A cross-sectional study investigating malaria prevalence and associated predictors of infection among migrants to a newly established gold mining settlement in the Gambella Region of Ethiopia.

BACKGROUND: Malaria is a major disease burden in Ethiopia. Migration can influence malaria transmission dynamics, with individuals relocating from malaria-free highland regions to malarious lowlands potentially facing elevated risks of contracting malaria. Migrants may find it difficult to protect themselves against malaria and have limited access to diagnosis or treatment. Settlers in gold mining sites are one type of migrant and are often neglected in malaria research yet may have particularly high malaria risk. This study was a malaria prevalence survey among settlers in a new gold mining settlement in the highly malarious Gambella Region, Ethiopia. METHODS: n = 590 people were surveyed for demographic information and their knowledge and practices of malaria. Participants were tested for malaria using rapid diagnostic tests and microscopy. Using logistic regressions, the influence of demographic characteristics on malaria infections and bed net access were analysed. A sub-sample of participants was interviewed to comprehend settlement living conditions and healthcare accessibility. RESULTS: The overall prevalence of Plasmodium falciparum was 37.5% (CI 32.4-42.3%). Young children were most likely to have malaria, with individuals aged 15-24 having 67% lower odds (aOR: 0.33; CI 0.13-0.86) of infection compared to those aged 1-4 years old. Meanwhile, those age 25-plus had 75% decreased odds of malaria infection (aOR 0.25; CI 0.10-0.65). Individuals with bed nets had ~ 50% decreased odds of testing positive for falciparum malaria than those reporting having no bed net (aOR: 0.47; CI 0.22-0.97). Individuals who relocated from low elevation with high malaria test positivity rate areas were more prone to testing positive for malaria, as were those residing in densely populated households with multiple malaria cases. Conversely, individuals from higher elevations with low malaria test positivity rates, and those living in households with 5-10 occupants and < 2 malaria infections, were more likely to possess bed nets. CONCLUSIONS: This gold mining settlement provides an example of an oft-neglected atypical community where malaria is a significant, but under-addressed, health problem. Within this community, future interventions focused on distributing bed nets, particularly to larger households and those with children, have great potential to alleviate the malaria burden. Efforts should also be made to provide affordable, and accessible, early diagnosis and treatment.

Ecological study measuring the association between conflict, environmental factors, and annual global cutaneous and mucocutaneous leishmaniasis incidence (2005-2022).

BACKGROUND: Cutaneous and mucocutaneous leishmaniasis (CL/ML) cause significant morbidity globally and are vulnerable to changes from environmental events and conflict. In this ecological study, we aim to measure the associations between annual CL/ML cases, conflict intensity, and environmental factors between 2005 and 2022 globally. METHODS: We pulled annual case data from the WHO for 52 nations that had conflict intensity scores (ranging from 1-10) from the Bertelsmann Transformation Index. Using Earth observation tools, we gathered temperature, precipitation, vegetation, and humidity data, in addition to data on annual estimates of population, internal displacement, and GDP. We fit a negative binomial generalized additive model with a random nation-level intercept. RESULTS: Conflict was positively associated with increased CL/ML across the studied nations (IRR: 1.09, 95% CI: 1.01-1.16, p = 0.02). Given this, intense conflict (a score of ten) was associated with over double the risk of CL/ML compared to the lowest conflict levels (score of one). We also identified a curvilinear relationship between mean temperature and cases, as well as between vegetation level and cases. Each had small pockets of significant increased and decreased risk, respectively. Larger mean humidity ranges were negatively associated with cases. Importantly, the relationship between conflict intensity and cases was mediated by displacement. DISCUSSION: Conflict is significantly associated with increased CL/ML cases. This is especially true at higher conflict levels, marking when conflict turns violent. The destruction of critical infrastructure (e.g., that related to healthcare, water, and sanitation) often seen during conflict could drive this association. Such environments can be hospitable to sandflies and can heighten individuals' vulnerability through increased malnutrition, poverty, and displacement. Understanding this relationship is crucial for public health preparedness and response, especially as conflicts become increasingly violent and protracted.

Climate, demography, immunology, and virology combine to drive two decades of dengue virus dynamics in Cambodia.

The incidence of dengue virus disease has increased globally across the past half-century, with highest number of cases ever reported in 2019 and again in 2023. We analyzed climatological, epidemiological, and phylogenomic data to investigate drivers of two decades of dengue in Cambodia, an understudied endemic setting. Using epidemiological models fit to a 19-y dataset, we first demonstrate that climate-driven transmission alone is insufficient to explain three epidemics across the time series. We then use wavelet decomposition to highlight enhanced annual and multiannual synchronicity in dengue cycles between provinces in epidemic years, suggesting a role for climate in homogenizing dynamics across space and time. Assuming reported cases correspond to symptomatic secondary infections, we next use an age-structured catalytic model to estimate a declining force of infection for dengue through time, which elevates the mean age of reported cases in Cambodia. Reported cases in >70-y-old individuals in the 2019 epidemic are best explained when also allowing for waning multitypic immunity and repeat symptomatic infections in older patients. We support this work with phylogenetic analysis of 192 dengue virus (DENV) genomes that we sequenced between 2019 and 2022, which document emergence of DENV-2 Cosmopolitan Genotype-II into Cambodia. This lineage demonstrates phylogenetic homogeneity across wide geographic areas, consistent with invasion behavior and in contrast to high phylogenetic diversity exhibited by endemic DENV-1. Finally, we simulate an age-structured, mechanistic model of dengue dynamics to demonstrate how expansion of an antigenically distinct lineage that evades preexisting multitypic immunity effectively reproduces the older-age infections witnessed in our data.

Semiparametric inference of effective reproduction number dynamics from wastewater pathogen surveillance data.

Concentrations of pathogen genomes measured in wastewater have recently become available as a new data source to use when modeling the spread of infectious diseases. One promising use for this data source is inference of the effective reproduction number, the average number of individuals a newly infected person will infect. We propose a model where new infections arrive according to a time-varying immigration rate which can be interpreted as an average number of secondary infections produced by one infectious individual per unit time. This model allows us to estimate the effective reproduction number from concentrations of pathogen genomes, while avoiding difficulty to verify assumptions about the dynamics of the susceptible population. As a byproduct of our primary goal, we also produce a new model for estimating the effective reproduction number from case data using the same framework. We test this modeling framework in an agent-based simulation study with a realistic data generating mechanism which accounts for the time-varying dynamics of pathogen shedding. Finally, we apply our new model to estimating the effective reproduction number of SARS-CoV-2, the causative agent of COVID-19, in Los Angeles, CA, using pathogen RNA concentrations collected from a large wastewater treatment facility.

Characterisation of Fe Distribution in the Liquid-Solid Boundary of Al-Zn-Mg-Si Alloy Using Synchrotron X-ray Fluorescence Microscopy.

Al-Zn-Mg-Si alloy coatings have been developed to inhibit the corrosion of cold-rolled steel sheets by offering galvanic and barrier protection to the substrate steel. It is known that Fe deposited from the steel strip modifies the microstructure of the alloy. We cast samples of Al-Zn-Mg-Si coating alloys containing 0.4 wt% Fe and directionally solidified them using a Bridgman furnace to quantify the effect of this Fe addition between 600 °C and 240 °C. By applying a temperature gradient, growth is encouraged, and by then quenching the sample in coolant, the microstructure may be frozen. These samples were analysed using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) to determine the morphological effects of the Fe distribution across the experimental temperature range. However, due to the sub 1 wt% concentration of Fe, synchrotron X-ray fluorescence microscopy (XFM) was applied to quantitatively confirm the Fe distribution. Directionally solidified samples were scanned at 7.05 keV and 18.5 keV using X-ray fluorescence at the Australian Synchrotron using the Maia array detector. It was found that a mass nucleation event of the Fe-based τ6 phase occurred at 495 °C following the nucleation of the primary α-Al phase as a result of a peritectic reaction with remaining liquid.

Speak Up: How Hearing Loss and the Lack of Hearing Aids Affect Conversations in Quiet.

PURPOSE: The study examines the effect of hearing loss and hearing aid (HA) amplification on the conversational dynamics between hearing-impaired (HI) and normal-hearing (NH) interlocutors. Combining data from the current and a prior study, we explore how the speech levels of both interlocutors correlate and relate to HI interlocutors' degree of hearing loss. METHOD: Sixteen pairs of younger NH and elderly HI interlocutors conversed in quiet, with the HI interlocutor either unaided or wearing HAs. We analyzed the effect of hearing status and HA amplification on the conversational dynamics, including turn-taking times (floor-transfer offsets), utterance lengths, and speech levels. Furthermore, we conducted an in-depth analysis of the speech levels using combined data sets from the current and previously published data by Petersen, MacDonald, and Sørensen (2022). RESULTS: Unaided HI interlocutors were slower and more variable at timing their turns, but wearing HAs reduced the differences between the HI and NH interlocutors. Conversations were less interactive, and pairs were slower at solving the conversational tasks when the HI interlocutor was unaided. Both interlocutors spoke louder when the HI interlocutor was unaided. The speech level of the NH interlocutors was related to that of the HI interlocutors, with the HI speech levels also correlating with their own degree of hearing loss. CONCLUSIONS: Despite typically being unchallenging for HI individuals, one-on-one conversations in quiet were impacted by the HI interlocutor not wearing HAs. Additionally, combining data sets revealed that NH interlocutors adjusted their speech level to match that of HI interlocutors.

The efficacy of custom-made offloading devices for diabetic foot ulcer prevention: a systematic review.

INTRODUCTION: Therapeutic offloading devices, including insoles, shoes, and other orthoses, are some of the most commonly used interventions to treat or prevent diabetic foot ulceration. Custom-made offloading devices are increasingly used to offset the development of foot ulcers. However, whether these devices are more effective than prefabricated standard offloading devices is uncertain. Therefore, this systematic review collates and examines evidence on the efficacy of custom-made offloading devices in preventing foot ulcer incidence and recurrence in people diagnosed with diabetes. METHODS: Five scientific databases were searched, covering 2011-2023. Initial searches and screening were carried out independently by two researchers. Studies meeting the inclusion criteria were further examined through additional screenings, and critical appraisal. Data relevant to the review aims were extracted and analysed within a narrative synthesis. RESULTS: Of the 1,715 articles found in the initial searches, nine papers were found to meet inclusion criteria and were included in the review. The evidence shows that custom-made offloading devices are likely to be more effective for reducing or preventing diabetic foot ulcers than standard offloading devices. However, due to a lack of data it remains uncertain whether custom-made offloading devices are more cost-effective for preventing ulceration compared to standard insoles. Likewise, due to measurement heterogeneity between studies and lack of data, it is unclear whether adherence is higher in users of custom-made offloading devices, and whether such devices deliver significantly greater reductions in peak pressure as compared to standard offloading devices. CONCLUSION: Custom-made offloading devices are more effective than standard devices for preventing diabetic foot ulceration, and we recommended their use when feasible; however, there remains uncertainty regarding their cost-effectiveness compared to standard insoles and offloading devices.

Effectiveness, Safety, and Acceptability of Primaquine Mass Drug Administration in Low-Endemicity Areas in Southern Thailand: Proof-of-Concept Study.

BACKGROUND: A challenge in achieving the malaria-elimination target in the Greater Mekong Subregion, including Thailand, is the predominance of Plasmodium vivax malaria, which has shown extreme resilience to control measures. OBJECTIVE: This proof-of-concept study aimed to provide evidence for implementing primaquine mass drug administration (pMDA) as a strategy for P. vivax elimination in low-endemicity settings. METHODS: The study employed a mixed-methods trial to thoroughly evaluate the effectiveness, safety, acceptability, and community engagement of pMDA. The quantitative part was designed as a 2-period cluster-crossover randomized controlled trial. The intervention was pMDA augmented to the national prevention and control standards with directly observed treatment (DOT) by village health volunteers. The qualitative part employed in-depth interviews and brainstorming discussions. The study involved 7 clusters in 2 districts of 2 southern provinces in Thailand with persistently low P. vivax transmission. In the quantitative part, 5 cross-sectional blood surveys were conducted in both the pMDA and control groups before and 3 months after pMDA. The effectiveness of pMDA was determined by comparing the proportions of P. vivax infections per 1000 population between the 2 groups, with a multilevel zero-inflated negative binomial model adjusted for cluster and time as covariates and the interaction. The safety data comprised adverse events after drug administration. Thematic content analysis was used to assess the acceptability and engagement of stakeholders. RESULTS: In the pre-pMDA period, the proportions of P. vivax infections in the pMDA (n=1536) and control (n=1577) groups were 13.0 (95% CI 8.2-20.4) and 12.0 (95% CI 7.5-19.1), respectively. At month 3 post-pMDA, these proportions in the pMDA (n=1430) and control (n=1420) groups were 8.4 (95% CI 4.6-15.1) and 5.6 (95% CI 2.6-11.5), respectively. No statistically significant differences were found between the groups. The number of malaria cases reduced in all clusters in both groups, and thus, the impact of pMDA was inconclusive. There were no major safety concerns. Acceptance among the study participants and public health care providers at local and national levels was high, and they believed that pMDA had boosted awareness in the community. CONCLUSIONS: pMDA was associated with high adherence, safety, and tolerability, but it may not significantly impact P. vivax transmission. As this was a proof-of-concept study, we decided not to scale up the intervention with larger clusters and samples. An alternative approach involving a targeted primaquine treatment strategy with primaquine and DOT is currently being implemented. We experienced success regarding effective health care workforces at point-of-care centers, effective collaborations in the community, and commitment from authorities at local and national levels. Our efforts boosted the acceptability of the malaria-elimination initiative. Community engagement is recommended to achieve elimination targets. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20190806004; https://www.thaiclinicaltrials.org/show/TCTR20190806004.

Semiparametric inference of effective reproduction number dynamics from wastewater pathogen surveillance data.

Concentrations of pathogen genomes measured in wastewater have recently become available as a new data source to use when modeling the spread of infectious diseases. One promising use for this data source is inference of the effective reproduction number, the average number of individuals a newly infected person will infect. We propose a model where new infections arrive according to a time-varying immigration rate which can be interpreted as an average number of secondary infections produced by one infectious individual per unit time. This model allows us to estimate the effective reproduction number from concentrations of pathogen genomes while avoiding difficult to verify assumptions about the dynamics of the susceptible population. As a byproduct of our primary goal, we also produce a new model for estimating the effective reproduction number from case data using the same framework. We test this modeling framework in an agent-based simulation study with a realistic data generating mechanism which accounts for the time-varying dynamics of pathogen shedding. Finally, we apply our new model to estimating the effective reproduction number of SARS-CoV-2 in Los Angeles, California, using pathogen RNA concentrations collected from a large wastewater treatment facility.

Urine Biopsy as Dynamic Biomarker to Enhance Clinical Staging of Bladder Cancer in Radical Cystectomy Candidates.

PURPOSE: There is significant interest in identifying complete responders to neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) to potentially avoid removal of a pathologically benign bladder. However, clinical restaging after NAC is highly inaccurate. The objective of this study was to develop a next-generation sequencing-based molecular assay using urine to enhance clinical staging of patients with bladder cancer. METHODS: Urine samples from 20 and 44 patients with bladder cancer undergoing RC were prospectively collected for retrospective analysis for molecular correlate analysis from two clinical trials, respectively. The first cohort was used to benchmark the assay, and the second was used to determine the performance characteristics of the test as it correlates to responder status as measured by pathologic examination. RESULTS: First, to benchmark the assay, known mutations identified in the tissue (MT) of patients from the Accelerated Methotrexate, Vinblastine, Doxorubicin, Cisplatin trial (ClinicalTrials.gov identifier: NCT01611662, n = 16) and a cohort from University of California-San Francisco (n = 4) were cross referenced against mutation profiles from urine (MU). We then determined the correlation between MU persistence and residual disease in pre-RC urine samples from a second prospective clinical trial (The pT0 trial; ClinicalTrials.gov identifier: NCT02968732). Residual MU status correlated strongly with residual disease status (pT0 trial; n = 44; P = .0092) when MU from urine supernatant and urine pellet were assessed separately and analyzed in tandem. The sensitivity, specificity, PPV, and NPV were 91%, 50%, 86%, and 63% respectively, with an overall accuracy of 82% for this second cohort. CONCLUSION: MU are representative of MT and thus can be used to enhance clinical staging of urothelial carcinoma. Urine biopsy may be used as a reliable tool that can be further developed to identify complete response to NAC in anticipation of safe RC avoidance.

Aqueous and Plasma Levels of Phosphorylated Tau 181 in Individuals with Normal Cognition.

Background: Plasma and cerebrospinal fluid (CSF) levels of p-tau181 have been associated with Alzheimer's disease (AD). The retina and vitreous have shown measurable quantities of phosphorylated tau 181 (p-tau181). The aqueous humor, which can be collected during cataract surgery, may have measurable concentrations of p-tau181. Objective: To determine whether p-tau181 is detectable in the aqueous humor and if so, whether it is associated with other measures that might be consistent with AD such as higher plasma p-tau181 concentration and lower Montreal Cognitive Assessment (MoCA-BLIND version 7.1) score. Methods: Aqueous humor samples, blood samples, and MoCA-BLIND scores were collected from patients who did not carry a clinical diagnosis of cognitive impairment at the time of cataract surgery. Aqueous p-tau181 concentrations and plasma p-tau181 concentrations were then measured using ultra-sensitive single-molecule assay ELISA technology. A rank-transformed mixed-effects multivariate regression model was used to determine associations between aqueous concentrations, plasma concentrations, and MoCA-BLIND scores. Results: 16 eyes of 16 participants were enrolled with an average age of 71.6. Average MoCA-BLIND score was 20.6/22, average aqueous p-tau181 concentration was 6.4 pg/mL, and average plasma p-tau181 concentration was 3.1 pg/mL. Higher plasma p-tau181 was significantly associated with higher aqueous p-tau181 (p = 0.02). Aqueous p-tau181 and plasma p-tau181 were negatively associated with MoCA-BLIND scores (p = 0.005 and p = 0.001 respectively) in these patients. Conclusions: Aqueous p-tau181 is positively correlated with plasma p-tau181 and is negatively correlated with MoCA-BLIND scores. Further study in individuals with mild cognitive impairment or AD characterized by cerebrospinal fluid and volumetric MRI metrics may yield further insights.

Molecular markers of artemisinin resistance during falciparum malaria elimination in Eastern Myanmar.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. CONCLUSION: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance.

LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes.

BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.METHODSMonocyte mRNA expression of 11 CMTN genes was quantified among 934 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of prediabetes/T2D; cellular cholesterol was measured in a subset of 24 monocyte samples.RESULTSDuring a median 6-year follow-up, lower expression of 3 highly correlated LXR target genes - ABCG1 and ABCA1 (cholesterol efflux) and MYLIP (cholesterol uptake suppression) - and not other CMTN genes, was significantly associated with higher risk of incident prediabetes/T2D. Lower expression of the LXR target genes correlated with higher cellular cholesterol levels (e.g., 47% of variance in cellular total cholesterol explained by ABCG1 expression). Further, adding the LXR target genes to overweight/obesity and other known predictors significantly improved prediction of incident prediabetes/T2D.CONCLUSIONThese data suggest that the aberrant LXR/ABCG1-ABCA1-MYLIP pathway (LAAMP) is a major T2D risk factor and support a potential role for aberrant LAAMP and cellular cholesterol accumulation in diabetogenesis.FUNDINGThe MESA Epigenomics and Transcriptomics Studies were funded by NIH grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by funding from NIDDK R01DK103531 and NHLBI R01HL119962.

Latched detection of zeptojoule spin echoes with a kinetic inductance parametric oscillator.

When strongly pumped at twice their resonant frequency, nonlinear resonators develop a high-amplitude intracavity field, a phenomenon known as parametric self-oscillations. The boundary over which this instability occurs can be extremely sharp and thereby presents an opportunity for realizing a detector. Here, we operate such a device based on a superconducting microwave resonator whose nonlinearity is engineered from kinetic inductance. The device indicates the absorption of low-power microwave wavepackets by transitioning to a self-oscillating state. Using calibrated pulses, we measure the detection efficiency to zeptojoule energy wavepackets. We then apply it to measurements of electron spin resonance, using an ensemble of 209Bi donors in silicon that are inductively coupled to the resonator. We achieve a latched readout of the spin signal with an amplitude that is five hundred times greater than the underlying spin echoes.

Anti-CMV IgG Seropositivity is Associated with Plasma Biomarker Evidence of Amyloid-ß Accumulation.

Background: Some human studies have identified infection with cytomegalovirus (CMV), a member of the alpha herpesvirus family, as a risk factor for Alzheimer's disease and related dementias (ADRD). To our knowledge, no studies have evaluated associations of CMV seropositivity with plasma biomarkers of ADRD risk in middle-aged adults. Objective: In participants recruited for an exercise study, we evaluated cross-sectional associations of CMV seropositivity with: Aß42/Aß40 ratio, a low ratio suggestive of central nervous system Aß accumulation; glial fibrillary acidic protein (GFAP), a measure of neuroinflammation; and neurofilament light (NfL), a measure of neurodegeneration. Methods: Anti-CMV IgG was quantified by ELISA. Plasma ADRD biomarkers were quantified using the ultrasensitive SIMOA assay. We used linear regression to evaluate associations of CMV seropositivity with the ADRD biomarkers, adjusting for age, sex, and race (n = 303; Age = 55.7±9.2 years). For ADRD biomarkers significantly associated with CMV seropositivity, we evaluated continuous associations of anti-CMV IgG levels with the ADRD biomarkers, excluding CMV seronegative participants. Results: 53% of participants were CMV seropositive. CMV seropositivity was associated with a lesser Aß42/Aß40 ratio (ß=-3.02e-03 95% CI [-5.97e-03, -7.18e-05]; p = 0.045). In CMV seropositive participants, greater anti-CMV IgG levels were associated with a lesser Aß42/Aß40 ratio (ß=-4.85e-05 95% CI[-8.45e-05, -1.25e-05]; p = 0.009). CMV seropositivity was not associated with plasma GFAP or NfL in adjusted analyses. Conclusions: CMV seropositivity was associated with a lesser plasma Aß42/Aß40 ratio. This association may be direct and causally related to CMV neuro-cytotoxicity or may be indirect and mediated by inflammatory factors resulting from CMV infection burden and/or the immune response.

Association between air raids and reported incidence of cholera in Yemen, 2016-19: an ecological modelling study.

BACKGROUND: Yemen continues to endure cholera outbreaks during ongoing conflict and destructive environmental events. Air raids have been used throughout the conflict to target military and civilian infrastructure. We aimed to assess the association between air raids and cholera incidence while taking into account geographical, environmental, economic, and demographic factors that drive outbreaks. METHODS: In this ecological modelling study, we used data from Sept 12, 2016, to Dec 29, 2019, for the number of air raids, vegetation coverage, surface water, precipitation, temperature, economic variables, and cholera case and population data to model the association between conflict and the weekly incidence of cholera (per 100 000 people) in Yemen. Data were transformed into weekly intervals and governorates were categorised according to air raid severity (the number of raids in the previous 3 months). We used a negative binomial generalised additive model that accounted for geographical location and environmental, temporal, economic, and demographic variables to estimate incidence rate ratios for the association between air raid severity and cases of cholera. FINDINGS: During the study period, 2 107 912 cases of cholera were reported in Yemen, and a minimum of 11 366 air raids were recorded. After controlling for relevant factors, compared with no air raids, all other levels of air raid severity were significantly associated with cholera incidence. The largest effect was noted in governorates with severe air raid levels (ie, ≥76 during the previous 3 months), which had an incidence rate ratio of 2·06 (95% CI 1·59-2·69; p<0·0001) for cholera compared with governorates with no air raids in the previous 3 months. Economic factors were also significantly associated with increased cholera incidence. INTERPRETATION: Air raids were significantly associated with the burden of cholera in Yemen, even after controlling for other relevant factors. Quantification of this relationship further shows that the cholera outbreak is largely a result of human action rather than a natural occurrence, and demonstrates the conflict's devastating effects on health. Our findings highlight the need for ceasefire and peacebuilding efforts, as well as infrastructure and economic restoration, to reduce Yemen's cholera burden. FUNDING: None. TRANSLATION: For the Arabic translation of the abstract see Supplementary Materials section.

Composite Fermi Liquid at Zero Magnetic Field in Twisted MoTe_{2}.

The pursuit of exotic phases of matter outside of the extreme conditions of a quantizing magnetic field is a long-standing quest of solid state physics. Recent experiments have observed spontaneous valley polarization and fractional Chern insulators in zero magnetic field in twisted bilayers of MoTe_{2}, at partial filling of the topological valence band (ν=-2/3 and -3/5). We study the topological valence band at half filling, using exact diagonalization and density matrix renormalization group calculations. We discover a composite Fermi liquid (CFL) phase even at zero magnetic field that covers a large portion of the phase diagram near twist angle ∼3.6°. The CFL is a non-Fermi liquid phase with metallic behavior despite the absence of Landau quasiparticles. We discuss experimental implications including the competition between the CFL and a Fermi liquid, which can be tuned with a displacement field. The topological valence band has excellent quantum geometry over a wide range of twist angles and a small bandwidth that is, remarkably, reduced by interactions. These key properties stabilize the exotic zero field quantum Hall phases. Finally, we present an optical signature involving "extinguished" optical responses that detects Chern bands with ideal quantum geometry.

Evaluation of in-shoe plantar pressure and shear during walking for diabetic foot ulcer prevention.

OBJECTIVE: To investigate reliability and changes of in-shoe plantar pressure and shear during walking at three cadences with two insole designs. This was a precursor to the investigation of plantar loading in people with diabetes for potential foot ulcer prevention. METHOD: A sensorised insole system, capable of measuring plantar pressure and shear at the heel, fifth metatarsal head (5MH), first metatarsal head (1MH) and hallux, was tested with ten healthy participants during level walking. Reliability was evaluated, using intra-class correlation coefficient (ICC), while varying the cadences and insole types. Percentage changes in pressure and shear relative to values obtained at self-selected cadence with a flat insole design were investigated. RESULTS: Mean±standard deviation of maximum pressure, medial-lateral and anterior-posterior shear of up to 380±24kPa, 46±2kPa and -71±4kPa, respectively, were measured. The ICC in ranges of 0.762-0.973, 0.758-0.987 and 0.800-0.980 were obtained for pressure, anterior-posterior and medial-lateral shear, respectively. Opposite anterior-posterior shear directions between 5MH and 1MH (stretching), and between 1MH and hallux (pinching) were observed for some participants. Increasing cadence increased pressure and anterior-posterior shear (by up to +77%) but reduced medial-lateral shear at the heel and hallux (by up to -34%). Slower cadence increased anterior-posterior shear (+114%) but decreased medial-lateral shear (-46%) at the hallux. The use of a flexible contoured insole resulted in pressure reduction at the heel and 5MH but an increase in anterior-posterior shear at the heel (+69%) and hallux (+75%). CONCLUSION: The insole system demonstrated good reliability and is comparable to reported pressure-only systems. Pressure measurements were sensitive to changes in cadence and insole designs in ways that were consistent with the literature. However, our plantar shear showed localised shear changes with cadences and insoles for the first time, as well as stretching and pinching effects on plantar tissue. This opens new possibilities to investigate plantar tissue viability, loading characteristics and orthotic designs aimed towards foot ulcer prevention.