Hard to Swallow Results.

The American Neurogastroenterology and Motility Society (ANMS) proposed quality measures (QMs) for performance and interpretation of esophageal manometry (EM). We implemented a quality improvement (QI) study at a large community hospital to assess and improve procedural adherence and interpretation of EM studies based on the ANMS QMs using the Chicago Classification 3.0 (CC) Guidelines. For pre-intervention, three motility independent reviewers reinterpreted 60 EM studies conducted by community gastroenterologists without Tier II-III motility training from October to December 2018 for compliance with pre-procedural, procedural, and data interpretation ANMS QMs. In December 2018, we developed a pre-procedural form, educated nurses on EM procedural compliance, and provided preliminary pre-intervention results to gastroenterologists along with literature utilizing the CC 3.0 Guidelines. For post-intervention, we reinterpreted 54 EM studies from January to August 2019 and investigated whether they met QMs for data interpretation with respect to the CC Guidelines and resulted in appropriate treatment. We found a statistically significant improvement in procedural compliance among nursing staff for 30 s of swallows (76% post-intervention versus 12% pre-intervention, p < 0.001) and 7 evaluable swallows (94% post-intervention versus 53% pre-intervention, p < 0.001). However, quality metrics within data interpretation by physicians post-intervention showed mixed results. An incorrect diagnosis was made in 50% (n = 27)) of studies with 72% (n = 39) having at least one missing item based on the CC. The most missed diagnosis was fragmented peristalsis (30%, n = 29). Among the 39% (n = 21) of surgery referrals, 24% (n = 5) were incorrectly referred. Our study shows poor data interpretation by community gastroenterologists without formal motility training despite adequate performance by nursing staff. This further supports the need for a national ANMS certification process for formal HRM education.

Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.

Detection of Cross-Correlation between Gravitational Lensing and γ Rays.

In recent years, many γ-ray sources have been identified, yet the unresolved component hosts valuable information on the faintest emission. In order to extract it, a cross-correlation with gravitational tracers of matter in the Universe has been shown to be a promising tool. We report here the first identification of a cross-correlation signal between γ rays and the distribution of mass in the Universe probed by weak gravitational lensing. We use data from the Dark Energy Survey Y1 weak lensing data and the Fermi Large Area Telescope 9-yr γ-ray data, obtaining a signal-to-noise ratio of 5.3. The signal is mostly localized at small angular scales and high γ-ray energies, with a hint of correlation at extended separation. Blazar emission is likely the origin of the small-scale effect. We investigate implications of the large-scale component in terms of astrophysical sources and particle dark matter emission.

A close-pair binary in a distant triple supermassive black hole system.

Galaxies are believed to evolve through merging, which should lead to some hosting multiple supermassive black holes. There are four known triple black hole systems, with the closest black hole pair being 2.4 kiloparsecs apart (the third component in this system is at 3 kiloparsecs), which is far from the gravitational sphere of influence (about 100 parsecs for a black hole with mass one billion times that of the Sun). Previous searches for compact black hole systems concluded that they were rare, with the tightest binary system having a separation of 7 parsecs (ref. 10). Here we report observations of a triple black hole system at redshift z = 0.39, with the closest pair separated by about 140 parsecs and significantly more distant from Earth than any other known binary of comparable orbital separation. The effect of the tight pair is to introduce a rotationally symmetric helical modulation on the structure of the large-scale radio jets, which provides a useful way to search for other tight pairs without needing extremely high resolution observations. As we found this tight pair after searching only six galaxies, we conclude that tight pairs are more common than hitherto believed, which is an important observational constraint for low-frequency gravitational wave experiments.

Does labelling a rare cancer diagnosis 'good' affect the patient's experience of treatment and recovery?

Doctors sometimes tell patients with rare but highly treatable cancers that they have 'good' cancer which some patients have found unhelpful, but this has been little explored. The aim of this study was to explore how patients reacted to being told they had a 'good' cancer. Qualitative interviews were carried out with 25 people with rare but prognostically favourable cancers who had received treatment at two hospitals within a cancer network. Results showed that despite good treatment outcomes, patients are still very shocked to hear the word cancer and react in similar ways to those with other forms of cancer. The potential effects of treatment should be recognised as having a detrimental effect on patient well-being whatever the prognosis. We should therefore avoid using 'good' and 'cancer' in the same sentence. In addition, the impact on all family members should not be underestimated. The data can be used to improve clinical practice and improve support for people affected by cancer.

Wide-Field Lensing Mass Maps from Dark Energy Survey Science Verification Data.

We present a mass map reconstructed from weak gravitational lensing shear measurements over 139 deg2 from the Dark Energy Survey science verification data. The mass map probes both luminous and dark matter, thus providing a tool for studying cosmology. We find good agreement between the mass map and the distribution of massive galaxy clusters identified using a red-sequence cluster finder. Potential candidates for superclusters and voids are identified using these maps. We measure the cross-correlation between the mass map and a magnitude-limited foreground galaxy sample and find a detection at the 6.8σ level with 20 arc min smoothing. These measurements are consistent with simulated galaxy catalogs based on N-body simulations from a cold dark matter model with a cosmological constant. This suggests low systematics uncertainties in the map. We summarize our key findings in this Letter; the detailed methodology and tests for systematics are presented in a companion paper.

Electronic cigarette use in young people in Great Britain 2013-2014.

OBJECTIVES: The recent growth in the market for electronic cigarettes (e-cigarettes) has led to concerns over their use by young people. It is therefore important to examine trends in the perception and use of e-cigarettes and conventional cigarettes in this group. STUDY DESIGN: Two-wave cross-sectional survey design. METHODS: Young people aged 11-18 in Great Britain were surveyed online by YouGov in 2013 and 2014. Use of e-cigarettes, together with perceived health harms and intention to use were assessed and compared in relation to cigarette smoking history, age and gender. RESULTS: Ever-use of e-cigarettes increased significantly from 4.6% (95% CI 3.8-5.7) in 2013 to 8.2% (95% CI 7.0-9.6) in 2014. Monthly or more use of e-cigarettes increased from 0.9% (95% CI 0.5-1.5) to 1.7 (1.2-2.4), but remained rare in never-smokers at under 0.2%. The proportion of young people who perceived e-cigarettes to be less harmful to users than cigarettes fell from 73.4% (95% CI 71.0-75.8) to 66.9% (95% CI 64.5-69.2), while the proportion who considered e-cigarettes to cause similar levels of harm increased from 11.8% (95% CI 10.0-13.5) to 18.2% (95% CI 16.3-20.1). Of the 8.2% of e-cigarette ever-users in 2014, 69.8% (95% CI 62.2%-77.3%) had smoked a cigarette prior to using an e-cigarette, while 8.2% (95% CI 4.1%-12.2%) first smoked a cigarette after e-cigarette use. CONCLUSIONS: A growing proportion of young people in Great Britain believe e-cigarettes are as harmful as smoking tobacco. Use of e-cigarettes by young people is increasing, but is largely confined to those who smoke.

Sickle cell solubility test: evaluation of an in-house method.

This study aims to assess the performance of an in-house sickle cell solubility test (SCT) and compare it against data published on other in-house and commercial methods. Also assessed are the effects of possible interference due to haemoglobin (Hb) level, Hb F and Hb S levels, as well as lipaemia, icterus and haemolysis index. A total of 1030 patient samples were tested by the SCT and subsequently confirmed by high-performance liquid chromatography (HPLC). Seventy-five (7.3%) samples revealed a positive SCT whereas 955 (92.7%) were negative. The sensitivity and specificity of the method was 100% and it was shown to detect low levels of Hb S (12.1%). These data show that the authors' in-house SCT method has an excellent performance against other documented methods (including some commercial kits), which is probably explained by its robustness against low levels of Hb S and interfering substances such as lipaemia. The authors believe this shows that in-house tests are able to produce highly reliable results comparable to, if not better than, certain commercially available CE-marked kits.

Reflections on a nursing education institution transitioning to online education during the Covid-19 pandemic.

In 2022, nursing faculty reflect on the transition without global or national benchmarks or blueprints of a South African Nursing Education Institution to online education during the Covid-19 pandemic. Objective: To provide policy makers a resource in preparation for future crises in education. A theoretical-reflective study supported by a SWOT analysis aimed to understand the transition to online teaching and learning and assessments for the Nursing Discipline (nursing faculty n = 22; undergraduate students n = 291) of a select South African university. It revealed four key lessons learned. Firstly, whether change is planned or unplanned, policy frameworks should guide it. Secondly, resources exist within faculty, and at times, change agents might not be necessary as strengths can be drawn from within. Thirdly, through managing a crisis, faculty-service partnership can be strengthened. Lastly, a need exists for continual surveillance as the inequality gap in Higher Education students has become increasingly visible and amplified further marginalisation. Our reflections have highlighted that opportunities and strengths abound as the pandemic has fast-tracked nursing education institutions to embrace technology for teaching and learning and assessments. Three of the key lessons learned emphasise what is known about the successful outcome of working together.

Bacterial production of recombinant contraceptive vaccine antigen from CatSper displayed on a human papilloma virus-like particle.

CatSper is a voltage dependent calcium ion channel present in the principal piece of sperm tail. It plays a crucial role in sperm hyperactivated motility and so in fertilization. Extracellular loops of mouse sperm CatSper were used to develop a vaccine to achieve protection from pregnancy. These loops were inserted at one of the three hypervariable regions of Human Papilloma Virus (HPV) capsid protein (L1). Recombinant vaccines were expressed in E.coli as inclusion body (IB), purified, refolded and assembled into virus-like particles (VLP) in vitro, and adsorbed on alum. Four vaccine candidates were tested in Balb/C mice. All the constructs proved immunogenic, one showed contraceptive efficacy. This recombinant contraceptive vaccine is a non-hormonal intervention and is expected to give long-acting protection from undesired pregnancies.

A survey in the West Midlands of the United Kingdom of current practice in managing hypotension in lower segment caesarean section under spinal anaesthesia.

BACKGROUND: Spinal anaesthesia, the most common form of anaesthesia for caesarean section, leads to sympathetic blockade and profound maternal hypotension resulting in adverse maternal and neonatal outcomes. Hypotension, nausea and vomiting remain common but until the publication of the National Institute of Health and Care Excellence (NICE) 2021 guidance, no national guideline existed on how best to manage maternal hypotension following spinal anaesthesia for caesarean section. A 2017 international consensus statement recommended prophylactic vasopressor administration to maintain a systolic blood pressure of >90% of an accurate pre-spinal value, and to avoid a drop to <80% of this value. This survey aimed to assess regional adherence to these recommendations, the presence of local guidelines for management of hypotension during caesarean section under spinal anaesthesia, and the individual clinician's treatment thresholds for maternal hypotension and tachycardia. METHODS: The West Midlands Trainee-led Research in Anaesthesia and Intensive Care Network co-ordinated surveys of obstetric anaesthetic departments and consultant obstetric anaesthetists across 11 National Health Service Trusts in the Midlands, England. RESULTS: One-hundred-and-two consultant obstetric anaesthetists returned the survey and 73% of sites had a policy for vasopressor use; 91% used phenylephrine as the first-line drug but a wide range of recommended delivery methods was noted and target blood pressure was only listed in 50% of policies. Significant variation existed in both vasopressor delivery methods and target blood pressures. CONCLUSIONS: Although NICE has since recommended prophylactic phenylephrine infusion and a target blood pressure, the previous international consensus statement was not adhered to routinely.

Dos and don'ts for mHealth-based clinical support among clinicians in South Africa: Results from a 1-day workshop.

Digital technologies continue to penetrate the South African (SA) healthcare sector at an increasing rate. Clinician-to-clinician diagnostic and management assistance through mHealth is expanding rapidly, reducing professional isolation and unnecessary referrals, and promoting better patient outcomes and more equitable healthcare systems. However, the widespread uptake of mHealth use raises ethical concerns around patient autonomy and safety, and guidance for healthcare workers around the ethical use of mHealth is needed. This article presents the results of a multi-stakeholder workshop at which the 'dos and don'ts' pertaining to mHealth ethics in the SA context were formulated and aligned to seven basic recommendations derived from the literature and previous multi-stakeholder, multi-country meetings.

UK B.1.1.7 variant exhibits increased respiratory replication and shedding in nonhuman primates.

The continuing emergence of SARS-CoV-2 variants calls for regular assessment to identify differences in viral replication, shedding and associated disease. In this study, African green monkeys were infected intranasally with either a contemporary D614G or the UK B.1.1.7 variant. Both variants caused mild respiratory disease with no significant differences in clinical presentation. Significantly higher levels of viral RNA and infectious virus were found in upper and lower respiratory tract samples and tissues from B.1.1.7 infected animals. Interestingly, D614G infected animals showed significantly higher levels of viral RNA and infectious virus in rectal swabs and gastrointestinal tract tissues. Our results indicate that B.1.1.7 infection in African green monkeys is associated with increased respiratory replication and shedding but no disease enhancement similar to human B.1.1.7 cases. ONE-SENTENCE SUMMARY: UK B.1.1.7 infection of African green monkeys exhibits increased respiratory replication and shedding but no disease enhancement.

Smoke-free homes in England: prevalence, trends and validation by cotinine in children.

OBJECTIVE: To examine the prevalence of smoke-free homes in England between 1996 and 2007 and their impact on children's exposure to second-hand smoke via a series of annual cross-sectional surveys: the Health Survey for England. These comprised nationally representative samples of non-smoking children aged 4-15 (n = 13 365) and their parents interviewed in the home. Main outcome measures were cotinine measured in saliva, smoke-free homes defined by "no" response to "Does anyone smoke inside this house/flat on most days?", self-reported smoking status of parents and self-reported and cotinine validated smoking status in children. RESULTS: The proportion of homes where one parent was a smoker that were smoke free increased from 21% in 1996 to 37% in 2007, and where both parents were smokers from 6% to 21%. The overwhelming majority of homes with non-smoking parents were smoke free (95% in 1996; 99% in 2007). For children with non-smoking parents and living in a smoke-free home the geometric mean cotinine across all years was 0.22 ng/ml. For children with one smoking parent geometric mean cotinine levels were 0.37 ng/ml when the home was smoke free and 1.67 ng/ml when there was smoking in the home; and for those with two smoking parents, 0.71 ng/ml and 2.46 ng/ml. There were strong trends across years for declines in cotinine concentrations in children in smoke-free homes for the children of smokers and non-smokers. CONCLUSIONS: There has been a marked secular trend towards smoke-free homes, even when parents themselves are smokers. Living in a smoke-free home offers children a considerable, but not complete, degree of protection against exposure to parental smoking.

Imipramine induced elevation of prolactin levels in patients with HIV/AIDS improved their immune status.

Prolactin is known to have significant immunomodulatory properties. Imipramine, a monoamine oxidase inhibitor stimulates prolactin production because it decreases dopamine which inhibits secretion of prolactin. The study objective was to determine if use of imipramine can result in immunological benefits for HIV-positive patients by restoration and preservation of immunological function. A cohort of 19 retroviral positive patients was identified for the prospective study which continued for a 28-week period. Three patients dropped out before the study began. Inclusion criteria accepted only patients on the same highly active antiretroviral therapy (HAART) regimen for a nine-month period and who had reached a plateau with respect to the CD4 cell count and also had no prior history of antidepressant use for a 12-month period. This study had a "before and after" design, patients serving as their own control. The study drug imipramine was prescribed for a 12-week period up to visit 4, and then discontinued for 4-weeks (washout period) at which time blood investigations were done at visit 5. Finally, patients were prescribed the study drug for a further 12-week period to the end of the trial (visit 7). At the 95 per cent probability level, significant differences in average prolactin and CD4 levels from visit 4 to the end of the trial period were recorded. Results showed a trend of prolactin levels decreasing after washout (p = 0.015) and increasing by the end of the trial period once imipramine dispensation had recommenced (p = 0.006). With respect to the CD4 cell count, there was a significant increase after wash-out (p = 0.022). These results indicate a trend to immune boosting in HIV-positive patients who had obtained the maximum response from HAART.

Modelling polymer interactions of the 'molecular Velcro' type in wood under mechanical stress.

Trees withstand wind and snow loads by synthesising wood that varies greatly in mechanical properties: flexible in twigs and in the stem of the sapling, and rigid in the outer part of the mature stem. The 'molecular Velcro' model of Keckes et al. [2003. Cell-wall recovery after irreversible deformation of wood. Nat. Mater. 2, 810-814] permits the simulation of the tensile properties of water-saturated wood as found in living trees. A basic feature of this model is the presence of non-covalent interactions between hemicellulose chains attached to adjacent cellulose microfibrils, which are disrupted above a threshold level of interfibrillar shear. However, other evidence does not confirm the importance of hemicellulose-hemicellulose association in the cohesion of the interfibrillar matrix. Here, we present an alternative model in which hemicellulose chains bridging continuously from one microfibril aggregate (macrofibril) to the next provide most of the cohesion. We show that such hemicellulose bridges exist and that the stripping of the bridging chains from the cellulose surfaces under the tensile stress component normal to the macrofibrils can provide an alternative triggering mechanism for shear deformation between one macrofibril and the next. When one macrofibril then slides past another, a domain of the wood cell wall can extend but simultaneously it twists until the spacing between macrofibrils is reduced again and contact through hemicelluloses bridges is restored. Overall deformation therefore takes place through a series of local stick-slip events involving temporary twisting of small domains within the wood cell wall. Modelled load-deformation curves for this modified 'molecular Velcro' model are similar, although not identical, to those for the original model. However, the mechanism is different and more consistent with current views of the structure of wood cell walls, providing a framework within which the developmental control of rigidity in wood synthesised in different parts of a tree may be considered.

The scientific basis of tobacco product regulation.

This report presents the conclusions and recommendations of TobReg from its fourth meeting, where the Study Group deliberated on a number of topics in the field of tobacco product regulation and produced the following advisory notes and recommendations: an advisory note on smokeless tobacco products: health effects, implications for harm reduction and research needs; an advisory note on 'fire safer' cigarettes: approaches to reduced ignition propensity; a recommendation on mandated lowering of toxicants in cigarette smoke: tobacco-specific nitrosamines and selected other constituents; and a recommendation on cigarette machine smoking regimens. The four sections of this report address these four issues, and the Study Group's recommendations are set out at the end of each section. Its overall recommendations are summarized in section 5.

P2X7-related modulation of pathological nociception in rats.

Growing evidence supports a role for the immune system in the induction and maintenance of chronic pain. ATP is a key neurotransmitter in this process. Recent studies demonstrate that the glial ATP receptor, P2X7, contributes to the modulation of pathological pain. To further delineate the endogenous mechanisms that are involved in P2X7-related antinociception, we utilized a selective P2X7 receptor antagonist, A-438079, in a series of in vivo and in vitro experiments. Injection of A-438079 (10-300 micromol/kg, i.p.) was anti-allodynic in three different rat models of neuropathic pain and it attenuated formalin-induced nocifensive behaviors. Using in vivo electrophysiology, A-438079 (80 micromol/kg, i.v.) reduced noxious and innocuous evoked activity of different classes of spinal neurons (low threshold, nociceptive specific, wide dynamic range) in neuropathic rats. The effects of A-438079 on evoked firing were diminished or absent in sham rats. Spontaneous activity of all classes of spinal neurons was also significantly reduced by A-438079 in neuropathic but not sham rats. In vitro, A-438079 (1 microM) blocked agonist-induced (2,3-O-(4-benzoylbenzoyl)-ATP, 30 microM) current in non-neuronal cells taken from the vicinity of the dorsal root ganglia. Furthermore, A-438079 dose-dependently (0.3-3 microM) decreased the quantity of the cytokine, interleukin-1beta, released from peripheral macrophages. Thus, ATP, acting through the P2X7 receptor, exerts a wide-ranging influence on spinal neuronal activity following a chronic injury. Antagonism of the P2X7 receptor can in turn modulate central sensitization and produce antinociception in animal models of pathological pain. These effects are likely mediated through immuno-neural interactions that affect the release of endogenous cytokines.

Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states.

ATP-sensitive P2X(7) receptors are localized on cells of immunological origin including peripheral macrophages and glial cells in the CNS. Activation of P2X(7) receptors leads to rapid changes in intracellular calcium concentrations, release of the proinflammatory cytokine interleukin-1beta and following prolonged agonist exposure, the formation of cytolytic pores in plasma membranes. Both the localization and functional consequences of P2X(7) receptor activation indicate a role in inflammatory processes. The phenotype of P2X(7) receptor gene-disrupted mice also indicates that P2X(7) receptor activation contributes to ongoing inflammation. More recently, P2X(7) receptor knockout data has also suggested a specific role in inflammatory and neuropathic pain states. The recent discovery of potent and highly selective antagonists for P2X(7) receptors has helped to further clarify P2X receptor pharmacology, expanded understanding of P2X(7) receptor signaling, and offers new evidence that P2X(7) receptors play a specific role in nociceptive signaling in chronic pain states. In this review, we incorporate the recent discoveries of novel P2X(7) receptor-selective antagonists with a brief update on P2X(7) receptor pharmacology and its therapeutic potential.