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BACKGROUND: A major challenge to malaria elimination is identifying and targeting populations that are harbouring residual infections and contributing to persistent transmission. In many near-elimination settings in Southeast Asia, it is known that forest-goers are at higher risk for malaria infection, but detailed information on their behaviours and exposures is not available. METHODS: In Aceh Province, Indonesia, a near-elimination setting where a growing proportion of malaria is due to Plasmodium knowlesi, a case-control study was conducted to identify risk factors for symptomatic malaria, characteristics of forest-goers, and key intervention points. From April 2017 to September 2018, cases and controls were recruited and enrolled in a 1:3 ratio. Cases had confirmed malaria infection by rapid diagnostic test or microscopy detected at a health facility (HF). Gender-matched controls were recruited from passive case detection among individuals with suspected malaria who tested negative at a health facility (HF controls), and community-matched controls were recruited among those testing negative during active case detection. Multivariable logistic regression (unconditional for HF controls and conditional for community controls) was used to identify risk factors for symptomatic malaria infection. RESULTS: There were 45 cases, of which 27 were P. knowlesi, 17 were Plasmodium vivax, and one was not determined. For controls, 509 and 599 participants were recruited from health facilities and the community, respectively. Forest exposures were associated with high odds of malaria; in particular, working and sleeping in the forest (HF controls: adjusted odds ratio (aOR) 21.66, 95% CI 5.09-92.26; community controls: aOR 16.78, 95% CI 2.19-128.7) and having a second residence in the forest (aOR 6.29, 95% CI 2.29-17.31 and 13.53, 95% CI 2.10-87.12). Male forest-goers were a diverse population employed in a variety of occupations including logging, farming, and mining, sleeping in settings, such as huts, tents, and barracks, and working in a wide range of group sizes. Reported use of protective measures, such as nets, hammock nets, mosquito coils, and repellents was low among forest-goers and interventions at forest residences were absent. CONCLUSIONS: Second residences in the forest and gaps in use of protective measures point to key malaria interventions to improve coverage in forest-going populations at risk for P. knowlesi and P. vivax in Aceh, Indonesia. Intensified strategies tailored to specific sub-populations will be essential to achieve elimination.

IntroductionDespite evidence suggesting deleterious effects of cannabis and nicotine tobacco product (NTP) use on white matter integrity, there have been limited studies examining white matter integrity among users of both cannabis and nicotine. Further, updated white matter methodology provides opportunities to investigate use patterns on neurite orientation dispersion and density (NODDI) indices and subtle tissue changes related to the intra- and extra-neurite compartment. We aimed to investigate how cannabis and NTP use among adolescents and young adults interacts to impact the white matter integrity microstructure.Materials and methodsA total of 221 participants between the ages of 16 and 22 completed the Customary Drinking and Drug Use Record (CDDR) to measure substance use, and underwent a magnetic resonance imaging (MRI) session. Participants were divided into NTP-control and NTP groupings and cannabis-control and cannabis groupings (≥26 NTP/cannabis uses in past 6 months). Tract-Based Spatial Statistics (TBSS) and two-way between-subjects ANOVA investigated the effects of NTP use group, cannabis use group, and their interaction on fractional anisotropy (FA) and NODDI indices while controlling for age and biological sex.ResultsNTP use was associated with decreased FA values and increased orientation dispersion in the left anterior capsule. There were no significant effects of cannabis use or the interaction of NTP and cannabis use on white matter outcomes.DiscussionNTP use was associated with altered white matter integrity in an adolescent and young adult sample. Findings suggest that NTP-associated alterations may be linked to altered fiber tract geometry and dispersed neurite structures versus myelination, as well as differential effects of NTP and cannabis use on white matter structure. Future work is needed to investigate how altered white matter is related to downstream behavioral effects from NTP use.

2022 marked the third consecutive La Niña and extended the longest consecutive stretch of negative Oceanic Niño Index since 1998-2001. While physical and biological conditions in winter and spring largely adhered to prior La Niña conditions, summer and fall were very different. Similar to past La Niña events, in winter and spring coastal upwelling was either average or above average, temperature average or below average, salinity generally above average. In summer and fall, however, upwelling and temperature were generally average or slightly below average, salinity was close to average and chlorophyll a was close to average. Again, as during prior La Niña events, biomass of northern/southern copepods was above/below average off Oregon in winter, and body size of North Pacific krill in northern California was above average in winter. By contrast, later in the year the abundance of northern krill dropped off Oregon while southern copepods increased and body sizes of North Pacific krill fell in northern California. Off Oregon and Washington abundances of market squid and Pacific pompano (indicators of warm, non-typical La Niña conditions) were high. In the 20th century, Northern anchovy recruitment tended to be high during cold conditions, but despite mostly warm conditions from 2015-2021 anchovy populations boomed and remained high in 2022. Resident seabird reproductive success, which tended in the past to increase during productive La Niña conditions was highly variable throughout the system as common murre and pelagic cormorant, experienced complete reproductive failure at Yaquina Head, Oregon while Brandt’s cormorant reproduction was average. At three sampling locations off central California, however, common murre reproduction was close to or above average while both pelagic and Brandt’s cormorant were above average. California sealion reproduction has been above average each year since 2016, and pup weight was also above average in 2022, likely in response not to La Niña or El Niño but continuous high abundance of anchovy. The highly variable and often unpredictable physical and biological conditions in 2022 highlight a growing recognition of disconnects between basin-scale indices and local conditions in the CCE. “July-December 2022 is the biggest outlier from individual “strong” La Niña (events) ever going back to the 50s.” – Nate Mantua

OBJECTIVES: There is little evidence guiding the management of grade I-II traumatic splenic injuries with contrast blush (CB). We aimed to analyze the failure rate of nonoperative management (NOM) of grade I-II splenic injuries with CB in hemodynamically stable patients. METHODS: A multicenter, retrospective cohort study examining all grade I-II splenic injuries with CB was performed at 21 institutions from January 1, 2014, to October 31, 2019. Patients >18 years old with grade I or II splenic injury due to blunt trauma with CB on CT were included. The primary outcome was the failure of NOM requiring angioembolization/operation. We determined the failure rate of NOM for grade I versus grade II splenic injuries. We then performed bivariate comparisons of patients who failed NOM with those who did not. RESULTS: A total of 145 patients were included. Median Injury Severity Score was 17. The combined rate of failure for grade I-II injuries was 20.0%. There was no statistical difference in failure of NOM between grade I and II injuries with CB (18.2% vs 21.1%, p>0.05). Patients who failed NOM had an increased median hospital length of stay (p=0.024) and increased need for blood transfusion (p=0.004) and massive transfusion (p=0.030). Five patients (3.4%) died and 96 (66.2%) were discharged home, with no differences between those who failed and those who did not fail NOM (both p>0.05). CONCLUSION: NOM of grade I-II splenic injuries with CB fails in 20% of patients. LEVEL OF EVIDENCE: IV.

BackgroundHospital readmission trends for persons with human immunodeficiency virus (PWH) in North America in the context of policy changes, improved antiretroviral therapy (ART), and aging are not well-known. We examined readmissions during 2005-2018 among adult PWH in NA-ACCORD.MethodsLinear risk regression estimated calendar trends in 30-day readmissions, adjusted for demographics, CD4 count, AIDS history, virologic suppression (

We investigate the role of physician agency in determining health care sup-ply and patient outcomes. We show that an increase in health care supplydue to a change in private physician incentives has a theoretically ambiguous impact on patient welfare. The increase can reflect either induced demand for ineffective care or a reduction in prior rationing of effective care. Furthermore, physician market structure matters in determining the welfare effects of changes in private physician incentives. We then analyze a change to Medicare fees that caused physicians to increase their provision of chemotherapy. We find that this increase in treatment improved patient survival, extending median life expectancy for lung cancer patients by about 18%. Consistent with the model, we find that while the treatment response was larger in less concentrated markets, survival improvements were larger in more concentrated markets.

Abstract: Understanding the amount of space required by animals to fulfill their biological needs is essential for comprehending their behavior, their ecological role within their community, and for effective conservation planning and resource management. The space-use patterns of habituated primates often are studied by using handheld GPS devices, which provide detailed movement information that can link patterns of ranging and space-use to the behavioral decisions that generate these patterns. However, these data may not accurately represent an animal’s total movements, posing challenges when the desired inference is at the home range scale. To address this problem, we used a 13-year dataset from 11 groups of white-faced capuchins (Cebus capucinus imitator) to examine the impact of sampling elements, such as sample size, regularity, and temporal coverage, on home range estimation accuracy. We found that accurate home range estimation is feasible with relatively small absolute sample sizes and irregular sampling, as long as the data are collected over extended time periods. Also, concentrated sampling can lead to bias and overconfidence due to uncaptured variations in space use and underlying movement behaviors. Sampling protocols relying on handheld GPS for home range estimation are improved by maximizing independent location data distributed across time periods much longer than the target species’ home range crossing timescale.

PURPOSE: Patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) have limited therapeutic options. Clinical use of genomic profiling provides an opportunity to identify targetable alterations to inform therapy. EXPERIMENTAL DESIGN: We describe a cohort of 14 pediatric patients with relapsed or refractory T-ALL enrolled on the Leukemia Precision-based Therapy (LEAP) Consortium trial (NCT02670525) and a patient with T-LBL, discovering alterations in platelet-derived growth factor receptor-α (PDGFRA) in 3 of these patients. We identified a novel mutation in PDGFRA, p.D842N, and used an integrated structural modeling and molecular biology approach to characterize mutations at D842 to guide therapeutic targeting. We conducted a preclinical study of avapritinib in a mouse patient-derived xenograft (PDX) model of FIP1L1-PDGFRA and PDGFRA p.D842N leukemia. RESULTS: Two patients with T-ALL in the LEAP cohort (14%) had targetable genomic alterations affecting PDGFRA, a FIP1-like 1 protein/PDGFRA (FIP1L1-PDGFRA) fusion and a novel mutation in PDGFRA, p.D842N. The D842N mutation resulted in PDGFRA activation and sensitivity to tested PDGFRA inhibitors. In a T-ALL PDX model, avapritinib treatment led to decreased leukemia burden, significantly prolonged survival, and even cured a subset of mice. Avapritinib treatment was well tolerated and yielded clinical benefit in a patient with refractory T-ALL. CONCLUSIONS: Refractory T-ALL has not been fully characterized. Alterations in PDGFRA or other targetable kinases may inform therapy for patients with refractory T-ALL who otherwise have limited treatment options. Clinical genomic profiling, in real time, is needed for fully informed therapeutic decision making.

The performance of electrochemical energy devices, such as fuel cells and batteries, is dictated by intricate physiochemical processes within. To better understand and rationally engineer these processes, we need robust operando characterization tools that detect and distinguish multiple interacting components/interfaces in high contrast. Here, we uniquely combine dual-modality tomography (simultaneous neutron and x-ray tomography) and advanced image processing (iterative reconstruction and metal artifact reduction) for high-contrast multimaterial imaging, with signal and contrast enhancements of up to 10 and 48 times, respectively, compared to conventional single-modality imaging. Targeted development and application of these methods to electrochemical devices allow us to resolve operando distributions of six interacting fuel cell components (including void space) with the highest reported pairwise contrast for simultaneous yet decoupled spatiotemporal characterization of component morphology and hydration. Such high-contrast tomography ushers in key gold standards for operando electrochemical characterization, with broader applicability to numerous multimaterial systems.

BackgroundWith the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need.MethodsSafety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.govNCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized and initiated either orally inhaled nebulized SNG001 given once daily for 14 days (n = 110) or blinded pooled placebo (n = 110) between February 10 and August 18, 2021.FindingsThe proportion of participants reporting premature treatment discontinuation was 9% among SNG001 and 13% among placebo participants. There were no differences between participants who received SNG001 or placebo in the primary outcomes of treatment emergent Grade 3 or higher adverse events (3.6% and 8.2%, respectively), time to symptom improvement (median 13 and 9 days, respectively), or proportion with unquantifiable nasopharyngeal SARS-CoV-2 RNA at days 3 (28% [26/93] vs. 39% [37/94], respectively), 7 (65% [60/93] vs. 66% [62/94]) and 14 (91% [86/95] vs. 91% [83/81]). There were fewer hospitalizations with SNG001 (n = 1; 1%) compared with placebo (n = 7; 6%), representing an 86% relative risk reduction (p = 0.07). There were no deaths in either arm.InterpretationIn this trial, SNG001 was safe and associated with a non-statistically significant decrease in hospitalization for COVID-19 pneumonia.FundingThe ACTIV-2 platform study is funded by the NIH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Abstract Background The COVID-19 pandemic negatively impacted tuberculosis (TB) treatment services, including directly observed therapy (DOT) programs used to promote medication adherence. We compared DOT adherence embedded in a research study before and after COVID-19 lockdowns in South Africa. Methods We analyzed data from 263 observational study participants undergoing drug susceptible (DS)-TB DOT between May 2017 to March 2022. Participants enrolled before October 2019 were considered ‘pre-COVID-19’ and those enrolled after September 2020 were considered ‘post-COVID-19 lockdown groups. Negative binomial regression models were used to compare DOT non-adherence rates between the two lockdown groups. We then conducted a sensitivity analysis which only included participants enrolled in the immediate period following the first COVID-19 lockdown. Results DOT non-adherence rate was higher in the post-COVID-19 lockdown group (aIRR = 1.42, 95% CI = 1.04–1.96; p = 0.028) compared to pre-COVID-19 lockdown period, adjusting for age, sex, employment status, household hunger, depression risk, and smoked substance use. DOT non-adherence was highest immediately following the initial lockdown (aIRR = 1.74, 95% CI = 1.17–2.67; p = 0.006). Conclusion The COVID-19 lockdowns adversely effected adherence to TB DOT in the period after lockdowns were lifted. The change in DOT adherence persisted even after adjusting for socioeconomic and behavioral variables. We need a better understanding of what treatment adherence barriers were exacerbated by COVID-19 lockdowns to improve outcomes in post-pandemic times. Trial registration ClinicalTrials.gov Registration Number: NCT02840877. Registered on 19 July 2016.

Abstract Introduction Fine-needle aspiration cytology (FNAC) is an effective tool in the diagnostic work-up of patients with thyroid nodules. The aim of our study was to assess the diagnostic sensitivity of FNAC in thyroid cancer (TC) in Sweden by correlating the findings of preoperative FNAC with those obtained through final histology of the surgical specimen. Methods A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing patient FNAC and histology reports. Results Among the 2519 cases operated with a final diagnosis of TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%), included in the present study. Among these, 1679 patients (72%) were female and the median age at TC diagnosis was 52.3 years (range 18-94.6). In 353 cases (15.1%) FNAC was not performed at all; whereas in the remaining 1965 cases, the diagnostic sensitivity of FNAC was 81.6%. In lesions > 1 cm, FNAC diagnostic sensitivity reached 86.5%, whereas in lesions 1 cm, the diagnostic sensitivity of US-guided FNAC (n = 1504) was 86.9% as compared to 76.9% in clinically applied FNAC without US utilization (n = 118). Conclusions FNAC is performed in most patients operated for TC in Sweden (85%) and retains its value as a tool in TC diagnostic work-up with an overall sensitivity of 82%, reaching 87% in lesions > 1 cm, that harbor clinically relevant TC.

Abstract Factors such as obesity, alcohol consumption, and tobacco use are associated with both increased psoriasis severity and inadequate response to systemic and biologic therapies. Obesity is linked to chronic inflammation, which can contribute to psoriasis pathogenesis. Fixed-dose therapies may have reduced efficacy in patients with a higher body mass index, while weight-based dosing can increase the burden of drug-specific side effects. Alcohol and nicotine from tobacco have also been shown to stimulate keratinocyte and immune cell proliferation and production of proinflammatory cytokines. While these risk factors are prevalent among patients with moderate-to-severe psoriasis, their influence on treatment outcomes may be overlooked when evaluating therapeutic options. Brodalumab is a fully human interleukin-17 receptor A antagonist approved for the treatment of moderate-to-severe psoriasis. In this review, we describe the lifestyle-related risk factors associated with decreased response to treatment. We further summarize the post hoc analyses of brodalumab in participant subgroups with moderate-to-severe psoriasis and a history of prior biologic failure, obesity, and alcohol or tobacco use from two phase 3 clinical trials (AMAGINE-2 and AMAGINE-3; ClinicalTrials.gov identifiers: NCT01708603 and NCT01708629, respectively). Our review of clinical trial and real-world data suggests that brodalumab is an efficacious and safe treatment option for patients with lifestyle factors that increase the likelihood of treatment failure, allowing them to achieve skin clearance and improve quality of life.

Abstract Depression and anxiety frequently co-occur with opioid use disorder (OUD) yet are often overlooked in standard OUD treatments. This study evaluated the feasibility, acceptability, and preliminary effectiveness of a mobile application designed to address these symptoms in individuals receiving medications for OUD (MOUD). A randomized controlled trial recruited N = 63 adults with OUD who received MOUD and screened positive for moderate depression or generalized anxiety. Participants were randomized to an app-based digital intervention or treatment-as-usual for 4 weeks, and completed follow-ups at 4 and 8 weeks. Primary outcomes were self-reported severity measures for depression and generalized anxiety, and urine drug screens (UDS). Secondary outcomes included self-reported OUD severity, craving intensity, and digital biomarkers derived from passive smartphone sensors. The application was well-received (median app rating = 4/5 stars). The intervention group showed significant reductions in depressive and generalized anxiety symptoms post-intervention and at 8 weeks follow-up (d > 0.70), with large (d = 0.78) and moderate (d = 0.38) effect sizes, respectively, compared to controls. Both groups exhibited substantial decreases in self-reported severity of opioid use symptoms (d > 2.50). UDS suggested similar between-group adherence to MOUD, with a marginal decrease in opioid (MOP) use in the intervention group and increase in controls, yielding medium between group effect sizes (d = 0.44). Passive sensor data suggested significant increases in social connectedness in the intervention group, evidenced by a significant rise in incoming and outgoing calls and text connections. Initial evidence supports the feasibility and acceptability of a digital intervention for treating anxiety and depressive symptoms in persons receiving MOUD. While underpowered to confidently determine statistical significance beyond directionality, the intervention showed promise in reducing depressive and anxiety symptoms, suggesting its potential as a cost-effective and scalable adjunctive therapy alongside standard OUD treatment. Due to the preliminary nature of this pilot study, further research with sample sizes permitting greater statistical power is needed to confirm findings and explore long-term effects.

Introduction: Existing theories and empirical works link phone use with anxiety; however, most leverage subjective self-reports of phone use (e.g., validated questionnaires) that may not correspond well with true behavior. Moreover, most works linking phone use with anxiety do not interrogate associations within a temporal framework. Accordingly, the present study sought to investigate the utility of passively sensed phone use as a longitudinal predictor of anxiety symptomatology within a population particularly vulnerable to experiencing anxiety. Methods: Using data from the GLOBEM study, which continuously collected longitudinal behavioral data from a college cohort of N = 330 students, weekly PHQ-4 anxiety subscale scores across 3 years (2019–2021) were paired with median daily phone use records from the 2 weeks prior to anxiety self-report completion. Phone use was operationalized through unlock duration which was passively curated via Apple’s “Screen Time” feature. GPS-tracked location data was further utilized to specify whether an individual’s phone use was at home or away from home. Within-individual and temporal associations between phone use and anxiety were modeled within an ordinal mixed-effects logistic regression framework. Results: While there was no significant association between anxiety levels and either median total phone use or median phone use at home, participants in the top quartile of median phone use away from home were predicted to exhibit clinically significant anxiety levels 20% more frequently than participants in the bottom quartile during the first study year; however, this association weakened across successive years. Importantly, these associations remained after controlling for age, physical activity, sleep, and baseline anxiety levels and were not recapitulated when operationalizing phone use with unlock frequency. Conclusions: These findings suggest that phone use may be leveraged as a means of mitigating or coping with anxiety in social situations outside the home, while pandemic-related developments may also have attenuated this behavior later in the study. Nevertheless, the present results suggest promise in interrogating a larger suite of objectively measured phone use behaviors within the context of social anxiety.

Abstract Agroforestry practices (AFPs) play a critical role in enhancing income and reducing poverty. This study assessed the effect of AFPs on income and poverty status of farmers in Lay Armachiho (LA), Bahir Dar Zuria (BDR), and Banja districts of Northwestern Ethiopia. 387 households, and 63 key informants were interviewed. Data were analyzed using descriptive statistics, FGT index, Gini coefficient, and multiple linear regression. About 49.35% of the respondents are categorized poor with a poverty gap of 18.93 and a poverty severity level of 9.7. Banja was the greatest with persons below poverty level (59.2%), followed by BDR (49.72%). Agroforestry practices contribute 28.43% to household income. Income from AFPs lowered the poverty ratio, poverty gap index, and poverty severity level of households by 13%, 9%, and 7%, respectively. Income from AFPs lowered the area between the line of equality and the Lorenz curve, as well as the Gini coefficient, by 7.97%. AFPs also lowered the income disparity of households in all districts. Age, AFPs land size, road accessibility, irrigation, AFPs experience, and AFPs types affect households AFPs income positively. Family size and membership to credit institutions had a negative effect. Thus, in order to lower poverty and raise household income, labor productivity, the credit service system, the road and irrigation infrastructure, and AFPs all need to be improved and scaled up.

Abstract Suicidal thought and behavior (STB) is highly stigmatized and taboo. Prone to censorship, yet pervasive online, STB risk detection may be improved through development of uniquely insightful digital markers. Focusing on Sanctioned Suicide, an online pro-choice suicide forum, this work derived 17 egocentric network features to capture dynamics of social interaction and engagement within this uniquely uncensored community. Using network data generated from over 3.2 million unique interactions of N = 192 individuals, n = 48 of which were determined to be highest risk users (HRUs), a machine learning classification model was trained, validated, and tested to predict HRU status. Model prediction dynamics were analyzed using introspection techniques to uncover patterns in feature influence and highlight social phenomena. The model achieved a test AUC = 0.73 ([0.61, 0.85], 95% CI), suggesting that network-based socio-behavioral patterns of online interaction can signal for heightened suicide risk. Transitivity, density, and in-degree centrality were among the most important features driving this performance. Moreover, predicted HRUs tended to be targets of social exchanges with lesser frequency and possessed egocentric networks with “small world” network properties. Through the implementation of an underutilized method on an unlikely data source, findings support future incorporation of network-based social interaction features in descriptive, predictive, and preventative STB research.

Abstract Background Unhealthy alcohol use is widespread in South Africa and has been linked to tuberculosis (TB) disease and poor treatment outcomes. This study used qualitative methods to explore the relationship between TB and alcohol use during TB treatment. Methods Focus group discussions (FGDs) were conducted with 34 participants who had previous or current drug-susceptible TB and self-reported current alcohol use. Eight interviews were conducted with healthcare workers who provide TB services in Worcester, South Africa. Results In this rural setting, heavy episodic drinking is normalized and perceived to be related to TB transmission and decreased adherence to TB medication. Both healthcare workers and FGD participants recommended the introduction of universal screening, brief interventions, and referral to specialized care for unhealthy alcohol use. However, participants also discussed barriers to the provision of these services, such as limited awareness of the link between alcohol and TB. Healthcare workers also specified resource constraints, while FGD participants or patients mentioned widespread stigma towards people with alcohol concerns. Both FGD participants and health providers would benefit from education on the relationship between TB and unhealthy alcohol use and had specific recommendations about interventions for alcohol use reduction. Healthcare workers also suggested that community health worker-delivered interventions could support access to and engagement in both TB and alcohol-related services. Conclusion Findings support strengthening accessible, specialized services for the identification and provision of interventions and psychosocial services for unhealthy alcohol use among those with TB.