39 research outputs found
Preference and behavior : A response to Buss
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29157/1/0000202.pd
Fat, sex, class, adaptive flexibility, and cultural change
In modern industrial nations, the traditional positive correlation between female body fat and social class has turned strongly inverse, thinness in women is admired and plumpness is a handicap. This recent reversal of what had seemed to be stable aspects of human nature is analyzed as a potentially adaptive response to two ecological novelties: chronic food surplus and the breakdown of barriers between men's and women's work, which, together, may have made thinness helpful to women competing for status and resources in both mating and job markets. Whether status and resources still promote long-term Darwinian fitness is an open question. Progress in understanding the unique properties of the human mind depends on widespread recognition that the mind has been designed by natural selection to seek and sometimes find adaptive solutions to the novel problems we ourselves create. Adaptive flexibility and cultural change are two sides of the same coin.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29883/1/0000236.pd
The present also explains the past : A response to Tooby and Cosmides
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29423/1/0000502.pd
Characterization of mtDNA variation in a cohort of South African paediatric patients with mitochondrial disease
Mitochondrial disease can be attributed to both mitochondrial and nuclear gene mutations. It has a heterogeneous clinical and biochemical profile, which is compounded by diversity of the genetic background. Disease-based epidemiological information has expanded significantly in recent decades, but little information is known that clarifies the aetiology in African patients. The aim of this study was to investigate mitochondrial DNA variation and pathogenic mutations in muscle of diagnosed paediatric patients from South Africa. A cohort of 71 South African paediatric patients was included and a high-throughput nucleotide sequencing approach was used to sequence full-length muscle mtDNA. The average coverage of the mtDNA genome was 81 ± 26 per position. After assigning haplogroups, it was determined that although the nature of non-haplogroup defining variants was similar in African and non-African haplogroup patients, the number of substitutions were significantly higher in African patients. We describe previously reported disease-associated and novel variants in this cohort. We observed a general lack of commonly reported syndrome-associated mutations, which supports clinical observations and confirms general observations in African patients when using single mutation screening strategies based on (predominantly non-African) mtDNA disease-based information. It is finally concluded that this first extensive report on muscle mtDNA sequences in African paediatric patients highlights the need for a full length mtDNA sequencing strategy, which applies to all populations where specific mutations is not present. This, in addition to nuclear DNA gene mutation and pathogenicity evaluations, will be required to better unravel the aetiology of these disorders in African patients.http://www.nature.com/ejhg/index.htm
International Paediatric Mitochondrial Disease Scale
Objective: There is an urgent need for reliable and universally applicable outcome measures for children with mitochondrial diseases. In this study, we aimed to adapt the currently available Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) to the International Paediatric Mitochondrial Disease Scale (IPMDS) during a Delphi-based process with input from international collaborators, patients and caretakers, as well as a pilot reliability study in eight patients. Subsequently, we aimed to test the feasibility, construct validity and reliability of the IPMDS in a multicentre study. Methods: A clinically, biochemically and genetically heterogeneous group of 17 patients (age 1.6â16Â years) from five different expert centres from four different continents were evaluated in this study. Results: The feasibility of the IPMDS was good, as indicated by a low number of missing items (4Â %) and the positive evaluation of patients, parents and users. Principal component analysis of our small sample identified three factors, which explained 57.9Â % of the variance. Good construct validity was found using hypothesis testing. The overall interrater reliability was good [median intraclass correlation coefficient for agreement between raters (ICCagreement) 0.85; range 0.23â0.99). Conclusion: In conclusion, we suggest using the IPMDS for assessing natural history in children with mitochondrial diseases. These data should be used to further explore construct validity of the IPMDS and to set age limits. In parallel, responsiveness and the minimal clinically important difference should be studied to facilitate sample size calculations in future clinical trials
Neuromuscular disease genetics in under-represented populations: increasing data diversity
Neuromuscular diseases (NMDs) affect âŒ15 million people globally. In high income settings DNA-based diagnosis has transformed care pathways and led to gene-specific therapies. However, most affected families are in low-to-middle income countries (LMICs) with limited access to DNA-based diagnosis. Most (86%) published genetic data is derived from European ancestry. This marked genetic data inequality hampers understanding of genetic diversity and hinders accurate genetic diagnosis in all income settings. We developed a cloud-based transcontinental partnership to build diverse, deeply-phenotyped and genetically characterized cohorts to improve genetic architecture knowledge, and potentially advance diagnosis and clinical management.
We connected 18 centres in Brazil, India, South Africa, Turkey, Zambia, Netherlands and the UK. We co-developed a cloud-based data solution and trained 17 international neurology fellows in clinical genomic data interpretation. Single gene and whole exome data were analysed via a bespoke bioinformatics pipeline and reviewed alongside clinical and phenotypic data in global webinars to inform genetic outcome decisions.
We recruited 6001 participants in the first 43 months. Initial genetic analyses âsolvedâ or âpossibly solvedâ âŒ56% probands overall. In-depth genetic data review of the four commonest clinical categories (limb girdle muscular dystrophy, inherited peripheral neuropathies, congenital myopathy/muscular dystrophies and Duchenne/Becker muscular dystrophy) delivered a âŒ59% âsolvedâ and âŒ13% âpossibly solvedâ outcome. Almost 29% of disease causing variants were novel, increasing diverse pathogenic variant knowledge. Unsolved participants represent a new discovery cohort. The dataset provides a large resource from under-represented populations for genetic and translational research.
In conclusion, we established a remote transcontinental partnership to assess genetic architecture of NMDs across diverse populations. It supported DNA-based diagnosis, potentially enabling genetic counselling, care pathways and eligibility for gene-specific trials. Similar virtual partnerships could be adopted by other areas of global genomic neurological practice to reduce genetic data inequality and benefit patients globally
Rebuffing Royals? Afrikaners and the royal visit to South Africa in 1947â
This article traces the responses of Afrikaners to the symbolism and political purposes of the 1947 royal visit to Southern Africa, the first post-war royal tour and the first visit of a reigning sovereign to the Union of South Africa. Taking place in the aftermath of a war that had caused bitter political divisions within Afrikaner ranks and stimulated radical populist nationalism, a royal tour intended to express the crown's gratitude for South Africa's participation in that war was bound to be contentious. Drawing on press accounts, biographies, autobiographies and archival sources, this article argues that the layered reactions of Afrikaners demonstrate that, even on the eve of the National Party's electoral victory on a republican and apartheid platform, attitudes towards monarchy and the British connection were more fluid and ambiguous than either contemporary propaganda or recent accounts have allowed. The diverse meanings attributed to this iconic royal tour reveal a process of intense contestation and reflection about South Africa's place in an empire that was in the throes of post-war redefinition and transformation, and confirm recent characterisations of the 1940s as one of manifold possibilities such that outcomes, like the electoral victory of the National Party in the following year, was far from pre-determined
Social Bonding and Nurture Kinship: Compatibility between Cultural and Biological Approaches
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 nonâcritically 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 (nâ=â257), ARB (nâ=â248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; nâ=â10), or no RAS inhibitor (control; nâ=â264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ supportâfree 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 supportâfree days among critically ill patients was 10 (â1 to 16) in the ACE inhibitor group (nâ=â231), 8 (â1 to 17) in the ARB group (nâ=â217), and 12 (0 to 17) in the control group (nâ=â231) (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 supportâfree 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