Cloverleaf Clusters: A Common Macrostructural Organization across Human Visual and Auditory Cortex

One of the fundamental properties of mammalian brains is that sensory regions of cortex are organized into multiple, functionally specialized cortical field maps (CFMs). An individual CFM is composed of two orthogonal topographical representations, reflecting two essential aspects of a sensory feature space. Each CFM is thought to subserve a specific computation or set of computations that underlie particular perceptual behaviors by enabling the comparison and combination of the information carried by the various specialized neuronal populations within this cortical region. Multiple adjacent CFMs, in turn, have now been shown by multiple laboratories to be organized in visual and auditory cortex into a macrostructural pattern called the cloverleaf cluster. CFMs within cloverleaf clusters tend to share properties such as receptive field distribution, cortical magnification, and processing specialization. This chapter will review the evidence for CFM and cloverleaf cluster organization across human visual and auditory cortex and will discuss the utility of these measurements for determining cortical structure and function and for investigating what changes occur in sensory cortex following various types of trauma or disease

Changes in Visual Cortex in Healthy Aging and Dementia

This chapter reviews the differences in specific structural and functional characteristics of human visual cortex among young adults, healthy aging adults, and patients with dementia, with a primary focus on those with Alzheimer’s disease (AD). Such visual cortex changes have been shown to underlie many of the behavioral deficits that develop in healthy aging and AD. Measurements of disordered visual cortex in dementia patients may be possible early in the course of neurodegeneration and thus may be useful for improving early diagnosis of these devastating diseases

Process evaluation of a workplace-based health promotion and exercise cluster-randomised trial to increase productivity and reduce neck pain in office workers: A RE-AIM approach

© 2020 The Author(s). Background: This study uses the RE-AIM framework to provide a process evaluation of a workplace-based cluster randomised trial comparing an ergonomic plus exercise intervention to an ergonomic plus health promotion intervention; and to highlight variations across organisations; and consider the implications of the findings for intervention translation. Method: This study applied the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) methodology to examine the interventions' implementation and to explore the extent to which differences between participating organisations contributed to the variations in findings. Qualitative and quantitative data collected from individual participants, research team observations and organisations were interrogated to report on the five RE-AIM domains. Results: Overall reach was 22.7% but varied across organisations (range 9 to 83%). Participants were generally representative of the recruitment pool though more females (n = 452 or 59%) were recruited than were in the pool (49%). Effectiveness measures (health-related productivity loss and neck pain) varied across all organisations, with no clear pattern emerging to indicate the source of the variation. Organisation-level adoption (66%) and staffing level adoption (91%) were high. The interventions were implemented with minimal protocol variations and high staffing consistency, but organisations varied in their provision of resources (e.g. training space, seniority of liaisons). Mean adherence of participants to the EET intervention was 56% during the intervention period, but varied from 41 to 71% across organisations. At 12 months, 15% of participants reported regular EET adherence. Overall mean (SD) adherence to EHP was 56% (29%) across organisations during the intervention period (range 28 to 77%), with 62% of participants reporting regular adherence at 12 months. No organisations continued the interventions after the follow-up period. Conclusion: Although the study protocol was implemented with high consistency and fidelity, variations in four domains (reach, effectiveness, adoption and implementation) arose between the 14 participating organisations. These variations may be the source of mixed effectiveness across organisations. Factors known to increase the success of workplace interventions, such as strong management support, a visible commitment to employee wellbeing and participant engagement in intervention design should be considered and adequately measured for future interventions. Trial registration: ACTRN12612001154897; 29 October 2012

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-Adjusted life-years for 29 cancer groups, 1990 to 2017 : A systematic analysis for the global burden of disease study

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570