Randomized Trial of Partial Gland Ablation with Vascular Targeted Phototherapy versus Active Surveillance for Low Risk Prostate Cancer: Extended Followup and Analyses of Effectiveness

PURPOSE: The prospective PCM301 trial randomized 413 men with low risk prostate cancer to partial gland ablation with vascular targeted photodynamic therapy in 207 and active surveillance in 206. Two-year outcomes were reported previously. We report 4-year rates of intervention with radical therapy and further assess efficacy with biopsy results. MATERIALS AND METHODS: Prostate biopsies were mandated at 12 and 24 months. Thereafter patients were monitored for radical therapy with periodic biopsies performed according to the standard of care at each institution. Ablation efficacy was assessed by biopsy results overall and in field in the treated lobe or the lobe with index cancer. RESULTS: Conversion to radical therapy was less likely in the ablation cohort than in the surveillance cohort, including 7% vs 32% at 2 years, 15% vs 44% at 3 years and 24% vs 53% at 4 years (HR 0.31, 95% CI 0.21-0.46). Radical therapy triggers were similar in the 2 arms. Cancer progression rates overall and by grade were significantly lower in the ablation cohort (HR 0.42, 95% CI 0.29-0.59). End of study biopsy results were negative throughout the prostate in 50% of patients after ablation vs 14% after surveillance (risk difference 36%, 95% CI 28-44). Gleason 7 or higher cancer was less likely for ablation than for surveillance (16% vs 41%). Of the in field biopsies 10% contained Gleason 7 cancer after ablation vs 34% after surveillance. CONCLUSIONS: In this randomized trial of partial ablation of low risk prostate cancer photodynamic therapy significantly reduced the subsequent finding of higher grade cancer on biopsy. Consequently fewer cases were converted to radical therapy, a clinically meaningful benefit that lowered treatment related morbidity

Soziale Sicherung im Lebenslauf – Finanzielle Aspekte in längerfristiger Perspektive am Beispiel der Alterssicherung in Deutschland

"Zunehmende Risiken im Lebenslauf und die Forderung nach vermehrter individueller Flexibilität stellen eine Herausforderung für die adäquate Gestaltung sozialer Sicherung dar, z.B. für die Alterssicherung. In diesem Beitrag wird dargestellt, wie 'soziale Risiken' in öffentlichen und (subventionierten) privaten Alterssicherungssystemen (einschließlich betrieblicher Einrichtungen) berücksichtigt werden. Dies erfolgt am Beispiel der Situation in Deutschland. Ein solcher Vergleich unterschiedlicher Sicherungssysteme wird um so wichtiger, da in vielen Ländern die Rolle des Staates als 'Produzent' sozialer Leistungen reduziert wird. Ausgehend von Zielen und Konzeptionen zur Gestaltung sozialer Sicherung im Alter stehen im Zentrum dieses Beitrags Auswirkungen verschiedener Typen öffentlicher und privater Alterssicherungssysteme auf die Einkommenslage im Alter bei Eintritt bestimmter sozialer Risiken, wie Einkommensverlust durch Arbeitslosigkeit, Krankheit, Pflege von Kindern. Dabei wird der Einsatz unterschiedlicher Instrumente - unter ihnen der von Zeitkonten - betrachtet. Schließlich wird die Verlagerung von Risiken und Verantwortung im Falle zumindest partieller Privatisierung sozialer Sicherung diskutiert - Verlagerungen vom Staat auf private Haushalte, von Arbeitgebern auf Arbeitnehmer. Für den Fall, dass private Sicherungssysteme obligatorisch werden, ist zu erwarten, dass sie mit zu einem Instrument der staatlichen Sozialpolitik werden und manche der sozialen Risiken zu berücksichtigen haben, wie dies bislang in staatlichen Systemen erfolgte." (Autorenreferat)"Growing insecurity over the life course and an increasing demand for more individual flexibility are a challenge for adequate social security, for example in old age. This paper outlines how 'social risks' are taken into account in public as well as (subsidised) private pension schemes (including occupational schemes), such as those in Germany. This becomes more important because in many countries the role of the state as provider of social security benefits is being scaled down. Starting from objectives and concepts for designing social security for old age, the major focus of the paper is the effects of different types of public as well as private pension schemes on income in old age in relation to different social risks, such as loss of income in case of unemployment, illness, caring for children and by using different instruments (among other things, time saving accounts). Finally, the shift of risks and responsibility in the (at least partial) privatisation of social security - from state to private households, from employers to employees - is discussed. If private schemes become mandatory, they may become an instrument of (public) social policy and have to cover some of the social risks that public schemes have in the past." (author's abstract

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Measurements of differential production cross sections for a Z boson in association with jets in pp collisions at root s=8 TeV

Peer reviewe

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health