Reduced-bias estimator of the Conditional Tail Expectation of heavy-tailed distributions

International audienceSeveral risk measures have been proposed in the literature. In this paper, we focus on the estimation of the Conditional Tail Expectation (CTE). Its asymptotic normality has been first established in the literature under the classical assumption that the second moment of the loss variable is finite, this condition being very restrictive in practical applications. Such a result has been extended by Necir {\it et al.} (2010) in the case of infinite second moment. In this framework, we propose a reduced-bias estimator of the CTE. We illustrate the efficiency of our approach on a small simulation study and a real data analysis

Low specificity of determine HIV1/2 RDT using whole blood in south west Tanzania

Objective: To evaluate the diagnostic performance of two rapid detection tests (RDTs) for HIV 1/2 in plasma and in whole blood samples. Methods: More than 15,000 study subjects above the age of two years participated in two rounds of a cohort study to determine the prevalence of HIV. HIV testing was performed using the Determine HIV 1/2 test (Abbott) in the first (2006/2007) and the HIV 1/2 STAT-PAK Dipstick Assay (Chembio) in the second round (2007/2008) of the survey. Positive results were classified into faint and strong bands depending on the visual appearance of the test strip and confirmed by ELISA and Western blot. Results: The sensitivity and specificity of the Determine RDT were 100% (95% confidence interval = 86.8 to 100%) and 96.8% (95.9 to 97.6%) in whole blood and 100% (99.7 to 100%) and 97.9% (97.6 to 98.1%) in plasma respectively. Specificity was highly dependent on the tested sample type: when using whole blood, 67.1% of positive results were false positive, as opposed to 17.4% in plasma. Test strips with only faint positive bands were more often false positive than strips showing strong bands and were more common in whole blood than in plasma. Evaluation of the STAT-PAK RDT in plasma during the second year resulted in a sensitivity of 99.7% (99.1 to 99.9%) and a specificity of 99.3% (99.1 to 99.4%) with 6.9% of the positive results being false. Conclusions: Our study shows that the Determine HIV 1/2 strip test with its high sensitivity is an excellent tool to screen for HIV infection, but that – at least in our setting – it can not be recommended as a confirmatory test in VCT campaigns where whole blood is used

West Africa International Centers of Excellence for Malaria Research: Drug Resistance Patterns to Artemether-Lumefantrine in Senegal, Mali, and The Gambia.

In 2006, artemether-lumefantrine (AL) became the first-line treatment of uncomplicated malaria in Senegal, Mali, and the Gambia. To monitor its efficacy, between August 2011 and November 2014, children with uncomplicated Plasmodium falciparum malaria were treated with AL and followed up for 42 days. A total of 463 subjects were enrolled in three sites (246 in Senegal, 97 in Mali, and 120 in Gambia). No early treatment failure was observed and malaria infection cleared in all patients by day 3. Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) was 100% in Mali, and the Gambia, and 98.8% in Senegal. However, without PCR adjustment, ACPR was 89.4% overall; 91.5% in Mali, 98.8% in Senegal, and 64.3% in the Gambia (the lower value in the Gambia attributed to poor compliance of the full antimalarial course). However, pfmdr1 mutations were prevalent in Senegal and a decrease in parasite sensitivity to artesunate and lumefantrine (as measured by ex vivo drug assay) was observed at all sites. Recrudescent parasites did not show Kelch 13 (K13) mutations and AL remains highly efficacious in these west African sites

Tau Herculids 2022 from the McDonald Observatory, Texas -- a progress report

As part of an intensive effort to observe the predicted 2022 Tau Herculids outburst, we recorded almost 800 individual meteor streaks on May 30th and 31st, 2022, using a high-sensitivity Sony~$\alpha$7 camera. The video recordings were obtained under perfect conditions at the McDonald Observatory, Texas, USA. The meteor sample is dominated by the predicted Tau Herculids shower, however, we also noted significant activity of sporadic meteors and other possible weak showers. We found that the time of the maximum activity matched very well the predictions, while we note the large fraction of faint meteors that were not detectable visually. We determined the radiant, and the time evolution of the activities and currently we are working on the determination of the brightness statistics

A new approach to analyse single-site video observations: A Tau Her 2022 case study

Here we present a continuation of the work that was based on video observations of the Tau Her 2022 outburst from the McDonald Observatory, Texas, US. On the night of the maximum in 2022 we detected 626 individual Tau Her meteors, for which we estimated photovisual magnitudes and analysed their distribution on the sky to determine the radiant position in an innovative way. The derived population index is $5.56 \pm 1.83$, while the radiant position for the mid-time of the observations is: $\mathrm{RA} = 209.71 ^\circ \pm 1.01 ^\circ$, $\mathrm{Dec} = 27.73 ^\circ \pm 0.07 ^\circ$. Both measurements are in good agreement with other results in the literature, although our population index seems to be higher than most of the published values. We speculate this might be due to the higher sensitivity of our equipment to fainter meteors

Structural basis for antibiotic transport and inhibition in PepT2

The uptake and elimination of beta-lactam antibiotics in the human body are facilitated by the proton-coupled peptide transporters PepT1 (SLC15A1) and PepT2 (SLC15A2). The mechanism by which SLC15 family transporters recognize and discriminate between different drug classes and dietary peptides remains unclear, hampering efforts to improve antibiotic pharmacokinetics through targeted drug design and delivery. Here, we present cryo-EM structures of the proton-coupled peptide transporter, PepT2 from Rattus norvegicus, in complex with the widely used beta-lactam antibiotics cefadroxil, amoxicillin and cloxacillin. Our structures, combined with pharmacophore mapping, molecular dynamics simulations and biochemical assays, establish the mechanism of beta-lactam antibiotic recognition and the important role of protonation in drug binding and transport

Structural insights into the mechanism of protein transport by the Type 9 Secretion System translocon

Secretion systems are protein export machines that enable bacteria to exploit their environment through the release of protein effectors. The Type 9 Secretion System (T9SS) is responsible for protein export across the outer membrane (OM) of bacteria of the phylum Bacteroidota. Here we trap the T9SS of Flavobacterium johnsoniae in the process of substrate transport by disrupting the T9SS motor complex. Cryo-EM analysis of purified substrate-bound T9SS translocons reveals an extended translocon structure in which the previously described translocon core is augmented by a periplasmic structure incorporating the proteins SprE, PorD and a homologue of the canonical periplasmic chaperone Skp. Substrate proteins bind to the extracellular loops of a carrier protein within the translocon pore. As transport intermediates accumulate on the translocon when energetic input is removed, we deduce that release of the substrate–carrier protein complex from the translocon is the energy-requiring step in T9SS transport

New national and regional bryophyte records, 52

Marchantia paleacea is a new species for the Umbria Region and is rare in central and southern Italy. This record is in a Site of Community Importance (SCI) IT5220017 and a Special Area of Conservation (SAC) of the Natura 2000 EU-wide network due to the presence of the 7220* ‘Petrifying springs with tufa formation (Cratoneurion)’ Annexe I priority habitat. The particular environment, with a gorge and waterfall, created a very special microclimate that allowed the establishment of interesting liverworts and mosses

Discussion of costs and financial burden in clinical practice: A survey of medical oncologists in Australia

Background A diagnosis of cancer is associated with significant physical, psychological and financial burden. Including costs of cancer is an important component of shared decision making. Doctors bear a responsibility towards educating patients about the financial aspects of care. Multiple organisations have advocated for price transparency and implementing Informed Financial Consent in the clinic. However, few studies have evaluated the perspectives of oncologists on the current state of this discussion. Aims The aim of this study is to determine the views and perspectives of medical oncologists regarding communication of costs and financial burden in patients with cancer. Methods We conducted a prospective cross-sectional online survey via REDCap. The survey was distributed to medical oncologists and advanced trainees currently registered with Medical Oncology Group of Australia (MOGA). Data was collected using the online survey comprising socio-demographic characteristics, discussion of costs and financial burden, and facilitators and barriers to these discussions. Results 547 members of MOGA were invited to participate in the study, and 106 of 547 MOGA members (19%) completed the survey. Most oncologists (66%) felt that it was their responsibility to discuss costs of care, however a majority of oncologists (59.3%) reported discussing costs with less than half of their patients. Only 25% of oncologists discussed financial concerns with more than half of their patients, and most oncologists were unfamiliar with cancer-related financial burden. Most Oncologists with greater clinical experience and those working in private practice were more likely to discuss costs with a majority of their patients. Conclusions Certain characteristics of medical oncologists and their practices were associated with reported prevalence of discussing costs of care and financial burden with their patients. In the context of rising costs of cancer care, interventions targeting modifiable factors such as raising oncologist awareness of costs of care and financial burden, screening for financial toxicity and availability of costs information in an easily accessible manner, may help increase the frequency of patient-doctor discussions about costs of care, contributing to informed decision-making and higher-quality cancer care