Multimodal decoding of human liver regeneration.

The liver has a unique ability to regenerate1,2; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option3-5. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2+ migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration. Interrogation of necrotic wound closure and hepatocyte proliferation across multiple timepoints following APAP-induced liver injury in mice demonstrates that wound closure precedes hepatocyte proliferation. Four-dimensional intravital imaging of APAP-induced mouse liver injury identifies motile hepatocytes at the edge of the necrotic area, enabling collective migration of the hepatocyte sheet to effect wound closure. Depletion of hepatocyte ANXA2 reduces hepatocyte growth factor-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury. Together, our work dissects unanticipated aspects of liver regeneration, demonstrating an uncoupling of wound closure and hepatocyte proliferation and uncovering a novel migratory hepatocyte subpopulation that mediates wound closure following liver injury. Therapies designed to promote rapid reconstitution of normal hepatic microarchitecture and reparation of the gut-liver barrier may advance new areas of therapeutic discovery in regenerative medicine.

Improved Tensor Current Limit from

A precision measurement of the ß^{+} decay of ^{8}B was performed using the Beta-decay Paul Trap to determine the ß-ν angular correlation coefficient a_{ßν}. The experimental results were combined with new ab initio symmetry-adapted no-core shell-model calculations to yield the second-most precise measurement from Gamow-Teller decays, a_{ßν}=-0.3345±0.0019_{stat}±0.0021_{syst}. This value agrees with the standard model value of -1/3 and improves uncertainties in ^{8}B by nearly a factor of 2. By combining results from ^{8}B and ^{8}Li, a tight limit on tensor current coupling to right-handed neutrinos was obtained. A recent global evaluation of all other precision ß decay studies suggested a nonzero value for right-handed neutrino coupling in contradiction with the standard model at just above 3σ. The present results are of comparable sensitivity and do not support this finding.

The gravitationally unstable gas disk of a starburst galaxy 12 billion years ago.

Galaxies in the early Universe that are bright at submillimetre wavelengths (submillimetre-bright galaxies) are forming stars at a rate roughly 1,000 times higher than the Milky Way. A large fraction of the new stars form in the central kiloparsec of the galaxy1-3, a region that is comparable in size to the massive, quiescent galaxies found at the peak of cosmic star-formation history4 and the cores of present-day giant elliptical galaxies. The physical and kinematic properties inside these compact starburst cores are poorly understood because probing them at relevant spatial scales requires extremely high angular resolution. Here we report observations with a linear resolution of 550 parsecs of gas and dust in an unlensed, submillimetre-bright galaxy at a redshift of z = 4.3, when the Universe was less than two billion years old. We resolve the spatial and kinematic structure of the molecular gas inside the heavily dust-obscured core and show that the underlying gas disk is clumpy and rotationally supported (that is, its rotation velocity is larger than the velocity dispersion). Our analysis of the molecular gas mass per unit area suggests that the starburst disk is gravitationally unstable, which implies that the self-gravity of the gas is stronger than the differential rotation of the disk and the internal pressure due to stellar-radiation feedback. As a result of the gravitational instability in the disk, the molecular gas would be consumed by star formation on a timescale of 100 million years, which is comparable to gas depletion times in merging starburst galaxies5.

A pilot study evaluating online training for therapist delivery of interpersonal psychotherapy for eating disorders.

OBJECTIVE: Individuals with eating disorders (EDs) often do not receive evidence-based care, such as interpersonal psychotherapy (IPT), partly due to lack of accessible training in these treatments. The standard method of training (i.e., in-person workshops) is expensive and time consuming, prompting a need for more scalable training tools. The primary aim of this pilot and open trial was to examine the effects of an IPT online training platform on training outcomes (i.e., IPT fidelity, knowledge, and acceptance) and, secondarily, whether online training was different from in-person training (using a comparative sample from a separate study) in terms of training outcomes and patient symptoms. METHOD: Participants were therapists (N = 60) and student patients (N = 42) at 38 college counseling centers. Therapists completed baseline questionnaires and collected data from a student patient with ED symptoms. Therapists then participated in an IPT online training program and completed post-training assessments. RESULTS: Following online training, acceptance of evidence-based treatments, therapist knowledge of IPT, therapist acceptance of IPT, and treatment fidelity increased; acceptance of online training was high at baseline and remained stable after training. Using the 90% confidence interval on outcome effect sizes, results suggested IPT online training was not different from in-person training on most outcomes. Results are based on 60% of therapists who originally enrolled due to high dropout rate of therapist participants. CONCLUSIONS: Findings from this preliminary pilot study support the use of IPT online training, which could increase access to evidence-based ED treatment and improve patient care. PUBLIC SIGNIFICANCE: Lack of accessible therapist training has contributed to many therapists not delivering, and therefore many patients not receiving, evidence-based treatment. This study evaluated a highly disseminable online training and compared outcomes to traditional in-person training and found that training and patient outcomes were not different. Online training has the potential to enhance access to evidence-base care, which could in turn optimize patient outcomes.

'Insight' in medical training: what, why, and how?

The term 'insight' is generically defined in English language as the ability to perceive deeper truths about people and situations. In clinical practice, patient insight is known to have important implications in treatment compliance and clinical outcomes, and can be assessed clinically by looking for the presence of illness awareness, correct attribution of symptoms to underlying condition, and acceptance of treatment. In this article, we suggest that cultivating insight is actually a highly important, yet often overlooked, component of medical training, which may explain why some consistently learn well, communicate effectively, and quickly attain clinical competency, while others struggle throughout their clinical training and may even be difficult to remediate. We herein define 'insight' in the context of medical training as having an astute perception of personal cognitive processes, motivations, emotions, and ability (strengths, weaknesses, and limitations) that should drive self-improvement and effective behavioural regulation. We then describe the utility of cultivating 'insight' in medical training through three lenses of (i) promoting self-regulated, lifelong clinical learning, (ii) improving clinical competencies and person-centred care, and (iii) enhancing physician mental health and well-being. In addition, we review educational pedagogies that are helpful to create a medical eco-system that promotes the cultivation of insight among its trainees and practitioners. Finally, we highlight several tell-tale signs of poor insight and discuss psychological and non-psychological interventions that may help those severely lacking in insight to become more amenable to change and remediation.

Providing family updates: a primer for the medical trainee.

Providing family updates is a common clinical task for medical trainees and practitioners working in hospital settings. Good clinical communication skills are essential in clinical care as it is associated with improved patient satisfaction, understanding of condition, treatment adherence, and better overall clinical outcomes. Moreover, poor communications are often the source of medical complaints. However, while patient-centred communication skills training has generally been incorporated into clinical education, there hitherto remains inadequate training on clinical communications with patients' families, which carry different nuances. In recent years, it is increasingly recognized that familial involvement in the care of hospitalized patients leads to better clinical and psychological outcomes. In fact, in Asian populations with more collectivistic cultures, families are generally highly involved in patient care and decision-making. Therefore, effective clinical communications and regular provision of family updates are essential to build therapeutic rapport, facilitate familial involvement in patient care, and also provide a more holistic understanding of the patient's background and psychosocial set-up. In this article, we herein describe a seven-step understand the clinical context, gather perspectives, deliver medical information, address questions, concerns and expectations, provide tentative plans, demonstrate empathy, postcommunication reflections model as a practical guide for medical trainees and practitioners in provision of structured and effective family updates in their clinical practice.

Study of the

The ^{22}Mg(α,p)^{25}Al reaction rate has been identified as a major source of uncertainty for understanding the nucleosynthesis flow in Type-I x-ray bursts. We report a direct measurement of the energy- and angle-integrated cross sections of this reaction in a 3.3-6.9 MeV center-of-mass energy range using the MUlti-Sampling Ionization Chamber (MUSIC). The new ^{22}Mg(α,p)^{25}Al reaction rate is a factor of ∼4 higher than the previous direct measurement of this reaction within temperatures relevant for x-ray bursts, resulting in the ^{22}Mg waiting point of x-ray burst nucleosynthesis flow to be significantly bypassed via the (α,p) reaction.

Direct Determination of Fission-Barrier Heights Using Light-Ion Transfer in Inverse Kinematics.

We demonstrate a new technique for obtaining fission data for nuclei away from ß stability. These types of data are pertinent to the astrophysical r process, crucial to a complete understanding of the origin of the heavy elements, and for developing a predictive model of fission. These data are also important considerations for terrestrial applications related to power generation and safeguarding. Experimentally, such data are scarce due to the difficulties in producing the actinide targets of interest. The solenoidal-spectrometer technique, commonly used to study nucleon-transfer reactions in inverse kinematics, has been applied to the case of transfer-induced fission as a means to deduce the fission-barrier height, among other variables. The fission-barrier height of ^{239}U has been determined via the ^{238}U(d,pf) reaction in inverse kinematics, the results of which are consistent with existing neutron-induced fission data indicating the validity of the technique.

Identification of traits to improve co-assimilation of glucose and xylose by adaptive evolution of Spathaspora passalidarum and Scheffersomyces stipitis yeasts.

Lignocellulosic biomass is a renewable raw material for producing several high-value-added chemicals and fuels. In general, xylose and glucose are the major sugars in biomass hydrolysates, and their efficient utilization by microorganisms is critical for an economical production process. Yeasts capable of co-consuming mixed sugars might lead to higher yields and productivities in industrial fermentation processes. Herein, we performed adaptive evolution assays with two xylose-fermenting yeasts, Spathaspora passalidarum and Scheffersomyces stipitis, to obtain derived clones with improved capabilities of glucose and xylose co-consumption. Adapted strains were obtained after successive growth selection using xylose and the non-metabolized glucose analog 2-deoxy-D-glucose as a selective pressure. The co-fermentation capacity of evolved and parental strains was evaluated on xylose-glucose mixtures. Our results revealed an improved co-assimilation capability by the evolved strains; however, xylose and glucose consumption were observed at slower rates than the parental yeasts. Genome resequencing of the evolved strains revealed genes affected by non-synonymous variants that might be involved with the co-consumption phenotype, including the HXT2.4 gene that encodes a putative glucose transporter in Sp. passalidarum. Expression of this mutant HXT2.4 in Saccharomyces cerevisiae improved the cells' co-assimilation of glucose and xylose. Therefore, our results demonstrated the successful improvement of co-fermentation through evolutionary engineering and the identification of potential targets for further genetic engineering of different yeast strains. KEY POINTS: • Laboratory evolution assay was used to obtain improved sugar co-consumption of non-Saccharomyces strains. • Evolved Sp. passalidarum and Sc. stipitis were able to more efficiently co-ferment glucose and xylose. • A mutant Hxt2.4 permease, which co-transports xylose and glucose, was identified.

Links between the timing of life-history transitions and dietary and morphological variation during early life history in the sand goby, Pomatoschistus minutus.

Bipartite life histories involve a suite of morphological changes that support the pelagic to demersal transition and an expanded range of prey options and microhabitats. Pelagic individuals are thought to shift (settle) to their preferred benthic habitat at the earliest opportunity once they have attained a minimum level of morphological competency to access their new environment. In theory, early changes in larval morphology (collectively termed 'metamorphosis'), habitat and diet-a measure of habitat-use-ought to be synchronous. Yet relationships may be decoupled by factors linked to behaviour, prey availability or morphological complexity, and few descriptions exist to allow such synchrony to be assessed. The sand goby, Pomatoschistus minutus, is a common coastal fish across north-western Europe, with a size at larval metamorphosis and settlement of around 10 and 16-18 mm standard length (SL), respectively. We sampled shoreline larval and juvenile populations to examine relationships between morphology, diet and life stage. Prey diversity increased with body length; however, dietary change was clearest at 16-18 mm SL, with a reduction in calanoid copepods and shift to larger prey such as Nereis polychaetes and mysid and amphipod crustacea. Early growth in five prey capture and processing morphologies was rapid. Four of these showed a subsequent marked shift to slower growth, but none of these changes were aligned with size at metamorphosis and only that of mouth width coincided with body size at settlement. Early life history in P. minutus appears geared towards a protracted morphological reorganization prior to demersal life and an alternative suite of prey resources. Larval metamorphosis seems to be of limited consequence in this regard. Comparable studies of other Baltic Sea fishes would confirm whether these dynamics relate to shared environmental pressures or to factors intrinsic to P. minutus biology.

Quenching of Single-Particle Strength in A=15 Nuclei.

Absolute cross sections for the addition of s- and d-wave neutrons to ^{14}C and ^{14}N have been determined simultaneously via the (d,p) reaction at 10 MeV/u. The difference between the neutron and proton separation energies, ΔS, is around -20 MeV for the ^{14}C+n system and +8 MeV for ^{14}N+n. The population of the 1s_{1/2} and 0d_{5/2} orbitals for both systems is reduced by a factor of approximately 0.5 compared with the independent single-particle model, or about 0.6 when compared with the shell model. This finding strongly contrasts with results deduced from intermediate-energy knockout reactions between similar nuclei on targets of ^{9}Be and ^{12}C. The simultaneous technique used removes many systematic uncertainties.

Assessing the quality of cardiac rehabilitation programs by measuring adherence to the Australian quality indicators.

BACKGROUND: Every year, over 65,000 Australians experience an acute coronary syndrome (ACS) and around one-third occur in people with prior coronary heart disease. Cardiac rehabilitation (CR) aims to prevent a repeat ACS by supporting patients' return to an active and fulfilling lifestyle. CR programs are efficacious, but audits of clinical practice show variability of program delivery, which may compromise patient outcomes. Core components, quality indicators and accreditation of programs have been introduced internationally to increase program standardisation. With Australian quality indicators (QIs) for cardiac rehabilitation recently introduced, we aimed to conduct a survey in one state of Australia to assess the extent to which programs adhere to the measurement of QIs comparing country, metropolitan, telephone and face to face programs. METHODS: A cross- sectional survey design with face validity testing was used to formulate questions to evaluate cardiac rehabilitation program and personnel characteristics and QI adherence. Between October 2020- December 2021, 23 cardiac rehabilitation programs across country and metropolitan areas were invited to participate. Quality improvement was defined as adherence to the Australian Quality Indicators, and we developed an objective score to calculate program performance categorised by quartiles. Significance of CR completion and time to enrolment between program type (telephone versus face to face) and location (country versus metropolitan were compared using Pearson's Chi-square and Mann-Whitney U tests. RESULTS: Among the 23 CR programs, 15 were country and 8 metropolitan-based and 22 were face to face and 1 telephone-based. Median wait time from discharge was 27.0 days, (interquartile range 19.3-46.0) across all programs and country completions of enrolled were 76.9% versus metropolitan 56.5%, p < 0.001 and telephone versus face to face 92.9% versus 59.6% p < 0.001. Pre-program QI adherence was higher than post program for depression, medication adherence, health-related quality of life and comprehensive re-assessment. Seventy four percent of programs were ranked at a medium level of performance (mean score: 11.4/16, SD ± 0.79). CONCLUSIONS: A survey of 23 cardiac rehabilitation programs, showed variability in adherence to measurement of the Australian Cardiovascular and Rehabilitation Association and Australian Heart Foundation Cardiac Rehabilitation Quality Indicators. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR), ACTRN12621000222842 , registered 03/03/2021.

Laparoscopic and open liver resection for hepatocellular carcinoma with Child-Pugh B cirrhosis: multicentre propensity score-matched study.

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

Search for Nova Presolar Grains: γ-Ray Spectroscopy of

The discovery of presolar grains in primitive meteorites has initiated a new era of research in the study of stellar nucleosynthesis. However, the accurate classification of presolar grains as being of specific stellar origins is particularly challenging. Recently, it has been suggested that sulfur isotopic abundances may hold the key to definitively identifying presolar grains with being of nova origins and, in this regard, the astrophysical ^{33}Cl(p,γ)^{34}Ar reaction is expected to play a decisive role. As such, we have performed a detailed γ-ray spectroscopy study of ^{34}Ar. Excitation energies have been measured with high precision and spin-parity assignments for resonant states, located above the proton threshold in ^{34}Ar, have been made for the first time. Uncertainties in the ^{33}Cl(p,γ) reaction have been dramatically reduced and the results indicate that a newly identified ℓ=0 resonance at E_{r}=396.9(13) keV dominates the entire rate for T=0.25-0.40 GK. Furthermore, nova hydrodynamic simulations based on the present work indicate an ejected ^{32}S/^{33}S abundance ratio distinctive from type-II supernovae and potentially compatible with recent measurements of a presolar grain.

Assessment of subpatent Plasmodium infection in northwestern Ethiopia.

BACKGROUND: Ethiopia has set a goal for malaria elimination by 2030. Low parasite density infections may go undetected by conventional diagnostic methods (microscopy and rapid diagnostic tests) and their contribution to malaria transmission varies by transmission settings. This study quantified the burden of subpatent infections from samples collected from three regions of northwest Ethiopia. METHODS: Sub-samples of dried blood spots from the Ethiopian Malaria Indicator Survey 2015 (EMIS-2015) were tested and compared using microscopy, rapid diagnostic tests (RDTs), and nested polymerase chain reaction (nPCR) to determine the prevalence of subpatent infection. Paired seroprevalence results previously reported along with gender, age, and elevation of residence were explored as risk factors for Plasmodium infection. RESULTS: Of the 2608 samples collected, the highest positive rate for Plasmodium infection was found with nPCR 3.3% (95% CI 2.7-4.1) compared with RDT 2.8% (95% CI 2.2-3.5) and microscopy 1.2% (95% CI 0.8-1.7). Of the nPCR positive cases, Plasmodium falciparum accounted for 3.1% (95% CI 2.5-3.8), Plasmodium vivax 0.4% (95% CI 0.2-0.7), mixed P. falciparum and P. vivax 0.1% (95% CI 0.0-0.4), and mixed P. falciparum and Plasmodium malariae 0.1% (95% CI 0.0-0.3). nPCR detected an additional 30 samples that had not been detected by conventional methods. The majority of the nPCR positive cases (61% (53/87)) were from the Benishangul-Gumuz Region. Malaria seropositivity had significant association with nPCR positivity [adjusted OR 10.0 (95% CI 3.2-29.4), P < 0.001]. CONCLUSION: Using nPCR the detection rate of malaria parasites increased by nearly threefold over rates based on microscopy in samples collected during a national cross-sectional survey in 2015 in Ethiopia. Such subpatent infections might contribute to malaria transmission. In addition to strengthening routine surveillance systems, malaria programmes may need to consider low-density, subpatent infections in order to accelerate malaria elimination efforts.

Social isolation and loneliness of UK veterans: a Delphi study.

BACKGROUND: Evidence increasingly acknowledges the impact of social isolation and loneliness on the lives of military veterans and the wider Armed Forces Community. AIMS: The study gathered expert consensus to (i) understand if veterans are considered 'unique' in their experiences of social isolation and loneliness; (ii) examine perceived factors leading to social isolation and loneliness of veterans; (iii) identify ways to tackle veterans' social isolation and loneliness. METHODS: This study adopted a three-phase Delphi method. Phase 1 utilized a qualitative approach and Phase 2 and Phase 3 utilized a mixed-methods approach. RESULTS: Several outcomes were identified across the three phases. Transition out of the military was viewed as a period to build emotional resilience and raise awareness of relevant services. It was also concluded that veterans would benefit from integrating into services within the wider community, and that social prescribing services could be a vehicle to link veterans to relevant services. Furthermore, access to, and the content of, programmes was also of importance. CONCLUSIONS: These findings illustrate various important interventional aspects to consider when funding and implementing programmes focussed on tackling social isolation and loneliness.

Xylitol production on sugarcane biomass hydrolysate by newly identified Candida tropicalis JA2 strain.

Xylitol is a building block for a variety of chemical commodities, besides being widely used as a sugar substitute in the food and pharmaceutical industries. The aim of this work was to develop a microbial process for xylitol production using sugarcane bagasse hydrolysate as substrate. In this context, 218 non-Saccharomyces yeast strains were screened by growth on steam-exploded sugarcane bagasse hydrolysate containing a high concentration of acetic acid (8.0 g/L). Seven new Candida tropicalis strains were selected and identified, and their ability to produce xylitol on hydrolysate at low pH (4.6) under aerobic conditions was evaluated. The most efficient strain, designated C. tropicalis JA2, was capable of producing xylitol with a yield of 0.47 g/g of consumed xylose. To improve xylitol production by C. tropicalis JA2, a series of experimental procedures were employed to optimize pH and temperature conditions, as well as nutrient source, and initial xylose and inoculum concentrations. C. tropicalis JA2 was able to produce 109.5 g/L of xylitol with a yield of 0.86 g/g of consumed xylose, and with a productivity of 2.81 g·L·h, on sugarcane bagasse hydrolysate containing 8.0 g/L acetic acid and177 g/L xylose, supplemented with 2.0 g/L yeast nitrogen base and 4.0 g/L urea. Thus, it was possible to identify a new C. tropicalis strain and to optimize the xylitol production process using sugarcane bagasse hydrolysate as a substrate. The xylitol yield on biomass hydrolysate containing a high concentration of acetic acidobtained in here is among the best reported in the literature.

Key

Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the ß^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.

Environmental and meteorological factors linked to malaria transmission around large dams at three ecological settings in Ethiopia.

BACKGROUND: A growing body of evidence suggests that dams intensify malaria transmission in sub-Saharan Africa. However, the environmental characteristics underpinning patterns in malaria transmission around dams are poorly understood. This study investigated local-scale environmental and meteorological variables linked to malaria transmission around three large dams in Ethiopia. METHODS: Monthly malaria incidence data (2010-2014) were collected from health centres around three dams located at lowland, midland and highland elevations in Ethiopia. Environmental (elevation, distance from the reservoir shoreline, Normalized Difference Vegetation Index (NDVI), monthly reservoir water level, monthly changes in water level) and meteorological (precipitation, and minimum and maximum air temperature) data were analysed to determine their relationship with monthly malaria transmission at each dam using correlation and stepwise multiple regression analysis. RESULTS: Village distance to reservoir shoreline (lagged by 1 and 2 months) and monthly change in water level (lagged by 1 month) were significantly correlated with malaria incidence at all three dams, while NDVI (lagged by 1 and 2 months) and monthly reservoir water level (lagged by 2 months) were found to have a significant influence at only the lowland and midland dams. Precipitation (lagged by 1 and 2 months) was also significantly associated with malaria incidence, but only at the lowland dam, while minimum and maximum air temperatures (lagged by 1 and 2 months) were important factors at only the highland dam. CONCLUSION: This study confirmed that reservoir-associated factors (distance from reservoir shoreline, monthly average reservoir water level, monthly water level change) were important predictors of increased malaria incidence in villages around Ethiopian dams in all elevation settings. Reservoir water level management should be considered as an additional malaria vector control tool to help manage malaria transmission around dams.

Multiplex serology demonstrate cumulative prevalence and spatial distribution of malaria in Ethiopia.

BACKGROUND: Measures of malaria burden using microscopy and rapid diagnostic tests (RDTs) in cross-sectional household surveys may incompletely describe the burden of malaria in low-transmission settings. This study describes the pattern of malaria transmission in Ethiopia using serological antibody estimates derived from a nationwide household survey completed in 2015. METHODS: Dried blood spot (DBS) samples were collected during the Ethiopian Malaria Indicator Survey in 2015 from malarious areas across Ethiopia. Samples were analysed using bead-based multiplex assays for IgG antibodies for six Plasmodium antigens: four human malaria species-specific merozoite surface protein-1 19kD antigens (MSP-1) and Apical Membrane Antigen-1 (AMA-1) for Plasmodium falciparum and Plasmodium vivax. Seroprevalence was estimated by age, elevation and region. The seroconversion rate was estimated using a reversible catalytic model fitted with maximum likelihood methods. RESULTS: Of the 10,278 DBS samples available, 93.6% (9622/10,278) had valid serological results. The mean age of participants was 15.8 years and 53.3% were female. National seroprevalence for antibodies to P. falciparum was 32.1% (95% confidence interval (CI) 29.8-34.4) and 25.0% (95% CI 22.7-27.3) to P. vivax. Estimated seroprevalences for Plasmodium malariae and Plasmodium ovale were 8.6% (95% CI 7.6-9.7) and 3.1% (95% CI 2.5-3.8), respectively. For P. falciparum seroprevalence estimates were significantly higher at lower elevations (< 2000 m) compared to higher (2000-2500 m) (aOR 4.4; p < 0.01). Among regions, P. falciparum seroprevalence ranged from 11.0% (95% CI 8.8-13.7) in Somali to 65.0% (95% CI 58.0-71.4) in Gambela Region and for P. vivax from 4.0% (95% CI 2.6-6.2) in Somali to 36.7% (95% CI 30.0-44.1) in Amhara Region. Models fitted to measure seroconversion rates showed variation nationally and by elevation, region, antigen type, and within species. CONCLUSION: Using multiplex serology assays, this study explored the cumulative malaria burden and regional dynamics of the four human malarias in Ethiopia. High malaria burden was observed in the northwest compared to the east. High transmission in the Gambela and Benishangul-Gumuz Regions and the neglected presence of P. malariae and P. ovale may require programmatic attention. The use of a multiplex assay for antibody detection in low transmission settings has the potential to act as a more sensitive biomarker.