Cuban Marine Policy: A Case of Context

MA University of Hawaii at Manoa 2016Includes bibliographical references (leaf 95).In this time of great change, Cuba’s environment will be challenged as economic growth and an emerging tourism industry threaten to pull Cuba out of its time capsule. A case study of the people’s perception of coastal livelihoods in the Villa Clara province, an archipelago experiencing rapid tourism development, illuminates the many environmental, social, and economic issues that are arising along much of Cuba’s coastline. Focusing on perceptions of the Marine Protected Area (MPA) management method to conserve coral reefs and attitudes toward a state-­run fishing cooperative, this case study shows how these methods of marine resource conservation, dating from different political eras in Cuba, interact. This case study also considers how the “lost Eden” discourse surrounding Cuba’s coral reefs has shaped management implementation and how it is perceived locally, and whether these perceptions suggest future conflict between conservation and development in this region. Political changes in the 20th century have left Cuba a legacy of pristine coral reef ecosystems and a strong, domestic environmental policy framework. The Cuban State now seeks capital and foreign investment to expand employment and to grow the economy. As these dynamics change, Cuba has the opportunity to adapt to encroaching market demands for tourism development or develop new industries that will prioritize the maintenance of its natural resources

MECP2 regulates cortical plasticity underlying a learned behavior in adult female mice

Neurodevelopmental disorders begin with the emergence of inappropriate synaptic connectivity early in life, yet how the sustained disruption of experience-dependent plasticity aggravates symptoms in adulthood is unclear. Here we used pup retrieval learning to assay adult cortical plasticity in a female mouse model of Rett syndrome (MeCP2het). We show that auditory cortical plasticity and retrieval learning are impaired in MeCP2het. Specifically, normal MECP2 expression in the adult auditory cortex is required for efficient retrieval learning. In wild-type mice, cohabitation with a mother and her pups triggered transient changes to auditory cortical inhibitory networks, including elevated levels of the GABA-synthesizing enzyme GAD67. However, MeCP2het further exhibited increased expression of parvalbumin (PV) and perineuronal nets (PNNs), events thought to suppress plasticity at the closure of critical periods and in adult learning. Averting these events with genetic and pharmacological manipulations of the GABAergic network restored retrieval behavior. We propose that adult retrieval learning triggers a transient episode of inhibitory plasticity in the auditory cortex that is dysregulated in MeCP2het. This window of heightened sensitivity to social sensory cues reveals a role of MeCP2 mutations in facilitating adult plasticity that is distinct from their effects on early development

An AMPKa2-specific phospho-switch controls lysosomal targeting for activation

AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) are metabolic kinases that co-ordinate nutrient supply with cell growth. AMPK negatively regulates mTORC1, and mTORC1 reciprocally phosphorylates S345/7 in both AMPK α-isoforms. We report that genetic or torin1-induced loss of α2-S345 phosphorylation relieves suppression of AMPK signaling; however, the regulatory effect does not translate to α1-S347 in HEK293T or MEF cells. Dephosphorylation of α2-S345, but not α1-S347, transiently targets AMPK to lysosomes, a cellular site for activation by LKB1. By mass spectrometry, we find that α2-S345 is basally phosphorylated at 2.5-fold higher stoichiometry than α1-S347 in HEK293T cells and, unlike α1, phosphorylation is partially retained after prolonged mTORC1 inhibition. Loss of α2-S345 phosphorylation in endogenous AMPK fails to sustain growth of MEFs under amino acid starvation conditions. These findings uncover an α2-specific mechanism by which AMPK can be activated at lysosomes in the absence of changes in cellular energy

Neuromatch Academy: a 3-week, online summer school in computational neuroscience

Neuromatch Academy (https://academy.neuromatch.io; (van Viegen et al., 2021)) was designed as an online summer school to cover the basics of computational neuroscience in three weeks. The materials cover dominant and emerging computational neuroscience tools, how they complement one another, and specifically focus on how they can help us to better understand how the brain functions. An original component of the materials is its focus on modeling choices, i.e. how do we choose the right approach, how do we build models, and how can we evaluate models to determine if they provide real (meaningful) insight. This meta-modeling component of the instructional materials asks what questions can be answered by different techniques, and how to apply them meaningfully to get insight about brain function

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Improving diversity in study participation: Patient perspectives on barriers, racial differences and the role of communities

Abstract Introduction The lack of racial/ethnic diversity in research potentially limits the generalizability of findings to a broader population, highlighting the need for greater diversity and inclusion in clinical research. Qualitative research (i.e., focus groups) was conducted to identify (i) the potential motivators and barriers to study participation across different races and ethnicities; (ii) preferred delivery of education and information to support healthcare decision‐making and the role of the community. Methods Patient focus groups were conducted with 26 participants from the sponsor's Patient Engagement Research Councils selected through subjective sampling. Recruitment prioritized adequate representation across different race/ethnic groups. Participation was voluntary and participants underwent a confidential interview process before selection. Narrative analysis was used to identify themes and draw insights from interactions. Experienced research specialists identified emerging concepts, and these were tested against new observations. The frequency of each concept was examined to understand its importance. Results Based on self‐selected race/ethnicity, participants were divided into five focus groups (Groups: African American/Black: 2; Hispanic/Latino, Asian American, and white: 1 each) and were asked to share their experiences/opinions regarding the stated objectives. Barriers to study participation included: limited awareness of opportunities to participate in research, fears about changes in standard therapy, breaking cultural norms/stigma, religion‐related concerns and mistrust of clinical research. Participants identified the importance of transparency by pharmaceutical companies and other entities to build trust and partnership and cited key roles that communities can play. The perceptions of the African American group regarding diversity/inclusion in research studies appeared to be different from other groups; a lack of trust in healthcare providers, concerns about historical instances of research abuse and the importance of prayer were cited. Conclusion This study provided insights into barriers to study participation, and also highlighted the need for pharmaceutical companies and other entities to authentically engage in strategies that build trust within communities to enhance recruitment among diverse populations. Patient or Public Contribution The data collected in the present study was provided by the participants in the focus groups

The Medical Home and Mental Health Services in Children and Youth with Special Health Care Needs.

BACKGROUND AND OBJECTIVES: Children and youth with special health care needs (CYSHCN) commonly experience mental health concerns, but conditions are often not identified or treated within primary care. Mental health care is often not a primary focus of pediatric primary care, but the medical home model has potential to address these concerns more adequately. The purpose of this study is to examine the relationship between the medical home and use of mental health services in CYSHCN. METHODS: Data came from the Medical Expenditure Panel Survey years 2015-2017, a nationally representative survey of health and healthcare in US families. The study included CYSHCN ages 6-17. We compared the use of mental health services, expenditures, and psychotropic medications across CYSHCN with and without a medical home using multivariable regression. RESULTS: 45% of CYSHCN received care within a medical home. CYSHCN with and without a medical home reported similar frequency of office-based mental health visits (21.2% versus 25.2%), average expenditures for visits ($147 versus$128), and psychotropic medications (11.9% versus 15.1%). Medical home status was not associated with office-based mental health visits, use of psychotropic medications, or cost for either. CONCLUSIONS: CYSHCN with mental health care needs face barriers to satisfactory care. Creating better connections between primary and mental health care could help to ameliorate this problem. Findings suggest the medical home, a more comprehensive primary care model, may not address mental health care needs of CYSHCN