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

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.Fil: Pinto, Emilia M.. St. Jude Children's Research Hospital; Estados UnidosFil: Figueiredo, Bonald C.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Chen, Wenan. St. Jude Children's Research Hospital; Estados UnidosFil: Galvao, Henrique C.R.. Hospital de Câncer de Barretos; BrasilFil: Formiga, Maria Nirvana. A.c.camargo Cancer Center; BrasilFil: Fragoso, Maria Candida B.V.. Universidade de Sao Paulo; BrasilFil: Ashton Prolla, Patricia. Universidade Federal do Rio Grande do Sul; BrasilFil: Ribeiro, Enilze M.S.F.. Universidade Federal do Paraná; BrasilFil: Felix, Gabriela. Universidade Federal da Bahia; BrasilFil: Costa, Tatiana E.B.. Hospital Infantil Joana de Gusmao; BrasilFil: Savage, Sharon A.. National Cancer Institute; Estados UnidosFil: Yeager, Meredith. National Cancer Institute; Estados UnidosFil: Palmero, Edenir I.. Hospital de Câncer de Barretos; BrasilFil: Volc, Sahlua. Hospital de Câncer de Barretos; BrasilFil: Salvador, Hector. Hospital Sant Joan de Deu Barcelona; EspañaFil: Fuster Soler, Jose Luis. Hospital Clínico Universitario Virgen de la Arrixaca; EspañaFil: Lavarino, Cinzia. Hospital Sant Joan de Deu Barcelona; EspañaFil: Chantada, Guillermo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. St. Jude Children's Research Hospital; Estados UnidosFil: Vaur, Dominique. Comprehensive Cancer Center François Baclesse; FranciaFil: Odone Filho, Vicente. Universidade de Sao Paulo; BrasilFil: Brugières, Laurence. Institut de Cancerologie Gustave Roussy; FranciaFil: Else, Tobias. University of Michigan; Estados UnidosFil: Stoffel, Elena M.. University of Michigan; Estados UnidosFil: Maxwell, Kara N.. University of Pennsylvania; Estados UnidosFil: Achatz, Maria Isabel. Hospital Sirio-libanês; BrasilFil: Kowalski, Luis. A.c.camargo Cancer Center; BrasilFil: De Andrade, Kelvin C.. National Cancer Institute; Estados UnidosFil: Pappo, Alberto. St. Jude Children's Research Hospital; Estados UnidosFil: Letouze, Eric. Centre de Recherche Des Cordeliers; FranciaFil: Latronico, Ana Claudia. Universidade de Sao Paulo; BrasilFil: Mendonca, Berenice B.. Universidade de Sao Paulo; BrasilFil: Almeida, Madson Q.. Universidade de Sao Paulo; BrasilFil: Brondani, Vania B.. Universidade de Sao Paulo; BrasilFil: Bittar, Camila M.. Universidade Federal do Rio Grande do Sul; BrasilFil: Soares, Emerson W.S.. Hospital Do Câncer de Cascavel; BrasilFil: Mathias, Carolina. Universidade Federal do Paraná; BrasilFil: Ramos, Cintia R.N.. Hospital de Câncer de Barretos; BrasilFil: Machado, Moara. National Cancer Institute; Estados UnidosFil: Zhou, Weiyin. National Cancer Institute; Estados UnidosFil: Jones, Kristine. National Cancer Institute; Estados UnidosFil: Vogt, Aurelie. National Cancer Institute; Estados UnidosFil: Klincha, Payal P.. National Cancer Institute; Estados UnidosFil: Santiago, Karina M.. A.c.camargo Cancer Center; BrasilFil: Komechen, Heloisa. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Paraizo, Mariana M.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Parise, Ivy Z.S.. Instituto de Pesquisa Pelé Pequeno Principe; BrasilFil: Hamilton, Kayla V.. St. Jude Children's Research Hospital; Estados UnidosFil: Wang, Jinling. St. Jude Children's Research Hospital; Estados UnidosFil: Rampersaud, Evadnie. St. Jude Children's Research Hospital; Estados UnidosFil: Clay, Michael R.. St. Jude Children's Research Hospital; Estados UnidosFil: Murphy, Andrew J.. St. Jude Children's Research Hospital; Estados UnidosFil: Lalli, Enzo. Institut de Pharmacologie Moléculaire et Cellulaire; FranciaFil: Nichols, Kim E.. St. Jude Children's Research Hospital; Estados UnidosFil: Ribeiro, Raul C.. St. Jude Children's Research Hospital; Estados UnidosFil: Rodriguez-Galindo, Carlos. St. Jude Children's Research Hospital; Estados UnidosFil: Korbonits, Marta. Queen Mary University of London; Reino UnidoFil: Zhang, Jinghui. St. Jude Children's Research Hospital; Estados UnidosFil: Thomas, Mark G.. Colegio Universitario de Londres; Reino UnidoFil: Connelly, Jon P.. St. Jude Children's Research Hospital; Estados UnidosFil: Pruett-Miller, Shondra. St. Jude Children's Research Hospital; Estados UnidosFil: Diekmann, Yoan. Colegio Universitario de Londres; Reino UnidoFil: Neale, Geoffrey. St. Jude Children's Research Hospital; Estados UnidosFil: Wu, Gang. St. Jude Children's Research Hospital; Estados UnidosFil: Zambetti, Gerard P.. St. Jude Children's Research Hospital; Estados Unido

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

Differential aggressiveness of fungi implicated in esca and associated diseases of grapevine in France

We tested differences in the aggressiveness of six fungal species, Phaeomoniella chlamydospora, Phaeoacremonium aleophilum, Fomitiporia mediterranea, Eutypa lata, Diplodia seriata and Neofusicoccum parvum, all of which are associated with esca, Eutypa dieback or ‘black dead arm’ (BDA) of grapevines in France. Ten isolates per species (nine isolates for P. aleophilum), originating in various regions of France, were tested on rooted cuttings of cv. Cabernet Sauvignon by inoculating the mycelium of the species on wounds made in the vine wood. The inoculated plants were incubated in an open greenhouse and the experiment was repeated twice. The isolates were divided into three groups depending on the severity of the infection. Infection severity was based on the extent of the external cankers and the internal lesions, measured 5 and 15 months after inoculation, as compared with the controls. The fi rst group included all the P. chlamydospora and N. parvum isolates and two of the E. lata isolates. These isolates induced internal necrosis and external cankers developing from the point of inoculation. P. chlamydospora and N. parvum, produced large cankers and the longest internal lesions, and were the most virulent. The second group, comprising those E. lata isolates not in Group one and all isolates of D. seriata and of P. aleophilum, caused internal necrosis from which the vine afterwards totally healed. The third group included all the F. mediterranea isolates. These isolates caused the smallest lesions, generally not different from those in the controls, and developed a characteristic mycelium in the pith. No foliar symptoms were observed on any of the inoculated cuttings, except with the two E. lata isolates. Some seedlings displayed the typical foliar symptoms of Eutypa dieback. Different isolates within individual species exhibited signifi cant differences (P&lt;0.05) in lesion development. This made it possible to select the most aggressive isolates for further study