Assessment of maximum inspiratory pressure: Prior submaximal respiratory muscle activity (‘warm-up’) enhances maximum inspiratory activity and attenuates the learning effect of repeated measurement

The official published version can be obtained from the link belowBackground: The variability of maximal inspiratory pressure (PImax) in response to repeated measurement affects its reliability; published studies have used between three and twenty PImax measurements on a single occasion. Objective: This study investigated the influence of a specific respiratory ‘warm-up’ upon the repeated measurement of inspiratory muscle strength and attempts to establish a procedure by which PImax can be assessed with maximum reliability using the smallest number of manoeuvres. Methods: Fourteen healthy subjects, familiar with the Mueller manoeuvre, were studied. The influence of repeated testing on a single occasion was assessed using an 18-measurement protocol. Using a randomised cross-over design, subjects performed the protocol, preceded by a specific respiratory warm-up (RWU) and on another occasion, without any preliminary activity (control). Comparisons were made amongst ‘baseline’ (best of the first 3 measurements), ‘short’ series (best of 7th to 9th measurement) and ‘long’ series (best of the last 3 measurements). Results: Under control conditions, the mean increase (‘baseline’ vs. ‘long’ series) was 11.4 (5.8)%; following the RWU, the increase (post RWU ‘baseline’ vs. ‘long’ series) was 3.2 (10.0)%. There were statistically significant differences between measurements made at all 3 protocol stages (‘baseline’, ‘short’ and ‘long’ series) under control conditions, but none following the RWU. Conclusions: The present data suggest that a specific RWU may attenuate the ‘learning effect’ during repeated PImax measurements, which is one of the main contributors of the test variability. The use of a RWU may provide a means of obtaining reliable values of PImax following just 3 measurements.This work was partially supported by a grant from the University of Wolverhampton, UK

Out-of-hours primary percutaneous coronary intervention for ST-elevation myocardial infarction is not associated with excess mortality: a study of 3347 patients treated in an integrated cardiac network

OBJECTIVES: Timely delivery of primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-segment elevation myocardial infarction (STEMI). Optimum delivery of PPCI requires an integrated network of hospitals, following a multidisciplinary, consultant-led, protocol-driven approach. We investigated whether such a strategy was effective in providing equally effective in-hospital and long-term outcomes for STEMI patients treated by PPCI within normal working hours compared with those treated out-of-hours (OOHs). DESIGN: Observational study. SETTING: Large PPCI centre in London. PARTICIPANTS: 3347 STEMI patients were treated with PPCI between 2004 and 2012. The follow-up median was 3.3 years (IQR: 1.2–4.6 years). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was long-term major adverse cardiac events (MACE) with all-cause mortality a secondary endpoint. RESULTS: Of the 3347 STEMI patients, 1299 patients (38.8%) underwent PPCI during a weekday between 08:00 and 18:00 (routine-hours group) and 2048 (61.2%) underwent PPCI on a weekday between 18:00 and 08:00 or a weekend (OOHs group). There were no differences in baseline characteristics between the two groups with comparable door-to-balloon times (in-hours (IHs) 67.8 min vs OOHs 69.6 min, p=0.709), call-to-balloon times (IHs 116.63 vs OOHs 127.15 min, p=0.60) and procedural success. In hospital mortality rates were comparable between the two groups (IHs 3.6% vs OOHs 3.2%) with timing of presentation not predictive of outcome (HR 1.25 (95% CI 0.74 to 2.11). Over the follow-up period there were no significant differences in rates of mortality (IHs 7.4% vs OFHs 7.2%, p=0.442) or MACE (IHs 15.4% vs OFHs 14.1%, p=0.192) between the two groups. After adjustment for confounding variables using multivariate analysis, timing of presentation was not an independent predictor of mortality (HR 1.04 95% CI 0.78 to 1.39). CONCLUSIONS: This large registry study demonstrates that the delivery of PPCI with a multidisciplinary, consultant-led, protocol-driven approach provides safe and effective treatment for patients regardless of the time of presentation

Oligoclonal expansions of CD8(+) T cells in chronic HIV infection are antigen specific

Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8(+) T cells. These 'expansions', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8(+) T cells. However, due to the difficulties in studying antigen-specific T cells in vivo, it has been hard to prove that oligoclonal BV expansions are actually HIV specific. The use of tetrameric major histocompatibility complex-peptide complexes has recently enabled direct visualization of antigen-specific T cells ex vivo but has not provided information on their clonal composition. We have now made use of these tetrameric complexes in conjunction with anti-BV chain-specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8(+) T cells are HIV specific in vivo

Hyperglycemia Has a Greater Impact on Left Ventricle Function in South Asians Than in Europeans

OBJECTIVE Diabetes is associated with left ventricular (LV) diastolic and systolic dysfunction. South Asians may be at particular risk of developing LV dysfunction owing to a high prevalence of diabetes. We investigated the role of diabetes and hyperglycemia in LV dysfunction in a community-based cohort of older South Asians and white Europeans. RESEARCH DESIGN AND METHODS Conventional and Doppler echocardiography was performed in 999 participants (542 Europeans and 457 South Asians aged 58–86 years) in a population-based study. Anthropometry, fasting bloods, coronary artery calcification scoring, blood pressure, and renal function were measured. RESULTS Diabetes and hyperglycemia across the spectrum of HbA1c had a greater adverse effect on LV function in South Asians than Europeans (N-terminal-probrain natriuretic peptide β ± SE 0.09 ± 0.04, P = 0.01, vs. −0.04 ± 0.05, P = 0.4, P for HbA1c/ethnicity interaction 0.02), diastolic function (E/e′ 0.69 ± 0.12, P < 0.0001, vs. 0.09 ± 0.2, P = 0.6, P for interaction 0.005), and systolic function (s′ −0.11 ± 0.06, P = 0.04, vs. 0.14 ± 0.09, P = 0.1, P for interaction 0.2). Multivariable adjustment for hypertension, microvascular disease, LV mass, coronary disease, and dyslipidemia only partially accounted for the ethnic differences. Adverse LV function in diabetic South Asians could not be accounted for by poorer glycemic control or longer diabetes duration. CONCLUSIONS Diabetes and hyperglycemia have a greater adverse effect on LV function in South Asians than Europeans, incompletely explained by adverse risk factors. South Asians may require earlier and more aggressive treatment of their cardiometabolic risk factors to reduce risks of LV dysfunction

The lived experience of Black, Asian and Mixed-race girls in predominantly white secondary schools

This thesis explores the experiences of racialised girls in predominately white secondary schools in England. Using multiple qualitative methods, thematic analysis and informed by feminist Critical Race Theory, the thesis gives centre stage to the voices of girls who, seen through a 'white gaze', describe being racialised in schools using stereotypes, racial and gendered tropes, and constructions of 'outsider' and otherness. It addresses gaps in empirical data necessary to substantiate understandings of feminist Critical Race Theory with reference to Black, Asian and Mixed-race girls in relation to the specific context of the English predominantly white secondary school. I present evidence that reveals the effect of visible difference in fuelling assumptions and stereotypes about different racial groups. Racialisation leads to failures to 'see' each girl as an individual. This thesis therefore extends theoretical understandings of racialisation and racism as gendered, dependent on context, and experienced differently depending on which racial group individuals are visually most associated with, as seen through a white lens. Having established the importance of context and visual difference, I examine how white privilege, marginalisation, racism, racialised sexism and classism function in school. Still based on the thematic analysis of racialised girls' narratives, I present evidence which extends the understanding of key tenets of intersectionality and Critical Race Theory. Consideration of what constitutes a 'hostile environment' leads to an exploration of the ability of racism to morph and remain deeply embedded in structures and business-as-usual practices of schooling. I also develop empirically-based understandings of Critical Race Theory’s concepts of interest convergence, interest divergence, and retrenchment, showing the applicability of these concepts to understand a specifically UK context, and useful for analysis of the predominantly white secondary school as a hostile environment for Black, Asian and Mixed-race girls. Nonetheless, in this thesis, I argue that cognisant of constraints, racialised girls resist the harmful effects of a hostile environment. Despite wanting change, they do not centre all their efforts of resistance on addressing individual, institutional or systemic racism or sexism. Black, Asian and Mixed-race girls remain agentic, able to fashion their own individual and collective expressions of resistance to the circumstances that they face in the predominantly white secondary school, creating opportunities centred on their sense of who they are and their ambitions for the future

In Vitro Functional Analyses of Infrequent Nucleotide Variants in the Lactase Enhancer Reveal Different Molecular Routes to Increased Lactase Promoter Activity and Lactase Persistence

The genetic trait that allows intestinal lactase to persist into adulthood in some 35% of humans worldwide operates at the level of transcription, the effect being caused by cis-acting nucleotide changes upstream of the lactase gene (LCT). A single nucleotide substitution, -13910 C>T, the first causal variant to be identified, accounts for lactase persistence over most of Europe. Located in a region shown to have enhancer function in vitro, it causes increased activity of the LCT promoter in Caco-2 cells, and altered transcription factor binding. Three other variants in close proximity, -13907 C>G, -13915 T>C and -14010 G>C, were later shown to behave in a similar manner. Here, we study four further candidate functional variants. Two, -14009 T>G and -14011 C>T, adjacent to the well-studied -14010 G>C variant, also have a clear effect on promoter activity upregulation as assessed by transfection assays, but notably are involved in different molecular interactions. The results for the two other variants (-14028 T>C, -13779 G>C) were suggestive of function, -14028*C showing a clear change in transcription factor binding, but no obvious effect in transfections, while -13779*G showed greater effect in transfections but less on transcription factor binding. Each of the four variants arose on independent haplotypic backgrounds with different geographic distribution

Maintained physical activity and physiotherapy in the management of distal upper limb pain – a protocol for a randomised controlled trial (the arm pain trial)

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Distal upper limb pain (pain affecting the elbow, forearm, wrist, or hand) can be non-specific, or can arise from specific musculoskeletal disorders. It is clinically important and costly, the best approach to clinical management is unclear. Physiotherapy is the standard treatment and, while awaiting treatment, advice is often given to rest and avoid strenuous activities, but there is no evidence base to support these strategies. This paper describes the protocol of a randomised controlled trial to determine, among patients awaiting physiotherapy for distal arm pain, (a) whether advice to remain active and maintain usual activities results in a long-term reduction in arm pain and disability, compared with advice to rest; and (b) whether immediate physiotherapy results in a long-term reduction in arm pain and disability, compared with physiotherapy delivered after a seven week waiting list period.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods/Design&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Between January 2012 and January 2014, new referrals to 14 out-patient physiotherapy departments were screened for potential eligibility. Eligible and consenting patients were randomly allocated to one of the following three groups in equal numbers: 1) advice to remain active, 2) advice to rest, 3) immediate physiotherapy. Patients were and followed up at 6, 13, and 26 weeks post-randomisation by self-complete postal questionnaire and, at six weeks, patients who had not received physiotherapy were offered it at this time. The primary outcome is the proportion of patients free of disability at 26 weeks, as determined by the modified DASH (Disabilities of the Arm, Shoulder and Hand) questionnaire.&lt;p&gt;&lt;/p&gt; We hypothesise (a) that advice to maintain usual activities while awaiting physiotherapy will be superior than advice to rest the arm; and (b) that fast-track physiotherapy will be superior to normal (waiting list) physiotherapy. These hypotheses will be examined using an intention-to-treat analysis.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Discussion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Results from this trial will contribute to the evidence base underpinning the clinical management of patients with distal upper limb pain, and in particular, will provide guidance on whether they should be advised to rest the arm or remain active within the limits imposed by their symptoms

Electrophysiological responses to alcohol cues are not associated with Pavlovian-to-instrumental transfer in social drinkers

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tPavlovian to Instrumental Transfer (PIT) refers to the behavioral phenomenon of increased instrumental responding for a reinforcer when in the presence of Pavlovian conditioned stimuli that were separately paired with that reinforcer. PIT effects may play an important role in substance use disorders, but little is known about the brain mechanisms that underlie these effects in alcohol consumers. We report behavioral and electroencephalographic (EEG) data from a group of social drinkers (n = 31) who performed a PIT task in which they chose between two instrumental responses in pursuit of beer and chocolate reinforcers while their EEG reactivity to beer, chocolate and neutral pictorial cues was recorded. We examined two markers of the motivational salience of the pictures: the P300 and slow wave event-related potentials (ERPs). Results demonstrated a behavioral PIT effect: responding for beer was increased when a beer picture was presented. Analyses of ERP amplitudes demonstrated significantly larger slow potentials evoked by beer cues at various electrode clusters. Contrary to hypotheses, there were no significant correlations between behavioral PIT effects, electrophysiological reactivity to the cues, and individual differences in drinking behaviour. Our findings are the first to demonstrate a PIT effect for beer, accompanied by increased slow potentials in response to beer cues, in social drinkers. The lack of relationship between behavioral and EEG measures, and between these measures and individual differences in drinking behaviour may be attributed to methodological features of the PIT task and to characteristics of our sample.Funded by a research grant from Alcohol Research UK (http://alcoholresearchuk.org/), reference SG 10/11 16

Training emergency services’ dispatchers to recognise stroke: an interrupted time-series analysis

Background: Stroke is a time-dependent medical emergency in which early presentation to specialist care reduces death and dependency. Up to 70% of all stroke patients obtain first medical contact from the Emergency Medical Services (EMS). Identifying ‘true stroke’ from an EMS call is challenging, with over 50% of strokes being misclassified. The aim of this study was to evaluate the impact of the training package on the recognition of stroke by Emergency Medical Dispatchers (EMDs). Methods: This study took place in an ambulance service and a hospital in England using an interrupted time-series design. Suspected stroke patients were identified in one week blocks, every three weeks over an 18 month period, during which time the training was implemented. Patients were included if they had a diagnosis of stroke (EMS or hospital). The effect of the intervention on the accuracy of dispatch diagnosis was investigated using binomial (grouped) logistic regression. Results: In the Pre-implementation period EMDs correctly identified 63% of stroke patients; this increased to 80% Post-implementation. This change was significant (p=0.003), reflecting an improvement in identifying stroke patients relative to the Pre-implementation period both the During-implementation (OR=4.10 [95% CI 1.58 to 10.66]) and Post-implementation (OR=2.30 [95% CI 1.07 to 4.92]) periods. For patients with a final diagnosis of stroke who had been dispatched as stroke there was a marginally non-significant 2.8 minutes (95% CI −0.2 to 5.9 minutes, p=0.068)reduction between Pre- and Post-implementation periods from call to arrival of the ambulance at scene. Conclusions: This is the first study to develop, implement and evaluate the impact of a training package for EMDs with the aim of improving the recognition of stroke. Training led to a significant increase in the proportion of stroke patients dispatched as such by EMDs; a small reduction in time from call to arrival at scene by the ambulance also appeared likely. The training package has been endorsed by the UK Stroke Forum Education and Training, and is free to access on-line

Comparative Morphology of the Penis and Clitoris in Four Species of Moles (Talpidae).

The penile and clitoral anatomy of four species of Talpid moles (broad-footed, star-nosed, hairy-tailed, and Japanese shrew moles) were investigated to define penile and clitoral anatomy and to examine the relationship of the clitoral anatomy with the presence or absence of ovotestes. The ovotestis contains ovarian tissue and glandular tissue resembling fetal testicular tissue and can produce androgens. The ovotestis is present in star-nosed and hairy-tailed moles, but not in broad-footed and Japanese shrew moles. Using histology, three-dimensional reconstruction, and morphometric analysis, sexual dimorphism was examined with regard to a nine feature masculine trait score that included perineal appendage length (prepuce), anogenital distance, and presence/absence of bone. The presence/absence of ovotestes was discordant in all four mole species for sex differentiation features. For many sex differentiation features, discordance with ovotestes was observed in at least one mole species. The degree of concordance with ovotestes was highest for hairy-tailed moles and lowest for broad-footed moles. In relationship to phylogenetic clade, sex differentiation features also did not correlate with the similarity/divergence of the features and presence/absence of ovotestes. Hairy-tailed and Japanese shrew moles reside in separated clades, but they exhibit a high degree of congruence. Broad-footed and hairy-tailed moles reside within the same clade but had one of the lowest correlations in features and presence/absence of ovotestes. Thus, phylogenetic affinity and the presence/absence of ovotestes are poor predictors for most sex differentiation features within mole external genitalia