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Abstract The distribution of certain permissive intermediate snail host species in freshwater is a crucial factor shaping transmission of intestinal schistosomiasis, a neglected tropical disease that causes much human suffering in Africa. To shed new light on southern Malawi, where cases of intestinal schistosomiasis have been found, repeated malacological surveys were conducted in Chikwawa and Nsanje Districts in the Lower Shire Valley, to detect and to characterize populations of Biomphalaria, the intermediate host for intestinal schistosomiasis. Sampling took place across a total of 45 freshwater sites, noting water conductivity, pH, temperature, total dissolved salts (TDS) and geographical elevation. The presence or absence of snails was predicted upon physiochemical and environmental conditions in Random Forest modelling. Water conductivity, TDS and geographical elevation were most important in predicting abundance of snails with water temperature and pH of slightly less important roles. This first report of B. pfeifferi in the Lower Shire Valley enhances understanding of the environmental factors that strongly associate and allow prediction of its local distribution. This represents a useful step towards developing appropriate intervention strategies to mitigate intestinal schistosomiasis transmission.

Abstract Background Alternative payment models (APMs) are methods through which insurers reimburse health care providers and are widely used to improve the quality and value of health care. While there is a growing movement to utilize APMs for substance use disorder (SUD) treatment services, they have rarely included SUD prevention strategies. Challenges to using APMs for SUD prevention include underdeveloped program outcome measures, inadequate SUD prevention funding, and lack of clarity regarding what prevention strategies might fit within the scope of APMs. Methods In November 2023, the Substance Abuse and Mental Health Services Administration (SAMHSA), through a contract with Westat, convened an expert panel to refine a preliminary conceptual framework developed for utilizing APMs for SUD prevention and to identify strategies to encourage their adoption. Results The conceptual framework agreed upon by the panel provides expert consensus on how APMs could finance a variety of prevention programs across diverse populations and settings. Additional efforts are needed to accelerate the support for and adoption of APMs for SUD prevention, and the principles of health equity and community engagement should underpin these efforts. Opportunities to increase the use of APMs for SUD prevention include educating key groups, expanding and promoting the SUD prevention workforce, establishing funding for pilot studies, identifying evidence-based core components of SUD prevention, analyzing the cost effectiveness of APMs for SUD prevention, and aligning funding across federal agencies. Conclusion Given that the use of APMs for SUD prevention is a new practice, additional research, education, and resources are needed. The conceptual framework and strategies generated by the expert panel offer a path for future research. SUD health care stakeholders should consider ways that SUD prevention can be effectively and equitably implemented within APMs.

Background: Distal triceps tendon ruptures are an uncommon injury with several reported repair techniques. Outcomes research between the repair techniques is complicated by the rarity of the injury as most published materials are based on small sample sizes and specific surgical techniques. This study compared surgical complications, reoperations, and range of motion between all suture transosseous tunnel only (TT), suture anchor only (SA), and transosseous tunnel plus suture anchor (TTSA) repair techniques. Methods: We retrospectively identified patients who underwent a distal triceps repair at our tertiary-care institution from 2011 to 2021. The electronic medical record was reviewed for patient demographics, triceps rupture characteristics, repair technique, and postoperative complications. Results: This study includes 199 patients who underwent a repair by TT (82), SA (69), or TTSA (48) techniques. No differences were identified between groups with regards to demographics and medical comorbidities. Patients treated by SA technique were more likely to have a loss of elbow extension (SA: 14 [26.4%], TT: 6 [8.57%], TTSA: 4 [10.0%], P = .014) postoperatively with an average loss of 9° for the patients in all groups. However, no differences were identified between the groups with regards to postoperative complications (TT: 15.9%, SA: 17.4%, TTSA: 18.8%, P = .911), including triceps rerupture (TT: 6.10%, SA: 4.35%, TTSA: 12.5%, P = .260), and reoperation (TT: 11.0%, SA: 11.6%, TTSA: 14.6%, P = .822) rates. Conclusion: Regardless of repair technique, distal triceps tendon repair surgery has a relatively high complication and reoperation rate. However, given the similarities between the various methods of repair, surgeons can be confident in repairing this type of injury by whichever modality they deem appropriate.

Receptor tyrosine kinase (RTK) overexpression is linked to the development and progression of multiple cancers. RTKs are classically considered to initiate cytoplasmic signalling pathways via ligand-induced tyrosine phosphorylation, however recent evidence points to a second tier of signalling contingent on interactions mediated by the proline-rich motif (PRM) regions of non-activated RTKs. The presence of PRMs on the C-termini of >40 % of all RTKs and the abundance of PRM-binding proteins encoded by the human genome suggests that there is likely to be a large number of previously unexplored interactions which add to the RTK intracellular interactome. Here, we explore the RTK PRM interactome and its potential significance using affinity purification mass spectrometry and in silico enrichment analyses. Peptides comprising PRM-containing C-terminal tail regions of EGFR, FGFR2 and HER2 were used as bait to affinity purify bound proteins from different cancer cell line lysates. 490 unique interactors were identified, amongst which proteins with metabolic, homeostatic and migratory functions were overrepresented. This suggests that PRMs from RTKs may sustain a diverse interactome in cancer cells. Since RTK overexpression is common in cancer, RTK PRM-derived signalling may be an important, but as yet underexplored, contributor to negative cancer outcomes including resistance to kinase inhibitors.

Abstract Background Maintaining a healthy body weight and reaching long-term dietary goals requires ongoing self-monitoring and behavioral adjustments. How individuals respond to successes and failures is described in models of self-regulation: while cybernetic models propose that failures lead to increased self-regulatory efforts and successes permit a reduction of such efforts, motivational models (e.g., social-cognitive theory) make opposite predictions. Here, we tested these conflicting models in an ecological momentary assessment (EMA) context and explored whether effort adjustments are related to inter-individual differences in perceived self-regulatory success in dieting (i.e., weight management). Methods Using linear mixed effects models, we tested in 174 diet-interested individuals whether current day dietary success or failure (e.g., on Monday) was followed by self-regulatory effort adjustment for the next day (e.g., on Tuesday) across 14 days. Success vs. failure was operationalized with two EMA items: first, whether food intake was higher vs. lower than usual and second, whether food intake was perceived as more vs. less goal-congruent than usual. Trait-level perceived self-regulatory success in dieting was measured on a questionnaire. Results Intended self-regulatory effort increased more strongly after days with dietary success (i.e., eating less than usual / rating intake as goal-congruent) than after days with dietary failure (i.e., eating more than usual / rating intake as goal-incongruent), especially in those individuals with lower scores on perceived self-regulatory success in dieting. Conclusions Findings support mechanisms proposed by social-cognitive theory, especially in unsuccessful dieters. Thus, future dietary interventions could focus on preventing the decrease in self-regulatory effort after instances of dietary failures and thereby mitigate the potential risk that a single dietary failure initiates a downward spiral into unhealthy eating.

Purpose: Opioid stewardship ensures effective pain management while avoiding overprescribing of opioids after surgery. This prospective randomized study investigates the efficacy of a multimodal postoperative pain regimen compared to a traditional opioid-only pain regimen following elective outpatient orthopedic hand surgery. We hypothesized that patients receiving multimodal pain management would consume fewer opioids and report greater satisfaction than patients receiving only opioids. Methods: Consecutive patients undergoing outpatient hand and upper extremity surgery performed by two board-certified fellowship-trained orthopedic hand surgeons at one institution were recruited and randomized into either a study or control group. The study group received a standing multimodal postoperative regimen consisting of scheduled oral acetaminophen and naproxen as well as oxycodone to be taken as needed. The control group received only oxycodone to be taken as needed. Postoperatively, daily pain levels, medication usage, refills, satisfaction, and adverse events were recorded. Descriptive statistics were performed. Results: Of the 112 patients enrolled, 54 were randomized to the control group, and 58 were randomized to the study group. Study and control group patients did not differ significantly based on daily average pain scores or daily worst pain scores. However, study group patients reported fewer average daily oxycodone intake and total oxycodone pill count (7.0 vs 2.4 total pills, P

Purpose: Intramedullary screw fixation has emerged as a popular approach for the treatment of displaced metacarpal fractures. The purpose of this study was to investigate the functional and radiographic outcomes of a newly designed, headless noncompressive fully threaded intramedullary nail (TIMN) for the treatment of metacarpal fractures. Methods: A retrospective chart review was performed on patients who were treated with the INnate TIMN (ExsoMed) at a single academic institution with a minimum of 1-year follow-up. Patient-reported functional outcomes included Quick Disabilities for the Arm, Shoulder, and Hand (QuickDASH) questionnaires, return to work and physical activity time, and overall satisfaction. Radiographs were retrospectively reviewed to determine radiographic union, change in angulation, and metacarpal shortening. Results: A total of 49 patients (58 fractures) with a mean age of 36 years (range: 17–75 years) were included. The mean follow-up time was 2.7 years (range: 1.4–4.3 years). Overall, the mean patient satisfaction rating was 4.9 of 5 (range: 3–5). The mean return to work time was 7.2 weeks (range: 0.14–28 weeks), and the mean return to sport or activity was 8.3 weeks (range: 1–28 weeks). Average QuickDASH scores across all patients were 4 (range: 0–56.9). The median radiographic healing time was 6.1 weeks (range: 4.7–15.4 weeks). Mean postoperative shortening in the fifth metacarpal fracture was 3 mm (range: −4.2 to 8 mm) at the initial postoperative visit and 3.6 mm (range: −3.3 to 7.9 mm) at the final radiographic follow-up. Subgroup analysis showed that postoperative shortening was similar, regardless of the fracture pattern. The following four complications were reported: one case of persistent pain and stiffness, one case of carpal tunnel syndrome, one nonunion, and one fractured intramedullary nail. Conclusions: Our findings suggest that the TIMN allows for a reliable return to work and physical activity, high patient satisfaction, low complication rate, and minimal shortening at the final radiographic follow-up. Type of study/level of evidence: Therapeutic IV.

Abstract Nitrate ammonification is important for soil nitrogen retention. However, the ecology of ammonifiers and their prevalence compared with denitrifiers, being competitors for nitrate, are overlooked. Here, we screen 1 million genomes for nrfA and onr, encoding ammonifier nitrite reductases. About 40% of ammonifier assemblies carry at least one denitrification gene and show higher potential for nitrous oxide production than consumption. We then use a phylogeny-based approach to recruit gene fragments of nrfA, onr and denitrification nitrite reductase genes (nirK, nirS) in 1861 global terrestrial metagenomes. nrfA outnumbers the nearly negligible onr counts in all biomes, but denitrification genes dominate, except in tundra. Random forest modelling teases apart the influence of the soil C/N on nrfA-ammonifier vs denitrifier abundance, showing an effect of nitrate rather than carbon content. This study demonstrates the multiple roles nitrate ammonifiers play in nitrogen cycling and identifies factors ultimately controlling the fate of soil nitrate.

BackgroundThe effects of SARS-CoV-2 have varied between significant waves of hospitalization.Research questionAre cardiovascular complications different among the first, delta and omicron waves of hospitalized COVID-19 pneumonia patients?Study design and methodsThis was a multi-centre retrospective study of patients hospitalized with SARS-CoV-2 pneumonia: 632 were hospitalized during the first wave (March–July 2020), 1013 during the delta wave (September 2020–March 2021), and 323 during the omicron wave (January 2022–July 2022). Patients were stratified by wave and occurrence of cardiovascular events.ResultsAmong all hospitalized patients with cardiovascular events, patients in the omicron wave were younger (62.4 ± 14 years) than patients in the first wave (67.4 ± 7.8 years) and the delta wave (66.9 ± 12.6 years) and had a higher proportion of non-Hispanic White people than in the first wave (78.6% vs. 61.7%). For COVID-19 patients who suffered from cardiovascular events, the omicron wave patients had significantly higher neutrophil/lymphocyte ratio, white blood cell and platelet counts when compared to the first wave. Omicron wave patients had significantly lower albumin and B-type natriuretic peptide levels (only 5.8% of the first wave and 14.6% of the delta wave) when compared to either the first wave or delta wave patients. In COVID-19 patients who suffered cardiovascular events during hospitalization, mortality rate in the omicron wave (26.8%) was significantly lower than the first wave (48.3%), time to mortality for non-survivors of COVID-19 patients who suffered cardiovascular events was significantly longer in the omicron wave (median 16 days) than in the first wave (median 10 days).ConclusionsYounger and white patients were affected with cardiovascular complications more often by the omicron variant. Despite higher neutrophil/lymphocyte ratio and WBC counts, the omicron patients with cardiovascular events showed lower heart injuries, lower mortality and longer time to mortality for non-survivors when compared to the first and delta waves.

Our study rationale was to establish contemporary epidemiological data on malaria and schistosomiasis among school-going children in Chikwawa District before future environmental changes associated with the Shire Valley Transformation Programme occurred. Our cross-sectional surveys tested 1134 children from 21 government-owned primary schools (approximately 50 children per school); rapid diagnostic tests for malaria (Humasis Pf/PAN) and intestinal schistosomiasis (urine-Circulating Cathodic Antigen) were used, with urine reagents strips and egg-filtration with microscopy for urogenital schistosomiasis. All infected children were treated with an appropriate dose of Lonart® (for malaria) and/or Cesol® (for schistosomiasis). Across 21 schools the overall prevalence was 9.7% (95% CI: 8.8–10.6%) for malaria, 1.9% (95% CI: 1.4–2.3%) for intestinal schistosomiasis, and 35.0% (95% CI: 33.6–36.5%) for egg-patent urogenital schistosomiasis. The prevalence of co-infection of malaria with urogenital schistosomiasis was 5.5% (95% CI: 4.8–6.2%). In a third of the schools, the prevalence of malaria and urogenital schistosomiasis was above national averages of 10.5% and 40–50%, respectively, with two schools having maxima of 36.8% and 84.5%, respectively. Set against a background of ongoing control, our study has revealed an alarming burden of malaria and schistosomiasis in southern Malawi. These findings call for an immediate mitigating response that significantly bolsters current control interventions to better safeguard children's future health.

The Grb2 splice variant Grb3-3 results in decreased activation of the Ras-MAPK pathway due competition with Grb2 for SOS binding, with reduced Grb3-3 levels observed in tumour tissue suggestive of a mechanism for enhancing Ras pathway activity.

BackgroundHealth-related misinformation on social media is a key challenge to effective and timely public health responses. Existing mitigation measures include flagging misinformation or providing links to correct information, but they have not yet targeted social processes. Current approaches focus on increasing scrutiny, providing corrections to misinformation (debunking), or alerting users prospectively about future misinformation (prebunking and inoculation). Here, we provide a test of a complementary strategy that focuses on the social processes inherent in social media use, in particular, social reinforcement, social identity, and injunctive norms. ObjectiveThis study aimed to examine whether providing balanced social reference cues (ie, cues that provide information on users sharing and, more importantly, not sharing specific content) in addition to flagging COVID-19–related misinformation leads to reductions in sharing behavior and improvement in overall sharing quality. MethodsA total of 3 field experiments were conducted on Twitter’s native social media feed (via a newly developed browser extension). Participants’ feed was augmented to include misleading and control information, resulting in 4 groups: no-information control, Twitter’s own misinformation warning (misinformation flag), social cue only, and combined misinformation flag and social cue. We tracked the content shared or liked by participants. Participants were provided with social information by referencing either their personal network on Twitter or all Twitter users. ResultsA total of 1424 Twitter users participated in 3 studies (n=824, n=322, and n=278). Across all 3 studies, we found that social cues that reference users’ personal network combined with a misinformation flag reduced the sharing of misleading but not control information and improved overall sharing quality. We show that this improvement could be driven by a change in injunctive social norms (study 2) but not social identity (study 3). ConclusionsSocial reference cues combined with misinformation flags can significantly and meaningfully reduce the amount of COVID-19–related misinformation shared and improve overall sharing quality. They are a feasible and scalable way to effectively curb the sharing of COVID-19–related misinformation on social media.

Background. Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood. Methods. In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. Results. The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. Conclusions. Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548

Summary: Background: The utility of early metabolic response assessment to guide selection of the systemic component of definitive chemoradiotherapy (dCRT) for oesophageal cancer is uncertain. Methods: In this multi-centre, randomised, open-label, phase II substudy of the radiotherapy dose-escalation SCOPE2 trial we evaluated the role of 18F-Fluorodeoxyglucose positron emission tomography (PET) at day 14 of cycle 1 of three-weekly induction cis/cap (cisplatin (60 mg/m2)/capecitabine (625 mg/m2 days 1–21)) in patients with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC). Non-responders, who had a less than 35% reduction in maximum standardised uptake value (SUVmax) from pre-treatment baseline, were randomly assigned to continue cis/cap or switch to car/pac (carboplatin AUC 5/paclitaxel 175 mg/m2) for a further induction cycle, then concurrently with radiotherapy over 25 fractions. Responders continued cis/cap for the duration of treatment. All patients (including responders) were randomised to standard (50Gy) or high (60Gy) dose radiation as part of the main study. Primary endpoint for the substudy was treatment failure-free survival (TFFS) at week 24. The trial was registered with International Standard Randomized Controlled Trial Number 97125464 and ClinicalTrials.gov NCT02741856. Findings: This substudy was closed on 1st August 2021 by the Independent Data Monitoring Committee on the grounds of futility and possible harm. To this point from 22nd November 2016, 103 patients from 16 UK centres had participated in the PET-CT substudy; 63 (61.2%; 52/83 OSCC, 11/20 OAC) of whom were non-responders. Of these, 31 were randomised to car/pac and 32 to remain on cis/cap. All patients were followed up until at least 24 weeks, at which point in OSCC both TFFS (25/27 (92.6%) vs 17/25 (68%); p = 0.028) and overall survival (42.5 vs. 20.4 months, adjusted HR 0.36; p = 0.018) favoured cis/cap over car/pac. There was a trend towards worse survival in OSCC + OAC cis/cap responders (33.6 months; 95%CI 23.1-nr) vs. non-responders (42.5 (95%CI 27.0-nr) months; HR = 1.43; 95%CI 0.67–3.08; p = 0.35). Interpretation: In OSCC, early metabolic response assessment is not prognostic for TFFS or overall survival and should not be used to personalise systemic therapy in patients receiving dCRT. Funding: Cancer Research UK.

ABSTRACT The microbial process of denitrification is the primary source of the greenhouse gas nitrous oxide (N2O) from terrestrial ecosystems. Fungal denitrifiers, unlike many bacteria, lack the N2O reductase, and thereby are sources of N2O. Still, their diversity, global distribution, and environmental determinants, as well as their relative importance, compared to bacterial and archaeal denitrifiers, remain unresolved. Employing a phylogenetically informed approach to analyze 1,980 global soil and rhizosphere metagenomes for the denitrification marker gene nirK, which codes for the copper dependent nitrite reductase in denitrification, we show that fungal denitrifiers are sparse, yet cosmopolitan and that they are dominated by saprotrophs and pathogens. Few showed biome-specific distribution patterns, although members of the Fusarium oxysporum species complex, which are known to produce substantial amounts of N2O, were proportionally more abundant and diverse in the rhizosphere than in other biomes. Fungal denitrifiers were most frequently detected in croplands, but they were most abundant in forest soils when normalized to metagenome size. Nevertheless, the overwhelming dominance of bacterial and archaeal denitrifiers suggests a much lower fungal contribution to N2O emissions than was previously estimated. In relative terms, they could play a role in soils that are characterized by a high carbon to nitrogen ratio and a low pH, especially in the tundra as well as in boreal and temperate coniferous forests. Because global warming predicts the proliferation of fungal pathogens, the prevalence of potential plant pathogens among fungal denitrifiers and the cosmopolitan distribution of these organisms suggest that fungal denitrifier abundance may increase in terrestrial ecosystems. IMPORTANCE Fungal denitrifiers, in contrast to their bacterial counterparts, are a poorly studied functional group within the nitrogen cycle, even though they produce the greenhouse gas N2O. To curb soil N2O emissions, a better understanding of their ecology and distribution in soils from different ecosystems is needed. Here, we probed a massive amount of DNA sequences and corresponding soil data from a large number of samples that represented the major soil environments for a broad understanding of fungal denitrifier diversity at the global scale. We show that fungal denitrifiers are predominantly cosmopolitan saprotrophs and opportunistic pathogens. Fungal denitrifiers constituted, on average, 1% of the total denitrifier community. This suggests that earlier estimations of fungal denitrifier abundance, and, thereby, it is also likely that the contributions of fungal denitrifiers to N2O emissions have been overestimated. Nevertheless, with many fungal denitrifiers being plant pathogens, they could become increasingly relevant, as soilborne pathogenic fungi are predicted to increase with ongoing climate change.

Background: Limited data exist on risk factors for illicit stimulant use, including associations between prescription stimulant use/nonmedical use (NMU) and illicit stimulant use. Methods: We used 2017–2021 data from adults assessed for substance use disorder (SUD) treatment using the National Addictions Vigilance Intervention and Prevention Program Addiction Severity Index-Multimedia Version® tool. Multivariable Poisson regression models analyzed associations between past 30-day prescription stimulant use as prescribed or NMU and past 30-day illicit stimulant use. Separate models examined past 30-day illicit stimulant, methamphetamine, and cocaine use. We explored problem severity across seven biopsychosocial domains (e.g., drug, psychiatric, family) by past 30-day prescription stimulant use/NMU and illicit stimulant use. Results: Among 218,981 assessments, 1.8% reported prescription stimulant NMU; 1.6% reported use as prescribed. Past 30-day prescription stimulant NMU (vs. no use) was associated with past 30-day illicit stimulant use (adjusted prevalence ratio [aPR] [95% CI]: 2.67 [2.59, 2.75]), methamphetamine use (aPR: 2.81 [2.71, 2.92]), and cocaine use (aPR: 3.53 [3.33, 3.74]). Prescription stimulant use as prescribed (vs. no use) was associated with lower prevalence of past 30-day illicit stimulant use. Assessments reporting prescription stimulant NMU (vs. no use, or use as prescribed) appeared more likely to have moderate-to-extreme problem scores across biopsychosocial domains, indicating greater need for treatment or assistance. Assessments reporting prescription stimulant use as prescribed or NMU frequently reported opioids, alcohol, or other substances as their primary substance problem. Conclusions: Adults using illicit stimulants/nonmedically using prescription stimulants may benefit from care addressing polysubstance use, mental health, social, and recovery support services.

Abstract Background Despite recent rises in fatal overdoses involving multiple substances, there is a paucity of knowledge about stimulant co-use patterns among people who use opioids (PWUO) or people being treated with medications for opioid use disorder (PTMOUD). A better understanding of the timing and patterns in stimulant co-use among PWUO based on mentions of these substances on social media can help inform prevention programs, policy, and future research directions. This study examines stimulant co-mention trends among PWUO/PTMOUD on social media over multiple years. Methods We collected publicly available data from 14 forums on Reddit (subreddits) that focused on prescription and illicit opioids, and medications for opioid use disorder (MOUD). Collected data ranged from 2011 to 2020, and we also collected timelines comprising past posts from a sample of Reddit users (Redditors) on these forums. We applied natural language processing to generate lexical variants of all included prescription and illicit opioids and stimulants and detect mentions of them on the chosen subreddits. Finally, we analyzed and described trends and patterns in co-mentions. Results Posts collected for 13,812 Redditors showed that 12,306 (89.1%) mentioned at least 1 opioid, opioid-related medication, or stimulant. Analyses revealed that the number and proportion of Redditors mentioning both opioids and/or opioid-related medications and stimulants steadily increased over time. Relative rates of co-mentions by the same Redditor of heroin and methamphetamine, the substances most commonly co-mentioned, decreased in recent years, while co-mentions of both fentanyl and MOUD with methamphetamine increased. Conclusion Our analyses reflect increasing mentions of stimulants, particularly methamphetamine, among PWUO/PTMOUD, which closely resembles the growth in overdose deaths involving both opioids and stimulants. These findings are consistent with recent reports suggesting increasing stimulant use among people receiving treatment for opioid use disorder. These data offer insights on emerging trends in the overdose epidemic and underscore the importance of scaling efforts to address co-occurring opioid and stimulant use including harm reduction and comprehensive healthcare access spanning mental-health services and substance use disorder treatment.

Abstract Irrigation schemes provide an ideal habitat for Anopheles mosquitoes particularly during the dry season. Reliable estimates of outdoor host-seeking behaviour are needed to assess the impact of vector control options and this is particularly the case for Anopheles arabiensis which displays a wide range of behaviours that circumvent traditional indoor-insecticide based control. In this study we compared the sampling efficiency of the host decoy trap (HDT) with the human landing catch (HLC) and Suna trap in a repeated Latin square design in two villages (Lengwe and Mwanza) on an irrigated sugar estate in southern Malawi. Over the course of 18 trapping nights, we caught 379 female Anopheles, the majority of which were identified as An. arabiensis. Across both villages, there was no detectable difference in Anopheles catch between the HDT compared with the HLC (RR = 0.85, P = 0.508). The overall sensitivity of the HLC was greater than the Suna trap regardless of mosquito density (Lengwe, α = 2.75, 95% credible interval: 2.03–3.73; Mwanza, α = 3.38, 95% credible interval: 1.50–9.30) whereas the sensitivity of the HDT was only greater than the Suna trap when mosquito numbers were high (Lengwe, α = 2.63, 95% credible interval: 2.00–3.85).We conclude that the HDT is an effective sampling device for outdoor host seeking An. arabiensis in southern Malawi. The presence of An. arabiensis in irrigated lands during the dry season poses a challenge for ongoing indoor vector control efforts.

Abstract Background Timely data from official sources regarding the impact of the COVID-19 pandemic on people who use prescription and illegal opioids is lacking. We conducted a large-scale, natural language processing (NLP) analysis of conversations on opioid-related drug forums to better understand concerns among people who use opioids. Methods In this retrospective observational study, we analyzed posts from 14 opioid-related forums on the social network Reddit. We applied NLP to identify frequently mentioned substances and phrases, and grouped the phrases manually based on their contents into three broad key themes: (i) prescription and/or illegal opioid use; (ii) substance use disorder treatment access and care; and (iii) withdrawal. Phrases that were unmappable to any particular theme were discarded. We computed the frequencies of substance and theme mentions, and quantified their volumes over time. We compared changes in post volumes by key themes and substances between pre-COVID-19 (1/1/2019—2/29/2020) and COVID-19 (3/1/2020—11/30/2020) periods. Results Seventy-seven thousand six hundred fifty-two and 119,168 posts were collected for the pre-COVID-19 and COVID-19 periods, respectively. By theme, posts about treatment and access to care increased by 300%, from 0.631 to 2.526 per 1000 posts between the pre-COVID-19 and COVID-19 periods. Conversations about withdrawal increased by 812% between the same periods (0.026 to 0.235 per 1,000 posts). Posts about drug use did not increase (0.219 to 0.218 per 1,000 posts). By substance, among medications for opioid use disorder, methadone had the largest increase in conversations (20.751 to 56.313 per 1,000 posts; 171.4% increase). Among other medications, posts about diphenhydramine exhibited the largest increase (0.341 to 0.927 per 1,000 posts; 171.8% increase). Conclusions Conversations on opioid-related forums among people who use opioids revealed increased concerns about treatment and access to care along with withdrawal following the emergence of COVID-19. Greater attention to social media data may help inform timely responses to the needs of people who use opioids during COVID-19.

Long-term, replicated fertilization field trials show that increased potential N2O production is associated with specific phylogenetic shifts in communities of frequently occurring soil microbes. This sheds light on the link between legacy effects of reactive nitrogen on microbial communities and altered regulation of N2O emissions.

Infectious diseases are emerging at an unprecedented rate while food production intensifies to keep pace with population growth. Large-scale irrigation schemes have the potential to permanently transform the landscape with health, nutritional and socio-economic benefits; yet, this also leads to a shift in land-use patterns that can promote endemic and invasive insect vectors and pathogens. The balance between ensuring food security and preventing emerging infectious disease is a necessity; yet the impact of irrigation on vector-borne diseases at the epidemiological, entomological and economic level is uncertain and depends on the geographical and climatological context. Here, we highlight the risk factors and challenges facing vector-borne disease surveillance and control in an emerging agricultural ecosystem in the lower Shire Valley region of southern Malawi. A phased large scale irrigation programme (The Shire Valley Transformation Project, SVTP) promises to transform over 40,000 ha into viable and resilient farmland, yet the valley is endemic for malaria and schistosomiasis and experiences frequent extreme flooding events following tropical cyclones. The latter exacerbate vector-borne disease risk while simultaneously making any empirical assessment of that risk a significant hurdle. We propose that the SVTP provides a unique opportunity to take a One Health approach at mitigating vector-borne disease risk while maintaining agricultural output. A long-term and multi-disciplinary approach with buy-in from multiple stakeholders will be needed to achieve this goal.

Abstract Understanding the population structure and movements of the invasive fall armyworm (FAW, Spodoptera frugiperda) is important as it can help mitigate crop damage, and highlight areas at risk of outbreaks or evolving insecticide resistance. Determining population structure in invasive FAW has been a challenge due to genetic mutations affecting the markers traditionally used for strain and haplotype identification; mitochondrial cytochrome oxidase I (COIB) and the Z-chromosome-linked Triosephosphate isomerase (Tpi). Here, we compare the results from COIB and Tpi markers with highly variable repeat regions (microsatellites) to improve our understanding of FAW population structure in Africa. There was very limited genetic diversity using the COIB marker, whereas using the TpiI4 marker there was greater diversity that showed very little evidence of genetic structuring between FAW populations across Africa. There was greater genetic diversity identified using microsatellites, and this revealed a largely panmictic population of FAW alongside some evidence of genetic structuring between countries. It is hypothesised here that FAW are using long-distance flight and prevailing winds to frequently move throughout Africa leading to population mixing. These approaches combined provide important evidence that genetic mixing between invasive FAW populations may be more common than previously reported.

Summary: Background: Effective surveillance strategies are required for patients diagnosed with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC) for whom chemoradiotherapy (CRT) is used as a potentially-curative, organ-sparing, alternative to surgery. In this study, we evaluated the safety, acceptability and tolerability of a non-endoscopic immunocytological device (the Cytosponge™) to assess treatment response following CRT. Methods: This multicentre, single-arm feasibility trial took place in 10 tertiary cancer centres in the UK. Patients aged at least 16 years diagnosed with OSCC or OAC, and who were within 4-16 weeks of completing definitive or neo-adjuvant CRT, were included. Participants were required to have a Mellow-Pinkas dysphagia score of 0-2 and be able to swallow tablets. All patients underwent a single Cytosponge™ assessment in addition to standard of care (which included post-treatment endoscopic evaluation with biopsy for patients undergoing definitive CRT; surgery for those who received neo-adjuvant CRT). The primary outcome was the proportion of consented, evaluable patients who successfully underwent Cytosponge™ assessment. Secondary and tertiary outcomes included safety, study consent rate, acceptance rate, the suitability of obtained samples for biomarker analysis, and the comparative efficacy of Cytosponge™ to standard histology (endoscopy and biopsy or post-resection specimen) in assessing for residual disease. The trial is registered with ClinicalTrials.gov, NCT03529669. Findings: Between 18th April 2018 and 16th January 2020, 41 (42.7%; 95% confidence interval (CI) 32.7-53.2) of 96 potentially eligible patients consented to participate. Thirty-nine (95.1%, 95% CI 83.5-99.4) successfully carried out the Cytosponge™ procedure. Of these, 37 (95%) would be prepared to repeat the procedure. There were only two grade 1 adverse events attributed to use of the Cytosponge™. Thirty-five (90%) of the completed Cytosponge™ samples were suitable for biomarker analysis; 29 (83%) of these were concordant with endoscopic biopsies, three (9%) had findings suggestive of residual cancer on Cytosponge™ not found on endoscopic biopsies, and three (9%) had residual cancer on endoscopic biopsies not detected by Cytosponge™. Interpretation: Use of the CytospongeTM is safe, tolerable, and acceptable for the assessment of treatment response following CRT in OAC and OSCC. Further evaluation of Cytosponge™ in this setting is warranted. Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council.

Abstract Background Spatio-temporal trends in mosquito-borne diseases are driven by the locations and seasonality of larval habitat. One method of disease control is to decrease the mosquito population by modifying larval habitat, known as larval source management (LSM). In malaria control, LSM is currently considered impractical in rural areas due to perceived difficulties in identifying target areas. High resolution drone mapping is being considered as a practical solution to address this barrier. In this paper, the authors’ experiences of drone-led larval habitat identification in Malawi were used to assess the feasibility of this approach. Methods Drone mapping and larval surveys were conducted in Kasungu district, Malawi between 2018 and 2020. Water bodies and aquatic vegetation were identified in the imagery using manual methods and geographical object-based image analysis (GeoOBIA) and the performances of the classifications were compared. Further, observations were documented on the practical aspects of capturing drone imagery for informing malaria control including cost, time, computing, and skills requirements. Larval sampling sites were characterized by biotic factors visible in drone imagery and generalized linear mixed models were used to determine their association with larval presence. Results Imagery covering an area of 8.9 km2 across eight sites was captured. Larval habitat characteristics were successfully identified using GeoOBIA on images captured by a standard camera (median accuracy = 98%) with no notable improvement observed after incorporating data from a near-infrared sensor. This approach however required greater processing time and technical skills compared to manual identification. Larval samples captured from 326 sites confirmed that drone-captured characteristics, including aquatic vegetation presence and type, were significantly associated with larval presence. Conclusions This study demonstrates the potential for drone-acquired imagery to support mosquito larval habitat identification in rural, malaria-endemic areas, although technical challenges were identified which may hinder the scale up of this approach. Potential solutions have however been identified, including strengthening linkages with the flourishing drone industry in countries such as Malawi. Further consultations are therefore needed between experts in the fields of drones, image analysis and vector control are needed to develop more detailed guidance on how this technology can be most effectively exploited in malaria control.

Abstract Offshore decommissioning activities are expected to increase as oil and gas subsea infrastructure becomes obsolete. Decisions on decommissioning alternatives will benefit from quantifying and understanding the marine communities associated with these structures. As a case study, fish assemblages associated with an inshore network of subsea pipelines located on the North West shelf of Western Australia were compared to those in surrounding natural reef and soft sediment habitats using remotely operated vehicles fitted with a stereo-video system (stereo-ROVs). The number of species, the abundance, biomass, feeding guild composition and the economic value of fishes were compared among habitats. The community composition of fish associated with pipelines was distinct from those associated with natural habitats, and was characterised by a greater abundance and/or biomass of fish from higher trophic levels (e.g. piscivores, generalist carnivores and invertivores), including many species considered to be of value to commercial and recreational fishers. Biomass of fish on pipelines was, on average, 20 times greater than soft sediments, and was similar to natural reefs. However, the biomass of species considered important to fisheries recorded on the pipelines was, on average 3.5 times greater than reef and 44.5 times greater than soft sediment habitats. This study demonstrates that fish assemblages on the pipeline infrastructure exhibit high ecological and socioeconomic values.

Malaria hotspots have been the focus of public health managers for several years due to the potential elimination gains that can be obtained from targeting them. The identification of hotspots must be accompanied by the description of the overall network of stable and unstable hotspots of malaria, especially in medium and low transmission settings where malaria elimination is targeted. Targeting hotspots with malaria control interventions has, so far, not produced expected benefits. In this work we have employed a mechanistic-stochastic algorithm to identify clusters of super-spreader houses and their related stable hotspots by accounting for mosquito flight capabilities and the spatial configuration of malaria infections at the house level. Our results show that the number of super-spreading houses and hotspots is dependent on the spatial configuration of the villages. In addition, super-spreaders are also associated to house characteristics such as livestock and family composition. We found that most of the transmission is associated with winds between 6pm and 10pm although later hours are also important. Mixed mosquito flight (downwind and upwind both with random components) were the most likely movements causing the spread of malaria in two out of the three study areas. Finally, our algorithm (named MALSWOTS) provided an estimate of the speed of malaria infection progression from house to house which was around 200-400 meters per day, a figure coherent with mark-release-recapture studies of Anopheles dispersion. Cross validation using an out-of-sample procedure showed accurate identification of hotspots. Our findings provide a significant contribution towards the identification and development of optimal tools for efficient and effective spatio-temporal targeted malaria interventions over potential hotspot areas.

BackgroundExpanding access to and use of medication for opioid use disorder (MOUD) is a key component of overdose prevention. An important barrier to the uptake of MOUD is exposure to inaccurate and potentially harmful health misinformation on social media or web-based forums where individuals commonly seek information. There is a significant need to devise computational techniques to describe the prevalence of web-based health misinformation related to MOUD to facilitate mitigation efforts. ObjectiveBy adopting a multidisciplinary, mixed methods strategy, this paper aims to present machine learning and natural language analysis approaches to identify the characteristics and prevalence of web-based misinformation related to MOUD to inform future prevention, treatment, and response efforts. MethodsThe team harnessed public social media posts and comments in the English language from Twitter (6,365,245 posts), YouTube (99,386 posts), Reddit (13,483,419 posts), and Drugs-Forum (5549 posts). Leveraging public health expert annotations on a sample of 2400 of these social media posts that were found to be semantically most similar to a variety of prevailing opioid use disorder–related myths based on representational learning, the team developed a supervised machine learning classifier. This classifier identified whether a post’s language promoted one of the leading myths challenging addiction treatment: that the use of agonist therapy for MOUD is simply replacing one drug with another. Platform-level prevalence was calculated thereafter by machine labeling all unannotated posts with the classifier and noting the proportion of myth-indicative posts over all posts. ResultsOur results demonstrate promise in identifying social media postings that center on treatment myths about opioid use disorder with an accuracy of 91% and an area under the curve of 0.9, including how these discussions vary across platforms in terms of prevalence and linguistic characteristics, with the lowest prevalence on web-based health communities such as Reddit and Drugs-Forum and the highest on Twitter. Specifically, the prevalence of the stated MOUD myth ranged from 0.4% on web-based health communities to 0.9% on Twitter. ConclusionsThis work provides one of the first large-scale assessments of a key MOUD-related myth across multiple social media platforms and highlights the feasibility and importance of ongoing assessment of health misinformation related to addiction treatment.

In contrast to a robust literature on known pathogenic fungi such as Cryptococcus and Aspergillus species that cause pulmonary infections, reports of the uncommon genus Sporopachydermia causing infections are very limited. We present the first case report describing the fungus, Sporopachydermia lactativora as a likely cause of pneumonia in a patient with a history of polysubstance abuse and injection drug use (IDU). The patient recovered following antifungal treatment. The organism was recovered from a blood culture, 3 days post collection. Although CHROMagar was of little value, only yeast-like organisms were observed on cornmeal agar. The organism was not in the matrix-assisted laser desorption/ionization—time of flight (MALDI-TOF) mass spectrometry database. Definitive identification was achieved using the ribosomal DNA (rDNA) sequence analysis by targeting the ITS1 (internal transcribed spacer 1) region. This case report is intended to promote awareness of this fungus as a potential pathogen, by providing new information that has not yet been reported in the literature, and prompts physician awareness to suspect a fungal infection when managing patients with a history of IDU as a potential source of unique environmental organisms not previously encountered, warranting more comprehensive diagnosis and treatment options.

Consumption-based greenhouse gas (GHG) emissions inventories have emerged to describe full life cycle contributions of households to climate change at country, state and increasingly city scales. Using this approach, how much carbon footprint abatement potential is within the control of local governments, and which policies hold the most potential to reduce emissions? This study quantifies the potential of local policies and programs to meet aggressive GHG reduction targets using a consumption-based, high geospatial resolution planning model for the state of California. We find that roughly 35% of all carbon footprint abatement potential statewide is from activities at least partially within the control of local governments. The study shows large variation in the size and composition of carbon footprints and abatement opportunities by ~23,000 Census block groups (i.e., neighborhood-scale within cities), 717 cities and 58 counties across the state. These data and companion online tools can help cities better understand priorities to reduce GHGs from a comprehensive, consumption-based perspective, with potential application to the full United States and internationally.

The genes and genomes of insect pests are shaped by the wide array of selective forces encountered in their environments. While the molecular adaptations that evolve are beginning to be understood at the genomic and transcriptomic level, they have been less well characterized at an epigenetic level. Here, we present a genome-wide map of DNA methylation at single-nucleotide resolution for the cotton bollworm moth, Helicoverpa armigera, a globally invasive pest of agriculture. We show that methylation is almost identical in the larvae and adults of H. armigera and that, through whole-genome bisulfite sequencing (WGBS), at the most ∼0.9% of CpG sites in this species are methylated. We find that DNA methylation occurs primarily in exons, is positively correlated with gene expression, and that methylated genes are enriched for cellular “housekeeping” roles. H. armigera has an exceptional capacity for long-range migration. To explore the role of methylation in influencing the migratory phenotype of H. armigera, we performed targeted bisulfite sequencing on selected loci from 16 genes that were differentially expressed between adult moths exhibiting distinct flight performance in behavioral assays. While most CpG sites in these genes were not methylated between flight phenotypes, we identified hypermethylation in a demethylase (KDM4) that targets lysine-specific histone modifications, which are strongly associated with transcription and methylation. The H. armigera methylome provides new insights into the role of DNA methylation in a noctuid moth and is a valuable resource for further research into the epigenetic control of adaptive traits in this important pest.

Convulsive seizures are known to cause severe cardiopulmonary changes and increased autonomic activity. Limited reports describe peri-ictal cardiac arrhythmias such as atrial fibrillation (AF) with generalized tonic–clonic seizures (GTCS). We present a unique case of a healthy 23-year-old male patient with new onset prolonged AF in the setting of new onset seizures, occurring on three independent occasions. Over two years, our patient had multiple hospitalizations for seizures with an electrocardiogram (ECG) diagnosis of AF made on three different occasions, occurring during his post-ictal state (all within 30 min of seizure onset). These seizures were never captured by electroencephalography (EEG) or witnessed by the medical staff, but were reported by family and/or reviewed on video provided by them. After his first GTCS, his AF persisted and was medically cardioverted. Two additional instances of AF after witnessed GTCS have been captured. After his second unprovoked seizure, an anti-seizure drug (ASD) was prescribed. A multi-disciplinary approach may be adopted to address comorbidities associated with seizures. Aggressive evaluation and treatment should be employed for newly diagnosed and refractory seizure patients associated with arrhythmias, in our case AF. Peri-ictal arrhythmias may be considered a potential marker for increased sudden unexpected death in epilepsy (SUDEP) risk. Keywords: Atrial fibrillation, Seizures, Epilepsy, Arrhythmias, EEG, ECG, SUDEP

Objectives: The goal of this study was to define the parameters of movement of indocyanine green in the upper extremity of normal control and hand transplant recipients. The purpose was to establish a non-invasive method of determining the level of lymphatic function in hand transplant recipients. In hand transplantation (and replantation), the deep lymphatic vessels are rarely repaired, resulting in altered lymphatic connections. In most cases, the relatively rapid inosculation of superficial lymphatic networks and drainage via the venous systems results in sufficient interstitial fluid and lymph drainage of the graft to prevent edema. However, our group and others have determined that some transplant recipients demonstrate chronic edema which is associated with lymphatic stasis. In one case, a patient with chronic edema has developed chronic rejection characterized by thinning of the skin, loss of adnexal structures, and fibrosis and contracture of the hand. Methods: Lymphatic function was evaluated by intradermal administration of near-infrared fluorescent dye, indocyanine green, and dynamic imaging with an infrared camera system (LUNA). To date, the assessment of lymphatic drainage in the upper extremity by clearance of indocyanine green dye has been studied primarily in oncology patients with abnormal lymphatic function, making assessment of normal drainage problematic. To establish normal parameters, indocyanine green lymphatic clearance functional tests were performed in a series of normal controls, and subsequently compared with indocyanine green clearance in hand transplant recipients. Results: The results demonstrate varied patterns of lymphatic drainage in the hand transplant patients that partially mimic normal hand lymphatic drainage, but also share characteristics of lymphedema patients defined in other studies. The study revealed significant deceleration of the dye drainage in the allograft of a patient with suspected chronic rejection and edema of the graft. Analysis of other hand transplant recipients revealed differing levels of dye deceleration, often localized at the level of surgical anastomosis. Conclusion: These studies suggest intradermal injection of indocyanine green and near-infrared imaging may be a useful clinical tool to assess adequacy of lymphatic function in hand transplant recipients.

Effects of nitrogen (N) deposition on microbially-driven processes in oligotrophic freshwater ecosystems are poorly understood. We quantified guilds in the main N-transformation pathways in benthic habitats of 11 mountain lakes along a dissolved inorganic nitrogen gradient. The genes involved in denitrification (nirS, nirK, nosZ), nitrification (archaeal and bacterial amoA), dissimilatory nitrate reduction to ammonium (DNRA, nrfA) and anaerobic ammonium oxidation (anammox, hdh) were quantified, and the bacterial 16S rRNA gene was sequenced. The dominant pathways and associated bacterial communities defined four main N-transforming clusters that differed across habitat types. DNRA dominated in the sediments, except in the upper layers of more productive lakes where nirS denitrifiers prevailed with potential N2O release. Loss as N2 was more likely in lithic biofilms, as indicated by the higher hdh and nosZ abundances. Archaeal ammonia oxidisers predominated in the isoetid rhizosphere and rocky littoral sediments, suggesting nitrifying hotspots. Overall, we observed a change in potential for reactive N recycling via DNRA to N losses via denitrification as lake productivity increases in oligotrophic mountain lakes. Thus, N deposition results in a shift in genetic potential from an internal N accumulation to an atmospheric release in the respective lake systems, with increased risk for N2O emissions from productive lakes.

Agricultural soils are a significant source of anthropogenic nitrous oxide (N2O) emissions, because of fertilizer application and decomposition of crop residues. We studied interactions between nitrogen (N) amendments and soil conditions in a 2-year field experiment with or without catch crop incorporation before seeding of spring barley, and with or without application of N in the form of digested liquid manure or mineral N fertilizer. Weather conditions, soil inorganic N dynamics, and N2O emissions were monitored during spring, and soil samples were analyzed for abundances of nitrite reduction (nirK and nirS) and N2O reduction genes (nosZ clade I and II), and structure of nitrite- and N2O-reducing communities. Fertilization significantly enhanced soil mineral N accumulation compared to treatments with catch crop residues as the only N source. Nitrous oxide emissions, in contrast, were stimulated in rotations with catch crop residue incorporation, probably as a result of concurrent net N mineralization, and O2 depletion associated with residue degradation in organic hotspots. Emissions of N2O from digested manure were low in both years, while emissions from mineral N fertilizer were nearly absent in the first year, but comparable to emissions from catch crop residues in the second year with higher precipitation and delayed plant N uptake. Higher gene abundances, as well as shifts in community structure, were also observed in the second year, which were significantly correlated to NO3- availability. Both the size and structure of the nitrite- and N2O-reducing communities correlated to the difference in N2O emissions between years, while there were no consistent effects of management as represented by catch crops or fertilization. It is concluded that N2O emissions were constrained by environmental, rather than the genetic potential for nitrite and N2O reduction.