EFFECT OF AUTOLOGOUS PLATELET-RICH PLASMA ON DISTRACTION OSTEOGENESIS IN THE MANDIBLE OF RABBITS: A MORPHOLOGIC AND MORPHOMETRIC APPROACH

Distraction osteogenesis of the jaws is a common surgical practice in the treatment of pediatric craniofacial deformities. Autologous platelet rich plasma (PRP) has been used to increase the healing potential of bones in humans during distraction osteogenesis. This article aims to study the morphometric and morphologic parameters resulting from the effect of PRP on bone healing after mandibular distraction in rabbits. Right mandibular distraction was performed in 12 rabbits divided equally into 2 groups. PRP and physiological saline were injected, according to a defined protocol, in the callus following distraction of the experimental and control groups respectively. The rabbits were sacrificed after a consolidation period of 45 days and the mandibles were surgically removed. Bone mineral density, radiographic analysis, mechanical properties and histological features of the lengthened bones were assessed using radiographic examination, dual X-ray absorptiometry, biomechanical testing and histology. Results showed that the regenerate bone density, the amount of trabeculation in addition to the bone mineral density and mineral content, as measured by absorptiometry, were better with PRP but not significantly different between groups. Two radiographs revealed a more consistent healing in the experimental mandibles compared with erratic outcomes in corresponding controls. Two of the latter could not be subjected to any mechanical testing because the mandibular parts, connected with fibrous tissue, were separated. Consequently, the biomechanical test depicted greater maximal loads in the experimental group. The histological studies exhibited more ossification and less connective tissue fibers in the experimental group. PRP accelerated healing of mandibles in rabbits following distraction and improved their biomechanical properties. These findings have significant clinical implications on reducing the period of consolidation of the mandibles which may not be immobilized like other bones for long period tim

Predictors of human PBDE body burdens for a UK cohort

Human exposure to polybrominated diphenyl ethers (PBDEs) was investigated in a cohort of 20 UK adults along with their anthropometric covariates and relevant properties such as room surveys, lifestyle, diet and activity details. Selected PBDE congeners were measured in matched samples of indoor dust (n = 41), vehicles (n = 8), duplicate diet (n = 24), serum (n = 24) and breast milk (n = 6).Combined exposure estimates via dust and diet revealed total PBDE intakes of 104 to 1,440 pg kg−1 bw d−1 for ΣBDEs3–7 and 1,170 to 17,000 pg kg−1 bw d−1 for BDE-209. These adult intakes are well within health reference doses suggested by the European Food Safety Authority (EFSA) and the US EPA. Diet was the primary source of intake of BDE3–7 congeners for the majority of the cohort, with dust the primary source of BDE-209. Primary sources of PBDE exposure vary between countries and regions with differing fire prevention regulations. Estimated infant exposures (ages 1.5–4.5 years) showed that BDE-99 intake for one of the households did not meet EFSA's recommended margin of exposure, a further two households had borderline PBDE exposures for high level dust and diet intake.Males and those having a lower body fat mass had higher serum BDE-153. Higher meat consumption was significantly correlated with higher BDEs3–7 in serum. A reduction in dietary BDEs3–7 would therefore result in the greatest reduction in BDE-99 exposure. Rooms containing PUF sofas or armchairs over 20 years old had more BDEs3–7 in their dust, and rooms with carpets or rugs of that age had higher dust BDE-209. Dusting rooms more frequently resulted in significantly lower concentrations of all major congeners in their dust. Correlation between BDE-209 body burden and dust or diet exposure was limited by its low bioaccessibility. Although vehicle dust contained the highest concentrations of BDEs3–7 and BDE-209, serum BDEs3–7 correlated most strongly with bedroom dust

Centrality and rapidity dependence of inclusive jet production in root sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Measurements of the centrality and rapidity dependence of inclusive jet production in √sNN = 5.02 TeV proton–lead (p+Pb) collisions and the jet cross-section √s = 2.76 TeV proton–proton collisions are presented. These quantities are measured in datasets corresponding to an integrated luminosity of 27.8 nb⁻¹and 4.0 pb⁻¹, respectively, recorded with the ATLAS detector at the Large Hadron Collider in 2013. The p+Pb collision centrality was characterised using the total transverse energy measured in the pseudorapidity interval −4.9<η<−3.2 in the direction of the lead beam. Results are presented for the double-differential per-collision yields as a function of jet rapidity and transverse momentum (pT) for minimum-bias and centrality-selected p+Pb collisions, and are compared to the jet rate from the geometric expectation. The total jet yield in minimum-bias events is slightly enhanced above the expectation in a pT-dependent manner but is consistent with the expectation within uncertainties. The ratios of jet spectra from different centrality selections show a strong modification of jet production at all pT at forward rapidities and for large pTpT at mid-rapidity, which manifests as a suppression of the jet yield in central events and an enhancement in peripheral events. These effects imply that the factorisation between hard and soft processes is violated at an unexpected level in proton–nucleus collisions. Furthermore, the modifications at forward rapidities are found to be a function of the total jet energy only, implying that the violations may have a simple dependence on the hard parton–parton kinematics.G. Aad ... P. Jackson ... L. Lee ... A. Petridis ... N. Soni ... M.J. White ... et al. (ATLAS Collaboration

Social dilemmas among unequals

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record.Direct reciprocity is a powerful mechanism for evolution of cooperation, based on repeated interactions. It requires that interacting individuals are sufficiently equal, such that everyone faces similar consequences when they cooperate or defect. Yet inequality is ubiquitous among humansand is generally considered to undermine cooperation and welfar. Most previous models of reciprocity neglect inequality. They assume that individuals are the same in all relevant aspects. Here we introduce a general framework to study direct reciprocity among unequals. Our model allows for multiple sources of inequality. Subjects can differ in their endowments, their productivities, and in how much they benefit from public goods. We find that extreme inequality prevents cooperation. But if subjects differ in productivity, some endowment inequality can be necessary for cooperation to prevail. Our mathematical predictions are supported by a behavioral experiment where we vary the subjects’ endowments and their productivities. We observe that overall welfare is maximized when the two sources of heterogeneity are aligned, such that more productive individuals receive higher endowments. In contrast, when endowments and productivities are misaligned, cooperation quickly breaks down. Our findings have implications for policy-makers concerned with equity, efficiency, and public goods provisioning.European Research Council Start GrantGraph GamesAustrian Science Fund (FWF)Office of Naval ResearchJohn Templeton FoundationISTFELLOW program

Beam-induced and cosmic-ray backgrounds observed in the ATLAS detector during the LHC 2012 proton-proton running period

Published: May 20, 2016This paper discusses various observations on beam-induced and cosmic-ray backgrounds in the ATLAS detector during the LHC 2012 proton-proton run. Building on published results based on 2011 data, the correlations between background and residual pressure of the beam vacuum are revisited. Ghost charge evolution over 2012 and its role for backgrounds are evaluated. New methods to monitor ghost charge with beam-gas rates are presented and observations of LHC abort gap population by ghost charge are discussed in detail. Fake jets from colliding bunches and from ghost charge are analysed with improved methods, showing that ghost charge in individual radio-frequency buckets of the LHC can be resolved. Some results of two short periods of dedicated cosmic-ray background data-taking are shown; in particular cosmic-ray muon induced fake jet rates are compared to Monte Carlo simulations and to the fake jet rates from beam background. A thorough analysis of a particular LHC fill, where abnormally high background was observed, is presented. Correlations between backgrounds and beam intensity losses in special fills with very high β* are studied.G. Aad ... P. Jackson ... L. Lee ... A. Petridis ... M. J. White ... et al. (The ATLAS Collaboration

Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis

Background: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing. Findings: Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77–0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45–0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72–0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes. Interpretation: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20–2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7–6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2–11·5]). INTERPRETATION: In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. FUNDING: UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust

Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19. Methods: RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69–0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86–1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab. Interpretation: In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

BACKGROUND: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). INTERPRETATION: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks