A comparison of stage-specific all-cause mortality between testicular sex cord stromal tumors and germ cell tumors: results from the National Cancer Database.

BackgroundTesticular sex cord stromal tumors (SCSTs) are managed similarly to germ cell tumors (GCTs); however, few studies have directly compared outcomes between these tumor types. Using the National Cancer Database (NCDB), we sought to compare overall and stage-specific all-cause mortality (ACM) between SCSTs versus GCTs.MethodsNCDB was queried for patients diagnosed with SCSTs and GCTs between 2004 and 2013. Descriptive statistics were used to compare sociodemographic and clinical characteristics between groups. Univariable and multivariable Cox proportional hazards regression analyses were used to assess associations with ACM.ResultsWe identified 42,192 patients diagnosed with testicular cancer between 2004 and 2013, with 280 having SCSTs and 41,912 patients having GCTs. Median age for SCSTs and GCTs was 45 (interquartile range [IQR] 34-59) and 34 (IQR 27-43), respectively (p < 0.001). Median follow-up was 39 and 52 months, respectively. Overall, patients with SCSTs had greater risk of ACM compared to those with GCTs (HR 1.69, 95% CI 1.14-2.50). Private insurance, greater education, and fewer comorbidities were associated with reduced risk of ACM (p < 0.05 for all). Among those with stage I disease, tumor type was not associated with ACM on multivariable analysis. Among those with stage II/III disease, patients with SCSTs had increased risk of ACM compared to patients with GCTs (HR 3.29, 95% CI 1.89-5.72).ConclusionsPatients with advanced SCSTs had worse survival outcomes compared to those with advanced GCTs. These data suggest a need for further investigation to ascertain effective management recommendations for SCSTs

Strategien zur Regulation der Schwarzfäule (Guignardia bidwellii) im ökologischen Weinbau

Die Schwarzfäule tritt in einigen deutschen Weinbaugebieten flächendeckend auf und kann gravierende Ertragsausfälle verursachen. Um die Produktionssicherheit im ökologischen Weinbau zu gewährleisten, wurde ein Kooperationsprojekt mit der Zielsetzung initiiert, Informationen über die Biologie des Schadpilzes zu erarbeiten und Strategien zur Prävention und Bekämpfung der Krankheit unter den spezifischen Bedingungen des ökologischen Weinbaus zu entwickeln. Die Biologie des Schaderregers und seiner Interaktionen mit der Rebe wurde in Hinblick auf die Fruchtkörperentwicklung, die Sporenbildung und den Infektionsprozess eingehend untersucht und in Beziehung zu Witterungsbedingungen und Bewirtschaftungsparametern gesetzt. Die Ergebnisse bilden eine Grundlage für die Einschätzung des Infektionsrisikos und die Entwicklung von Entscheidungshilfen für den Rebschutz. Traditionelle und „pilzwiderstandsfähige“ Rebsorten wurden hinsichtlich ihrer Anfälligkeit für die Schwarzfäule charakterisiert, wodurch den Winzern Informationen für die Auswahl weniger Anfälliger Sorten zum Anbau in Befallsgebieten zur Verfügung stehen. Befallenes Rebholz und befallene Ranken wurden als bedeutende Quellen des Primärinokulums der Schwarzfäule identifiziert. Das Entfernen befallener Blätter bei Laubarbeiten erwies sich als Möglichkeit, das Infektionsrisiko für die Trauben zu reduzieren. Aus einer Vielzahl von Mikroorganismen, Pflanzenextrakten, Pflanzenschutz- und –stärkungsmitteln wurden wirksame Agenzien selektiert und im Freiland unter Praxisbedingungen geprüft. Die Kombination von Pflanzenschutzmitteln auf der Basis von Schwefel und Kupfer war besonders wirksam. Wurde, abhängig vom Entwicklungsstadium und dem Infektionsrisiko, das Kupfer mit Gesteinsmehl ersetzt, ließ sich der Kupferaufwand erheblich reduzieren. Im Gegensatz zu Gewächshausversuchen war die Wirkung saponinhaltiger Pflanzenextrakte im Freiland unzureichend. Bei entsprechender Formulierung zur Verbesserung der Regenfestigkeit könnte das große Potential dieser Pflanzenextrakte jedoch genutzt werden. Aufgrund der Ergebnisse des Forschungsprojekts stehen dem ökologischen Weinbau Informationen als Grundlage eines umfassenden Managementkonzepts für die Schwarzfäule zur Verfügung

Multi-annual comparisons demonstrate differences in the bunch rot susceptibility of nine Vitis vinifera L. 'Riesling' clones

Botrytis bunch rot is a major fungal disease of grapevines, and causes severe economic damage worldwide. Under humid climatic conditions, the development of bunch rot on grapes cannot be suppressed completely. Selection of planting material with lower bunch rot susceptibility represents one of the most efficient long-term tools in the complex bunch rot minimisation strategy. The present investigation conducted over four consecutive years (2013-2016) under the environmental conditions of the Moselle valley aimed at (i) detecting consistent differences in the bunch rot susceptibility within a group of nine commercially available Vitis vinifera L. 'White Riesling' clones, (ii) investigating potential underlying causes and (iii) deriving recommendations for 'Riesling' clone selection in practical viticulture. Disease severity and grape maturity (total soluble solids) progress could be well simulated by sigmoidal curves (R2 > 0.89; P < 0.038). On average of all four years, the dates when 5 % bunch rot disease severity were reached differed significantly by 9 days between the clone with the earliest epidemic (Trier 34) and the clone with the latest epidemic (Heinz 65). Multi-annual results enabled a classification of the nine clones according to (i) their relative bunch rot susceptibility as well as (ii) their relative precocity. Based on this, practical recommendations concerning a targeted clone selection as an integral long-term tool (i) in Integrated Pest Management contributing to pesticide reduction in viticulture as well as (ii) in the viticultural climate change adaptation strategy were derived

Employing an orthotopic model to study the role of epithelial-mesenchymal transition in bladder cancer metastasis.

Epithelial-to-mesenchymal transition (EMT) has been implicated in the progression of bladder cancer. To study its contribution to bladder cancer metastasis, we established new xenograft models derived from human bladder cancer cell lines utilizing an orthotopic "recycling" technique that allowed us to isolate and examine the primary tumor and its corresponding circulating tumor cells (CTC's) and metastatic lesions. Using whole genome mRNA expression profiling, we found that a reversible epithelial-to-mesenchymal transition (EMT) characterized by TGFβ pathway activation and SNAIL expression was associated with the accumulation of CTCs. Finally, we observed that conditional silencing of SNAIL completely blocked CTC production and regional/distant metastasis. Using this unique bladder cancer xenograft model, we conclude that metastasis is dependent on a reversible EMT mediated by SNAIL

Unacceptably High Mortality Related to Measles Epidemics in Niger, Nigeria, and Chad

BACKGROUND: Despite the comprehensive World Health Organization (WHO)/United Nations Children's Fund (UNICEF) measles mortality–reduction strategy and the Measles Initiative, a partnership of international organizations supporting measles mortality reduction in Africa, certain high-burden countries continue to face recurrent epidemics. To our knowledge, few recent studies have documented measles mortality in sub-Saharan Africa. The objective of our study was to investigate measles mortality in three recent epidemics in Niamey (Niger), N'Djamena (Chad), and Adamawa State (Nigeria). METHODS AND FINDINGS: We conducted three exhaustive household retrospective mortality surveys in one neighbourhood of each of the three affected areas: Boukoki, Niamey, Niger (April 2004, n = 26,795); Moursal, N'Djamena, Chad (June 2005, n = 21,812); and Dong District, Adamawa State, Nigeria (April 2005, n = 16,249), where n is the total surveyed population in each of the respective areas. Study populations included all persons resident for at least 2 wk prior to the study, a duration encompassing the measles incubation period. Heads of households provided information on measles cases, clinical outcomes up to 30 d after rash onset, and health-seeking behaviour during the epidemic. Measles cases and deaths were ascertained using standard WHO surveillance-case definitions. Our main outcome measures were measles attack rates (ARs) and case fatality ratios (CFRs) by age group, and descriptions of measles complications and health-seeking behaviour. Measles ARs were the highest in children under 5 y old (under 5 y): 17.1% in Boukoki, 17.2% in Moursal, and 24.3% in Dong District. CFRs in under 5-y-olds were 4.6%, 4.0%, and 10.8% in Boukoki, Moursal, and Dong District, respectively. In all sites, more than half of measles cases in children aged under 5 y experienced acute respiratory infection and/or diarrhoea in the 30 d following rash onset. Of measles cases, it was reported that 85.7% (979/1,142) of patients visited a health-care facility within 30 d after rash onset in Boukoki, 73.5% (519/706) in Moursal, and 52.8% (603/1,142) in Dong District. CONCLUSIONS: Children in these countries still face unacceptably high mortality from a completely preventable disease. While the successes of measles mortality–reduction strategies and progress observed in measles control in other countries of the region are laudable and evident, they should not overshadow the need for intensive efforts in countries that have just begun implementation of the WHO/UNICEF comprehensive strategy

Thermal Links for the Implementation of an Optical Refrigerator

Optical refrigeration has been demonstrated by several groups of researchers, but the cooling elements have not been thermally linked to realistic heat loads in ways that achieve the desired temperatures. The ideal thermal link will have minimal surface area, provide complete optical isolation for the load, and possess high thermal conductivity. We have designed thermal links that minimize the absorption of fluoresced photons by the heat load using multiple mirrors and geometric shapes including a hemisphere, a kinked waveguide, and a tapered waveguide. While total link performance is dependent on additional factors, we have observed net transmission of photons with the tapered link as low as 0.04%. Our optical tests have been performed with a surrogate source that operates at 625 nm and mimics the angular distribution of light emitted from the cooling element of the Los Alamos solid state optical refrigerator. We have confirmed the optical performance of our various link geometries with computer simulations using CODE V optical modeling software. In addition we have used the thermal modeling tool in COMSOL MULTIPHYSICS to investigate other heating factors that affect the thermal performance of the optical refrigerator. Assuming an ideal cooling element and a nonabsorptive dielectric trapping mirror, the three dominant heating factors are (1) absorption of fluoresced photons transmitted through the thermal link, (2) blackbody radiation from the surrounding environment, and (3) conductive heat transfer through mechanical supports. Modeling results show that a 1 cm3 load can be chilled to 107 K with a 100Wpump laser. We have used the simulated steady-state cooling temperatures of the heat load to compare link designs and system configurations

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

A super-spreading ewe infects hundreds with Q fever at a farmers' market in Germany

BACKGROUND: In May 2003 the Soest County Health Department was informed of an unusually large number of patients hospitalized with atypical pneumonia. METHODS: In exploratory interviews patients mentioned having visited a farmers' market where a sheep had lambed. Serologic testing confirmed the diagnosis of Q fever. We asked local health departments in Germany to identiy notified Q fever patients who had visited the farmers market. To investigate risk factors for infection we conducted a case control study (cases were Q fever patients, controls were randomly selected Soest citizens) and a cohort study among vendors at the market. The sheep exhibited at the market, the herd from which it originated as well as sheep from herds held in the vicinity of Soest were tested for Coxiella burnetii (C. burnetii). RESULTS: A total of 299 reported Q fever cases was linked to this outbreak. The mean incubation period was 21 days, with an interquartile range of 16–24 days. The case control study identified close proximity to and stopping for at least a few seconds at the sheep's pen as significant risk factors. Vendors within approximately 6 meters of the sheep's pen were at increased risk for disease compared to those located farther away. Wind played no significant role. The clinical attack rate of adults and children was estimated as 20% and 3%, respectively, 25% of cases were hospitalized. The ewe that had lambed as well as 25% of its herd tested positive for C. burnetii antibodies. CONCLUSION: Due to its size and point source nature this outbreak permitted assessment of fundamental, but seldom studied epidemiological parameters. As a consequence of this outbreak, it was recommended that pregnant sheep not be displayed in public during the 3(rd )trimester and to test animals in petting zoos regularly for C. burnetii

Measles in Democratic Republic of Congo: an outbreak description from Katanga, 2010--2011

BACKGROUND: The Democratic Republic of Congo experiences regular measles outbreaks. From September 2010, the number of suspected measles cases increased, especially in Katanga province, where Medecins sans Frontieres supported the Ministry of Health in responding to the outbreak by providing free treatment, reinforcing surveillance and implementing non-selective mass vaccination campaigns. Here, we describe the measles outbreak in Katanga province in 2010--2011 and the results of vaccine coverage surveys conducted after the mass campaigns. METHODS: The surveillance system was strengthened in 28 of the 67 health zones of the province and we conducted seven vaccination coverage surveys in 2011. RESULTS: The overall cumulative attack rate was 0.71% and the case fatality ratio was 1.40%.The attack rate was higher in children under 4 and decreased with age. This pattern was consistent across districts and time. The number of cases aged 10 years and older barely increased during the outbreak. CONCLUSIONS: Early investigation of the age distribution of cases is a key to understanding the epidemic, and should guide the vaccination of priority age groups

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN