A stochastic design rainfall generator based on copulas and mass curves

The use of design storms can be very useful in many hydrological and hydraulic practices. In this study, the concept of a copula-based secondary return period in combination with the concept of mass curves is used to generate point-scale design storms. The analysis is based on storms selected from the 105 year rainfall time series with a 10 min resolution, measured at Uccle, Belgium. In first instance, bivariate copulas and secondary return periods are explained, together with a focus on which couple of storm variables is of highest interest for the analysis and a discussion of how the results might be affected by the goodness-of-fit of the copula. Subsequently, the fitted copula is used to sample storms with a predefined secondary return period for which characteristic variables such as storm duration and total storm depth can be derived. In order to construct design storms with a realistic storm structure, mass curves of 1st, 2nd, 3rd and 4th quartile storms are developed. An analysis shows that the assumption of independence between the secondary return period and the internal storm structure could be made. Based on the mass curves, a technique is developed to randomly generate an intrastorm structure. The coupling of both techniques eventually results in a methodology for stochastic design storm generation. Finally, its practical usefulness for design studies is illustrated based on the generation of a set of statistically identical design storm and rainfall-runoff modelling

Diagnosing overtraining in athletes using the two-bout exercise protocol

Objective: In this work, whether a two-bout exercise protocol can be used to make an objective, immediately available distinction between non-functional over reaching (NFO) and overtraining syndrome (OTS) was studied. Design: Underperforming athletes who were diagnosed with the suspicion of NFO or OTS were included in the study. Recovery of the athletes was monitored by a sports physician to retrospectively distinguish NFO from OTS. Setting: Sports medicine laboratory Participants: The protocol was started and completed by 10 underperforming athletes. NFO was retrospectively diagnosed in five athletes, and OTS was diagnosed in five athletes. Interventions: A two-bout maximal exercise protocol was used to measure physical performance and stressinduced hormonal reactions. Main outcome measurements: Exercise duration, heart rate and blood lactate concentration were measured at the end of both exercise tests. Venous concentrations cortisol, adrenocorticotrophic hormone (ACTH), prolactin and growth hormone were measured both before and after both exercise tests. Results: Maximal blood lactate concentration was lower in OTS compared with NFO, while resting concentrations of cortisol, ACTH and prolactin concentrations were higher. However, sensitivity of these measures was low. The ACTH and prolactin reactions to the second exercise bout were much higher in NFO athletes compared with OTS and showed the highest sensitivity for making the distinction. Conclusions: NFO might be distinguished from OTS based on ACTH and prolactin reactions to a two-bout exercise protocol. This protocol could be a useful tool for diagnosing NFO and OTS; however, more data should be collected before this test can be used as the gold standard

Niveaux hormonaux plasmatiques de poules albinos (sal-c) et non albinos (S)

Des poules albinos (mutation s al-c) et non-albinos (colorées) de même origine ont été comparées pour des niveaux plasmatiques hormonaux, triiodothyronine (T3), thyroxine (T4), hormone de croissance (GH) et corticostérone, avant l’entrée en ponte puis après 3 à 4 mois de ponte. Le rapport T3/T4 était plus élevé chez les poules albinos que chez les non-albinos aux 2 âges; cette différence s’approche de la signification après l’entrée en ponte. La variance intra-génotype de ce rapport est plus élevée pour les poules s al-c que pour les non-albinos (P < 0,01). D’autre part, le taux de l’hormone de croissance ne diffère pas entre génotypes avant l’entrée en ponte, mais en période de ponte il est significativement plus élevé chez les poules s al. Il existe donc certaines différences dans l’équilibre hormonal des 2 génotypes. On peut espérer que ceci aide à l’interprétation des effets trouvés associés au gène albinos sur la production d’oeufs.Albino (s al-c) and non-albino (colored) hens from the same origin were compared for several plasmatic hormonal levels (triiodothyronine (T3), thyroxine (T4), growth hormone (GH), and corticosterone) before the onset of laying and after 3-4 months of production. The T3/T4 ratio was higher among albino than among non-albino females at the 2 ages; this difference approached significance after sexuaL maturity. The within-genotype variance of this ratio was higher for s al-c hens than for non-albino ones (P<0.01). On the other hand, the GH level did not differ between the 2 genotypes before the onset of laying, but during laying it was significantly higher for the s al-c females. There are therefore some differences in the general hormonal balance of the 2 genotypes. It is hoped that this may help in an interpretation of the effects on egg production associated with the albino gene

Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5

Background The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). Patients and Methods Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m2) followed by 4 cycles of docetaxel (100 mg/m2). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year. Coprimary end points were (1) rate of cardiac events (CEs) in all patients defined as clinical congestive heart failure with a significant decrease in left ventricular ejection fraction or cardiac deaths; and (2) pathologic complete response (pCR) in breast and nodes in the neoadjuvant cohort. An independent cardiac review panel determined whether criteria for a CE were met. Results A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. Conclusion The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations

Surrogate markers and survival in women receiving first-line combination anthracycline chemotherapy for advanced breast cancer

Surrogate markers may help predict the effects of first-line treatment on survival. This metaregression analysis examines the relationship between several surrogate markers and survival in women with advanced breast cancer after receiving first-line combination anthracycline chemotherapy 5-fluorouracil, adriamycin and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin and cyclophosphamide (FEC) . From a systematic literature review, we identified 42 randomised trials. The surrogate markers were complete or partial tumour response, progressive disease and time to progression. The treatment effect on survival was quantified by the hazard ratio. The treatment effect on each surrogate marker was quantified by the odds ratio (or ratio of median time to progression). The relationship between survival and each surrogate marker was assessed by a weighted linear regression of the hazard ratio against the odds ratio. There was a significant linear association between survival and complete or partial tumour response (P<0.001, R2=34%), complete tumour response (P=0.02, R2=12%), progressive disease (P<0.001, R2=38%) and time to progression (P<0.0001, R2=56%); R2 is the proportion of the variability in the treatment effect on survival that is explained by the treatment effect on the surrogate marker. Time to progression may be a useful surrogate marker for predicting survival in women receiving first-line anthracycline chemotherapy and could be used to estimate the survival benefit in future trials of first-line chemotherapy compared to FAC or FEC. The other markers, tumour response and progressive disease, were less good

Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial: rational and protocol

Background: Hypertension and diabetes cause chronic kidney disease (CKD) and diastolic left ventricular dysfunction (DVD) as forerunners of disability and death. Home blood pressure telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling prevention. Methods: UPRIGHT-HTM (Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform [NCT04299529]) is an investigator-initiated 5-year clinical trial with patient-centred design, which will randomise 1148 patients to be recruited in Europe, sub-Saharan Africa and South America. During the whole study, HTM data will be collected and freely accessible for patients and caregivers. The UPP, measured at enrolment only, will be communicated early during follow-up to 50% of patients and their caregivers (intervention), but only at trial closure in 50% (control). The hypothesis is that early knowledge of the UPP risk profile will lead to more rigorous risk factor management and result in benefit. Eligible patients, aged 55-75 years old, are asymptomatic, but have ≥5 CKD- or DVD-related risk factors, preferably including hypertension, type-2 diabetes, or both. The primary endpoint is a composite of new-onset intermediate and hard cardiovascular and renal outcomes. Demonstrating that combining UPP with HTM is feasible in a multicultural context and defining the molecular signatures of early CKD and DVD are secondary endpoints. Expected outcomes: The expected outcome is that application of UPP on top of HTM will be superior to HTM alone in the prevention of CKD and DVD and associated complications and that UPP allows shifting emphasis from treating to preventing disease, thereby empowering patients

European regulatory agenices should employ full time statisticians

No abstract available

Fermentation of Arabinoxylan-Oligosaccharides, Oligofructose and their Monomeric Sugars by Hindgut Bacteria from Siberian Sturgeon and African Catfish in Batch Culture in vitro

The in vitro fermentation of two Non-Digestible Oligosaccharide (NDO) preparations, Arabinoxylan- Oligosaccharides (AXOS) and Oligofructose (OF), and their respective monomeric sugars, xylose and fructose, were investigated by hindgut microbiota of two major aquaculture fish species, Siberian sturgeon (Acipenser baerii) and African catfish (Clarias gariepinus). Inocula from the hindgut of both fish species were incubated for 48 h in bottles containing 1.0% of one of four substrates, i.e. AXOS, OF, xylose or fructose. Amounts and profiles of produced Short-Chain Fatty Acids (SCFAs) differed between the two fish species and substrates. The hindgut microbiota of Siberian sturgeon has a higher fermentation capacity than the microbiota from African catfish. Xylose was much easier fermented than AXOS by microbiota from Siberian sturgeon whereas OF was quicker fermented than fructose with African catfish inoculum. The SCFAs were dominated by acetic acid for both fish species and for all substrates. Fermentation of OF and fructose by hindgut microbiota of Siberian sturgeon also yielded high amounts of butyric and branched-chain fatty acids after 48 h incubation. Results of this study suggest that AXOS, OF, and their monomeric sugars have an impact on microbial fermentation activity of hindgut microbiota from Siberian sturgeon and African catfish in a substrate and species dependent manner