Justification for a Nuclear Global Health Workforce: multidisciplinary analysis of risk, survivability & preparedness, with emphasis on the triage management of thermal burns

An assessment of the risks of nuclear conflict and the global preparedness to deal with such a catastrophe. Includes a proposal for triage and management of burn injuries based on a model of what would happen if there was a nuclear attack on Washington DC. Summarises the need for a global nuclear workforce to establish guidelines and strategies to address a nuclear event, the risk of which would appear to be increasingly likely given current world geopolitics

The Ethical Triage and Management Guidelines of the Entrapped and Mangled Extremity in Resource Scarce Environments: A Systematic Literature Review.

ABSTRACTObjective:A systematic literature review (SLR) was performed to elucidate the current triage and treatment of an entrapped or mangled extremity in resource scarce environments (RSEs).Methods:A lead researcher followed the search strategy following inclusion and exclusion criteria. A first reviewer (FR) was randomly assigned sources. One of the 2 lead researchers was the second reviewer (SR). Each determined the level of evidence (LOE) and quality of evidence (QE) from each source. Any differing opinions between the FR and SR were discussed between them, and if differing opinions remained, then a third reviewer (the other lead researcher) discussed the article until a consensus was reached. The final opinion of each article was entered for analysis.Results:Fifty-eight (58) articles were entered into the final study. There was 1 study determined to be LOE 1, 29 LOE 2, and 28 LOE 3, with 15 determined to achieve QE 1, 37 QE 2, and 6 QE 3.Conclusion:This SLR showed that there is a lack of studies producing strong evidence to support the triage and treatment of the mangled extremity in RSE. Therefore, a Delphi process is suggested to adapt and modify current civilian and military triage and treatment guidelines to the RSE

Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls

Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10−16), 6p21 (P = 2.3 × 10−14) and 15q25 (P = 2.2 × 10−63). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16INK4A/p14ARF/CDKN2B/p15INK4B/ANRIL; rs1333040, P = 3.0 × 10−7) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10−8). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cance

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

NHV program components and rehabilitation services.

<p>NHV program components and rehabilitation services.</p

Relative combined effect of NHV and recovery over time (a) and individual effects of NHV-E and NHV-L and recovery over time (b).

<p>Relative combined effect of NHV and recovery over time (a) and individual effects of NHV-E and NHV-L and recovery over time (b).</p

Marginal predictions of Barthel Index mean scores for the NHV study groups at time points based on the three-level Tobit model.

<p>Marginal predictions of Barthel Index mean scores for the NHV study groups at time points based on the three-level Tobit model.</p