Autonomy Infused Teleoperation with Application to BCI Manipulation

Robot teleoperation systems face a common set of challenges including latency, low-dimensional user commands, and asymmetric control inputs. User control with Brain-Computer Interfaces (BCIs) exacerbates these problems through especially noisy and erratic low-dimensional motion commands due to the difficulty in decoding neural activity. We introduce a general framework to address these challenges through a combination of computer vision, user intent inference, and arbitration between the human input and autonomous control schemes. Adjustable levels of assistance allow the system to balance the operator's capabilities and feelings of comfort and control while compensating for a task's difficulty. We present experimental results demonstrating significant performance improvement using the shared-control assistance framework on adapted rehabilitation benchmarks with two subjects implanted with intracortical brain-computer interfaces controlling a seven degree-of-freedom robotic manipulator as a prosthetic. Our results further indicate that shared assistance mitigates perceived user difficulty and even enables successful performance on previously infeasible tasks. We showcase the extensibility of our architecture with applications to quality-of-life tasks such as opening a door, pouring liquids from containers, and manipulation with novel objects in densely cluttered environments

microRNA Expression Profile of Purified Alveolar Epithelial Type II Cells

Alveolar type II (ATII) cells are essential for the maintenance of the alveolar homeostasis. However, knowledge of the expression of the miRNAs and miRNA-regulated networks which control homeostasis and coordinate diverse functions of murine ATII cells is limited. Therefore, we asked how miRNAs expressed in ATII cells might contribute to the regulation of signaling pathways. We purified "untouched by antibodies" ATII cells using a flow cytometric sorting method with a highly autofluorescent population of lung cells. TaqMan® miRNA low-density arrays were performed on sorted cells and intersected with miRNA profiles of ATII cells isolated according to a previously published protocol. Of 293 miRNAs expressed in both ATII preparations, 111 showed equal abundances. The target mRNAs of bona fide ATII miRNAs were used for pathway enrichment analysis. This analysis identified nine signaling pathways with known functions in fibrosis and/or epithelial-to-mesenchymal transition (EMT). In particular, a subset of 19 miRNAs was found to target 21 components of the TGF-β signaling pathway. Three of these miRNAs (miR-16-5p, -17-5p and -30c-5p) were down-modulated by TGF-β1 stimulation in human A549 cells, and concomitant up-regulation of associated mRNA targets (BMPR2, JUN, RUNX2) was observed. These results suggest an important role for miRNAs in maintaining the homeostasis of the TGF-β signaling pathway in ATII cells under physiological conditions

The effect of community-based support for caregivers on the risk of virological failure in children and adolescents with HIV in Harare, Zimbabwe (ZENITH): an open-label, randomised controlled trial.

BACKGROUND: Children and adolescents have poorer HIV treatment outcomes than adults. We aimed to assess the effect of community-based support for caregivers of HIV-infected children and adolescents, who are key mediators to children engaging with care, on treatment outcomes. METHODS: In this open-label, randomised contolled trial, we recruited children aged 6-15 years with newly-diagnosed HIV attending primary health-care clinics in Harare, Zimbabwe. Children were randomly assigned to receive decentralised primary health-care clinic-based HIV care (control group), according to national guidelines for 18 months, or decentralised care plus structured support visits by trained community health workers (intervention group) according to national guidelines for 18 months. Primary outcomes were the proportion of participants who died or had an HIV viral load of 400 copies per mL or higher at 12 months after antiretroviral therapy (ART) initiation (among those who started ART within 6 months of enrolment); and the proportion who missed two or more scheduled clinic visits by 18 months post-enrolment (among all participants). Analyses were complete-case, modified-intention-to-treat. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201212000442288. FINDINGS: Between January, 2013, and January, 2015, 470 participants tested HIV-positive at seven study primary health-care clinics and were screened for eligibility. Of the 334 eligible children and adolescents, 166 were randomly assigned to the intervention group and 168 to the control group. The median age of participants was 11 years (IQR 8-13) and 178 (53%) were girls. Among the 238 participants who started ART within 6 months of enrolment, the proportion who died or had a viral load of 400 copies/mL or higher at 12 months post-ART initiation was significantly lower in the intervention group than in the control group (31 [33%] of 94 participants vs 42 [49%] of 86 participants, respectively, adjusted odds ratio [aOR] 0·46, 95% CI 0·23-0·89; p=0·02). The proportion of children missing two or more scheduled visits was similar in the intervention group and control group (27 [17%] of 155 vs 30 [18%] of 165, aOR 0·92, 95% CI 0·49-1·74; p=0·79). One participant withdrew from the trial 240 days after enrolment and 12 died during follow-up (five in the intervention group; seven in the control group). INTERPRETATION: Community-based support for caregivers has high potential for scalability and could have a substantial effect on HIV virological suppression in children and adolescents, a group with disproportionately poor treatment outcomes. FUNDING: Wellcome Trust

A kinematic analysis of a haptic handheld stylus in a virtual environment: a study in healthy subjects

<p>Abstract</p> <p>Background</p> <p>Virtual Reality provides new options for conducting motor assessment and training within computer-generated 3 dimensional environments. To date very little has been reported about normal performance in virtual environments. The objective of this study was to evaluate the test-retest reliability of a clinical procedure measuring trajectories with a haptic handheld stylus in a virtual environment and to establish normative data in healthy subjects using this haptic device.</p> <p>Methods</p> <p>Fifty-eight normal subjects; aged from 20 to 69, performed 3 dimensional hand movements in a virtual environment using a haptic device on three occasions within one week. Test-retest stability and standardized normative data were obtained for all subjects.</p> <p>Results</p> <p>No difference was found between test and retest. The limits of agreement revealed that changes in an individual's performance could not be detected. There was a training effect between the first test occasion and the third test occasion. Normative data are presented.</p> <p>Conclusion</p> <p>A new test was developed for recording the kinematics of the handheld haptic stylus in a virtual environment. The normative data will be used for purposes of comparison in future assessments, such as before and after training of persons with neurological deficits.</p

Effect of Once-Weekly Azithromycin vs Placebo in Children With HIV-Associated Chronic Lung Disease: The BREATHE Randomized Clinical Trial

Importance - HIV-associated chronic lung disease (HCLD) in children is associated with small airways disease, is common despite antiretroviral therapy (ART), and is associated with substantial morbidity. Azithromycin has antibiotic and immunomodulatory activity and may be effective in treating HCLD through reducing respiratory tract infections and inflammation. Objective - To determine whether prophylactic azithromycin is effective in preventing worsening of lung function and in reducing acute respiratory exacerbations (AREs) in children with HCLD taking ART. Design, Setting, and Participants - This double-blind, placebo-controlled, randomized clinical trial (BREATHE) was conducted between 2016 and 2019, including 12 months of follow-up, at outpatient HIV clinics in 2 public sector hospitals in Malawi and Zimbabwe. Participants were randomized 1:1 to intervention or placebo, and participants and study personnel were blinded to treatment allocation. Participants included children aged 6 to 19 years with perinatally acquired HIV and HCLD (defined as forced expiratory volume in 1 second [FEV1] z score Intervention - Once-weekly oral azithromycin with weight-based dosing, for 48 weeks. Main Outcomes and Measures - All outcomes were prespecified. The primary outcome was the mean difference in FEV1 z score using intention-to-treat analysis for participants seen at end line. Secondary outcomes included AREs, all-cause hospitalizations, mortality, and weight-for-age z score. Results - A total of 347 individuals (median [interquartile range] age, 15.3 [12.7-17.7] years; 177 boys [51.0%]) were randomized, 174 to the azithromycin group and 173 to the placebo group; 162 participants in the azithromycin group and 146 placebo group participants had a primary outcome available and were analyzed. The mean difference in FEV1 z score was 0.06 (95% CI, −0.10 to 0.21; P = .48) higher in the azithromycin group than in the placebo group, a nonsignificant difference. The rate of AREs was 12.1 events per 100 person-years in the azithromycin group and 24.7 events per 100 person-years in the placebo groups (hazard ratio, 0.50; 95% CI, 0.27 to 0.93; P = .03). The hospitalization rate was 1.3 events per 100 person-years in the azithromycin group and 7.1 events per 100 person-years in the placebo groups, but the difference was not significant (hazard ratio, 0.24; 95% CI, 0.06 to 1.07; P = .06). Three deaths occurred, all in the placebo group. The mean weight-for-age z score was 0.03 (95% CI, −0.08 to 0.14; P = .56) higher in the azithromycin group than in the placebo group, although the difference was not significant. There were no drug-related severe adverse events. Conclusions and Relevance - In this randomized clinical trial specifically addressing childhood HCLD, once-weekly azithromycin did not improve lung function or growth but was associated with reduced AREs; the number of hospitalizations was also lower in the azithromycin group but the difference was not significant. Future research should identify patient groups who would benefit most from this intervention and optimum treatment length, to maximize benefits while reducing the risk of antimicrobial resistance

A prognostic neural epigenetic signature in high-grade glioma

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Identifying youth at high risk for sexually transmitted infections in community-based settings using a risk prediction tool: a validation study.

BACKGROUND : Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common bacterial sexually transmitted infections (STIs) worldwide. In the absence of affordable point-of-care STI tests, WHO recommends STI testing based on risk factors. This study aimed to develop a prediction tool with a sensitivity of > 90% and efficiency (defined as the percentage of individuals that are eligible for diagnostic testing) of < 60%. METHODS: This study offered CT/NG testing as part of a cluster-randomised trial of community-based delivery of sexual and reproductive health services to youth aged 16-24 years in Zimbabwe. All individuals accepting STI testing completed an STI risk factor questionnaire. The outcome was positivity for either CT or NG. Backwards-stepwise logistic regression was performed with p ≥ 0.05 as criteria for exclusion. Coefficients of variables included in the final multivariable model were multiplied by 10 to generate weights for a STI risk prediction tool. A maximum likelihood Receiver Operating Characteristics (ROC) model was fitted, with the continuous variable score divided into 15 categories of equal size. Sensitivity, efficiency and number needed to screen were calculated for different cut-points. RESULTS: From 3 December 2019 to 5 February 2020, 1007 individuals opted for STI testing, of whom 1003 (99.6%) completed the questionnaire. CT/NG prevalence was 17.5% (95% CI 15.1, 19.8) (n = 175). CT/NG positivity was independently associated with being female, number of lifetime sexual partners, relationship status, HIV status, self-assessed STI risk and past or current pregnancy. The STI risk prediction score including those variables ranged from 2 to 46 with an area under the ROC curve of 0.72 (95% CI 0.68, 0.76). Two cut-points were chosen: (i) 23 for optimised sensitivity (75.9%) and specificity (59.3%) and (ii) 19 to maximise sensitivity (82.4%) while keeping efficiency at < 60% (59.4%). CONCLUSIONS: The high prevalence of STIs among youth, even in those with no or one reported risk factor, may preclude the use of risk prediction tools for selective STI testing. At a cut-point of 19 one in six young people with STIs would be missed