Physical and sexual violence, childhood sexual abuse and HIV/STI risk behaviour among alcohol-using women engaged in sex work in Mongolia

Although the prevalence of human immunodeficiency virus (HIV) in Mongolia is low, it could increase without strategic prevention strategies. Female sex workers (FSWs) often experience barriers to prevention, including interpersonal violence. This study investigated if childhood sexual abuse (CSA) or recent physical or sexual violence was associated with HIV sexual risk behaviours and if CSA modified associations between recent violence and HIV sexual risk behaviours. Two-hundred twenty-two women who (1) were at least 18 years old and clients at the National AIDS Foundation; (2) reported vaginal or anal sex in the past 90 days in exchange for money or goods and (3) met criteria for harmful alcohol use in the past year were enrolled. In-person interviews assessed sexual risk behaviours and violence in childhood and adulthood. Negative binomial regression, ordinary least squares regression and modified Poisson regression were performed. Sexual risk with paying partners was associated with penetrative CSA and sexual violence by paying partners. CSA and recent violence were not associated with sexual risk behaviours with intimate partners. CSA modified the association between recent sexual violence and unprotected sex with intimate partners. Findings highlight the need for integrated violence and sexual risk reduction services to ensure safe and effective prevention for FSWs

Chronic cigarette smoking is linked with structural alterations in brain regions showing acute nicotinic drug-induced functional modulations

Background Whereas acute nicotine administration alters brain function which may, in turn, contribute to enhanced attention and performance, chronic cigarette smoking is linked with regional brain atrophy and poorer cognition. However, results from structural magnetic resonance imaging (MRI) studies comparing smokers versus nonsmokers have been inconsistent and measures of gray matter possess limited ability to inform functional relations or behavioral implications. The purpose of this study was to address these interpretational challenges through meta-analytic techniques in the service of clarifying the impact of chronic smoking on gray matter integrity and more fully contextualizing such structural alterations. Methods We first conducted a coordinate-based meta-analysis of structural MRI studies to identify consistent structural alterations associated with chronic smoking. Subsequently, we conducted two additional meta-analytic assessments to enhance insight into potential functional and behavioral relations. Specifically, we performed a multimodal meta-analytic assessment to test the structural?functional hypothesis that smoking-related structural alterations overlapped those same regions showing acute nicotinic drug-induced functional modulations. Finally, we employed database driven tools to identify pairs of structurally impacted regions that were also functionally related via meta-analytic connectivity modeling, and then delineated behavioral phenomena associated with such functional interactions via behavioral decoding. Results Across studies, smoking was associated with convergent structural decreases in the left insula, right cerebellum, parahippocampus, multiple prefrontal cortex (PFC) regions, and the thalamus. Indicating a structural?functional relation, we observed that smoking-related gray matter decreases overlapped with the acute functional effects of nicotinic agonist administration in the left insula, ventromedial PFC, and mediodorsal thalamus. Suggesting structural-behavioral implications, we observed that the left insula?s task-based, functional interactions with multiple other structurally impacted regions were linked with pain perception, the right cerebellum?s interactions with other regions were associated with overt body movements, interactions between the parahippocampus and thalamus were linked with memory processes, and interactions between medial PFC regions were associated with face processing. Conclusions Collectively, these findings emphasize brain regions (e.g., ventromedial PFC, insula, thalamus) critically linked with cigarette smoking, suggest neuroimaging paradigms warranting additional consideration among smokers (e.g., pain processing), and highlight regions in need of further elucidation in addiction (e.g., cerebellum). Electronic supplementary material The online version of this article (doi:10.1186/s12993-016-0100-5) contains supplementary material, which is available to authorized users

ICA model order selection of task co-activation networks

Independent component analysis (ICA) has become a widely used method for extracting functional networks in the brain during rest and task. Historically, preferred ICA dimensionality has widely varied within the neuroimaging community, but typically varies between 20 and 100 components. This can be problematic when comparing results across multiple studies because of the impact ICA dimensionality has on the topology of its resultant components. Recent studies have demonstrated that ICA can be applied to peak activation coordinates archived in a large neuroimaging database (i.e., BrainMap Database) to yield whole-brain task-based co-activation networks. A strength of applying ICA to BrainMap data is that the vast amount of metadata in BrainMap can be used to quantitatively assess tasks and cognitive processes contributing to each component. In this study, we investigated the effect of model order on the distribution of functional properties across networks as a method for identifying the most informative decompositions of BrainMap-based ICA components. Our findings suggest dimensionality of 20 for low model order ICA to examine large-scale brain networks, and dimensionality of 70 to provide insight into how large-scale networks fractionate into sub-networks. We also provide a functional and organizational assessment of visual, motor, emotion, and interoceptive task co-activation networks as they fractionate from low to high model-orders

KILT: a Benchmark for Knowledge Intensive Language Tasks

Challenging problems such as open-domain question answering, fact checking, slot filling and entity linking require access to large, external knowledge sources. While some models do well on individual tasks, developing general models is difficult as each task might require computationally expensive indexing of custom knowledge sources, in addition to dedicated infrastructure. To catalyze research on models that condition on specific information in large textual resources, we present a benchmark for knowledge-intensive language tasks (KILT). All tasks in KILT are grounded in the same snapshot of Wikipedia, reducing engineering turnaround through the re-use of components, as well as accelerating research into task-agnostic memory architectures. We test both task-specific and general baselines, evaluating downstream performance in addition to the ability of the models to provide provenance. We find that a shared dense vector index coupled with a seq2seq model is a strong baseline, outperforming more tailor-made approaches for fact checking, open-domain question answering and dialogue, and yielding competitive results on entity linking and slot filling, by generating disambiguated text. KILT data and code are available at https://github.com/facebookresearch/KILT.Comment: accepted at NAACL 202

Extended Functional Connectivity of Convergent Structural Alterations Among Individuals with PTSD: A Neuroimaging Meta-Analysis

Background: Post-traumatic stress disorder (PTSD) is a debilitating disorder defined by the onset of intrusive, avoidant, negative cognitive or affective, and/or hyperarousal symptoms after witnessing or experiencing a traumatic event. Previous voxel-based morphometry studies have provided insight into structural brain alterations associated with PTSD with notable heterogeneity across these studies. Furthermore, how structural alterations may be associated with brain function, as measured by task-free and task-based functional connectivity, remains to be elucidated. Methods: Using emergent meta-analytic techniques, we sought to first identify a consensus of structural alterations in PTSD using the anatomical likelihood estimation (ALE) approach. Next, we generated functional profiles of identified convergent structural regions utilizing resting-state functional connectivity (rsFC) and meta-analytic co-activation modeling (MACM) methods. Finally, we performed functional decoding to examine mental functions associated with our ALE, rsFC, and MACM brain characterizations. Results: We observed convergent structural alterations in a single region located in the medial prefrontal cortex. The resultant rsFC and MACM maps identified functional connectivity across a widespread, whole-brain network that included frontoparietal and limbic regions. Functional decoding revealed overlapping associations with attention, memory, and emotion processes. Conclusions: Consensus-based functional connectivity was observed in regions of the default mode, salience, and central executive networks, which play a role in the tripartite model of psychopathology. Taken together, these findings have important implications for understanding the neurobiological mechanisms associated with PTSD

Single-Cell RNA Sequencing Reveals a Dynamic Stromal Niche That Supports Tumor Growth

Here, using single-cell RNA sequencing, we examine the stromal compartment in murine melanoma and draining lymph nodes (LNs) at points across tumor development, providing data at http://www.teichlab.org/data/. Naive lymphocytes from LNs undergo activation and clonal expansion within the tumor, before PD1 and Lag3 expression, while tumor-associated myeloid cells promote the formation of a suppressive niche. We identify three temporally distinct stromal populations displaying unique functional signatures, conserved across mouse and human tumors. Whereas "immune" stromal cells are observed in early tumors, "contractile" cells become more prevalent at later time points. Complement component C3 is specifically expressed in the immune population. Its cleavage product C3a supports the recruitment of C3aR(+) macrophages, and perturbation of C3a and C3aR disrupts immune infiltration, slowing tumor growth. Our results highlight the power of scRNA-seq to identify complex interplays and increase stromal diversity as a tumor develops, revealing that stromal cells acquire the capacity to modulate immune landscapes from early disease.Peer reviewe

Neural response to monetary loss among youth with disruptive behavior disorders and callous-unemotional traits in the ABCD study

Etiological models highlight reduced punishment sensitivity as a core risk factor for disruptive behavior disorders (DBD) and callous-unemotional (CU) traits. The current study examined neural sensitivity to the anticipation and receipt of loss, one key aspect of punishment sensitivity, among youth with DBD, comparing those with and without CU traits. Data were obtained from the Adolescent Brain and Cognitive Development (ABCD)SM Study (N = 11,874; Mage = 9.51; 48% female). Loss-related fMRI activity during the monetary incentive delay task was examined across 16 empirically-derived a priori brain regions (e.g., striatum, amygdala, insula, anterior cingulate cortex, medial prefrontal cortex) and compared across the following groups: (1) typically developing (n = 693); (2) DBD (n = 995), subdivided into those (3) with CU traits (DBD + CU, n = 198), and (4) without CU traits (DBD-only, n = 276). Latent variable modeling was also employed to examine network-level activity. There were no significant between-group differences in brain activity to loss anticipation or receipt. Null findings were confirmed with and without covariates, using alternative grouping approaches, and in dimensional models. Network-level analyses also demonstrated comparable activity across groups during loss anticipation and receipt. Findings suggest that differences in punishment sensitivity among youth with DBD are unrelated to loss anticipation or receipt. More precise characterizations of other aspects punishment sensitivity are needed to understand risk for DBD and CU traits

Association between multimorbidity patterns and chronic pain in elderly primary care patients: a cross-sectional observational study

Background: Multimorbidity is a highly prevalent health problem, which may reduce adherence, produce conflicts in treatment, and is not yet supported by evidence-based clinical recommendations. Many older people suffer from more than one chronic disease as well as from chronic pain. There is some evidence that disease management can become more complex if multimorbid patients suffer from chronic pain. In order to better consider the patients' comorbidity spectrum in clinical pain treatment recommendations, evidence is needed regarding which disease combinations are frequently related with the presence of chronic pain. Therefore, our aim is to identify diseases and disease combinations in a multimorbid population, which are associated with the patient-reported presence of chronic pain. Methods: Analyses are based on cross-sectional data of the MultiCare Cohort Study, an observational cohort study based on interviews with 3189 multimorbid patients aged 65+, randomly selected from 158 practices, and their GPs. The response rate was 46.2 %. Data were collected in GP interviews and comprehensive patient interviews. Diseases and disease combinations associated with chronic pain were identified by CART (classification and regression tree) analyses performed separately for both genders. 46 chronic conditions were used as predictor variables and a dichotomized score from the Graded Chronic Pain Scale was used as outcome variable. Results: About 60 % of the study participants were female. Women more often reported chronic pain than men. The most important predictor of a higher pain level in the female population was chronic low back problems, especially if combined with chronic gastritis, hyperuricemia/gout, cardiac insufficiency, neuropathies or depression. Regarding the pain level the male population was also divided best by chronic low back problems, especially if combined with intestinal diverticulosis, neuropathies or chronic ischemic heart disease. Conclusions: Our analyses are a first step in identifying diseases and disease combinations that are related to chronic pain. The most important condition seems to be low back problems. Back pain and pain in other body regions seems to be interrelated with cardiometabolic conditions. In women, psychosocial issues like depression also seem to be relevant

Self-rated health in multimorbid older general practice patients: a cross-sectional study in Germany

Background: With increasing life expectancy the number of people affected by multimorbidity rises. Knowledge of factors associated with health-related quality of life in multimorbid people is scarce. We aimed to identify the factors that are associated with self-rated health (SRH) in aged multimorbid primary care patients. Methods: Cross-sectional study with 3, 189 multimorbid primary care patients aged from 65 to 85 years recruited in 158 general practices in 8 study centers in Germany. Information about morbidity, risk factors, resources, functional status and socio-economic data were collected in face-to-face interviews. Factors associated with SRH were identified by multivariable regression analyses. Results: Depression, somatization, pain, limitations of instrumental activities (iADL),age, distress and Body Mass Index (BMI) were inversely related with SRH. Higher levels of physical activity, income and self-efficacy expectation had a positive association with SRH. The only chronic diseases remaining in the final model were Parkinson's disease and neuropathies. The final model accounted for 35% variance of SRH. Separate analyses for men and women detected some similarities;however, gender specific variation existed for several factors. Conclusion: In multimorbid patients symptoms and consequences of diseases such as pain and activity limitations, as well as depression, seem to be far stronger associated with SRH than the diseases themselves. High income and self-efficacy expectation are independently associated with better SRH and high BMI and age with low SRH

Single-Cell Transcriptomics of Regulatory T Cells Reveals Trajectories of Tissue Adaptation.

Non-lymphoid tissues (NLTs) harbor a pool of adaptive immune cells with largely unexplored phenotype and development. We used single-cell RNA-seq to characterize 35,000 CD4+ regulatory (Treg) and memory (Tmem) T cells in mouse skin and colon, their respective draining lymph nodes (LNs) and spleen. In these tissues, we identified Treg cell subpopulations with distinct degrees of NLT phenotype. Subpopulation pseudotime ordering and gene kinetics were consistent in recruitment to skin and colon, yet the initial NLT-priming in LNs and the final stages of NLT functional adaptation reflected tissue-specific differences. Predicted kinetics were recapitulated using an in vivo melanoma-induction model, validating key regulators and receptors. Finally, we profiled human blood and NLT Treg and Tmem cells, and identified cross-mammalian conserved tissue signatures. In summary, we describe the relationship between Treg cell heterogeneity and recruitment to NLTs through the combined use of computational prediction and in vivo validation