Pump-induced wavefront distortion in prototypical NIF/LMJ amplifiers-modeling and comparison with experiments

In large-aperture laser amplifiers such as those envisioned for the National Ignition Facility (NIF) and Laser Megajoules (LMJ) lasers, the geometry is such that the front and back faces of the laser slab are heated unevenly by the pump process. This uneven heating results in a mechanical deformation of the laser slab and consequent internal stresses. The deformation and stresses, along with a temperature-dependent refractive index variation, result in phase variations across the laser beam (so-called pump-induced wavefront distortions). These phase variations lead to beam steering which may affect frequency conversion as well as energy-on-target. We have developed a model which allows us to estimate the pump-induced wavefront distortion for a given amplifier configuration as well as the spatially-resolved depolarization. The model is compared with experiments taken in our amplifier development laboratory, AMPLA

Successful management of Influenza A associated fulminant myocarditis: mobile circulatory support in intensive care unit: a case report

A 26-year-old woman was referred to an Emergency Department because of common flu-like syndrome with hemodynamic collapse. In Intensive Care Unit (ICU), she was diagnosed as a probable septic shock. But despite treatment her condition rapidly deteriorated during the subsequent hours. Diagnosis of cardiogenic shock was established. Mechanical circulatory support was inserted into the patient. She was transferred in a Cardio-Vascular Surgical ICU where at the 5th day of mechanical circulatory support, echocardiography showed heart recovery which allowed weaning of mechanical circulatory support and progressive withdrawal of inotropic support. She was discharged at the 26th day. During her hospitalization, presence of Influenza A RNA was shown in myocardial biopsy

Do financial incentives for delivering health promotion counselling work? Analysis of smoking cessation activities stimulated by the quality and outcomes framework

<p>Abstract</p> <p>Background</p> <p>A substantial fraction of UK general practitioners' salaries is now intended to reflect the quality of care provided. This performance-related pay system has probably improved aspects of primary health care but, using the observational data available, disentangling the impacts of different types of targets set within this unique payment system is challenging.</p> <p>Discussion</p> <p>Financial incentives undoubtedly influence GPs' activities, however, those aimed at encouraging GPs' delivery of health promotion counselling may not always have the effects intended. There is strong, observational evidence that targets and incentives intended to increase smoking cessation counselling by GPs have merely increased their propensity to record this activity in patients' medical records. The limitations of using financial incentives to stimulate the delivery of counselling in primary care are discussed and a re-appraisal of their use within UK GPs' performance-related pay system is argued for.</p> <p>Summary</p> <p>The utility of targets employed by the system for UK General Practitioners' performance related pay may be inappropriate for encouraging the delivery of health promotion counselling interventions. An evaluation of these targets is essential before they are further developed or added to.</p

Mutational processes contributing to the development of multiple myeloma.

To gain insight into multiple myeloma (MM) tumorigenesis, we analyzed the mutational signatures in 874 whole-exome and 850 whole-genome data from the CoMMpass Study. We identified that coding and non-coding regions are differentially dominated by distinct single-nucleotide variant (SNV) mutational signatures, as well as five de novo structural rearrangement signatures. Mutational signatures reflective of different principle mutational processes-aging, defective DNA repair, and apolipoprotein B editing complex (APOBEC)/activation-induced deaminase activity-characterize MM. These mutational signatures show evidence of subgroup specificity-APOBEC-attributed signatures associated with MAF translocation t(14;16) and t(14;20) MM; potentially DNA repair deficiency with t(11;14) and t(4;14); and aging with hyperdiploidy. Mutational signatures beyond that associated with APOBEC are independent of established prognostic markers and appear to have relevance to predicting high-risk MM

XAF1 as a modifier of p53 function and cancer susceptibility

Cancer risk is highly variable in carriers of the common TP53-R337H founder allele, possibly due to the influence of modifier genes. Whole-genome sequencing identified a variant in the tumor suppressor XAF1 (E134*/Glu134Ter/rs146752602) in a subset of R337H carriers. Haplotype-defining variants were verified in 203 patients with cancer, 582 relatives, and 42,438 newborns. The compound mutant haplotype was enriched in patients with cancer, conferring risk for sarcoma (P = 0.003) and subsequent malignancies (P = 0.006). Functional analyses demonstrated that wild-type XAF1 enhances transactivation of wild-type and hypomorphic TP53 variants, whereas XAF1-E134* is markedly attenuated in this activity. We propose that cosegregation of XAF1-E134* and TP53-R337H mutations leads to a more aggressive cancer phenotype than TP53-R337H alone, with implications for genetic counseling and clinical management of hypomorphic TP53 mutant carriers