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BackgroundShared decision-making (SDM) has yet to be successfully adopted into routine use in psychiatric settings amongst people living with severe mental illnesses. Suboptimal rates of SDM are particularly prominent amongst patients with psychotic illnesses during antipsychotic treatment choices. Many interventions have been assessed for their efficacy in improving SDM within this context, although results have been variable and inconsistent.AimsTo generate an in-depth understanding of how, why, for whom, and to what extent interventions facilitating the application of SDM during antipsychotic treatment choices work and the impact of contextual factors on intervention effectiveness.MethodsThis review will use realist review methodology to provide a causal understanding of how and why interventions work when implementing SDM during antipsychotic treatment choices. The cohort of interest will be those experiencing psychosis where ongoing treatment with an antipsychotic is clinically indicated. The review will take place over five stages; (1) Locating existing theories, (2) Searching for evidence, (3) Selecting articles, (4) Extracting and organising data and (5) Synthesizing evidence and drawing conclusions. An understanding of how and why interventions work will be achieved by developing realist programme theories on intervention effectiveness through iterative literature reviews and engaging with various stakeholder groups, including patient, clinician and carer representatives.DiscussionThis is the first realist review aiming to identify generative mechanisms explaining how and why successful interventions aimed at improving SDM within the parameters outlined work and in which contexts desired outcomes are most likely to be achieved. Review findings will include suggestions for clinicians, policy and decision-makers about the most promising interventions to pursue and their ideal attributes.

BackgroundThe COVID-19 pandemic has accelerated the transition to remote work, leading to increased attention on presenteeism and absenteeism among remote workers. Understanding the implications of these phenomena on worker health and productivity is crucial for optimizing remote work arrangements and developing policies to improve employee well-being.ObjectivesThis scoping review aims to examine the occurrence of presenteeism and absenteeism among remote workers during the COVID-19 pandemic and the interrelated physical and mental health issues during these periods.MethodsPsycINFO, Medline, Embase, CINAHL, Eric, Business Source Premier, SCOPUS, and sociological abstracts were searched resulting in 1792 articles. Articles were included if the population of interest was 18+ (i.e., working age), engaged in full or part-time work, and the employees shifted from in-person to remote work due to the COVID-19 pandemic. All study designs, geographical areas, and papers written post-onset of the COVID-19 pandemic were included; however, systematic reviews were excluded. Data was charted into Microsoft Excel by 2 independent reviewers.ResultsThe literature search identified 10 studies (i.e., seven cross-sectional studies, two qualitative studies, and one observational study). Five major overarching themes were identified specifically (1) telework and mental health (2) telework and physical health (3) worker benefits (4) gender dynamics and (5) difficulty navigating the teleworking environment. While remote work offers flexibility in terms of saved commute time and flexible work schedules, it also exacerbates challenges related to presenteeism, absenteeism, and work-life balance. These challenges include experiencing psychological distress, depression, anxiety, stress, sleep deprivation, musculoskeletal pain, difficulties concentrating at work for both women and working parents, struggles disconnecting after hours, and the inability to delineate between the work and home environment.DiscussionThe findings suggest that remote work during the COVID-19 pandemic has both positive and negative implications for worker well-being and productivity. However, future research needs to incorporate the potential effects of telework frequency (full time vs. part time) on employee productivity and its role on presenteeism and absenteeism, to gain a more comprehensive understanding on remote work difficulties. Addressing these challenges requires proactive interventions and support mechanisms to promote worker health and productivity in remote settings.

Previous research demonstrating that positive episodic simulation enhances future expectancies has relied on explicit expectancy measures. The current study investigated the effects of episodic simulation on implicit expectancies. Using the Future Thinking Implicit Relational Assessment Procedure (FT-IRAP), participants made true/false decisions to indicate whether or not they expected positive/negative outcomes after adopting orientations consistent or inconsistent with an optimistic disposition. The outcome measure, DIRAP, was based on response time differences between consistent and inconsistent blocks. Participants then engaged in either positive simulation training, in which they imagined positive future events, or a neutral visualisation task before repeating the FT-IRAP twice following 10-minute intervals. Positive simulation training increased DIRAP scores for don't-expect-negative trials-boosting participants' readiness to affirm that negative events were unlikely to happen to them. Although findings did not generalise across all trial types, they show potential for positive simulation training to enhance implicit future expectancies.

Stress is a prevalent bodily response universally experienced and significantly affects a person's mental and cognitive state. The P300 response is a commonly observed brain behaviour that provides insight into a person's cognitive state. Previous works have documented the effects of stress on the P300 behaviour; however, only a few have explored the performance in a mobile and naturalistic experimental setup. Our study examined the effects of stress on the human brain's P300 behaviour through a height exposure experiment that incorporates complex visual, vestibular, and proprioceptive stimuli. A more complex sensory environment could produce translatable findings toward real-world behaviour and benefit emerging technologies such as brain-computer interfaces. Seventeen participants experienced our experiment that elicited the stress response through physical and virtual height exposure. We found two unique groups within our participants that exhibited contrasting behavioural performance and P300 target reaction response when exposed to stressors (from walking at heights). One group performed worse when exposed to heights and exhibited a significant decrease in parietal P300 peak amplitude and increased beta and gamma power. On the other hand, the group less affected by stress exhibited a change in their N170 peak amplitude and alpha/mu rhythm desynchronisation. The findings of our study suggest that a more individualised approach to assessing a person's behaviour performance under stress can aid in understanding P300 performance when experiencing stress.

Inundative biological control (biocontrol) efforts in pest management lead to the mass distribution of commercialized biocontrol agents. Many 'biocontrol gone awry' incidents have resulted in disastrous biodiversity impacts, leading to increased scrutiny of biocontrol efforts. The nematode Phasmarhabditis hermaphrodita is sold as a biocontrol agent on three continents and targets pest gastropods such as Deroceras reticulatum, the Grey Field Slug; P. hermaphrodita is not presently approved for use in the United States. Investigations into the potential for P. hermaphrodita to infect non-target gastropod species of conservation relevance, however, are limited. We examined the effects of three strains of P. hermaphrodita on mortality in Monadenia fidelis, the Pacific Sideband, a snail species endemic to the Pacific Northwest of North America, in laboratory conditions. Across a 71-day laboratory infectivity assay, snails exposed to each of the three nematode strains, each analyzed at two doses, experienced a mean 50% mortality by days 20-42. All nematode-treated snails were dead by the end of the study. By contrast, 30/30 water-control snails experienced no mortality. Nematodes killed smaller, juvenile-stage snails significantly faster than those in larger and more developmentally advanced hosts. Our results provide direct evidence that the biocontrol nematode P. hermaphrodita infects and kills M. fidelis, a non-target gastropod species endemic to the Pacific Northwest, in laboratory conditions. This study suggests that introduction of P. hermaphrodita to new ecosystems might negatively impact endemic gastropod biodiversity and advocates for further investigation of non-target effects, including in conditions closer to the natural environments of non-target species.

BackgroundT cell activation (HLA-DR, CD-38), proliferation (KI-67), and functional (IFN-γ, TNF-α) markers have recently been shown to be useful in predicting and monitoring anti-TB responses in smear positive TB, but previous research did not characterize the activation and proliferation profiles after therapy of smear negative TB.MethodologyIn this study, we used polychromatic flow cytometry to assess selected PPD-specific T cell markers using fresh PBMC of smear negative and positive pulmonary tuberculosis (PTB) patients, recruited from health facilities in Addis Ababa.ResultLevels of activation (HLA-DR, CD38) and proliferation (Ki-67) among total unstimulated CD4 T cells decreased significantly after therapy, particularly at month 6. Similarly, levels of PPD-specific T cell activation markers (HLA-DR, CD-38) were significantly lower in smear positive PTB patients following treatment, whereas a consistent decline in these markers was less apparent among smear negative PTB patients at the sixth month.ConclusionAfter six months of standard anti-TB therapy, persistent levels of activation of HLA-DR and CD-38 from PPD specific CD4+T cells in this study could indicate that those markers have little value in monitoring and predicting anti-TB treatment response in smear negative pulmonary TB patients in Ethiopian context.

Huanglongbing (HLB) is a deadly, incurable citrus disease putatively caused by the unculturable bacterium, 'Candidatus Liberibacter asiaticus' (CLas), and transmitted by Diaphorina citri. Prior studies suggest D. citri transmits CLas in a circulative and propagative manner; however, the precise interactions necessary for CLas transmission remain unknown, and the impact of insect sex on D. citri-CLas interactions is poorly understood despite reports of sex-dependent susceptibilities to CLas. We analyzed the transcriptome, proteome, metabolome, and microbiome of male and female adult D. citri reared on healthy or CLas-infected Citrus medica to determine shared and sex-specific responses of D. citri and its endosymbionts to CLas exposure. More sex-specific than shared D. citri responses to CLas were observed, despite there being no difference between males and females in CLas density or relative abundance. CLas exposure altered the abundance of proteins involved in immunity and cellular and oxidative stress in a sex-dependent manner. CLas exposure impacted cuticular proteins and enzymes involved in chitin degradation, as well as energy metabolism and abundance of the endosymbiont 'Candidatus Profftella armatura' in both sexes similarly. Notably, diaphorin, a toxic Profftella-derived metabolite, was more abundant in both sexes with CLas exposure. The responses reported here resulted from a combination of CLas colonization of D. citri as well as the effect of CLas infection on C. medica. Elucidating these impacts on D. citri and their endosymbionts contributes to our understanding of the HLB pathosystem and identifies the responses potentially critical to limiting or promoting CLas acquisition and propagation in both sexes.

Wearable smart glasses are an emerging technology gaining popularity in the assistive technologies industry. Smart glasses aids typically leverage computer vision and other sensory information to translate the wearer's surrounding into computer-synthesized speech. In this work, we explored the potential of a new technique known as "acoustic touch" to provide a wearable spatial audio solution for assisting people who are blind in finding objects. In contrast to traditional systems, this technique uses smart glasses to sonify objects into distinct sound auditory icons when the object enters the device's field of view. We developed a wearable Foveated Audio Device to study the efficacy and usability of using acoustic touch to search, memorize, and reach items. Our evaluation study involved 14 participants, 7 blind or low-visioned and 7 blindfolded sighted (as a control group) participants. We compared the wearable device to two idealized conditions, a verbal clock face description and a sequential audio presentation through external speakers. We found that the wearable device can effectively aid the recognition and reaching of an object. We also observed that the device does not significantly increase the user's cognitive workload. These promising results suggest that acoustic touch can provide a wearable and effective method of sensory augmentation.

BackgroundLateral flow tests (LFTs) have been used to screen for SARS-CoV2 in Wales since January 2021. Between May and August 2021, adult care home staff policy was for biweekly Innova LFT and weekly Polymerase Chain Reaction (PCR) testing while asymptomatic. We estimated test performance of LFTs conducted in adult care home staff using PCR tests as a reference standard.MethodsTest results from surveillance data were matched by individual where both LFT and PCR were taken on the same day. We calculated sensitivity, specificity, positive and negative predictive values, and agreement using Matthew's correlation coefficient. Ct values of positive PCR results were compared by matched LFT result. Analysis was conducted using R v4.1.3.ResultsWe analysed 115,593 test pairs, 499 (0.43%) of which were PCR positive. Median age was 48 (IQR: 22) and 85.00% of the study population were female. Test result agreement was 99.59% (95%CI 99.55-99.63; MCC: 0.38, pConclusionsSpecificity and negative predictive value were high in an asymptomatic population of care home staff indicating this test is an effective tool for identifying cases of SARS-CoV-2 infection during periods of high prevalence where transmission is likely, due to the presence of high viral loads. Positive predictive value results are lower than existing literature yet should be considered in light of the asymptomatic study population and low prevalence (under 1%) at the time most of these tests were conducted. Performance improved at times of higher prevalence during the study. These results suggest that whilst lateral flow tests are effective for identifying SARS-COV-2 infections with high viral loads, they are not effective at identifying cases with a low viral load. When an LFT provides a negative result, false negatives should be considered and additional diagnostic tests performed.

IntroductionThe maintenance phase of acute lymphoblastic leukemia treatment is the final and longest stage of treatment, mainly focused on antimetabolite therapy. This phase is essential to eliminate residual leukemic clones and prevent relapse. However, dose-limiting hematotoxicity is a major problem during this phase resulting in dose reduction or treatment discontinuation.ObjectiveIn this cohort study, the clinical features and risk factors of hematological toxicity during the maintenance phase of treatment were analyzed in pediatric patients from Ethiopia.MethodsA total of 160 patients from Tikur Anbessa specialized hospital were included in the study of which 142 had sufficient data available for analysis. Patient characteristics as well as information about the care-givers, sides-effects as reported by the care-givers and clinical factors were collected. Bivariable followed by multivariable analysis was performed to investigate which factors were associated with hematological toxicity during the maintenance phase.ResultsDuring the first six months of maintenance phase treatment grade 4 neutropenia was detected in 52.8% of the patients. The risk of developing grade 4 neutropenia was increased by about two fold in children with the age of 6 years and less compared to those with the age of more than 6 years. Similarly, the rate of developing grade 4 neutropenia among children with less than 4,500 maintenance day 1 white blood cell counts was significantly higher than that of children with normal maintenance day 1 white blood cell counts (AHR 2.477, 95% CI = 1.461-4.200, p = 0.001).ConclusionIn conclusion, child's age and day 1 maintenance white blood cell/absolute neutrophil counts significantly affected the occurrence of grade 4 hematotoxicity. Close monitoring for white blood cell and absolute neutrophil counts during maintenance phase treatment is recommended for early diagnosis of hematotoxicity.

Cardiovascular disease (CVD) is influenced by genetic and environmental factors. Childhood maltreatment is associated with CVD and may modify genetic susceptibility to cardiovascular risk factors. We used genetic and phenotypic data from 100,833 White British UK Biobank participants (57% female; mean age = 55.9 years). We regressed nine cardiovascular risk factors/diseases (alcohol consumption, body mass index [BMI], low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes, and stroke) on their respective polygenic scores (PGS) and self-reported exposure to childhood maltreatment. Effect modification was tested on the additive and multiplicative scales by including a product term (PGS*maltreatment) in regression models. On the additive scale, childhood maltreatment accentuated the effect of genetic susceptibility to higher BMI (Peffect modification: 0.003). Individuals not exposed to childhood maltreatment had an increase in BMI of 0.12 SD (95% CI: 0.11, 0.13) per SD increase in BMI PGS, compared to 0.17 SD (95% CI: 0.14, 0.19) in those exposed to all types of childhood maltreatment. On the multiplicative scale, similar results were obtained for BMI though these did not withstand to Bonferroni correction. There was little evidence of effect modification by childhood maltreatment in relation to other outcomes, or of sex-specific effect modification. Our study suggests the effects of genetic susceptibility to a higher BMI may be moderately accentuated in individuals exposed to childhood maltreatment. However, gene*environment interactions are likely not a major contributor to the excess CVD burden experienced by childhood maltreatment victims.

BackgroundMitochondria are organelles responsible for converting glucose into energy. Mitochondrial DNA is exclusively maternally inherited. The role of mitochondrial DNA haplogroups in the aetiology of cardiometabolic disease risk is not well understood.MethodsSex-specific associations between common European mitochondrial DNA haplogroups (H, U, J, T, K, V, W, I and X) and trajectories of cardiometabolic risk factors from birth to 18 years were examined in a prospective cohort. Cardiometabolic risk factors measured from birth/mid-childhood to 18 years included body mass index (BMI), fat and lean mass, systolic and diastolic blood pressure, pulse rate, high-density lipoprotein cholesterol (HDL-c), non-HDL-c and triglycerides. Fractional polynomial and linear spline multilevel models explored the sex-specific association between haplogroups and risk factor trajectories.ResultsAmong a total of 7,954 participants with 79,178 repeated measures per outcome, we found no evidence that haplogroups U, T, J, K and W were associated with cardiometabolic risk factors compared to haplogroup H. In females, haplogroup V was associated with 4.0% (99% CI: -7.5, -0.6) lower BMI at age one but associations did not persist at age 18. Haplogroup X was associated with 1.3kg (99% CI: -2.5, -0.2) lower lean mass at age 9 which persisted at 18. Haplogroup V and X were associated with 9.3% (99% CI: -0.4, 19.0) and 16.4% (99% CI: -0.5,33.3) lower fat mass at age 9, respectively, although confidence intervals spanned the null and associations did not persist at 18. In males, haplogroup I was associated with 2.4% (99% CI: -0.5, 5.3) higher BMI at age 7; widening to 5.1% (99% CI: -0.5, 10.6) at 18 with confidence intervals spanning the null.ConclusionsOur study demonstrated little evidence of sex-specific associations between mitochondrial DNA haplogroups and cardiometabolic risk factors.

Background: Shared decision-making (SDM) has yet to be successfully adopted into routine use in psychiatric settings amongst people living with severe mental illnesses. Suboptimal rates of SDM are particularly prominent amongst patients with psychotic illnesses during antipsychotic treatment choices. Many interventions have been assessed for their efficacy in improving SDM within this context, although results have been variable and inconsistent. Aims: To generate an in-depth understanding of how, why, for whom, and to what extent interventions facilitating the application of SDM during antipsychotic treatment choices work and the impact of contextual factors on intervention effectiveness. Methods: This review will use realist review methodology to provide a causal understanding of how and why interventions work when implementing SDM during antipsychotic treatment choices. The cohort of interest will be those experiencing psychosis where ongoing treatment with an antipsychotic is clinically indicated. The review will take place over five stages; (1) Locating existing theories, (2) Searching for evidence, (3) Selecting articles, (4) Extracting and organising data and (5) Synthesizing evidence and drawing conclusions. An understanding of how and why interventions work will be achieved by developing realist programme theories on intervention effectiveness through iterative literature reviews and engaging with various stakeholder groups, including patient, clinician and carer representatives. Discussion: This is the first realist review aiming to identify generative mechanisms explaining how and why successful interventions aimed at improving SDM within the parameters outlined work and in which contexts desired outcomes are most likely to be achieved. Review findings will include suggestions for clinicians, policy and decision-makers about the most promising interventions to pursue and their ideal attributes. [ABSTRACT FROM AUTHOR]

Previous research demonstrating that positive episodic simulation enhances future expectancies has relied on explicit expectancy measures. The current study investigated the effects of episodic simulation on implicit expectancies. Using the Future Thinking Implicit Relational Assessment Procedure (FT-IRAP), participants made true/false decisions to indicate whether or not they expected positive/negative outcomes after adopting orientations consistent or inconsistent with an optimistic disposition. The outcome measure, DIRAP, was based on response time differences between consistent and inconsistent blocks. Participants then engaged in either positive simulation training, in which they imagined positive future events, or a neutral visualisation task before repeating the FT-IRAP twice following 10-minute intervals. Positive simulation training increased DIRAP scores for don't-expect-negative trials–boosting participants' readiness to affirm that negative events were unlikely to happen to them. Although findings did not generalise across all trial types, they show potential for positive simulation training to enhance implicit future expectancies. [ABSTRACT FROM AUTHOR]

BackgroundApraxia and action disorganization syndrome (AADS) after stroke can disrupt activities of daily living (ADL). Occupational therapy has been effective in improving ADL performance, however, inclusion of multiple tasks means it is unclear which therapy elements contribute to improvement. We evaluated the efficacy of a task model approach to ADL rehabilitation, comparing training in making a cup of tea with a stepping training control condition.MethodsOf the 29 stroke survivors with AADS who participated in this cross-over randomized controlled feasibility trial, 25 were included in analysis [44% females; mean(SD) age = 71.1(7.8) years; years post-stroke = 4.6(3.3)]. Participants attended five 1-hour weekly tea making training sessions in which progress was monitored and feedback given using a computer-based system which implemented a Markov Decision Process (MDP) task model. In a control condition, participants received five 1-hour weekly stepping sessions.ResultsCompared to stepping training, tea making training reduced errors across 4 different tea types. The time taken to make a cup of tea was reduced so the improvement in accuracy was not due to a speed-accuracy trade-off. No improvement linked to tea making training was evident in a complex tea preparation task (making two different cups of tea simultaneously), indicating a lack of generalisation in the training.ConclusionsThe clearly specified but flexible training protocol, together with information on the distribution of errors, provide pointers for further refinement of task model approaches to ADL rehabilitation. It is recommended that the approach be tested under errorless learning conditions with more impaired patients in future research.Trial registrationRetrospectively registered at ClinicalTrials.gov on 5th August 2019 [NCT04044911] https://clinicaltrials.gov/ct2/show/NCT04044911?term=Cogwatch&rank=1.

BackgroundMaintaining patient privacy when geocoding and linking residential address information with neighborhood-level data can create challenges during research. Challenges may arise when study staff have limited training in geocoding and linking data, or when non-study staff with appropriate expertise have limited availability, are unfamiliar with a study's population or objectives, or are not affordable for the study team. Opportunities for data breaches may also arise when working with non-study staff who are not on-site. We detail a free, user-friendly protocol for constructing indices of the neighborhood risk environment during multisite, clinic-based cohort studies that rely on participants' protected health information. This protocol can be implemented by study staff who do not have prior training in Geographic Information Systems (GIS) and can help minimize the operational costs of integrating geographic data into public health projects.MethodsThis protocol demonstrates how to: (1) securely geocode patients' residential addresses in a clinic setting and match geocoded addresses to census tracts using Geographic Information System software (Esri, Redlands, CA); (2) ascertain contextual variables of the risk environment from the American Community Survey and ArcGIS Business Analyst (Esri, Redlands, CA); (3) use geoidentifiers to link neighborhood risk data to census tracts containing geocoded addresses; and (4) assign randomly generated identifiers to census tracts and strip census tracts of their geoidentifiers to maintain patient confidentiality.ResultsCompletion of this protocol generates three neighborhood risk indices (i.e., Neighborhood Disadvantage Index, Murder Rate Index, and Assault Rate Index) for patients' coded census tract locations.ConclusionsThis protocol can be used by research personnel without prior GIS experience to easily create objective indices of the neighborhood risk environment while upholding patient confidentiality. Future studies can adapt this protocol to fit their specific patient populations and analytic objectives.

Movement behaviors have been associated with mental health. The purposes of this study were to examine the association between movement behaviors and scores of depression/anxiety among adolescents and to determine the difference in depression/anxiety associated with reallocating time between different movement behaviors. This cross-sectional study included 217 Brazilian adolescents (15 to 18 years old, 49.3% female). Adolescents wore an accelerometer for one week to assess the four-movement behaviors which include sleep, sedentary behavior (SB), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). The depression/anxiety score was calculated by factor analysis using the 12-item General Health Questionnaire. Compositional data analyses were used to examine the association between movement behavior and the depression/anxiety score. Compositional isotemporal substitution models estimated the change in depression/anxiety score associated with reallocating 10, 30, and 60 min between movement behaviors. The composition of movement behaviors was significantly associated with depression/anxiety scores (p < 0.05). Replacing time from SB to LPA was associated with improvement in the depression/anxiety score, while the inverse was associated with an increase in this score. Replacing time of LPA with MVPA was associated with worsening in the depression/anxiety score. The 24-h time distribution of the day may play a crucial role in mental health. Compositions with more time spent in LPA at the expense of less SB are associated with improvement in the scores of depression/anxiety. The type of MVPA may moderate its effects on depression/anxiety in adolescents. Holistic interventions including the full range of movement behaviors may be a gateway to reduce the levels of depression/anxiety in adolescence.

In meiosis, cells undergo two sequential rounds of cell division, termed meiosis I and meiosis II. Textbook models of the meiosis I substage called pachytene show that nuclei have conspicuous 100-nm-wide, ladder-like synaptonemal complexes and ordered chromatin loops. It remains unknown if these cells have any other large, meiosis-related intranuclear structures. Here we present cryo-ET analysis of frozen-hydrated budding yeast cells before, during, and after pachytene. We found no cryo-ET densities that resemble dense ladder-like structures or ordered chromatin loops. Instead, we found large numbers of 12-nm-wide triple-helices that pack into ordered bundles. These structures, herein called meiotic triple helices (MTHs), are present in meiotic cells, but not in interphase cells. MTHs are enriched in the nucleus but not enriched in the cytoplasm. Bundles of MTHs form at the same timeframe as synaptonemal complexes (SCs) in wild-type cells and in mutant cells that are unable to form SCs. These results suggest that in yeast, SCs coexist with previously unreported large, ordered assemblies.

Very little is known about the role of early interactions in the development of peer relationships among toddlers. The present study examined whether behaviors early in the formation of toddler relationships predict interactions later in their relationships. Twenty-eight unfamiliar 20- and 30-month-old toddlers from a predominately European background met separately with each of two other toddlers for 18 playdates. Both positive and negative behaviors at the beginning of the relationship predicted a higher frequency of games later in the relationship. Positive behaviors at the beginning of the relationship predicted fewer conflicts later in the relationship. Negative behaviors at the beginning predicted more conflicts later in the relationship. These findings suggest that toddlers' behaviors, when they initially meet, underlie the pathway in which their relationship develops.

ImportanceA lack of internationally agreed standards for combining available data sources at scale risks inconsistent disease phenotyping limiting research reproducibility.ObjectiveTo develop and then evaluate if a rules-based algorithm can identify coronary artery disease (CAD) sub-phenotypes using electronic health records (EHR) and questionnaire data from UK Biobank (UKB).DesignCase-control and cohort study.SettingProspective cohort study of 502K individuals aged 40-69 years recruited between 2006-2010 into the UK Biobank with linked hospitalization and mortality data and genotyping.ParticipantsWe included all individuals for phenotyping into 6 predefined CAD phenotypes using hospital admission and procedure codes, mortality records and baseline survey data. Of these, 408,470 unrelated individuals of European descent had a polygenic risk score (PRS) for CAD estimated.ExposureCAD Phenotypes.Main outcomes and measuresAssociation with baseline risk factors, mortality (n = 14,419 over 7.8 years median f/u), and a PRS for CAD.ResultsThe algorithm classified individuals with CAD into prevalent MI (n = 4,900); incident MI (n = 4,621), prevalent CAD without MI (n = 10,910), incident CAD without MI (n = 8,668), prevalent self-reported MI (n = 2,754); prevalent self-reported CAD without MI (n = 5,623), yielding 37,476 individuals with any type of CAD. Risk factors were similar across the six CAD phenotypes, except for fewer men in the self-reported CAD without MI group (46.7% v 70.1% for the overall group). In age- and sex- adjusted survival analyses, mortality was highest following incident MI (HR 6.66, 95% CI 6.07-7.31) and lowest for prevalent self-reported CAD without MI at baseline (HR 1.31, 95% CI 1.15-1.50) compared to disease-free controls. There were similar graded associations across the six phenotypes per SD increase in PRS, with the strongest association for prevalent MI (OR 1.50, 95% CI 1.46-1.55) and the weakest for prevalent self-reported CAD without MI (OR 1.08, 95% CI 1.05-1.12). The algorithm is available in the open phenotype HDR UK phenotype library (https://portal.caliberresearch.org/).ConclusionsAn algorithmic, EHR-based approach distinguished six phenotypes of CAD with distinct survival and PRS associations, supporting adoption of open approaches to help standardize CAD phenotyping and its wider potential value for reproducible research in other conditions.

To investigate impression formation, researchers tend to rely on statements that describe a person’s behavior (e.g., “Alex ridicules people behind their backs”). These statements are presented to participants who then rate their impressions of the person. However, a corpus of behavior statements is costly to generate, and pre-existing corpora may be outdated and might not measure the dimension(s) of interest. The present study makes available a normed corpus of 160 contemporary behavior statements that were rated on 4 dimensions relevant to impression formation: morality, competence, informativeness, and believability. In addition, we show that the different dimensions are non-independent, exhibiting a range of linear and non-linear relationships, which may present a problem for past research. However, researchers interested in impression formation can control for these relationships (e.g., statistically) using the present corpus of behavior statements.

ObjectiveEmerging evidences suggest that the trans-neural propagation of phosphorylated 43-kDa transactive response DNA-binding protein (pTDP-43) contributes to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). We investigated whether Network Diffusion Model (NDM), a biophysical model of spread of pathology via the brain connectome, could capture the severity and progression of neurodegeneration (atrophy) in ALS.MethodsWe measured degeneration in limb-onset ALS patients (n = 14 at baseline, 12 at 6-months, and 9 at 12 months) and controls (n = 12 at baseline) using FreeSurfer analysis on the structural T1-weighted Magnetic Resonance Imaging (MRI) data. The NDM was simulated on the canonical structural connectome from the IIT Human Brain Atlas. To determine whether NDM could predict the atrophy pattern in ALS, the accumulation of pathology modelled by NDM was correlated against atrophy measured using MRI. In order to investigate whether network spread on the brain connectome derived from healthy individuals were significant findings, we compared our findings against network spread simulated on random networks.ResultsThe cross-sectional analyses revealed that the network diffusion seeded from the inferior frontal gyrus (pars triangularis and pars orbitalis) significantly predicts the atrophy pattern in ALS compared to controls. Whereas, atrophy over time with-in the ALS group was best predicted by seeding the network diffusion process from the inferior temporal gyrus at 6-month and caudal middle frontal gyrus at 12-month. Network spread simulated on the random networks showed that the findings using healthy brain connectomes are significantly different from null models.InterpretationOur findings suggest the involvement of extra-motor regions in seeding the spread of pathology in ALS. Importantly, NDM was able to recapitulate the dynamics of pathological progression in ALS. Understanding the spatial shifts in the seeds of degeneration over time can potentially inform further research in the design of disease modifying therapeutic interventions in ALS.

BackgroundT cell activation (HLA-DR, CD-38), proliferation (KI-67), and functional (IFN-γ, TNF-α) markers have recently been shown to be useful in predicting and monitoring anti-TB responses in smear positive TB, but previous research did not characterize the activation and proliferation profiles after therapy of smear negative TB.MethodologyIn this study, we used polychromatic flow cytometry to assess selected PPD-specific T cell markers using fresh PBMC of smear negative and positive pulmonary tuberculosis (PTB) patients, recruited from health facilities in Addis Ababa.ResultLevels of activation (HLA-DR, CD38) and proliferation (Ki-67) among total unstimulated CD4 T cells decreased significantly after therapy, particularly at month 6. Similarly, levels of PPD-specific T cell activation markers (HLA-DR, CD-38) were significantly lower in smear positive PTB patients following treatment, whereas a consistent decline in these markers was less apparent among smear negative PTB patients at the sixth month.ConclusionAfter six months of standard anti-TB therapy, persistent levels of activation of HLA-DR and CD-38 from PPD specific CD4+T cells in this study could indicate that those markers have little value in monitoring and predicting anti-TB treatment response in smear negative pulmonary TB patients in Ethiopian context.

K-mer abundance analysis is widely used for many purposes in nucleotide sequence analysis, including data preprocessing for de novo assembly, repeat detection, and sequencing coverage estimation. We present the khmer software package for fast and memory efficient online counting of k-mers in sequencing data sets. Unlike previous methods based on data structures such as hash tables, suffix arrays, and trie structures, khmer relies entirely on a simple probabilistic data structure, a Count-Min Sketch. The Count-Min Sketch permits online updating and retrieval of k-mer counts in memory which is necessary to support online k-mer analysis algorithms. On sparse data sets this data structure is considerably more memory efficient than any exact data structure. In exchange, the use of a Count-Min Sketch introduces a systematic overcount for k-mers; moreover, only the counts, and not the k-mers, are stored. Here we analyze the speed, the memory usage, and the miscount rate of khmer for generating k-mer frequency distributions and retrieving k-mer counts for individual k-mers. We also compare the performance of khmer to several other k-mer counting packages, including Tallymer, Jellyfish, BFCounter, DSK, KMC, Turtle and KAnalyze. Finally, we examine the effectiveness of profiling sequencing error, k-mer abundance trimming, and digital normalization of reads in the context of high khmer false positive rates. khmer is implemented in C++ wrapped in a Python interface, offers a tested and robust API, and is freely available under the BSD license at github.com/ged-lab/khmer.

Inundative biological control (biocontrol) efforts in pest management lead to the mass distribution of commercialized biocontrol agents. Many 'biocontrol gone awry' incidents have resulted in disastrous biodiversity impacts, leading to increased scrutiny of biocontrol efforts. The nematode Phasmarhabditis hermaphrodita is sold as a biocontrol agent on three continents and targets pest gastropods such as Deroceras reticulatum, the Grey Field Slug; P. hermaphrodita is not presently approved for use in the United States. Investigations into the potential for P. hermaphrodita to infect non-target gastropod species of conservation relevance, however, are limited. We examined the effects of three strains of P. hermaphrodita on mortality in Monadenia fidelis, the Pacific Sideband, a snail species endemic to the Pacific Northwest of North America, in laboratory conditions. Across a 71-day laboratory infectivity assay, snails exposed to each of the three nematode strains, each analyzed at two doses, experienced a mean 50% mortality by days 20–42. All nematode-treated snails were dead by the end of the study. By contrast, 30/30 water-control snails experienced no mortality. Nematodes killed smaller, juvenile-stage snails significantly faster than those in larger and more developmentally advanced hosts. Our results provide direct evidence that the biocontrol nematode P. hermaphrodita infects and kills M. fidelis, a non-target gastropod species endemic to the Pacific Northwest, in laboratory conditions. This study suggests that introduction of P. hermaphrodita to new ecosystems might negatively impact endemic gastropod biodiversity and advocates for further investigation of non-target effects, including in conditions closer to the natural environments of non-target species. [ABSTRACT FROM AUTHOR]

In recent years, a class of chemical compounds (benzoxaboroles) that are active against a range of parasites has been shown to target mRNA polyadenylation by inhibiting the activity of CPSF73, the endonucleolytic core of the eukaryotic polyadenylation complex. One particular compound, termed AN3661, is active against several apicomplexan parasites that cause disease in humans. In this study, we report that AN3661 is active against an apicomplexan that causes disease in horses and marine mammals (Sarcocystis neurona), with an approximate IC50 value of 14.99 nM. Consistent with the reported mode of action of AN3661 against other apicomplexans, S. neurona mutants resistant to AN3661 had an alteration in CPSF73 that was identical to a mutation previously documented in AN3661-resistant Toxoplasma gondii and Plasmodium falciparum. AN3661 had a wide-ranging effect on poly(A) site choice in S. neurona, with more than half of all expressed genes showing some alteration in mRNA 3’ ends. This was accompanied by changes in the relative expression of more than 25% of S. neurona genes and an overall 5-fold reduction of S. neurona transcripts in infected cells. In contrast, AN3661 had no discernible effect on poly(A) site choice or gene expression in the host cells. These transcriptomic studies indicate that AN3661 is exceedingly specific for the parasite CPSF73 protein, and has the potential to augment other therapies for the control of apicomplexan parasites in domestic animals.

MicroRNA (miRNA) circulating in plasma have been proposed as biomarkers for a variety of conditions and diseases, including complications during pregnancy. During pregnancy, about 15-25% of maternal plasma exosomes, a small size-class of EVs, are hypothesized to originate in the placenta, and may play a role in communication between the fetus and mother. However, few studies have addressed changes in miRNA over the course of pregnancy with repeated measures, nor focused on diverse populations. We describe changes in miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, CA. miRNA derived from extracellular-vesicles (EVs) were isolated from maternal blood plasma samples collected in early and late pregnancy. In this study, we identified 64 of 130 detectable miRNA which significantly increased with gestational age at the time of collection (GA), and 26 which decreased with GA. Possible fetal sex-specific associations were observed for 30 of these 90 significant miRNA. Predicted gene targets for miRNA significantly associated with GA were identified using MirDIP and were found to be enriched for Gene Ontology categories that included energetic and metabolic processes but were underrepresented in immune-related categories. Circulating EV-associated miRNA during pregnancy are likely important for maternal-fetal communication, and may play roles in supporting and maintaining a healthy pregnancy, given the changing needs of the fetus.

Building on previous research on the use of macroeconomic factors for conflict prediction and using data on political instability provided by the Political Instability Task Force, this article proposes two minimal forecasting models of political instability optimised to have the greatest possible predictive power for one-year and two-year event horizons, while still making predictions that are fully explainable. Both models employ logistic regression and use just three predictors: polity code (a measure of government type), infant mortality, and years of stability (i.e., years since the last instability event). These models make predictions for 176 countries on a country-year basis and achieve AUPRC's of 0.108 and 0.115 for the one-year and two-year models respectively. They use public data with ongoing availability so are readily reproducible. They use Monte Carlo simulations to construct confidence intervals for their predictions and are validated by testing their predictions for a set of reference years separate from the set of reference years used to train them. This validation shows that the models are not overfitted but suggests that some of the previous models in the literature may have been. The models developed in this article are able to explain their predictions by showing, for a given prediction, which predictors were the most influential and by using counterfactuals to show how the predictions would have been altered had these predictors taken different values. These models are compared to models created by lasso regression and it is shown that they have at least as good predictive power but that their predictions can be more readily explained. Because policy makers are more likely to be influenced by models whose predictions can explained, the more interpretable a model is the more likely it is to influence policy.

IntroductionPDL1 and its interaction with PD1 is implicated in immune dysfunction in TB and HIV. The expression of PDL1 on multiple subsets of monocytes as well as their associations with cytokines and microbial products have not been well studied.MethodHIV (TB-HIV+), TB (TB+HIV-) and TB/HIV co-infected (TB+HIV+) patients as well as apparently healthy controls (TB-HIV-) were recruited. TB and HIV patients were treatment naïve while TB/HIV patients were both ART naïve and experienced but not yet started TB therapy. Monocyte subsets were evaluated for PDL1 expression by flow cytometry; plasma TNFα, IL6, IP10, IFNγ and IL10 were measured by Luminex; and cytokine mRNA from purified monocytes quantitated by qPCR. The association of PDL1 with cytokines, clinical and microbial indices, including HIV viral load, TB smear microscopy and TB urinary lipoarabinomannan (LAM) were assessed.ResultsMonocyte expression of PDL1 was significantly higher in TB, HIV and TB/HIV co-infected patients compared with healthy controls (p = 0.0001), with the highest levels in TB/HIV co-infected patients. The highest expression of PDL1 was on intermediate (CD14+CD16+) monocytes in all participant groups. PDL1 strongly correlated with HIV viral load in TB/HIV while weakly correlated in HIV. PDL1 levels moderately correlated with plasma TNFα, IL6, IP10, IFNγ and IL10 level in TB subjects whereas weakly correlated with TNFα and IP10 in HIV patients. However, cytokine mRNA from purified monocytes showed no association with either plasma cytokines or monocyte PDL1 expression, implying that if cytokines modulate PDL1, they are likely not originating from circulating monocytes themselves. These results underscore the importance of further characterization of multiple monocyte subsets and their phenotypic and functional differences in different disease states.

Human modification of water and nutrient flows has resulted in widespread degradation of aquatic ecosystems. The resulting global water crisis causes millions of deaths and trillions of USD in economic damages annually. Semiarid regions have been disproportionately affected because of high relative water demand and pollution. Many proven water management strategies are not fully implemented, partially because of a lack of public engagement with freshwater ecosystems. In this context, we organized a large citizen science initiative to quantify nutrient status and cultivate connection in the semiarid watershed of Utah Lake (USA). Working with community members, we collected samples from ~200 locations throughout the 7,640 km2 watershed on a single day in the spring, summer, and fall of 2018. We calculated ecohydrological metrics for nutrients, major ions, and carbon. For most solutes, concentration and leverage (influence on flux) were highest in lowland reaches draining directly to the lake, coincident with urban and agricultural sources. Solute sources were relatively persistent through time for most parameters despite substantial hydrological variation. Carbon, nitrogen, and phosphorus species showed critical source area behavior, with 10-17% of the sites accounting for most of the flux. Unlike temperate watersheds, where spatial variability often decreases with watershed size, longitudinal variability showed an hourglass shape: high variability among headwaters, low variability in mid-order reaches, and high variability in tailwaters. This unexpected pattern was attributable to the distribution of human activity and hydrological complexity associated with return flows, losing river reaches, and diversions in the tailwaters. We conclude that participatory science has great potential to reveal ecohydrological patterns and rehabilitate individual and community relationships with local ecosystems. In this way, such projects represent an opportunity to both understand and improve water quality in diverse socioecological contexts.

Foam accumulation in swine manure deep-pits has been linked to explosions and flash fires that pose devastating threats to humans and livestock. It is clear that methane accumulation within these pits is the fuel for the fire; it is not understood what microbial drivers cause the accumulation and stabilization of methane. Here, we conducted a 13-month field study to survey the physical, chemical, and biological changes of pit-manure across 46 farms in Iowa. Our results showed that an increased methane production rate was associated with less digestible feed ingredients, suggesting that diet influences the storage pit's microbiome. Targeted sequencing of the bacterial 16S rRNA and archaeal mcrA genes was used to identify microbial communities' role and influence. We found that microbial communities in foaming and non-foaming manure were significantly different, and that the bacterial communities of foaming manure were more stable than those of non-foaming manure. Foaming manure methanogen communities were enriched with uncharacterized methanogens whose presence strongly correlated with high methane production rates. We also observed strong correlations between feed ration, manure characteristics, and the relative abundance of specific taxa, suggesting that manure foaming is linked to microbial community assemblage driven by efficient free long-chain fatty acid degradation by hydrogenotrophic methanogenesis.

AimThe aim of this scoping review was to determine the extent of off-patent prescription medicine use beyond registered indications in various Australian clinical settings.MethodThe review followed the Joanna Briggs Institute approach and reported using PRISMA Extension for Scoping Reviews. Online databases were used to identify published literature about off-patent registered prescription medicines used for off-label indications in Australian public hospital, community and primary healthcare settings. In addition, empirical data from the Queensland and the South Australian state-wide medicine formularies were screened for the same medication/off-label indication dyads identified in the literature, and other locally approved uses.ResultsOverall, fourteen studies were included, conducted in public hospitals (n = 11), palliative care units (n = 2) and the community setting (n = 1). There were 213 reports extracted from the literature describing off-patent registered prescription medicines used for off-label indications, representing 128 unique medication/off-label indication dyads and 32 different medicines. Of these, just five medication/off-label indication dyads were approved for use on both the Queensland and South Australian state-wide medicine formularies, with 12 others only approved for use in Queensland and 16 others only approved for use in South Australia. Further examination of these state-wide formularies demonstrated that the use of off-patent registered prescription medicines beyond registered indications is more extensive than has been reported to date in the literature. There were 28 additional medication/off-label indication dyads approved on the Queensland state-wide medicine formulary and 14 such examples approved for use in South Australia. Of these, just two medication/off-label indication dyads were approved for use on both formularies.ConclusionThe extent to which off-patent registered prescription medicines have been repurposed in clinical settings for off-label indications in Australia is greater than previously reported in the literature. Usage and funded availability of certain medication/off-label indication dyads, varies across Australia. These results further expose the two tiered system of medicines regulation in Australia, and its impact on equity of access to medicines. Further research is required to support policy change to encourage submission of registration updates for off-patent prescription medicines.

Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height2.7 (LVMi2.7) in adolescents. This study examined whether greater BP variability and reduced night-time dipping are associated with cardiac remodeling in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) LVMi2.7; 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. Measurement of BP variability, even in adolescents with blood pressure in the physiologic range, might benefit risk of cardiovascular remodeling assessment.

Antibiotics are administered to livestock in animal feeding operations (AFOs) for the control, prevention, and treatment of disease. Manure from antibiotic treated livestock contains unmetabolized antibiotics that provide selective pressure on bacteria, facilitating the expression of anti-microbial resistance (AMR). Manure application on row crops is an agronomic practice used by growers to meet crop nutrient needs; however, it can be a source of AMR to the soil and water environment. This study in central Iowa aims to directly compare AMR indicators in outlet runoff from two adjacent (221 to 229 ha) manured and non-manured catchments (manure comparison), and among three catchments (600 to 804 ha) with manure influence, no known manure application (control), and urban influences (mixed land use comparison). Monitored AMR indicators included antibiotic resistance genes (ARGs) ermB, ermF (macrolide), tetA, tetM, tetO, tetW (tetracycline), sul1, sul2 (sulfonamide), aadA2 (aminoglycoside), vgaA, and vgaB (pleuromutilin), and tylosin and tetracycline resistant enterococci bacteria. Results of the manure comparison showed significantly higher (p

A common approach to improving probabilistic forecasts is to identify and leverage the forecasts from experts in the crowd based on forecasters' performance on prior questions with known outcomes. However, such information is often unavailable to decision-makers on many forecasting problems, and thus it can be difficult to identify and leverage expertise. In the current paper, we propose a novel algorithm for aggregating probabilistic forecasts using forecasters' meta-predictions about what other forecasters will predict. We test the performance of an extremised version of our algorithm against current forecasting approaches in the literature and show that our algorithm significantly outperforms all other approaches on a large collection of 500 binary decision problems varying in five levels of difficulty. The success of our algorithm demonstrates the potential of using meta-predictions to leverage latent expertise in environments where forecasters' expertise cannot otherwise be easily identified.

Latent Class Analysis can assist researchers interested in a better understanding of behavioral patterns and their association with health outcomes. This study aimed to identify lifestyle latent classes related to distinct domains of physical activity (PA) and sedentary behavior (SB) among adolescents and their association with health outcomes. This cross-sectional study included 217 Brazilian adolescents (15 to 18 years old, 49.3% female). The classes were based on moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), number of steps, sedentary behavior (SB), and screen time (ST). To assess these behaviors, participants wore an accelerometer for one week. ST, demographic characteristics, socioeconomic status, and signs of common mental disorders (CMD) were evaluated through questionnaires. Latent Class Analysis was used to identify lifestyle classes. Three classes were recognized: "Active-Non-sedentary" (class 1) with 28.1% of adolescents; "Inactive-Non-sedentary" (class 2), 48.85%; and "Inactive-Sedentary" (class 3), 23.04%. Sex and signs of CMD were associated with the prevalence of the classes. Female adolescents presented 4.48 (95% CI 2.04-9.77) times more chance of belonging to the "Inactive-Sedentary" (class 3). Adolescents who presented CMD had 11.35 (95% CI 3.45-101.1) times more chance of belonging to the "Inactive-Non-sedentary" (class 2). The interaction between sex and signs of CMD showed that girls with signs of CMD were 9.20 (95% CI 1.17-71.52) more likely to belong to the Inactive-Sedentary class than the "Active-Non-sedentary". Results indicate that sex and signs of CMD can affect the prevalence of the classes. Our findings highlight that physical inactivity and SB can be associated with signs of CMD, especially in female adolescents.

Training prescription and monitoring of team-sport athletes rely on accurate quantification of player movement. Our aim was to determine the sensitivity, reliability and construct validity of measures derived from a wearable device incorporating Global Positioning System (GPS) and accelerometer technology to quantify the peak periods of rugby competition. Match movement data were collected from 30 elite and 30 sub-elite rugby union players across respective competitive seasons. Accelerometer and GPS measures were analysed using a rolling average to identify peak movement for epochs ranging from 5 to 600 seconds. General linear mixed modelling was used to quantify the effects of playing position and match-half on the peak movement and variabilities within and between players represented reliability of each measure. Mean positional differences and match-half changes were assessed via standardisation and magnitude-based decisions. Sensitivity of measures was quantified via evaluation of ("signal") and typical error of measurement ("noise"). GPS and accelerometer measures had poor sensitivity for quantifying peak movement across all epochs and both levels of rugby union competition (noise 4× to 5× the signal). All measures displayed correspondingly low reliability across most epochs and both levels of competition (ICC

Biological control (biocontrol) as a component of pest management strategies reduces reliance on synthetic chemicals, and seemingly offers a natural approach that minimizes environmental impact. However, introducing a new organism to new environments as a classical biocontrol agent can have broad and unanticipated biodiversity effects and conservation consequences. Nematodes are currently used in a variety of commercial biocontrol applications, including the use of Phasmarhabditis hermaphrodita as an agent targeting pest slug and snail species. This species was originally discovered in Germany, and is generally thought to have European origins. P. hermaphrodita is sold under the trade name Nemaslug®, and is available only in European markets. However, this nematode species was discovered in New Zealand and the western United States, though its specific origins remained unclear. In this study, we analyzed 45 nematode strains representing eight different Phasmarhabditis species, collected from nine countries around the world. A segment of nematode mitochondrial DNA (mtDNA) was sequenced and subjected to phylogenetic analyses. Our mtDNA phylogenies were overall consistent with previous analyses based on nuclear ribosomal RNA (rRNA) loci. The recently discovered P. hermaphrodita strains in New Zealand and the United States had mtDNA haplotypes nearly identical to that of Nemaslug®, and these were placed together in an intraspecific monophyletic clade with high support in maximum likelihood and Bayesian analyses. We also examined bacteria that co-cultured with the nematode strains isolated in Oregon, USA, by analyzing 16S rRNA sequences. Eight different bacterial genera were found to associate with these nematodes, though Moraxella osloensis, the bacteria species used in the Nemaslug® formulation, was not detected. This study provided evidence that nematodes deriving from the Nemaslug® biocontrol product have invaded countries where its use is prohibited by regulatory agencies and not commercially available.

Huanglongbing (HLB) is a deadly, incurable citrus disease putatively caused by the unculturable bacterium, 'Candidatus Liberibacter asiaticus' (CLas), and transmitted by Diaphorina citri. Prior studies suggest D. citri transmits CLas in a circulative and propagative manner; however, the precise interactions necessary for CLas transmission remain unknown, and the impact of insect sex on D. citri-CLas interactions is poorly understood despite reports of sex-dependent susceptibilities to CLas. We analyzed the transcriptome, proteome, metabolome, and microbiome of male and female adult D. citri reared on healthy or CLas-infected Citrus medica to determine shared and sex-specific responses of D. citri and its endosymbionts to CLas exposure. More sex-specific than shared D. citri responses to CLas were observed, despite there being no difference between males and females in CLas density or relative abundance. CLas exposure altered the abundance of proteins involved in immunity and cellular and oxidative stress in a sex-dependent manner. CLas exposure impacted cuticular proteins and enzymes involved in chitin degradation, as well as energy metabolism and abundance of the endosymbiont 'Candidatus Profftella armatura' in both sexes similarly. Notably, diaphorin, a toxic Profftella-derived metabolite, was more abundant in both sexes with CLas exposure. The responses reported here resulted from a combination of CLas colonization of D. citri as well as the effect of CLas infection on C. medica. Elucidating these impacts on D. citri and their endosymbionts contributes to our understanding of the HLB pathosystem and identifies the responses potentially critical to limiting or promoting CLas acquisition and propagation in both sexes.

Tuberous sclerosis complex is a dominant genetic disorder produced by mutations in either of two tumor suppressor genes, TSC1 and TSC2; it is characterized by hamartomatous tumors, and is associated with severe neurological and behavioral disturbances. Mutations in TSC1 or TSC2 deregulate a conserved growth control pathway that includes Ras homolog enriched in brain (Rheb) and Target of Rapamycin (TOR). To understand the function of this pathway in neural development, we have examined the contributions of multiple components of this pathway in both neuromuscular junction assembly and photoreceptor axon guidance in Drosophila. Expression of Rheb in the motoneuron, but not the muscle of the larval neuromuscular junction produced synaptic overgrowth and enhanced synaptic function, while reductions in Rheb function compromised synapse development. Synapse growth produced by Rheb is insensitive to rapamycin, an inhibitor of Tor complex 1, and requires wishful thinking, a bone morphogenetic protein receptor critical for functional synapse expansion. In the visual system, loss of Tsc1 in the developing retina disrupted axon guidance independently of cellular growth. Inhibiting Tor complex 1 with rapamycin or eliminating the Tor complex 1 effector, S6 kinase (S6k), did not rescue axon guidance abnormalities of Tsc1 mosaics, while reductions in Tor function suppressed those phenotypes. These findings show that Tsc-mediated control of axon guidance and synapse assembly occurs via growth-independent signaling mechanisms, and suggest that Tor complex 2, a regulator of actin organization, is critical in these aspects of neuronal development.