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Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality.

ABSTRACTThis study represents the first comprehensive qualitative systematic review on sport coaches’ and teachers’ perceptions and application of Game-Based Approaches (GBA) and Constraints-Led Approach (CLA). From searching 12 electronic academic databases from 1982 to 2020, 29 studies met the eligibility criteria and were included in the meta-study. Data revealed studies were conducted in several different countries, and case study design was the predominant methodology. The main data collection method reported was cross-sectional interviews. There were inconsistencies in the quality of reporting methodologies, sampling procedures, data analysis, and assessing quality. The meta-theory analysis identified weaknesses in the methodological and conceptual approaches, and a low number of studies stated philosophical perspectives. The meta-synthesis identified assumptions about learning, pedagogical knowledge and skills, content knowledge, and support as the overarching themes reported to impact coaches’ and teachers’ perceptions and application of GBAs and CLA. Finally, some recommendations for future research and practice are provided.

Study design: Descriptive. Objectives: The primary objective is to describe the intervention that will be provided in a large multi-centre randomised controlled trial titled: Early and Intensive Motor Training for people with Spinal Cord Injuries(the SCI-MT Trial). The secondary objective is to describe the strategies that will be used to operationalise and standardise the Motor Training provided to participants while keeping the intervention person-centred. Methods: The paper focuses on the rationale and principles of Motor Training for people with spinal cord injuries (SCI). The description of the intervention is based on the Template for Intervention Description and Replication (TIDieR) checklist. Specifically, it addresses the following 6 criteria of the TIDieR checklist: why the effectiveness of Motor Training is being examined; what, how, where and when the Motor Training will be administered; and how much Motor Training will be provided. Results: A detailed intervention manual has been developed to help standardise the delivery of the intervention. Conclusions: This paper describes the details of a complex intervention administered as part of a large randomised controlled trial. It will facilitate the subsequent interpretation of the trial results and enable the intervention to be reproduced in clinical practice and future trials.

A work on the analysis of five kinetic models for predicting methane yield is presented. The selected five common models for predicting methane yield include Gompertz, logistic, first-order, Richards and transfert models. Anaerobic digestion of orange and banana peels was simulated using the selected models. A comparative analysis of the models was carried out to determine the best-fit model. When predicting the methane yield of banana peels, all models reached a maximum of 99.23% and the model which was most accurate was the Gompertz model with 76% cumulative deviation and the least accurate model was the transfert model with 274.7% cumulative deviation. The prediction of methane yield on orange peels was 99.49% accurate for all models having the most accurate model being the Gompertz and first-order kinetic model with a cumulative deviation of 20.67% and the least accurate model being the transfert model with a cumulative deviation of 112%. This work presents the simulation considerations and application for each model.

What makes an odour pleasant or unpleasant? The inherent properties of the constituent chemical compounds, or the nose of the beholder, driven by idiosyncratic differences and culture-specific learning? Here, 582 individuals, including Tanzanian Hadza hunter–gatherers, Amazonian Tsimane’ horticulturalists, Yali from the Papuan highlands and two industrialized populations (Poles, Malaysians), rated the pleasantness of 15 odour samples. We find considerable similarities in odour assessments across cultures, but our data do not fully support a claim regarding the universality of smell preferences. Despite cross-cultural similarities in olfactory assessments, probably driven by odour properties, we suggest that odour availability in ecological and cultural niches bears an undeniable effect on human odour preferences.

Onshore wind electricity generation is key to mitigating greenhouse gas emissions.​ Poorly sited wind farms degrade high carbon soils and habitats, diminishing overall emission reductions. We explore the viability of the Scottish Government’s renewable energy plan with respect to land use, natural capital and low carbon storage. With avoidance of sensitive peatlands a main consideration, six constraining factors were combined to determine areas of least habitat and soil sensitivity to onshore wind development in Scotland. Currently, 14 out of 21 terrestrial habitats have been impacted by installation of 389 onshore wind sites. Accounting for 73% of the total area, Coniferous Woodland, Acid Grassland, Bog, and Heather Grassland have been the largest habitats impacted. The most common soils of the least sensitive areas available for installation are brown earth and podzols, and construction of new wind farms on environmentally sensitive areas can be minimised by targeting relatively disturbed habitats such as improved grasslands. Scotland has a potential of 2.75 Mha of relatively low sensitive land, the largest areas sited in the Highlands, Dumfries and Galloway and Aberdeenshire. Additional to current installed capacity (13.9 GW), Scotland would require 6.6 GW of installed onshore wind capacity to function without nuclear energy generation and 464 GWh additional storage capacity (provided by 8.2 GW wind capacity). This equates to an installed and additional total of 346.676 ha required for wind electricity generation, potentially satisfied by shared land use with 23% of Scottish improved grasslands. Scotland has the available land area to achieve the Scottish Government’s policy to move towards carbon-neutral, nuclear-free electricity generation through the use of renewables alone. Questions remain on which source of low carbon dispatchable (immediately accessible) energy to use in the case of a several day wind lull.

BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing.

Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection.

The clinical utility of rapamycin (Rapa) is limited by solubility, bioavailability, and side effects. To overcome this, our team recently reported an elastin-like polypeptide (ELP) nanoparticle with high affinity, noncovalent drug binding, and integrin-mediated cellular uptake. Given the scarcity of pharmacology/toxicology studies of ELP-based drug carriers, this article explores safety and efficacy of ELP-Rapa. ELP-Rapa nanoparticles tested negative for hemolysis, did not interfere in plasma coagulation nor in platelet function, and did not activate the complement. Upon incubation with HepG2 cells, ELP-Rapa revealed significant cellular uptake and trafficking to acidic organelles, consistent with lysosomes. Internalized ELP-Rapa nanoparticles increased oxidative stress 4-fold compared to free drug or free ELP controls. However, mice bearing orthotopic hormone receptor positive BT-474 breast tumors, given a high dose (∼10-fold above therapeutic dose) of 1 month administration of ELP-Rapa, did not induce hepatotoxicity. On the other hand, tumor growth and mTOR signaling were suppressed without affecting body weight. Nanoparticles assembled using ELP technology appear to be a safe and efficient strategy for delivering Rapa.

Background/Objectives: The iron-binding affinity of vaginal lactoferrin (Lf) reduces iron available to genital pathogens. We describe host reproductive, nutritional, infection and iron biomarker profiles affecting vaginal Lf concentration in young nulliparous and primigravid women in Burkina Faso. Subjects/Methods: Vaginal eluates from women who had participated in a randomized, controlled periconceptional iron supplementation trial were used to measure Lf using a competitive double-sandwich ELISA. For this analysis samples from both trial arms were combined and pregnant and non-pregnant cohorts compared. Following randomization Lf was measured after 18 months (end assessment) for women remaining non-pregnant, and at two antenatal visits for those becoming pregnant. Associations between log Lf levels and demographic, anthropometric, infection and iron biomarker variables were assessed using linear mixed models. Results: Lf samples were available for 712 non-pregnant women at end assessment and for 303 women seen at an antenatal visit. Lf concentrations of pregnant women were comparable to those of non-pregnant, sexually active women. Lf concentration increased with mid-upper-arm circumference, (P?=?0.047), body mass index (P?=?0.018), Trichomonas vaginalis(P?<?0.001) infection, bacterial vaginosis (P?<?0.001), serum C-reactive protein (P?=?0.048) and microbiota community state types III/IV. Adjusted Lf concentration was positively associated with serum hepcidin (P?=?0.047), serum ferritin (P?=?0.018) and total body iron stores (P?=?0.042). There was evidence that some women maintained persistently high or low Lf concentrations from before, and through, pregnancy. Conclusion: Lf concentrations increased with genital infection, higher BMI, MUAC, body iron stores and hepcidin, suggesting nutritional and iron status influence homeostatic mechanisms controlling vaginal Lf responses.

To investigate the incidence, nature and risk factors for patient-reported alopecia in survivors of critical illness.

Lymph node metastases are a major prognostic indicator in oesophageal cancer. Radiological staging largely influences treatment decisions and is becoming more reliant on PET and CT. However, the sensitivity of these modalities is suboptimal and is known to under-stage disease. The primary aim of this study was to validate a published prognostic model in oesophageal cancer patients staged N0 with PET/CT, which showed that EUS nodal status was an independent predictor of survival. The secondary aim was to assess the prognostic significance of pathological lymph node metastases in this cohort. An independent validation cohort included 139 consecutive patients from a regional upper gastrointestinal cancer network staged N0 with PET/CT between 1st January 2013 and 31st June 2015. Replicating the original study, two Cox regression models were produced: one included EUS T-stage and EUS N-stage, and one included EUS T-stage and EUS N0 versus N+. The primary outcome of the prognostic model was overall survival (OS). Kaplan–Meier analysis assessed differences in OS between pathological node-negative (pN0) and node-positive (pN+) groups. A pvalue of < 0.05 was considered statistically significant. The mean OS of the validation cohort was 29.8 months (95% CI 27.1–35.2). EUS T-stage was significantly and independently associated with OS in both models (p= 0.011 and p= 0.012, respectively). EUS N-stage and EUS N0 versus N+ were not significantly associated with OS (p= 0.553 and p= 0.359, respectively). There was a significant difference in OS between pN0 and pN+ groups (χ213.315, df1, p< 0.001). Lymph node metastases have a significant detrimental effect on OS. This validation study did not replicate the results of the developed prognostic model but the continued benefit of EUS in patients staged N0 with PET/CT was demonstrated. EUS remains a valuable component of a multi-modality approach to oesophageal cancer staging.

Acute type A aortic dissection (TAAD) with malperfusion syndrome remains a challenging diagnosis and optimal surgical management remains unsettled. We present a case and surgical approach employed for a patient with TAAD and malperfusion syndrome who presented with pulseless bilaterally extremities. Satisfactory outcomes can be achieved with early multidisciplinary collaboration and urgent repair of the aorta and simultaneous efforts to restore blood flow to ischemic tissue.

Recent research has highlighted how Lake Baikal, Siberia, has responded to the direct and indirect effects of climate change (e.g., ice‐cover duration), nutrient loading, and pollution, manifesting as changes in phytoplankton/zooplankton populations, community structure, and seasonal succession. Here, we combine and compare analyses of chlorophyll a(an estimate of total algal biomass), carotenoid pigments (biomarkers of algal groups), and lake water silicon isotope geochemistry (δ30SiDSi) to differentiate spatial patterns in dissolved silicon (DSi) uptake at Lake Baikal. A total of 15 sites across the three basins (south, central, and north) of Lake Baikal were sampled in August 2013 along a depth gradient of 0–180 m. Strong, significant correlations were found between vertical profiles of photic zone DSi concentrations and δ30SiDSicompositions (r= −0.81, p< 0.001), although these are strongest in the central basin aphotic zone (r= −0.98, p< 0.001). Data refute the hypothesis of DSi uptake by picocyanobacteria. Algal biomass profiles and high surface δ30SiDSicompositions suggest greater productivity in the south basin and more oligotrophic conditions in the north basin. δ30SiDSisignatures are highest at depth (20 m) in central basin sites, indicating greater (10–40%) DSi utilization at deep chlorophyll maxima. DSi limitation occurs in the pelagic central basin, probably reflecting a high diatom biomass bloom event (Aulacoseira baicalensis). Meanwhile in the more hydrologically restricted, shallow Maloe More region (central basin), both high δ30SiDSicompositions and picocyanobacteria (zeaxanthin) concentrations, respectively point to the legacy of an “Aulacoseirabloom year” and continuous nutrient supply in summer months (e.g., localized eutrophication).

Increased levels of interferon-γ (IFN-γ) are routinely observed in the respiratory tract following influenza virus infection, yet its potential role remains unclear. We now demonstrate that influenza-induced IFN-γ restricts protective innate lymphoid cell group II (ILC2) function in the lung following challenge with the pandemic H1N1 A/CA/04/2009 (CA04) influenza virus. Specifically, IFN-γ deficiency resulted in enhanced ILC2 activity, characterized by increased production of interleukin (IL)-5 and amphiregulin, and improved tissue integrity, yet no change in ILC2 numbers, viral load or clearance. We further found that IFN-γ-deficient mice, as well as wild-type animals treated with neutralizing anti-IFN-γ antibody, exhibited decreased susceptibility to lethal infection with H1N1 CA04 influenza virus, and moreover that survival was dependent on the presence of IL-5. The beneficial effects of IFN-γ neutralization were not observed in ILC2-deficient animals. These data support the novel concept that IFN-γ can have a detrimental role in the pathogenesis of influenza through a restriction in ILC2 activity. Thus, regulation of ILC2 activity is a potential target for post-infection therapy of influenza.

IntroductionThe evolution of medical practice is resulting in increasing subspecialisation, with head, face and neck (HFN) trauma in a civilian environment usually managed by a combination of surgical specialties working as a team. However, the full combination of HFN specialties commonly available in the NHS may not be available in future UK military-led operations, necessitating the identification of a group of skill sets that could be delivered by one or more deployed surgeons.MethodA systematic review was undertaken to identify those surgical procedures performed to treat acute military head, face, neck and eye trauma. A multidisciplinary consensus group was convened following this with military HFN trauma expertise to define those procedures commonly required to conduct deployed, in-theatre HFN surgical combat trauma management.ResultsHead, face, neck and eye damage control surgical procedures were identified as comprising surgical cricothyroidotomy, cervico-facial haemorrhage control and decompression of orbital haemorrhage through lateral canthotomy. Acute in-theatre surgical skills required within 24 hours consist of wound debridement, surgical tracheostomy, decompressive craniectomy, intracranial pressure monitor placement, temporary facial fracture stabilisation for airway management or haemorrhage control and primary globe repair. Delayed in-theatre procedures required within 5 days prior to predicted evacuation encompass facial fracture fixation, delayed lateral canthotomy, evisceration, enucleation and eyelid repair.ConclusionsThe identification of those skill sets required for deployment is in keeping with the General Medical Council’s current drive towards credentialing consultants, by which a consultant surgeon’s capabilities in particular practice areas would be defined. Limited opportunities currently exist for trainees and consultants to gain experience in the management of traumatic head, face, neck and eye injuries seen in a kinetic combat environment. Predeployment training requires that the surgical techniques described in this paper are covered and should form the curriculum of future military-specific surgical fellowships. Relevant continued professional development will be necessary to maintain required clinical competency.

Our objective was to determine the effect of castration timing, method, and use of the analgesic meloxicam (MEL) on inflammation, behavior, performance, and carcass traits in feedlot cattle. This study was a randomized complete block design conducted over a 3-yr period. In total, 194 crossbred beef calves from a single ranch origin were randomized at birth to receive one of five treatments arranged as a 2 × 2 + 1 factorial: 1) bulls castrated within 48 h of birth (CON), 2) bulls surgically castrated on day 0 without MEL (SUR), 3) bulls surgically castrated on day 0 with MEL (SUR + MEL), 4) bulls band castrated on d 0 without MEL (BAN), and 5) bulls band castrated on day 0 with MEL (BAN + MEL). Upon feedlot arrival (day −11; average 287 ± 2.03 d of age), animals were blocked by initial BW (224 ± 4.5 kg) and assigned randomly to treatment pens in three consecutive years (n= 2 pens per treatment in each year). Oral MEL was administered at 1 mg/kg BW concurrent with applicable castration treatment on day 0. Data were analyzed using the MIXED and GLIMMIX procedures of SAS with pen (year) serving as experimental unit. From days 0 to 7, ADG was reduced (P= 0.01) for surgical (−0.42) compared to band (0.43 kg/d) castration. Conversely, ADG was increased for surgical (1.74) vs. band (1.46 kg/d) castration from days 14 to 32. There was also an overall (day 0 to final) improvement in ADG for MEL (P= 0.02), but no effect of castration method was observed (P= 0.81). The CON group had the greatest (P= 0.05) marbling score. Backfat thickness was increased (P= 0.01) for MEL. A treatment × day interaction (P= 0.04) existed for serum haptoglobin, with SUR having the greatest (P< 0.01) concentration on days 1 and 4. Meloxicam administered in the surgically castrated treatment reduced (P= 0.01) serum haptoglobin concentration on day 1. Relative to baseline, standing duration for surgical castration was increased 113 min (P< 0.01), while banding caused 6.7 more lying bouts (P< 0.01) immediately following castration on day 0. Step count was greatest for BAN, intermediate for CON, and least for surgical (P< 0.01). Results suggest that MEL mitigated the more pronounced inflammation observed for surgical castration, whereas behavior was differentially altered for castration method indicative of a divergent pain response. Castration, regardless of method, transiently reduced ADG, but MEL administration improved overall ADG for both methods.

Increased levels of interferon-γ (IFN-γ) are routinely observed in the respiratory tract following influenza virus infection, yet its potential role remains unclear. We now demonstrate that influenza-induced IFN-γ restricts protective innate lymphoid cell group II (ILC2) function in the lung following challenge with the pandemic H1N1 A/CA/04/2009 (CA04) influenza virus. Specifically, IFN-γ deficiency resulted in enhanced ILC2 activity, characterized by increased production of interleukin (IL)-5 and amphiregulin, and improved tissue integrity, yet no change in ILC2 numbers, viral load or clearance. We further found that IFN-γ-deficient mice, as well as wild-type animals treated with neutralizing anti-IFN-γ antibody, exhibited decreased susceptibility to lethal infection with H1N1 CA04 influenza virus, and moreover that survival was dependent on the presence of IL-5. The beneficial effects of IFN-γ neutralization were not observed in ILC2-deficient animals. These data support the novel concept that IFN-γ can have a detrimental role in the pathogenesis of influenza through a restriction in ILC2 activity. Thus, regulation of ILC2 activity is a potential target for post-infection therapy of influenza.

The objective of this research was to examine the effects of dexamethasone (DEX) treatment on various aspects of immunity following administration of a multivalent respiratory vaccine, using a model intended to mimic acute versus chronic stress. Angus × Hereford steers (n= 32; 209 ± 8 kg) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) acute stress (ACU), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h only on d 0; 2) chronic stress (CHR), in which 0.5 mg/kg BW DEX was intravenously administered at 1000 h on d −3 to 0; or 3) control (CON), in which no DEX was administered. Steers were fitted with indwelling jugular catheters and rectal temperature (RT) recording devices on d −4 relative to vaccination and placed in individual stanchions in an environmentally controlled facility. Blood samples were collected and serum was isolated at −74, −50, and −26 h; at 0.5-h intervals from −4 to 6 h; and at 12, 24, 36, 48, and 72 h relative to multivalent respiratory vaccination at 1200 h on d 0. Additional blood samples were used to analyze complete blood cell count (CBC) and functional capacities of neutrophils. There was a treatment × time interaction (P< 0.01) for RT such that DEX treatment in CHR and ACU steers decreased RT on d −3 and 0, respectively. A treatment × time interaction (P< 0.01) was observed for total white blood cells (WBC), neutrophils, lymphocytes, and monocytes. Specifically, DEX increased WBC and neutrophils in CHR and ACU steers (P< 0.001) yet decreased lymphocytes in CHR steers (P= 0.02) compared with CON steers. Neutrophil concentration increased rapidly, within 2 h of the DEX infusion, in ACU steers. Monocytes transiently increased (P< 0.001) in response to DEX treatment in CHR and ACU steers. In contrast, eosinophils were greater (P< 0.01) in CON steers than in ACU and CHR steers. A treatment × time interaction (P= 0.004) was observed for interferon-γ, with CON cattle exhibiting greater concentrations than the ACU and CHR cattle at 5 h after vaccination, through d 3. Treatment also influenced (P≤ 0.001) the expression of L-selectin on the surface of neutrophils. The percentage of neutrophils engaging in phagocytosis and the oxidative burst were suppressed (P≤ 0.001) among only the CHR steers, whereas the intensity of the oxidative burst was suppressed (P≤ 0.001) for both ACU and CHR steers. These data suggest that our model induced acute and chronic immunosuppression and defined the acute response to a multivalent vaccine in CON steers.