The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

Bayesian Point Set Registration

Point set registration involves identifying a smooth invertible transformation between corresponding points in two point sets, one of which may be smaller than the other and possibly corrupted by observation noise. This problem is traditionally decomposed into two separate optimization problems: (i) assignment or correspondence, and (ii) identification of the optimal transformation between the ordered point sets. In this work, we propose an approach solving both problems simultaneously. In particular, a coherent Bayesian formulation of the problem results in a marginal posterior distribution on the transformation, which is explored within a Markov chain Monte Carlo scheme. Motivated by Atomic Probe Tomography (APT), in the context of structure inference for high entropy alloys (HEA), we focus on the registration of noisy sparse observations of rigid transformations of a known reference configuration.Lastly, we test our method on synthetic data sets.Comment: 15 pages, 20 figure

A high-throughput pipeline for scalable kit-free RNA extraction

An overreliance on commercial, kit-based RNA extraction in the molecular diagnoses of infectious disease presents a challenge in the event of supply chain disruptions and can potentially hinder testing capacity in times of need. In this study, we adapted a well-established, robust TRIzol-based RNA extraction protocol into a high-throughput format through miniaturization and automation. The workflow was validated by RT-qPCR assay for SARS-CoV-2 detection to illustrate its scalability without interference to downstream diagnostic sensitivity and accuracy. This semi-automated, kit-free approach offers a versatile alternative to prevailing integrated solid-phase RNA extraction proprietary systems, with the added advantage of improved cost-effectiveness for high volume acquisition of quality RNA whether for use in clinical diagnoses or for diverse molecular applications

Healthcare use for acute gastrointestinal illness in two Inuit communities: Rigolet and Iqaluit, Canada

Background. The incidence of self-reported acute gastrointestinal illness (AGI) in Rigolet, Nunatsiavut, and Iqaluit, Nunavut, is higher than reported elsewhere in Canada; as such, understanding AGI-related healthcare use is important for healthcare provision, public health practice and surveillance of AGI. Objectives: This study described symptoms, severity and duration of self-reported AGI in the general population and examined the incidence and factors associated with healthcare utilization for AGI in these 2 Inuit communities. Design: Cross-sectional survey data were analysed using multivariable exact logistic regression to examine factors associated with individuals’ self-reported healthcare and over-the-counter (OTC) medication utilization related to AGI symptoms. Results: In Rigolet, few AGI cases used healthcare services [4.8% (95% CI=1.5-14.4%)]; in Iqaluit, some cases used healthcare services [16.9% (95% CI=11.2-24.7%)]. Missing traditional activities due to AGI (OR=3.8; 95% CI=1.18-12.4) and taking OTC medication for AGI symptoms (OR=3.8; 95% CI=1.2-15.1) were associated with increased odds of using healthcare services in Iqaluit. In both communities, AGI severity and secondary symptoms (extreme tiredness, headache, muscle pains, chills) were significantly associated with increased odds of taking OTC medication. Conclusions: While rates of self-reported AGI were higher in Inuit communities compared to non-Inuit communities in Canada, there were lower rates of AGI-related healthcare use in Inuit communities compared to other regions in Canada. As such, the rates of healthcare use for a given disease can differ between Inuit and non-Inuit communities, and caution should be exercised in making comparisons between Inuit and non-Inuit health outcomes based solely on clinic records and healthcare use

What Are the Contextual Enablers and Impacts of Using Digital Technology to Extend Maternal and Child Health Services to Rural Areas? Findings of a Qualitative Study From Nigeria

Background: Strengthening health systems to improve access to maternity services remains challenging for Nigeria due partly to weak and irregular in-service training and deficient data management. This paper reports the implementation of digital health tools for video training (VTR) of health workers and digitization of health data at scale, supported by satellite communications (SatCom) technology and existing 3G mobile networks. Objective: To understand whether, and under what circumstances using digital interventions to extend maternal, newborn and child health (MNCH) services to remote areas of Nigeria improved standards of healthcare delivery. Methods: From March 2017 to March 2019, VTR and data digitization interventions were delivered in 126 facilities across three states of Nigeria. Data collection combined documents review with 294 semi-structured interviews of stakeholders across four phases (baseline, midline, endline, and 12-months post-project closedown) to assess acceptability and impacts of digital interventions. Data was analyzed using a framework approach, drawing on a modified Technology Acceptance Model to identify factors that shaped technology adoption and use. Results: Analysis of documents and interview transcripts revealed that a supportive policy environment, and track record of private-public partnerships facilitated adoption of technology. The determinants of technology acceptance among health workers included ease of use, perceived usefulness, and prior familiarity with technology. Perceptions of impact suggested that at the micro (individual) level, repeated engagement with clinical videos increased staff knowledge, motivation and confidence to perform healthcare roles. At meso (organizational) level, better-trained staff felt supported and empowered to provide respectful healthcare and improved management of obstetric complications, triggering increased use of MNCH services. The macro level saw greater use of reliable and accurate data for policymaking. Conclusions: Simultaneous and sustained implementation of VTR and data digitization at scale enabled through SatCom and 3G mobile networks are feasible approaches for supporting improvements in staff confidence and motivation and reported MNCH practices. By identifying mechanisms of impact of digital interventions on micro, meso, and macro levels of the health system, the study extends the evidence base for effectiveness of digital health and theoretical underpinnings to guide further technology use for improving MNCH services in low resource settings. Trial Registration: ISRCTN32105372

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

A Cytochrome b561 with Ferric Reductase Activity from the Parasitic Blood Fluke, Schistosoma japonicum

Parasites acquire their food from their hosts, either by feeding directly on tissues of the host, or by competing for ingested food. Adult schistosomes live within the vasculature of humans and rely on the blood cells and plasma they ingest and dissolved solutes they derive across their body surface, the tegument, for their nutrition. Schistosomes require host trace elements, notably iron, which is used as a co-factor in many biological reactions. Iron is especially important for schistosomes, for it has a significant role in egg formation and embryogenesis. In human tissues, iron predominates in the trivalent (ferric) form; however, it is the divalent (ferrous) form that is used as an essential co-factor for multiple biomolecules and enzymes. In order to be acquired from the host environment, the valency of iron must be modified to render it suitable for transport across the parasite membrane. This paper describes the molecular characterisation of a schistosome molecule that is crucial for bringing about this change in iron. Schistosoma japonicum Cytb561 is the first ferric reductase characterised in any parasitic helminth and emphasises the importance of iron, and other divalent cations, in these organisms