The transverse-momentum spectrum of Higgs bosons near threshold at NNLO

We give next-to-next-to-leading order (NNLO) predictions for the Higgs production cross section at large transverse momentum in the threshold limit. Near the partonic threshold, all radiation is either soft or collinear to the final state jet which recoils against the Higgs boson. We find that the real emission corrections are of moderate size, but that the virtual corrections are large. We discuss the origin of these corrections and give numerical predictions for the transverse-momentum spectrum. The threshold result is matched to the known NLO result and implemented in the public code PeTeR.Comment: 17 pages, 9 Figures; v2: journal version, correction in the qg channe

Transverse-momentum spectra of electroweak bosons near threshold at NNLO

We obtain the next-to-next-to-leading order corrections to transverse-momentum spectra of W, Z and Higgs bosons near the partonic threshold. In the threshold limit, the electroweak boson recoils against a low-mass jet and all radiation is either soft, or collinear to the jet or the beam directions. We extract the virtual corrections from known results for the relevant two-loop four-point amplitudes and combine them with the soft and collinear two-loop functions as defined in Soft-Collinear Effective Theory. We have implemented these results in a public code PeTeR and present numerical results for the threshold resummed cross section of W and Z bosons at next-to-next-to-next-to-leading logarithmic accuracy, matched to next-to-leading fixed-order perturbation theory. The two-loop corrections lead to a moderate increase in the cross section and reduce the scale uncertainty by about a factor of two. The corrections are significantly larger for Higgs production.Comment: 33 pages, 3 figures; v2: journal version, correction in (73); v3: corrected qg-channel in (73

Nutrition Controls Mitochondrial Biogenesis in the Drosophila Adipose Tissue through Delg and Cyclin D/Cdk4

Mitochondria are cellular organelles that perform critical metabolic functions: they generate energy from nutrients but also provide metabolites for de novo synthesis of fatty acids and several amino acids. Thus mitochondrial mass and activity must be coordinated with nutrient availability, yet this remains poorly understood. Here, we demonstrate that Drosophila larvae grown in low yeast food have strong defects in mitochondrial abundance and respiration activity in the larval fat body. This correlates with reduced expression of genes encoding mitochondrial proteins, particularly genes involved in oxidative phosphorylation. Second, genes involved in glutamine metabolism are also expressed in a nutrient-dependent manner, suggesting a coordination of amino acid synthesis with mitochondrial abundance and activity. Moreover, we show that Delg (CG6338), the Drosophila homologue to the alpha subunit of mammalian transcription factor NRF-2/GABP, is required for proper expression of most genes encoding mitochondrial proteins. Our data demonstrate that Delg is critical to adjust mitochondrial abundance in respect to Cyclin D/Cdk4, a growth-promoting complex and glutamine metabolism according to nutrient availability. However, in contrast to nutrients, Delg is not involved in the regulation of mitochondrial activity in the fat body. These findings are the first genetic evidence that the regulation of mitochondrial mass can be uncoupled from mitochondrial activity

The impact of immunotherapies on COVID-19 case fatality rates during the US vaccination campaign: a multidisciplinary open data analysis using FDA Adverse Event Reporting System and Our World in Data.

Introduction: Patients under immunotherapies were excluded from the pivotal trials of vaccinations against the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), and no population-level data on disease outcomes such as case fatality rates in relation to vaccination coverage exist. Our study aims to fill this gap by investigating whether CFRs in patients with immunotherapies decrease with increasing vaccination coverage in the total population. Methods: We combined aggregated open source data on COVID-19 vaccination coverage from "Our World in Data" with publicly available anonymized COVID-19 case reports from the FDA Adverse Event Reporting System to compute COVID-19 CFRs for patients under immunotherapy at different vaccination coverage levels in the total population. CFRs at different vaccination coverage levels were then compared to CFRs before vaccination campaign start. Results: While we found an overall decrease in CFRs on population level with increasing vaccination coverage, we found no decrease in people using anti-CD20 or glucocorticoids. Discussion: Risk-mitigation strategies on an individual- and population-level are thus still needed to lower the probability of fatal SARS-CoV2 infection for these vulnerable populations

A single FLOTAC is more sensitive than triplicate Kato-Katz for the diagnosis of low-intensity soil-transmitted helminth infections

Accurate diagnostic tools are pivotal for patient management and surveillance of helminth control programmes, particularly in the current era of preventive chemotherapy. Three consecutive stool samples were obtained from 279 schoolchildren from Zanzibar, an island where anthelminthic drugs have been administered on a large scale for more than a decade. All stool samples were examined with the Kato-Katz method. Additionally, one sample per child was preserved in sodium acetate-acetic acid-formalin solution, and examined with the FLOTAC technique. Considering the pooled results of both methods as diagnostic ‘gold' standard, the observed prevalences of Trichuris trichiura, hookworm and Ascaris lumbricoides were 63.4, 35.8 and 22.9%, respectively. The sensitivity of examining a single stool sample by FLOTAC for diagnosing T. trichiura, hookworm and A. lumbricoides was 88.7, 83.0 and 82.8%, respectively. Lower sensitivities were observed for Kato-Katz even after examining three stool samples: 71.8, 46.0 and 70.3%, respectively. Kato-Katz revealed considerably higher infection intensities than FLOTAC. The κ agreement between a single FLOTAC and triplicate Kato-Katz was 0.63 for diagnosing A. lumbricoides and 0.50 for T. trichiura, but only 0.30 for hookworm. The high sensitivity of FLOTAC holds promise for patient management, monitoring soil-transmitted helminth transmission and endpoint(s) of control at the population leve

FLOTAC: A promising technique for detecting helminth eggs in human faeces

There is a tendency to neglect diagnostic issues in the era of ‘preventive chemotherapy' in human helminthiases. However, accurate diagnosis cannot be overemphasized for adequate patient management and monitoring of community-based control programmes. Implicit is a diagnostic dilemma: the more effective interventions are in reducing helminth egg excretion, the less sensitive direct parasitological tests become. Here, experiences gained thus far with the FLOTAC technique for diagnosing common soil-transmitted helminth infections are summarized. A single FLOTAC has higher sensitivity than multiple Kato-Katz thick smears in detecting low-intensity infections. Further validation of the FLOTAC technique in different epidemiological settings is warranted, including diagnosis of intestinal schistosomiasis and food-borne trematodiase

Albendazole and Mebendazole Administered Alone or in Combination with Ivermectin against Trichuris trichiura: A Randomized Controlled Trial

Background. Single-dose albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 µg/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. Trial registration. isrctn.org Identifier: ISRCTN0833660

Albendazole and Mebendazole Administered Alone or in Combination with Ivermectin against Trichuris trichiura: A Randomized Controlled Trial

Background. Single-dose albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 µg/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. Trial registration. isrctn.org Identifier: ISRCTN0833660

Keras R-CNN: library for cell detection in biological images using deep neural networks

Background: A common yet still manual task in basic biology research, high-throughput drug screening and digital pathology is identifying the number, location, and type of individual cells in images. Object detection methods can be useful for identifying individual cells as well as their phenotype in one step. State-of-the-art deep learning for object detection is poised to improve the accuracy and efficiency of biological image analysis. Results: We created Keras R-CNN to bring leading computational research to the everyday practice of bioimage analysts. Keras R-CNN implements deep learning object detection techniques using Keras and Tensorflow (https://github.com/broadinstitute/keras-rcnn). We demonstrate the command line tool’s simplified Application Programming Interface on two important biological problems, nucleus detection and malaria stage classification, and show its potential for identifying and classifying a large number of cells. For malaria stage classification, we compare results with expert human annotators and find comparable performance. Conclusions: Keras R-CNN is a Python package that performs automated cell identification for both brightfield and fluorescence images and can process large image sets. Both the package and image datasets are freely available on GitHub and the Broad Bioimage Benchmark Collection