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

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

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

Physician-patient communication of costs and financial burden of cancer and its treatment: a systematic review of clinical guidelines

Background Optimising the care of individuals with cancer without imposing significant financial burden related to their anticancer treatment is becoming increasingly difficult. The American Society of Clinical Oncology (ASCO) has recommended clinicians discuss costs of cancer care with patients to enhance shared decision-making. We sought information to guide oncologists’ discussions with patients about these costs. Methods We searched Medline, EMBASE and clinical practice guideline databases from January 2009 to 1 June 2019 for recommendations about discussing the costs of care and financial burden. Guideline quality was assessed with the AGREE-II instrument. Results Twenty-seven guidelines met our eligibility criteria, including 16 from ASCO (59%). 21 of 27 (78%) guidelines included recommendations about discussion or consideration of treatment costs when prescribing, with information about actual costs in four (15%). Recognition of the risk of financial burden or financial toxicity was described in 81% (22/27) of guidelines. However, only nine guidelines (33%) included information about managing the financial burden. Conclusions Current clinical practice guidelines have little information to guide physician-patient discussions about costs of anticancer treatment and management of financial burden. This limits patients’ ability to control costs of treatment, and for the healthcare team to reduce the incidence and severity of financial burden. Current guidelines recommend clinician awareness of price variability and high costs of treatment. Clinicians are recommended to explore cost concerns and address financial worries, especially in high risk groups. Future guidelines should include advice on facilitating cost transparency discussions, with provision of cost information and resources

Development of electricity consumption profiles of residential buildings based on smart meter data clustering

In the present research, a high-resolution, detailed electric load dataset was assessed, collected by smart meters from nearly a thousand households in Hungary, many of them single-family houses. The objective was to evaluate this database in detail to determine energy consumption profiles from time series of daily and annual electric load. After representativity check of dataset daily and annual energy consumption profiles were developed, applying three different clustering methods (k-means, fuzzy k-means, agglomerative hierarchical) and three different cluster validity indexes (elbow method, silhouette method, Dunn index) in MATLAB environment. The best clustering method for our examination proved to be the kmeans clustering technique. Analyses were carried out to identify different consumer groups, as well as to clarify the impact of specific parameters such as meter type in the housing unit (e.g. peak, offpeak meter), day of the week (e.g. weekend, weekday), seasonality, geographical location, settlement type and housing type (single-family house, flat, age class of the building). Furthermore, four electric user profile types were proposed, which can be used for building energy demand simulation, summer heat load and winter heating demand calculatio

Targeted Next Generation Sequencing for malaria research in Africa:Current status and outlook

Targeted Next Generation Sequencing (TNGS) is an efficient and economical Next Generation Sequencing (NGS) platform and the preferred choice when specific genomic regions are of interest. So far, only institutions located in middle and high-income countries have developed and implemented the technology, however, the efficiency and cost savings, as opposed to more traditional sequencing methodologies (e.g. Sanger sequencing) make the approach potentially well suited for resource-constrained regions as well. In April 2018, scientists from the Plasmodium Diversity Network Africa (PDNA) and collaborators met during the 7th Pan African Multilateral Initiative of Malaria (MIM) conference held in Dakar, Senegal to explore the feasibility of applying TNGS to genetic studies and malaria surveillance in Africa. The group of scientists reviewed the current experience with TNGS platforms in sub-Saharan Africa (SSA) and identified potential roles the technology might play to accelerate malaria research, scientific discoveries and improved public health in SSA. Research funding, infrastructure and human resources were highlighted as challenges that will have to be mitigated to enable African scientists to drive the implementation of TNGS in SSA. Current roles of important stakeholders and strategies to strengthen existing networks to effectively harness this powerful technology for malaria research of public health importance were discussed

Large scale smart meter data assessment for energy benchmarking and occupant behaviour profile development

This paper will present objectives and first results of the research project entitled “Large Scale Smart Meter Data Assessment for Energy Benchmarking and Occupant Behaviour Profile Development of Building Clusters,” implemented in the geographical scope of Hungary. The project seeks to utilize a new and unique opportunity for accessing and processing an enormous dataset collected by smart meters. Recently in Hungary, nearly 10 000 buildings have been equipped with smart meters within the “Central Smart Grid Pilot Project”. By means of advanced data analysis techniques, consumption trends and motivations of building users are being investigated. The aims are to help building designers and engineers design more energy efficient buildings at lower investment costs by avoiding system oversizing, and to obtain better knowledge about hourly, daily and monthly energy consumption trends. Furthermore, standard net demand values for normative energy calculations can be updated and specified more precisely since consumption habits change with time and depend on the region

Composition and Distribution of Mosquito Vectors in a Peri-Urban Community Surrounding an Institution of Learning in Lafia Metropolis, Nasarawa State, Central Nigeria

Vector surveillance is very key in solving mosquito-borne health problems in Nigeria. To this end, the composition and distribution of mosquito vectors in a peri-urban community surrounding an institution of learning in Lafia metropolis, Nasarawa State, Central Nigeria was carried out between December 2016 and June 2017. The Prokopack Aspirator was used to collect indoor resting mosquitoes between 6:00 a.m. and 9:00 a.m. from 30 randomly selected houses. Mosquitoes collected were knocked down and transferred into a well labelled petri-dish and taken to the laboratory for processing. A total of 664 mosquitoes were collected which spread across Culex quinquefasciatus 572 (86.14%), Anopheles gambiae 88 (13.25%) and Aedes aegypti 4 (0.60%). The abundance of mosquitoes in relation to seasons, species, sex, abdominal conditions as well as transmission indices across seasons significantly varied (P 0.05). The inhabitants of the area should ensure that all drainages flow through so as to reduce mosquito breeding grounds. Also, members of the community should always protect themselves by sleeping under insecticide treated bed nets