Post-2020 climate agreements in the major economies assessed in the light of global models

Integrated assessment models can help in quantifying the implications of international climate agreements and regional climate action. This paper reviews scenario results from model intercomparison projects to explore different possible outcomes of post-2020 climate negotiations, recently announced pledges and their relation to the 2 °C target. We provide key information for all the major economies, such as the year of emission peaking, regional carbon budgets and emissions allowances. We highlight the distributional consequences of climate policies, and discuss the role of carbon markets for financing clean energy investments, and achieving efficiency and equity

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Antibiotic Releasing Biodegradable Sutures for the Prevention of Surgical Site Infections

Although a necessary component of surgery, sutures have been shown to exhibit an affinity for microbial adherence and colonization. The sutures offer a conduit for bacteria directly into the wound and infection can be difficult to treat post-colonization, even with antibiotics that are traditionally very effective. Infections associated with sutures are often difficult to resolve and require extended hospitalization, therapy, or additional surgical procedures. Drug eluting sutures offer a potential solution to this issue. In order to maximize antibiotic delivery, modeling changes in suture size, placement, and concentration could provide valuable information for surgeons and manufacturers to better develop and implant sutures, reducing the number of surgical site infections (SSIs) and thus morbidity and mortality. Using COMSOL software, we first generated both a 2D and a 3D model of MONOCRYL plus antibiotic sutures in the skin. Next, we modeled antibiotic-release and biodegradation by tracing the distance the drug penetrates into the surrounding tissue while the suture and the antibiotic are simultaneously being degraded by the body’s enzymatic processes. Finally, we adjusted the distance between adjacent sutures and suture size to ensure that the minimum inhibitory concentration (MIC) of triclosan for various bacteria strains was met at the wound site, without increasing the difficulty for surgeons to implant the suture. In our model, we showed the dispersion of antibiotics into the surrounding tissue over time, demonstrating up to what time point the sutures are able to maintain at least the minimum effective concentration level of antibiotic. We show that antibiotic levels sufficient enough to inhibit bacterial growth can be reached in complex environments, such as the skin. Based on our 3D model, the maximum spacing between adjacent 4-0 sutures to maintain a MIC for S. aureus for 72 hours after suture implantation is 2 mm. Suture spacing for other strains of bacteria can be determined through our predictive equations. The duration of antibacterial properties increases as the spacing between sutures is decreased, but increasing the initial concentration of triclosan in the suture does not significantly increase the duration of antibacterial properties of the suture. The suture decreases in volume by 45% seven days after implantation in the skin, indicating proper surface erosion and a significant loss in tensile strength after that time. The integrity of the suture is necessary to keep the wound closed over the entire healing period, preventing bacteria from entering through the open site and entering the tissue and subsequently traveling through the bloodstream. In this model, we reinforce in vivo and in vitro studies that suggest the effectiveness of antibiotic releasing sutures by modeling antibiotic concentrations in the skin following suture placement. This model will help surgeons determine the spacing for a variety of commercially available sutures, based on the bacterial inhibition properties required, in an effort to reduce the number of surgical site infections that occur. By ensuring effective distribution of antibiotic, following our developed standards in the surgical suite will reduce the number of surgical site infections, significantly reducing costs, morbidity, and mortality from post-operative infections

Non-pharmacological interventions for spatial neglect or inattention following stroke and other non-progressive brain injury.

Background People with spatial neglect after stroke or other brain injury have difficulty attending to one side of space. Various rehabilitation interventions have been used, but evidence of their benefit is unclear. Objectives The main objective was to determine the effects of non‐pharmacological interventions for people with spatial neglect after stroke and other adult‐acquired non‐progressive brain injury. Search methods We searched the Cochrane Stroke Group Trials Register (last searched October 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; last searched October 2020), MEDLINE (1966 to October 2020), Embase (1980 to October 2020), the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1983 to October 2020), and PsycINFO (1974 to October 2020). We also searched ongoing trials registers and screened reference lists. Selection criteria We included randomised controlled trials (RCTs) of any non‐pharmacological intervention specifically aimed at spatial neglect. We excluded studies of general rehabilitation and studies with mixed participant groups, unless separate neglect data were available. Data collection and analysis We used standard Cochrane methods. Review authors categorised the interventions into eight broad types deemed to be applicable to clinical practice through iterative discussion: visual interventions, prism adaptation, body awareness interventions, mental function interventions, movement interventions, non‐invasive brain stimulation, electrical stimulation, and acupuncture. We assessed the quality of evidence for each outcome using the GRADE approach. Main results We included 65 RCTs with 1951 participants, all of which included people with spatial neglect following stroke. Most studies measured outcomes using standardised neglect assessments. Fifty‐one studies measured effects on ADL immediately after completion of the intervention period; only 16 reported persisting effects on ADL (our primary outcome). One study (30 participants) reported discharge destination, and one (24 participants) reported depression. No studies reported falls, balance, or quality of life. Only two studies were judged to be entirely at low risk of bias, and all were small, with fewer than 50 participants per group. We found no definitive (phase 3) clinical trials. None of the studies reported any patient or public involvement. Visual interventions versus any control: evidence is very uncertain about the effects of visual interventions for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 55 participants) (standardised mean difference (SMD) ‐0.04, 95% confidence interval (CI) ‐0.57 to 0.49); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments. Prism adaptation versus any control: evidence is very uncertain about the effects of prism adaptation for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 39 participants) (SMD ‐0.29, 95% CI ‐0.93 to 0.35); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments. Body awareness interventions versus any control: evidence is very uncertain about the effects of body awareness interventions for spatial neglect based on measures of persisting functional ability in ADL (5 studies, 125 participants) (SMD 0.61, 95% CI 0.24 to 0.97); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events. Mental function interventions versus any control: we found no trials of mental function interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of mental function interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. Movement interventions versus any control: we found no trials of movement interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of body awareness interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. Non‐invasive brain stimulation (NIBS) versus any control: evidence is very uncertain about the effects of NIBS on spatial neglect based on measures of persisting functional ability in ADL (3 studies, 92 participants) (SMD 0.35, 95% CI ‐0.08 to 0.77); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events. Electrical stimulation versus any control: we found no trials of electrical stimulation for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of electrical stimulation on spatial neglect based on immediate neglect assessments. Acupuncture versus any control: we found no trials of acupuncture for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of acupuncture on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments. Authors' conclusions The effectiveness of non‐pharmacological interventions for spatial neglect in improving functional ability in ADL and increasing independence remains unproven. Many strategies have been proposed to aid rehabilitation of spatial neglect, but none has yet been sufficiently researched through high‐quality fully powered randomised trials to establish potential or adverse effects. As a consequence, no rehabilitation approach can be supported or refuted based on current evidence from RCTs. As recommended by a number of national clinical guidelines, clinicians should continue to provide rehabilitation for neglect that enables people to meet their rehabilitation goals. Clinicians and stroke survivors should have the opportunity, and are strongly encouraged, to participate in research. Future studies need to have appropriate high‐quality methodological design, delivery, and reporting to enable appraisal and interpretation of results. Future studies also must evaluate outcomes of importance to patients, such as persisting functional ability in ADL. One way to improve the quality of research is to involve people with experience with the condition in designing and running trials