Miracle-dz/UniFAR-FTUs huggingface dataset:
Controlled, prospective, observational study on the efficiency and tolerability of a combination of potential Nrf2-inducing antioxidants and micronutrients as pre-treatment for ICSI in dyspermic patients with previous failure.

OBJECTIVE To evaluate the efficiency of pre-treatment in dyspermic males in IVF couples with a combination of micronutrients, for the purpose of improving the fertilization rate, the implantation rate and the outcome of the pregnancy. PATIENTS AND METHODS This controlled prospective clinical study was performed in two medically assisted reproduction centers. 59 males with mild oligo-astheno-teratospermia (OAT) were admitted to the study. All of them had a history of previous in vitro fertilization (IVF) attempts with female partners aged < 40 diagnosed having tubal or idiopathic infertility. The subjects upon enrolment underwent a semen test and afterward were treated with alpha lipoic acid and glutathione (Fertiplus SOD®, Idi-Pharma, Catania, Italy) for 4 weeks (short-term). The primary endpoints that were evaluated are the following: fertilization rate (mean fertilization), implantation rate and pregnancy rate. RESULTS At the end of this study all the males (mean age 39.5 ± 5.1) reported in not having any side effects during the administration of Fertiplus. Their female partners (mean age 34.9 ± 4.5) underwent IVF using the ICSI technique. The number of oocytes retrieved and inseminated was not statistically different in comparison to previous attempts, but with the same number of oocytes treated, the fertilization rate per couple demonstrated statistically significant increase (p<0.001). We did not observe a percentage increase in evolutionary embryos, but we noticed an improvement in embryo quality per individual couple (p<0.001), associated with a net increase in the implantation rate per couple (p<0.001) in terms of clinical pregnancy. The estimated miscarriage risk after treatment was five times lower (p<0.001). CONCLUSIONS Short-term treatment with micronutrients in dyspermic subjects can improve the reproductive outcome of the IVF procedure.
Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer

Purpose: We investigated the safety and antitumor activity of the anti–programmed death 1 monoclonal antibody pembrolizumab in patients with estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer with programmed death ligand 1–positive (PD-L1–positive) tumors in the phase Ib open-label, multicohort KEYNOTE-028 (NCT02054806) study. Patients and Methods: Patients with ER+/HER2− advanced breast cancer with PD-L1–positive tumors (combined positive score ≥1) received pembrolizumab (10 mg/kg every 2 weeks) up to 2 years or until confirmed progression/intolerable toxicity. Primary endpoints were safety and overall response rate (ORR), based on Response Evaluation Criteria in Solid Tumors, version 1 (RECIST v1.1) as assessed by investigator review. Results: Between April 2014 and January 2015, 25 patients were enrolled. Median number of prior therapies for breast cancer, including endocrine agents, was 9 (range, 3–15). Median follow-up was 9.7 months (range, 0.7–31.8 months). Three patients experienced partial response (PR) and none experienced complete response (CR), resulting in an ORR of 12.0% (95% CI, 2.5%–31.2%); 16% of patients had stable disease (SD) and clinical benefit rate (CR + PR + [SD for ≥24 weeks]) was 20% (95% CI, 7–41). Median duration of response was 12.0 months (range, 7.4–15.9 months). The incidence of treatment-related adverse events was 64%; nausea (20%) and fatigue (12%) were most common and were predominantly grade 1/2. No treatment-related discontinuations or deaths occurred. Conclusions: Pembrolizumab was well tolerated with modest but durable overall response in certain patients with previously treated, advanced, PD-L1–positive, ER+/HER2− breast cancer. Clin Cancer Res; 24(12); 2804–11. ©2018 AACR.
Global parameterization and validation of a two‐leaf light use efficiency model for predicting gross primary production across FLUXNET sites

Light use efficiency (LUE) models are widely used to simulate gross primary production (GPP). However, the treatment of the plant canopy as a big leaf by these models can introduce large uncertainties in simulated GPP. Recently, a two‐leaf light use efficiency (TL‐LUE) model was developed to simulate GPP separately for sunlit and shaded leaves and has been shown to outperform the big‐leaf MOD17 model at six FLUX sites in China. In this study we investigated the performance of the TL‐LUE model for a wider range of biomes. For this we optimized the parameters and tested the TL‐LUE model using data from 98 FLUXNET sites which are distributed across the globe. The results showed that the TL‐LUE model performed in general better than the MOD17 model in simulating 8 day GPP. Optimized maximum light use efficiency of shaded leaves (εmsh) was 2.63 to 4.59 times that of sunlit leaves (εmsu). Generally, the relationships of εmsh and εmsu with εmax were well described by linear equations, indicating the existence of general patterns across biomes. GPP simulated by the TL‐LUE model was much less sensitive to biases in the photosynthetically active radiation (PAR) input than the MOD17 model. The results of this study suggest that the proposed TL‐LUE model has the potential for simulating regional and global GPP of terrestrial ecosystems, and it is more robust with regard to usual biases in input data than existing approaches which neglect the bimodal within‐canopy distribution of PAR.
Early arrival of Southern Source Water in the deep North Atlantic prior to Heinrich event 2

The Atlantic Meridional Overturning Circulation (AMOC) plays an important role in the Northern Hemisphere climate system. Significant interest went into the question of how excessive freshwater input through melting of continental ice can affect its overturning vigor and, hence, heat supply, to higher northern latitudes. Such forcing can be tested by investigating its behavior during extreme iceberg discharge events into the open North Atlantic during the last glacial period, the so-called Heinrich events (HE). Here we present neodymium (Nd) isotope compositions of past seawater, a sensitive chemical water mass tag, extracted from sediments of Ocean Drilling Program Site 1063 in the western North Atlantic (Bermuda Rise), covering the period surrounding HE 2, the Last Glacial Maximum, and the early deglaciation. These data are compared with a record of the kinematic circulation tracer (231Pa/230Th)xs extracted from the same sediment core. Both tracers indicate significant circulation changes preceding intense ice rafting during HE 2 by almost 2 kyr. Moreover, the Nd isotope record suggests the presence of deeply ventilating North Atlantic Deep Water early during Marine Isotope Stage 2 until it was replaced by Southern Source Water at ∼27 ka. The early switch to high (Pa/Th)xs and radiogenic ɛNd in relation to intensified ice rafting during HE 2 suggests that ice rafting into the open North Atlantic during major HE 2 was preceded by an early change of the AMOC. This opens the possibility that variations in AMOC contributed to or even triggered the ice sheet instability rather than merely responding to it.
Does Litter Size Variation Affect Models of Terrestrial Carnivore Extinction Risk and Management?

Background Individual variation in both survival and reproduction has the potential to influence extinction risk. Especially for rare or threatened species, reliable population models should adequately incorporate demographic uncertainty. Here, we focus on an important form of demographic stochasticity: variation in litter sizes. We use terrestrial carnivores as an example taxon, as they are frequently threatened or of economic importance. Since data on intraspecific litter size variation are often sparse, it is unclear what probability distribution should be used to describe the pattern of litter size variation for multiparous carnivores. Methodology/Principal Findings We used litter size data on 32 terrestrial carnivore species to test the fit of 12 probability distributions. The influence of these distributions on quasi-extinction probabilities and the probability of successful disease control was then examined for three canid species – the island fox Urocyon littoralis, the red fox Vulpes vulpes, and the African wild dog Lycaon pictus. Best fitting probability distributions differed among the carnivores examined. However, the discretised normal distribution provided the best fit for the majority of species, because variation among litter-sizes was often small. Importantly, however, the outcomes of demographic models were generally robust to the distribution used. Conclusion/Significance These results provide reassurance for those using demographic modelling for the management of less studied carnivores in which litter size variation is estimated using data from species with similar reproductive attributes.
POSTHARVEST ROTS OF AVOCADOS : IMPROVED CHEMICAL CONTROL BY USING DIFFERENT APPLICATION METHODS

Four methods of applying prochloraz to ‘Fuerte’ avocados postharvest were compared. These were: dipping, with and without a subsequent coating with polyethylene wax, ultra-low volume spray application followed by wax, and applying in wax. Prochloraz reduced rots best when applied as an ultra-low volume spray followed by waxing. It was also very effective when applied in wax. Dipping fruit in prochloraz increased the incidence of some types of rots. Waxing fruit without a prochloraz treatment reduced the incidence of internal and external stem end rots. This suggests that wax prevented stem end rot fungi from gaining entry to the fruit during packing.
Early deprivation and autonomic nervous system functioning in post-institutionalized children.

The relations between early deprivation and the development of the neuroendocrine and central components of the mammalian stress response have been examined frequently. However, little is known about the impact of early deprivation on the developmental trajectories of autonomic function. Children adopted between 15-36 months from institutional care were examined during their first 16 months post-adoption (N = 60). Comparison groups included same-aged peers reared in their birth families (N = 50) and children adopted internationally from overseas foster care (N = 46). The present study examined trajectories of baseline autonomic nervous system function longitudinally following entry into adopted families. Post-institutionalized children had higher sympathetic tone, measured by pre-ejection period (PEP). Individual differences in PEP soon after adoption served as a mediator between early deprivation and parent-reported behavioral problems 2 years post-adoption. There were no group differences in parasympathetic function, indexed by respiratory sinus arrhythmia. All three groups showed similar trajectories of ANS function across the 16 month period.
Irritable bowel syndrome, the microbiota and the gut-brain axis

ABSTRACT Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome.
Revisiting the Estimation of Dinosaur Growth Rates

Previous growth-rate studies covering 14 dinosaur taxa, as represented by 31 data sets, are critically examined and reanalyzed by using improved statistical techniques. The examination reveals that some previously reported results cannot be replicated by using the methods originally reported; results from new methods are in many cases different, in both the quantitative rates and the qualitative nature of the growth, from results in the prior literature. Asymptotic growth curves, which have been hypothesized to be ubiquitous, are shown to provide best fits for only four of the 14 taxa. Possible reasons for non-asymptotic growth patterns are discussed; they include systematic errors in the age-estimation process and, more likely, a bias toward younger ages among the specimens analyzed. Analysis of the data sets finds that only three taxa include specimens that could be considered skeletally mature (i.e., having attained 90% of maximum body size predicted by asymptotic curve fits), and eleven taxa are quite immature, with the largest specimen having attained less than 62% of predicted asymptotic size. The three taxa that include skeletally mature specimens are included in the four taxa that are best fit by asymptotic curves. The totality of results presented here suggests that previous estimates of both maximum dinosaur growth rates and maximum dinosaur sizes have little statistical support. Suggestions for future research are presented.
Munich Personal RePEc Archive The Quality of Insurance Intermediary Services –

Insurance intermediaries help consumers to economiz e on information and transaction costs in insurance markets. However, competing insurance int rmediaries provide heterogeneous services, which are difficult to assess by incomple tely informed consumers. Transaction costs economics, search theory and principal agent theory provide arguments on product quality differences between the two main distribution chann els in insurance markets (exclusive agents vs. independent intermediaries). The present paper uses a ample of 927 insurance intermediaries in Germany. By performing OLS estimations we test the impact of the different distribution channels, but also of other factors relating to the information processing activities on intermediaries’ service quality. Depending on the p roxies used for service quality, we find mixed evidence for the “product quality” hypothesis accor ding to which independent intermediaries provide better service quality than exclusive agent s. We find that service quality depends also to a large extent on the information gathering and pro cessing activities of the individual intermediaries.
Invasion Is a Community Affair: Clandestine Followers in the Bacterial Community Associated to Green Algae, Caulerpa racemosa, Track the Invasion Source

Biological invasions rank amongst the most deleterious components of global change inducing alterations from genes to ecosystems. The genetic characteristics of introduced pools of individuals greatly influence the capacity of introduced species to establish and expand. The recently demonstrated heritability of microbial communities associated to individual genotypes of primary producers makes them a potentially essential element of the evolution and adaptability of their hosts. Here, we characterized the bacterial communities associated to native and non-native populations of the marine green macroalga Caulerpa racemosa through pyrosequencing, and explored their potential role on the strikingly invasive trajectory of their host in the Mediterranean. The similarity of endophytic bacterial communities from the native Australian range and several Mediterranean locations confirmed the origin of invasion and revealed distinct communities associated to a second Mediterranean variety of C . racemosa long reported in the Mediterranean. Comparative analysis of these two groups demonstrated the stability of the composition of bacterial communities through the successive steps of introduction and invasion and suggested the vertical transmission of some major bacterial OTUs. Indirect inferences on the taxonomic identity and associated metabolism of bacterial lineages showed a striking consistency with sediment upheaval conditions associated to the expansion of their invasive host and to the decline of native species. These results demonstrate that bacterial communities can be an effective tracer of the origin of invasion and support their potential role in their eukaryotic host’s adaptation to new environments. They put forward the critical need to consider the 'meta-organism' encompassing both the host and associated micro-organisms, to unravel the origins, causes and mechanisms underlying biological invasions.
Distributionally Robust Solution to the Reserve Scheduling Problem With Partial Information of Wind Power

A distributionally robust optimization (DRO) model is presented for the reserve schedule decision-making problem with partial information of wind power, aiming to find a robust solution to the uncertainty of wind power probability distribution. The stochastic problem can be converted into an equivalent deterministic bilinear matrix inequality (BMI) problem. Numerical results verify the effectiveness of the proposed method.
Plant Functional Diversity and Species Diversity in the Mongolian Steppe

Background The Mongolian steppe is one of the most important grasslands in the world but suffers from aridization and damage from anthropogenic activities. Understanding structure and function of this community is important for the ecological conservation, but has seldom been investigated. Methodology/Principal Findings In this study, a total of 324 quadrats located on the three main types of Mongolian steppes were surveyed. Early-season perennial forbs (37% of total importance value), late-season annual forbs (33%) and late-season perennial forbs (44%) were dominant in meadow, typical and desert steppes, respectively. Species richness, diversity and plant functional type (PFT) richness decreased from the meadow, via typical to desert steppes, but evenness increased; PFT diversity in the desert and meadow steppes was higher than that in typical steppe. However, above-ground net primary productivity (ANPP) was far lower in desert steppe than in the other two steppes. In addition, the slope of the relationship between species richness and PFT richness increased from the meadow, via typical to desert steppes. Similarly, with an increase in species diversity, PFT diversity increased more quickly in both the desert and typical steppes than that in meadow steppe. Random resampling suggested that this coordination was partly due to a sampling effect of diversity. Conclusions/Significance These results indicate that desert steppe should be strictly protected because of its limited functional redundancy, which its ecological functioning is sensitive to species loss. In contrast, despite high potential forage production shared by the meadow and typical steppes, management of these two types of steppes should be different: meadow steppe should be preserved due to its higher conservation value characterized by more species redundancy and higher spatial heterogeneity, while typical steppe could be utilized moderately because its dominant grass genus Stipa is resistant to herbivory and drought.
Determinants of biofilm formation and cleanability of titanium surfaces

OBJECTIVE The aim of the present study was to analyze biofilm formation on four different titanium-based surfaces (machined titanium zirconium (TiZr) alloy, M; machined, acid-etched TiZr alloy, modMA; machined, sandblasted, acid-etched TiZr alloy, modSLA; and micro-grooved titanium aluminum vanadium alloy, TAV MG) in an experimental human model. MATERIAL AND METHODS Custom-made discs were mounted in individual intraoral splint housings and worn by 16 volunteers for 24 h. The safranin staining assay, isothermal microcalorimetry (IMC), and SEM were applied before and after surface cleaning. RESULTS The hydrophilic surfaces modMA and modSLA with greater surface micro-roughness exhibited significantly more biofilm than the hydrophobic surfaces TAV MG and M. The standardized cleaning procedure substantially reduced the biofilm mass on all surfaces. After cleaning, the IMC analyses demonstrated a longer lag time of the growth curve on TAV MG compared to modSLA. Inter- and intraindividual variations in biofilm formation on the titanium discs were evident throughout the study. CONCLUSIONS Surface hydrophilicity and roughness enhanced biofilm formation in vivo, whereas surface topography was the most influential factor that determined surface cleanability. While the grooved surface retained larger amounts of initial biofilm, the machined surface was easier to clean, but proliferation indicated by increased metabolic activity (growth rate) in IMC occurred despite mechanical biofilm removal.
Fluctuation Analysis: Can Estimates Be Trusted?

The estimation of mutation rates and relative fitnesses in fluctuation analysis is based on the unrealistic hypothesis that the single-cell times to division are exponentially distributed. Using the classical Luria-Delbrück distribution outside its modelling hypotheses induces an important bias on the estimation of the relative fitness. The model is extended here to any division time distribution. Mutant counts follow a generalization of the Luria-Delbrück distribution, which depends on the mean number of mutations, the relative fitness of normal cells compared to mutants, and the division time distribution of mutant cells. Empirical probability generating function techniques yield precise estimates both of the mean number of mutations and the relative fitness of normal cells compared to mutants. In the case where no information is available on the division time distribution, it is shown that the estimation procedure using constant division times yields more reliable results. Numerical results both on observed and simulated data are reported.
Translational development of splice-modifying antisense oligomers

ABSTRACT Introduction: Antisense nucleic acid analogues can interact with pre-mRNA motifs and influence exon or splice site selection and thereby alter gene expression. Design of antisense molecules to target specific motifs can result in either exon exclusion or exon inclusion during splicing. Novel drugs exploiting the antisense concept are targeting rare, life-limiting diseases; however, the potential exists to treat a wide range of conditions by antisense-mediated splice intervention. Areas covered: In this review, the authors discuss the clinical translation of novel molecular therapeutics to address the fatal neuromuscular disorders Duchenne muscular dystrophy and spinal muscular atrophy. The review also highlights difficulties posed by issues pertaining to restricted participant numbers, variable phenotype and disease progression, and the identification and validation of study endpoints. Expert opinion: Translation of novel therapeutics for Duchenne muscular dystrophy and spinal muscular atrophy has been greatly advanced by multidisciplinary research, academic-industry partnerships and in particular, the engagement and support of the patient community. Sponsors, supporters and regulators are cooperating to deliver new drugs and identify and define meaningful outcome measures. Non-conventional and adaptive trial design could be particularly suited to clinical evaluation of novel therapeutics and strategies to treat serious, rare diseases that may be problematic to study using more conventional clinical trial structures.