ASCR/HEP Exascale Requirements Review Report

This draft report summarizes and details the findings, results, and recommendations derived from the ASCR/HEP Exascale Requirements Review meeting held in June, 2015. The main conclusions are as follows. 1) Larger, more capable computing and data facilities are needed to support HEP science goals in all three frontiers: Energy, Intensity, and Cosmic. The expected scale of the demand at the 2025 timescale is at least two orders of magnitude -- and in some cases greater -- than that available currently. 2) The growth rate of data produced by simulations is overwhelming the current ability, of both facilities and researchers, to store and analyze it. Additional resources and new techniques for data analysis are urgently needed. 3) Data rates and volumes from HEP experimental facilities are also straining the ability to store and analyze large and complex data volumes. Appropriately configured leadership-class facilities can play a transformational role in enabling scientific discovery from these datasets. 4) A close integration of HPC simulation and data analysis will aid greatly in interpreting results from HEP experiments. Such an integration will minimize data movement and facilitate interdependent workflows. 5) Long-range planning between HEP and ASCR will be required to meet HEP's research needs. To best use ASCR HPC resources the experimental HEP program needs a) an established long-term plan for access to ASCR computational and data resources, b) an ability to map workflows onto HPC resources, c) the ability for ASCR facilities to accommodate workflows run by collaborations that can have thousands of individual members, d) to transition codes to the next-generation HPC platforms that will be available at ASCR facilities, e) to build up and train a workforce capable of developing and using simulations and analysis to support HEP scientific research on next-generation systems.Comment: 77 pages, 13 Figures; draft report, subject to further revisio

Biogeographic survey of soil bacterial communities across Antarctica

Background: Antarctica and its unique biodiversity are increasingly at risk from the effects of global climate change and other human influences. A significant recent element underpinning strategies for Antarctic conservation has been the development of a system of Antarctic Conservation Biogeographic Regions (ACBRs). The datasets supporting this classification are, however, dominated by eukaryotic taxa, with contributions from the bacterial domain restricted to Actinomycetota and Cyanobacteriota. Nevertheless, the ice-free areas of the Antarctic continent and the sub-Antarctic islands are dominated in terms of diversity by bacteria. Our study aims to generate a comprehensive phylogenetic dataset of Antarctic bacteria with wide geographical coverage on the continent and sub-Antarctic islands, to investigate whether bacterial diversity and distribution is reflected in the current ACBRs. Results: Soil bacterial diversity and community composition did not fully conform with the ACBR classification. Although 19% of the variability was explained by this classification, the largest differences in bacterial community composition were between the broader continental and maritime Antarctic regions, where a degree of structural overlapping within continental and maritime bacterial communities was apparent, not fully reflecting the division into separate ACBRs. Strong divergence in soil bacterial community composition was also apparent between the Antarctic/sub-Antarctic islands and the Antarctic mainland. Bacterial communities were partially shaped by bioclimatic conditions, with 28% of dominant genera showing habitat preferences connected to at least one of the bioclimatic variables included in our analyses. These genera were also reported as indicator taxa for the ACBRs. Conclusions: Overall, our data indicate that the current ACBR subdivision of the Antarctic continent does not fully reflect bacterial distribution and diversity in Antarctica. We observed considerable overlap in the structure of soil bacterial communities within the maritime Antarctic region and within the continental Antarctic region. Our results also suggest that bacterial communities might be impacted by regional climatic and other environmental changes. The dataset developed in this study provides a comprehensive baseline that will provide a valuable tool for biodiversity conservation efforts on the continent. Further studies are clearly required, and we emphasize the need for more extensive campaigns to systematically sample and characterize Antarctic and sub-Antarctic soil microbial communities. APsmQ8MphSAgg4BzZyqdNTVideo Abstrac

Neural Systems Underlying RDoC Social Constructs: An Activation Likelihood Estimation Meta-Analysis

Neuroscientists have sought to identify the underlying neural systems supporting social processing that allow interaction and communication, forming social relationships, and navigating the social world. Through the use of NIMH’s Research Domain Criteria (RDoC) framework, we evaluated consensus among studies that examined brain activity during social tasks to elucidate regions comprising the “social brain”. We examined convergence across tasks corresponding to the four RDoC social constructs, including Affiliation and Attachment, Social Communication, Perception and Understanding of Self, and Perception and Understanding of Others. We performed a series of coordinate-based meta-analyses using the activation likelihood estimate (ALE) method. Meta-analysis was performed on whole-brain coordinates reported from 864 fMRI contrasts using the NiMARE Python package, revealing convergence in medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, temporoparietal junction, bilateral insula, amygdala, fusiform gyrus, precuneus, and thalamus. Additionally, four separate RDoC-based meta-analyses revealed differential convergence associated with the four social constructs. These outcomes highlight the neural support underlying these social constructs and inform future research on alterations among neurotypical and atypical populations

Do community measures impact the effectiveness of a community led HIV testing intervention. Secondary analysis of an HIV self-testing intervention in rural communities in Zimbabwe

Background: There is a growing body of evidence for the role that communities can have in producing beneficial health outcomes. There is also an increasing recognition of the effectiveness and success of community-led interventions to promote public health efforts. This study investigated whether and how community-level measures facilitate a community-led intervention to achieve improved HIV outcomes. Methods: This is a secondary analysis of survey data from a cluster randomised trial in 40 rural communities in Zimbabwe. The survey was conducted four months after the intervention was initiated. Communities were randomised 1:1 to either paid distribution arm, where HIV self-test (HIVST) kits were distributed by a paid distributor, or community-led whereby members of the community were responsible for organising and conducting the distribution of HIVST kits. We used mixed effects logistic regression to assess the effect of social cohesion, problem solving, and HIV awareness on HIV testing and prevention. Results: We found no association between community measures and the three HIV outcomes (self-testing, new HIV diagnosis and linkage to VMMC or confirmatory testing). However, the interaction analyses highlighted that in high social cohesion communities, the odds of new HIV diagnosis was greater in the community-led arm than paid distribution arm (OR 2.06 95% CI 1.03–4.19). Conclusion: We found some evidence that community-led interventions reached more undiagnosed people living with HIV in places with high social cohesion. Additional research should seek to understand whether the effect of social cohesion is persistent across other community interventions and outcomes. Trial registration: PACTR201607001701788

Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science.

The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries

Consumer and Healthcare Professional Led Priority Setting for Quality Use of Medicines in People with Dementia: Gathering Unanswered Research Questions

Background: Historically, research questions have been posed by the pharmaceutical industry or researchers, with little involvement of consumers and healthcare professionals. Objective: To determine what questions about medicine use are important to people living with dementia and their care team and whether they have been previously answered by research. Methods: The James Lind Alliance Priority Setting Partnership process was followed. A national Australian qualitative survey on medicine use in people living with dementia was conducted with consumers (people living with dementia and their carers including family, and friends) and healthcare professionals. Survey findings were supplemented with key informant interviews and relevant published documents (identified by the research team). Conventional content analysis was used to generate summary questions. Finally, evidence checking was conducted to determine if the summary questions were 'unanswered'. Results: A total of 545 questions were submitted by 228 survey participants (151 consumers and 77 healthcare professionals). Eight interviews were conducted with key informants and four relevant published documents were identified and reviewed. Overall, analysis resulted in 68 research questions, grouped into 13 themes. Themes with the greatest number of questions were related to co-morbidities, adverse drug reactions, treatment of dementia, and polypharmacy. Evidence checking resulted in 67 unanswered questions. Conclusion: A wide variety of unanswered research questions were identified. Addressing unanswered research questions identified by consumers and healthcare professionals through this process will ensure that areas of priority are targeted in future research to achieve optimal health outcomes through quality use of medicines

Functional Stability of Unliganded Envelope Glycoprotein Spikes among Isolates of Human Immunodeficiency Virus Type 1 (HIV-1)

The HIV-1 envelope glycoprotein (Env) spike is challenging to study at the molecular level, due in part to its genetic variability, structural heterogeneity and lability. However, the extent of lability in Env function, particularly for primary isolates across clades, has not been explored. Here, we probe stability of function for variant Envs of a range of isolates from chronic and acute infection, and from clades A, B and C, all on a constant virus backbone. Stability is elucidated in terms of the sensitivity of isolate infectivity to destabilizing conditions. A heat-gradient assay was used to determine T90 values, the temperature at which HIV-1 infectivity is decreased by 90% in 1 h, which ranged between ∼40 to 49°C (n = 34). For select Envs (n = 10), the half-lives of infectivity decay at 37°C were also determined and these correlated significantly with the T90 (p = 0.029), though two ‘outliers’ were identified. Specificity in functional Env stability was also evident. For example, Env variant HIV-1ADA was found to be labile to heat, 37°C decay, and guanidinium hydrochloride but not to urea or extremes of pH, when compared to its thermostable counterpart, HIV-1JR-CSF. Blue native PAGE analyses revealed that Env-dependent viral inactivation preceded complete dissociation of Env trimers. The viral membrane and membrane-proximal external region (MPER) of gp41 were also shown to be important for maintaining trimer stability at physiological temperature. Overall, our results indicate that primary HIV-1 Envs can have diverse sensitivities to functional inactivation in vitro, including at physiological temperature, and suggest that parameters of functional Env stability may be helpful in the study and optimization of native Env mimetics and vaccines

The Early Royal Society and Visual Culture

Recent studies have fruitfully examined the intersection between early modern science and visual culture by elucidating the functions of images in shaping and disseminating scientific knowledge. Given its rich archival sources, it is possible to extend this line of research in the case of the Royal Society to an examination of attitudes towards images as artefacts –manufactured objects worth commissioning, collecting and studying. Drawing on existing scholarship and material from the Royal Society Archives, I discuss Fellows’ interests in prints, drawings, varnishes, colorants, images made out of unusual materials, and methods of identifying the painter from a painting. Knowledge of production processes of images was important to members of the Royal Society, not only as connoisseurs and collectors, but also as those interested in a Baconian mastery of material processes, including a “history of trades”. Their antiquarian interests led to discussion of painters’ styles, and they gradually developed a visual memorial to an institution through portraits and other visual records.AH/M001938/1 (AHRC