Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques

We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6±1.0 years, BMI 31.5±0.4 kg/m2; 30 males). HEP-IR was defined by measuring endogenous-glucose-production (EGP) with [6–62H2] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control). All five indices produced comparable prediction of HEP-IR, explaining 39–56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r2 = 27–32%) on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001). However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.54, P<0.001). Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations

Öffentlich geförderte Beschäftigung zur Förderung der Teilhabe von Langzeitarbeitslosen

Langzeitarbeitslosigkeit ist ein soziales Problem, das auch in wirtschaftlich guten Zeiten nie ganz verschwindet. Die Integration in Beschäftigung ist vor allem für ältere Personen, die bereits sehr lange Perioden von Arbeitslosigkeit erfahren haben, nicht einfach, mit entsprechenden negativen Folgen für die soziale Teilhabe. Öffentlich geförderte Beschäftigung für Langzeitarbeitslose kann jedoch nach einer aktuellen Studie eines Forschungskonsortiums von IAQ, ZOOM, SOKO und ZEW Mannheim helfen, die soziale Teilhabe der geförderten Personen zu erhöhen und auch effizient gestaltet werden – insbesondere wenn es gelingt, solche Programme auf die Gruppe der Langzeitarbeitslosen ohne Chancen auf eine ungeförderte Beschäftigung zu konzentrieren

Evaluation des Bundesprogramms "Soziale Teilhabe am Arbeitsmarkt" (Zb1-04812-2/31): zweiter Zwischenbericht

Das Bundesprogramm "Soziale Teilhabe am Arbeitsmarkt" zielt auf die Verbesserung der sozialen Teilhabe von arbeitsmarktfernen Langzeitleistungsbeziehenden im SGB II, die entweder mit Kindern in einer Bedarfsgemeinschaft leben und/oder auf Grund von gesundheitlichen Einschränkungen besonderer Förderung bedürfen. Es ist im Jahr 2015 gestartet und läuft bis zum 31.12.2018. An dem Programm nahmen zur Jahresmitte 2017 ca. 15.000 Personen in 195 Jobcentern teil. Das Bundesprogramm „Soziale Teilhabe am Arbeitsmarkt“ wird somit in knapp der Hälfte aller Jobcenter bundesweit umgesetzt. Der vorliegende Zwischenbericht stellt Zwischenergebnisse der programmbegleitenden Evaluation vor. Erstmals werden Ergebnisse aus Fallstudien zur lokalen Umsetzung vorgestellt, und es werden erstmals Ergebnisse aus der CATI-Befragung von Teilnehmenden und Kontrollpersonen zur sozialen Teilhabe, der zentralen Ergebnisvariable des Programms, vorgestellt.The programme "Social Inclusion in the Labour Market" (Soziale Teilhabe am Arbeitsmarkt) is a Federal labour market programme aiming to support social inclusion of persons with severe placement obstacles who are long-time receivers of Arbeitslosengeld II (minimum income support). The programme runs from 2015 to 31.12.2018 and focusses on persons who live together with children and / or who need special support due to health limitations. In 2017, about 15,000 persons from 195 Jobcenters participated, i.e. nearly a half of all Jobcenters in Germany have implemented the programme. This intermediate research report presents for the first time results from local case studies about the programme implementation. Furthermore, for the first time results concerning the social inclusion the main outcome variable of the programme of participants and non-participants are presented and discussed

Evaluation des Bundesprogramms "Soziale Teilhabe am Arbeitsmarkt": Erster Zwischenbericht

Das Bundesprogramm "Soziale Teilhabe am Arbeitsmarkt" zielt auf die Verbesserung der sozialen Teilhabe von arbeitsmarktfernen Langzeitleistungsbeziehenden im SGB II, die entweder mit Kindern in einer Bedarfsgemeinschaft leben und/oder auf Grund von gesundheitlichen Einschränkungen besonderer Förderung bedürfen. Es ist im Jahr 2015 gestartet und läuft bis zum 31.12.2018. Bislang nahmen knapp 10.000 Personen aus 105 Jobcentern an dem Programm teil. Eine Ausweitung des Programms hat zum Jahreswechsel 2016/17 stattgefunden. Der vorliegende Zwischenbericht stellt erste Ergebnisse der programmbegleitenden Evaluation vor.The programme "Social Inclusion in the Labour Market" (Soziale Teilhabe am Arbeitsmarkt) is a Federal labour market programme aiming to support social inclusion of persons with severe placement obstacles who are long-time receivers of Arbeitslosengeld II (minimum income support). The programme runs from 2015 to 31.12.2018 and focusses on persons who live together with children and/or who need special support due to health limitations. Until now, almost 10,000 persons from 105 Jobcenters participate in this programme. The programme will be extended from January 2017 on. This intermediate report presents first findings from the evaluation research team

Дослідження структури порушених відкритою розробкою земель й пошук шляхів вдосконалення рекультивації залишкових виробок кар'єрів

Стаття присвячена дослідженням структури порушених земель, на ділянках з видобутку корисних копалин відкритим способом. Наведено площі порушень земель при розробці основних видів корисних копалин. Проаналізовано ризики, що виникають із несвоєчасною рекультивацією земель гірничого відводу, а також від покинутих гірничих виробок старих кар'єрів. Паралельно розглянуті обсяги відходів гірничого виробництва та їх повторне використання в якості заповнювача для залишкових вироблених просторів кар'єрів.The article is devoted to the research of land violation indicators at the extraction of minerals by surface mining method. Data gives about the land violations area at the mining key minerals. Ana-lyzed the risks from the not-on-time reclamation of the mining clam and abandoned excavations of the old quarries. In parallel considered the volumes of mining wastes and their reuse as aggregate for filling residual spaces of surface mines.Статья посвящена исследованиям площадей нарушения земель, связанных с добычей полезных ископаемых открытым способом. Приведены площади нарушений земель при разработке основных видов полезных ископаемых. Проанализированы риски, представляемые несвоевременной рекультивацией земель горного отвода, а также заброшенными горными выработками старых карьеров. Параллельно рассмотрены объемы отходов горного производства и их повторное использование в качестве заполнителя для остаточных выработанных пространств карьеров

Nuclear Reprogramming: Kinetics of Cell Cycle and Metabolic Progression as Determinants of Success

Establishment of totipotency after somatic cell nuclear transfer (NT) requires not only reprogramming of gene expression, but also conversion of the cell cycle from quiescence to the precisely timed sequence of embryonic cleavage. Inadequate adaptation of the somatic nucleus to the embryonic cell cycle regime may lay the foundation for NT embryo failure and their reported lower cell counts. We combined bright field and fluorescence imaging of histone H2b-GFP expressing mouse embryos, to record cell divisions up to the blastocyst stage. This allowed us to quantitatively analyze cleavage kinetics of cloned embryos and revealed an extended and inconstant duration of the second and third cell cycles compared to fertilized controls generated by intracytoplasmic sperm injection (ICSI). Compared to fertilized embryos, slow and fast cleaving NT embryos presented similar rates of errors in M phase, but were considerably less tolerant to mitotic errors and underwent cleavage arrest. Although NT embryos vary substantially in their speed of cell cycle progression, transcriptome analysis did not detect systematic differences between fast and slow NT embryos. Profiling of amino acid turnover during pre-implantation development revealed that NT embryos consume lower amounts of amino acids, in particular arginine, than fertilized embryos until morula stage. An increased arginine supplementation enhanced development to blastocyst and increased embryo cell numbers. We conclude that a cell cycle delay, which is independent of pluripotency marker reactivation, and metabolic restraints reduce cell counts of NT embryos and impede their development

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Pseudorapidity and transverse momentum dependence of flow harmonics in pPb and PbPb collisions

info:eu-repo/semantics/publishe

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome

BACKGROUND: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. METHODS: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. RESULTS: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P&lt;5×10-8) near NOS1AP, KCNQ1, and KLF12, and 1 missense variant in KCNE1(p.Asp85Asn) at the suggestive threshold (P&lt;10-6). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (rg=0.40; P=3.2×10-3). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P&lt;10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P&lt;0.005). CONCLUSIONS: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.</p

Examining the generalizability of research findings from archival data

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability—for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples