Lesions of the Perirhinal Cortex but Not of the Frontal, Medial Prefrontal, Visual, or Insular Cortex Block Fear-Potentiated Startle Using a Visual Conditioned Stimulus

The present study is part of an ongoing series of experiments aimed at delineation of the neural pathways that mediate fear-potentiated startle, a model of conditioned fear in which the acoustic startle reflex is enhanced when elicited in the presence of a light previously paired with shock. A number of cortical areas that might be involved in relaying information about the visual conditioned stimulus (the light) in fear-potentiated startle were investigated. One hundred thirty-five rats were given 10 light-shock pairings on each of 2 consecutive days, and l-2 d later electrolytic or aspiration lesions in various cortical areas were performed. One week later, the magnitude of fear-potentiated startle was measured. Complete removal of the visual cortex, medial prefrontal cortex, insular cortex, or posterior perirhinal cortex had no significant effect on the magnitude of fear-potentiated startle. Lesions of the frontal cortex attenuated fear-potentiated startle by approximately 50%. However, lesions of the anterior perirhinal cortex completely eliminated fear-potentiated startle. The effective lesions included parts of the cortex both dorsal and ventral to the rhinal sulcus and extended from approximately 1.8 to 3.8 mm posterior to bregma. Lesions slightly more posterior (2.3-4.8 mm posterior to bregma) or lesions that included only the perirhinal cortex dorsal to the rhinal sulcus had no effect. The region of the perirhinal cortex in which lesions blocked fear-potentiated startle projects to the amygdala, and thus may be part of the pathway that relays the visual conditioned stimulus information to the amygdala, a structure that is also critical for fear-potentiated startle. In addition, the present findings are in agreement with numerous studies in primates suggesting that the perirhinal cortex may play a more general role in memory

Community-based Suicide Prevention Research in Remote On-Reserve First Nations Communities

Suicide is a complex problem linked to genetic, environmental, psychological and community factors. For the Aboriginal population more specifically, loss of culture, history of traumatic events, individual, family and community factors may also play a role in suicidal behaviour. Of particular concern is the high rate of suicide among Canadian Aboriginal youth. While the need to develop interventions to reduce suicidal behaviour for First Nations on-reserve populations is evident, there may be an element of distrust of researchers by Aboriginal communities. Furthermore, research in mental health and specifically suicide is much more sensitive than studying medical illnesses like diabetes. Clearly, this issue requires a unique and insightful approach. While numerous suicide prevention/intervention plans and guidelines have been published specifically for work involving Aboriginal people, the literature lacks a comprehensive discussion of the methodological and logistical issues faced by research teams and Aboriginal communities attempting to develop culturally-grounded and community-specific suicide prevention and intervention strategies. This paper outlines the research process, key challenges and lessons learned in a collaborative University-First Nations suicide prevention project conducted with eight north-western Manitoba First Nations communities (Canada)

Carbon dioxide fluxes of tundra vegetation communities on an esker top in the low-Arctic

Previous studies have shown that carbon dioxide fluxes vary considerably among Arctic environments and it is important to assess these differences in order to develop our understanding of the role of Arctic tundra in the global carbon cycle. Although many previous studies have examined tundra carbon dioxide fluxes, few have concentrated on elevated terrain (hills and ridge tops) that is exposed to harsh environmental conditions resulting in sparse vegetation cover and seemingly low productivity. In this study we measured carbon dioxide (CO2) exchange of four common tundra communities on the crest of an esker located in the central Canadian low-Arctic. The objectives were to quantify and compare CO2 fluxes from these communities, investigate responses to environmental variables and qualitatively compare fluxes with those from similar communities growing in less harsh lowland tundra environments. Measurements made during July and August 2010 show there was little difference in net ecosystem exchange (NEE) and gross ecosystem production (GEP) among the three deciduous shrub communities, Arctous alpina, Betula glandulosa and Vaccinium uliginosum, with means ranging from −4.09 to −6.57 μmol·m−2·s−1 and −7.92 to −9.24 μmol·m−2·s−1, respectively. Empetrum nigrum communities had significantly smaller mean NEE and GEP (−1.74 and −4.08 μmol·m−2·s−1, respectively). Ecosystem respiration (ER) was similar for all communities (2.56 to 3.03 μmol·m−2·s−1), except the B. glandulosa community which had a larger mean flux (4.66 μmol·m−2·s−1). Overall, fluxes for these esker-top communities were near the upper range of fluxes reported for other tundra communities. ER was related to soil temperature in all of the communities. Only B. glandulosa GEP and ER showed sensitivity to a persistent decline in soil moisture throughout the study. These findings may have important implications for how esker tops would be treated in construction of regional carbon budgets and for predicting the impacts of climate change on Arctic tundra future carbon budgets

Improving the forward kinematics of cable-driven parallel robots through cable angle sensors

This paper presents a sensor fusion method that aims at improving the accuracy of cable-driven planar parallel mechanisms (CDPMs) and simplifying the kinematic resolution. While the end-effector pose of the CDPM is usually obtained with the cable lengths, the proposed method combines the cable length measurement with the cable angle by using a data fusion algorithm. This allows for a resolution based on the loop closure equations and a weighted least squares method. The paper first presents the resolution of the forward kinematics for planar parallel mechanisms using cable angle only. Then, the proposed sensor fusion scheme is detailed. Finally, an experiment comparing the different procedures for obtaining the pose of the CDPM is carried out, in order to demonstrate the efficiency of the proposed fusion method

Gpr18 agonist dampens inflammation, enhances myogenesis, and restores muscle function in models of Duchenne muscular dystrophy

Introduction: Muscle wasting in Duchenne Muscular Dystrophy is caused by myofiber fragility and poor regeneration that lead to chronic inflammation and muscle replacement by fibrofatty tissue. Our recent findings demonstrated that Resolvin-D2, a bioactive lipid derived from omega-3 fatty acids, has the capacity to dampen inflammation and stimulate muscle regeneration to alleviate disease progression. This therapeutic avenue has many advantages compared to glucocorticoids, the current gold-standard treatment for Duchenne Muscular Dystrophy. However, the use of bioactive lipids as therapeutic drugs also faces many technical challenges such as their instability and poor oral bioavailability.Methods: Here, we explored the potential of PSB-KD107, a synthetic agonist of the resolvin-D2 receptor Gpr18, as a therapeutic alternative for Duchenne Muscular Dystrophy.Results and discussion: We showed that PSB-KD107 can stimulate the myogenic capacity of patient iPSC-derived myoblasts in vitro. RNAseq analysis revealed an enrichment in biological processes related to fatty acid metabolism, lipid biosynthesis, small molecule biosynthesis, and steroid-related processes in PSB-KD107-treated mdx myoblasts, as well as signaling pathways such as Peroxisome proliferator-activated receptors, AMP-activated protein kinase, mammalian target of rapamycin, and sphingolipid signaling pathways. In vivo, the treatment of dystrophic mdx mice with PSB-KD107 resulted in reduced inflammation, enhanced myogenesis, and improved muscle function. The positive impact of PSB-KD107 on muscle function is similar to the one of Resolvin-D2. Overall, our findings provide a proof-of concept that synthetic analogs of bioactive lipid receptors hold therapeutic potential for the treatment of Duchenne Muscular Dystrophy

The Impact of Experimental Pain on Shoulder Movement During an Arm Elevated Reaching Task in a Virtual Reality Environment

Background: People with chronic shoulder pain have been shown to present with motor adaptations during arm movements. These adaptations may create abnormal physical stress on shoulder tendons and muscles. However, how and why these adaptations develop from the acute stage of pain is still not well-understood. Objective: To investigate motor adaptations following acute experimental shoulder pain during upper limb reaching. Methods: Forty participants were assigned to the Control or Pain group. They completed a task consisting of reaching targets in a virtual reality environment at three time points: (1) baseline (both groups pain-free), (2) experimental phase (Pain group experiencing acute shoulder pain induced by injecting hypertonic saline into subacromial space), and (3) Post experimental phase (both groups pain-free). Electromyographic (EMG) activity, kinematics, and performance data were collected. Results: The Pain group showed altered movement planning and execution as shown by a significant increased delay to reach muscles EMG peak and a loss of accuracy, compared to controls that have decreased their mean delay to reach muscles peak and improved their movement speed through the phases. The Pain group also showed protective kinematic adaptations using less shoulder elevation and elbow flexion, which persisted when they no longer felt the experimental pain. Conclusion: Acute experimental pain altered movement planning and execution, which affected task performance. Kinematic data also suggest that such adaptations may persist over time, which could explain those observed in chronic pain populations

Pattern recognition based on HD-sEMG spatial features extraction for an efficient proportional control of a robotic arm.

To enable an efficient alternative control of an assistive robotic arm using electromyographic (EMG) signals, the control method must simultaneously provide both the direction and the velocity. However, the contraction variations of the forearm muscles, used to proportionally control the device’s velocity using a regression method, can disturb the accuracy of the classification used to estimate its direction at the same time. In this paper, the original set of spatial features takes advantage of the 2D structure of an 8 × 8 high-density surface EMG (HD-sEMG) sensor to perform a high accuracy classification while improving the robustness to the contraction variations. Based on the HD-sEMG sensor, different muscular activity images are extracted by applying different spatial filters. In order to characterize their distribution specific to each movement, instead of the EMG signals’ amplitudes, these muscular images are divided in sub-images upon which the proposed spatial features, such as the centers of the gravity coordinates and the percentages of influence, are computed. These features permits to achieve average accuracies of 97% and 96.7% to detect respectively 16 forearm movements performed by a healthy subject with prior experience with the control approach and 10 movements by ten inexperienced healthy subjects. Compared with the time-domain features, the proposed method exhibits significant higher accuracies in presence of muscular contraction variations, requires less training data and is more robust against the time of use. Furthermore, two fine real-time tasks illustrate the potential of the proposed approach to efficiently control a robotic arm

Improving lives by accelerating progress towards the UN Sustainable Development Goals for adolescents living with HIV: a prospective cohort study

BACKGROUND: Low-income and middle-income countries (LMICs) face major challenges in achieving the UN's Sustainable Development Goals (SDGs) for vulnerable adolescents. We aimed to test the UN Development Programme's proposed approach of development accelerators-provisions that lead to progress across multiple SDGs-and synergies between accelerators on achieving SDG-aligned targets in a highly vulnerable group of adolescents in South Africa. METHODS: We did standardised interviews and extracted longitudinal data from clinical records at baseline (2014-15) and 18-month follow-up (2016-17) for adolescents aged 10-19 years living with HIV in the Eastern Cape province of South Africa. We used standardised tools to measure 11 SDG-aligned targets-antiretroviral therapy adherence, good mental health, no substance use, HIV care retention, school enrolment, school progression, no sexual abuse, no high-risk sex, no violence perpetration, no community violence, and no emotional or physical abuse. We also assessed receipt at both baseline and follow-up of six hypothesised development accelerators-government cash transfers to households, safe schools (ie, without teacher or student violence), free schools, parenting support, free school meals, and support groups. Associations of all provisions with SDG-aligned targets were assessed jointly in a multivariate path model, controlling for baseline outcomes and sociodemographic and HIV-related covariates, and adjusted for multiple outcome testing. Cumulative effects were tested by marginal effects modelling. FINDINGS: 1063 (90%) of 1176 eligible adolescents were interviewed. Three provisions were shown to be development accelerators. Parenting support was associated with good mental health (odds ratio 2·13, 95% CI 1·43-3·15, p<0·0001), no high-risk sex (2·44, 1·45-5·03, p=0·005), no violence perpetration (2·59, 1·63-4·59, p<0·0001), no community violence (2·43, 1·65-3·86, p<0·0001), and no emotional or physical abuse (2·38, 1·65-3·76; p<0·0001). Cash transfers were associated with HIV care retention (1·87, 1·15-3·02, p=0·010), school progression (2·05, 1·33-3·24, p=0·003), and no emotional or physical abuse (1·76, 1·12-3·02, p=0·025). Safe schools were associated with good mental health (1·74, 1·30-2·34, p<0·0001), school progression (1·57, 1·17-2·13, p=0·004), no violence perpetration (2·02, 1·45-2·91, p<0·0001), no community violence (1·81, 1·30-2·55, p<0·0001), and no emotional or physical abuse (2·20, 1·58-3·17, p<0·0001). For five of 11 SDG-aligned targets, a combination of two or more accelerators showed cumulative positive associations, suggesting accelerator synergies of combination provisions. For example, the fitted probability of adolescents reporting no emotional or physical abuse (SDG 16.2) with no safe schools, cash transfers, or parenting support was 0·25 (0·16-0·34). With cash transfer alone it was 0·37 (0·33-0·42), with safe school alone 0·42 (0·30-0·55), and with parenting support alone 0·44 (0·30-0·59). With all three development accelerators combined, the probability of adolescents reporting no emotional or physical abuse was 0·76 (0·67-0·84). After correcting for multiple tests, four of the SDG-aligned targets (antiretroviral therapy adherence, no substance use, school enrolment, and no sexual abuse) were not associated with any hypothesised accelerators. INTERPRETATION: The findings suggest the UN's accelerator approach for this high-risk adolescent population has policy and potential financing usefulness. Services that simultaneously promote several SDG targets, or combine to support particular targets, might be important to meet not only health-related targets, but also to ensure that adolescents in LMICs thrive within a new development framework. FUNDING: Nuffield Foundation, UK Research and Innovation Global Challenges Research Fund, UKAID, Janssen Pharmaceutica, International AIDS Society, John Fell Fund, European Research Council, Economic and Social Research Council, Philip Leverhulme Trust, and UNICEF