from one cycle to the next (orbital). Differences between Stroop and Control trials were evaluated using a 2-factor repeated measures ANOVA.</p> <p>Results</p> <p>Mean variability of trunk movements was significantly reduced during the Stroop tests compared to normal walking. Conversely, local and orbital stability results were mixed: some measures showed slight increases, while others showed slight decreases. In many cases, different subjects responded differently to the Stroop test. While some of our comparisons reached statistical significance, many did not. In general, measures of variability and dynamic stability reflected different properties of walking dynamics, consistent with previous findings.</p> <p>Conclusion</p> <p>These findings demonstrate that the decreased movement variability associated with the Stroop task did <it>not </it>translate to greater dynamic stability.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Investigation of the causal etiology in a patient with T-B+NK+ immunodeficiency

Newborn screening for severe combined immunodeficiency (SCID) has not only accelerated diagnosis and improved treatment for affected infants, but also led to identification of novel genes required for human T cell development. A male proband had SCID newborn screening showing very low T cell receptor excision circles (TRECs), a biomarker for thymic output of nascent T cells. He had persistent profound T lymphopenia, but normal numbers of B and natural killer (NK) cells. Despite an allogeneic hematopoietic stem cell transplant from his brother, he failed to develop normal T cells. Targeted resequencing excluded known SCID genes; however, whole exome sequencing (WES) of the proband and parents revealed a maternally inherited X-linked missense mutation in MED14 (MED14V763A), a component of the mediator complex. Morpholino (MO)-mediated loss of MED14 function attenuated T cell development in zebrafish. Moreover, this arrest was rescued by ectopic expression of cDNA encoding the wild type human MED14 ortholog, but not by MED14V763A, suggesting that the variant impaired MED14 function. Modeling of the equivalent mutation in mouse (Med14V769A) did not disrupt T cell development at baseline. However, repopulation of peripheral T cells upon competitive bone marrow transplantation was compromised, consistent with the incomplete T cell reconstitution experienced by the proband upon transplantation with bone marrow from his healthy male sibling, who was found to have the same MED14V763A variant. Suspecting that the variable phenotypic expression between the siblings was influenced by further mutation(s), we sought to identify genetic variants present only in the affected proband. Indeed, WES revealed a mutation in the L1 cell adhesion molecule (L1CAMQ498H); however, introducing that mutation in vivo in mice did not disrupt T cell development. Consequently, immunodeficiency in the proband may depend upon additional, unidentified gene variants