69 research outputs found
Evidence that binding to the S2-subsite of papain may be coupled with catalytically relevant structural change involving the cysteine-25–histidine-159 diad. Kinetics of the reaction of papain with a two-protonic-state reactivity probe containing a hydrophobic side chain
Haemoglobin and Hematinic Status Before and After Bariatric Surgery over 4 years of Follow-Up
From Springer Nature via Jisc Publications RouterHistory: received 2020-03-02, rev-recd 2020-08-17, accepted 2020-08-18, registration 2020-08-19, pub-electronic 2020-09-01, online 2020-09-01, pub-print 2021-02Publication status: PublishedFunder: University of ManchesterAbstract: Purpose: Bariatric surgery is associated with deficiencies of vitamins and minerals, and patients are routinely advised supplements postoperatively. We studied prevalence of vitamin B12, folate and iron deficiencies and anaemia before and after bariatric surgery over 4 years of follow-up. Materials and Methods: We performed a retrospective cohort analysis of 353 people with obesity, including 257 (72.8%) women, who underwent gastric bypass (252, 71.4%) or sleeve gastrectomy (101, 28.6%) at our National Health Service bariatric centre in Northwest England. Results: At baseline, mean (standard error) age was 46.0 (0.6) years, body mass index 53.1 (0.4) kg/m2, serum vitamin B12 400.2 (16.4) pg/L, folate 7.7 (0.2) μg/L, iron 12.0 (0.3) μmol/L, ferritin 118.3 (8.4) μg/L and haemoglobin 137.9 (0.8) g/L. Frequency of low vitamin B12 levels reduced from 7.5% preoperatively to 2.3% at 48 months (P < 0.038). Mean folate levels increased from baseline to 48 months by 5.3 μg/L (P < 0.001) but frequency of low folate levels increased from 4.7% preoperatively to 10.3% (P < 0.048). Ferritin levels increased from baseline to 48 months by 51.3 μg/L (P < 0.009). Frequency of low ferritin levels was greater in women (39.1%) than in men (8.9%) at baseline (P < 0.001) and throughout the study period. Haemoglobin was low in 4.6% of all patients at baseline with no significant change over the study period. Conclusion: There were notable rates of haematinic insufficiencies in bariatric surgical candidates preoperatively. Our study lends further support to regular supplementation with vitamin B12, folic acid, and iron in people undergoing bariatric surgery
Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets
Human-mediated biological exchange has had global social and ecological impacts. In subS-aharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation
Plant virus particles carrying tumour antigen activate TLR7 and induce high levels of protective antibody
Induction of potent antibody is the goal of many vaccines targeted against infections or cancer. Modern vaccine designs that use virus-like particles (VLP) have shown efficacy for prophylactic vaccination against virus-associated cancer in the clinic. Here we used plant viral particles (PVP), which are structurally analogous to VLP, coupled to a weak idiotypic (Id) tumour antigen, as a conjugate vaccine to induce antibody against a murine B-cell malignancy. The Id-PVP vaccine incorporates a natural adjuvant, the viral ssRNA, which acts via TLR7. It induced potent protective anti-Id antibody responses in an in vivo mouse model, superior to the "gold standard" Id vaccine, with prevalence of the IgG2a isotype. Combination with alum further increased antibody levels and maintained the IgG2a bias. Engagement of TLR7 in vivo was followed by secretion of IFN-? by plasmacytoid dendritic cells and by activation of splenic CD11chi conventional dendritic cells. The latter was apparent from up-regulation of co-stimulatory molecules and from secretion of a wide range of inflammatory cytokines and chemokines including the Th1-governing cytokine IL-12, in keeping with the IgG2a antibody isotype distribution. PVP conjugates are a novel cancer vaccine design, offering an attractive molecular form, similar to VLP, and providing T-cell help. In contrast to VLP, they also incorporate a safe "in-built" ssRNA adjuvant
Why organizational and community diversity matter:Representativeness and the Emergence of Incivility and Organizational Performance
Integrating sociological and psychological perspectives, this research considers the value of organizational ethnic diversity as a function of community diversity. Employee and patient surveys, census data, and performance indexes relevant to 142 hospitals in the United Kingdom suggest that intraorganizational ethnic diversity is associated with reduced civility toward patients. However, the degree to which organizational demography was representative of community demography was positively related to civility experienced by patients and ultimately enhanced organizational performance. These findings underscore the understudied effects of community context and imply that intergroup biases manifested in incivility toward out-group members hinder organizational performance
Physical activity as an aid to smoking cessation during pregnancy (LEAP) trial: study protocol for a randomized controlled trial
Background: Many women try to stop smoking in pregnancy but fail. One difficulty is that there is insufficient evidence that medications for smoking cessation are effective and safe in pregnancy and thus many women prefer to avoid these. Physical activity (PA) interventions may assist cessation; however, trials examining these interventions have been too small to detect or exclude plausible beneficial effects. The London Exercise And Pregnant smokers (LEAP) trial is investigating whether a PA intervention is effective and cost-effective when used for smoking cessation by pregnant women, and will be the largest study of its kind to date.
Methods/design: The LEAP study is a pragmatic, multi-center, two-arm, randomized, controlled trial that will target pregnant women who smoke at least one cigarette a day (and at least five cigarettes a day before pregnancy), and are between 10 and 24 weeks pregnant. Eligible patients are individually randomized to either usual care (that is, behavioral support for smoking cessation) or usual care plus a intervention (entailing supervised exercise on a treadmill plus PA consultations). The primary outcome of the trial is self-reported and biochemically validated continuous abstinence from smoking between a specified quit date and the end of pregnancy. The secondary outcomes, measured at 1 and 4 weeks after the quit date, and at the end of pregnancy and 6 months after childbirth, are PA levels, depression, self-confidence, and cigarette withdrawal symptoms. Smoking status will also be self-reported at 6 months after childbirth. In addition, perinatal measures will be collected, including antenatal complications, duration of labor, mode of delivery, and birth and placental weight. Outcomes will be analyzed on an intention-to-treat basis, and logistic regression models used to compare treatment effects on the primary outcome.
Discussion: This trial will assess whether a PA intervention is effective when used for smoking cessation during pregnancy
The High Resolution Imaging Science Experiment (HiRISE) during MRO’s Primary Science Phase (PSP)
Vertical slice modelling of nonlinear Eady waves using a compatible finite element method
A vertical slice model is developed for the Euler–Boussinesq equations with a constant temperature gradient in the direction normal to the slice (the Eady–Boussinesq model). The model is a solution of the full three-dimensional equations with no variation normal to the slice, which is an idealised problem used to study the formation and subsequent evolution of weather fronts. A compatible finite element method is used to discretise the governing equations. To extend the Charney–Phillips grid staggering in the compatible finite element framework, we use the same node locations for buoyancy as the vertical part of velocity and apply a transport scheme for a partially continuous finite element space. For the time discretisation, we solve the semi-implicit equations together with an explicit strong-stability-preserving Runge–Kutta scheme to all of the advection terms. The model reproduces several quasi-periodic lifecycles of fronts despite the presence of strong discontinuities. An asymptotic limit analysis based on the semi-geostrophic theory shows that the model solutions are converging to a solution in cross-front geostrophic balance. The results are consistent with the previous results using finite difference methods, indicating that the compatible finite element method is performing as well as finite difference methods for this test problem. We observe dissipation of kinetic energy of the cross-front velocity in the model due to the lack of resolution at the fronts, even though the energy loss is not likely to account for the large gap on the strength of the fronts between the model result and the semi-geostrophic limit solution
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