Academics and community members collaborated in research to examine how best to apply ethics guidelines for research involving Indigenous communities in a community with complex and multiple ...political and cultural jurisdictions. We examined issues of NunatuKavut (Southern Inuit) authority and representation in relation to governance of research in a context where community identity is complex and shifting, and new provincial legislation mandates centralized ethics review. We scrutinize the taken-for-granted assumption of research ethics that community engagement is an unquestionable “good.” We examine the question of whether and how research ethics guidelines and associated assumptions about the value of community engagement may be grounded in, and inadvertently reinforce, ongoing colonialist relations of power. We present findings that community engagement—if done uncritically and in service to ethics guidelines rather than in service to ethical research—can itself cause harm by leading to community fatigue, undermining the community’s ability to be effectively involved in the research, and restricting the community’s ability to have oversight and control over research. We conclude by suggesting that the laudable goal of engaging communities in research requires careful reflection on the appropriate use of resources to operationalize meaningful collaboration.
Parental warmth and hostility are two key dimensions of parenting for child development, but the differential effects of these parenting dimensions on child prosocial and antisocial development has ...not been adequately investigated. The current study hypothesized that parental warmth would be uniquely related to child callous-unemotional traits and prosocial behavior, whereas parental hostility would be uniquely related to child delinquency and aggression. These hypotheses were investigated in a diverse sample of 1,216 adolescent males (13 to 17 years old, 46% Latino, 37% Black) with justice-system involvement in the 5 years following their first arrest. Hybrid models estimated within- and between-individual associations over time, while controlling for the overlap between parental warmth and hostility and between child prosocial and antisocial outcomes. Results indicated that maternal warmth showed consistent associations with callous-unemotional traits and prosocial behavior over time, whereas maternal hostility showed consistent associations with delinquency and aggression over time. Further, the findings were similar across racial and ethnic groups. Implications for developmental models of antisocial behavior, particularly for those including the role of callous-unemotional traits, are discussed.
In humans, most germline mutations are inherited from the father. This observation has been widely interpreted as reflecting the replication errors that accrue during spermatogenesis. If so, the male ...bias in mutation should be substantially lower in a closely related species with similar rates of spermatogonial stem cell divisions but a shorter mean age of reproduction. To test this hypothesis, we resequenced two 3-4 generation nuclear families (totaling 29 individuals) of olive baboons (Papio anubis), who reproduce at approximately 10 years of age on average, and analyzed the data in parallel with three 3-generation human pedigrees (26 individuals). We estimated a mutation rate per generation in baboons of 0.57×10-8 per base pair, approximately half that of humans. Strikingly, however, the degree of male bias in germline mutations is approximately 4:1, similar to that of humans-indeed, a similar male bias is seen across mammals that reproduce months, years, or decades after birth. These results mirror the finding in humans that the male mutation bias is stable with parental ages and cast further doubt on the assumption that germline mutations track cell divisions. Our mutation rate estimates for baboons raise a further puzzle, suggesting a divergence time between apes and Old World monkeys of 65 million years, too old to be consistent with the fossil record; reconciling them now requires not only a slowdown of the mutation rate per generation in humans but also in baboons.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although the prevalence of autism spectrum disorder (ASD) has risen sharply in the last few years reaching 1 in 68, the average age of diagnosis in the United States remains close to 4--well past the ...developmental window when early intervention has the largest gains. This emphasizes the importance of developing accurate methods to detect risk faster than the current standards of care. In the present study, we used machine learning to evaluate one of the best and most widely used instruments for clinical assessment of ASD, the Autism Diagnostic Observation Schedule (ADOS) to test whether only a subset of behaviors can differentiate between children on and off the autism spectrum. ADOS relies on behavioral observation in a clinical setting and consists of four modules, with module 2 reserved for individuals with some vocabulary and module 3 for higher levels of cognitive functioning. We ran eight machine learning algorithms using stepwise backward feature selection on score sheets from modules 2 and 3 from 4540 individuals. We found that 9 of the 28 behaviors captured by items from module 2, and 12 of the 28 behaviors captured by module 3 are sufficient to detect ASD risk with 98.27% and 97.66% accuracy, respectively. A greater than 55% reduction in the number of behaviorals with negligible loss of accuracy across both modules suggests a role for computational and statistical methods to streamline ASD risk detection and screening. These results may help enable development of mobile and parent-directed methods for preliminary risk evaluation and/or clinical triage that reach a larger percentage of the population and help to lower the average age of detection and diagnosis.
Trophic rewilding—the (re)introduction of missing large herbivores and/or their predators—is increasingly proposed to restore biodiversity and biotic interactions, but its effects on soils have been ...largely neglected. The high diversity of soil organisms and the ecological functions they perform mean that the full impact of rewilding on ecosystems cannot be assessed considering only above-ground food webs. Here we outline current understanding on how animal species of rewilding interest affect soil structure, processes and communities, and how in turn soil biota may affect species above ground. We highlight considerable uncertainty in soil responses to and feedbacks on above-ground consumers, with potentially large implications for rewilding interactions with global change. For example, the impact of large herbivores on soil decomposers and plant–soil interactions could lead to reduced carbon sequestration, whereas herbivore interactions with keystone biota such as mycorrhizal fungi, dung beetles and bioturbators could promote native plants and ecosystem heterogeneity. Moreover, (re)inoculation of keystone soil biota could be considered as a strategy to meet some of the objectives of trophic rewilding. Overall, we call for the rewilding research community to engage more with soil ecology experts and consider above-ground–below-ground linkages as integral to assess potential benefits as well as pitfalls.
This article is part of the theme issue ‘Trophic rewilding: consequences for ecosystems under global change'.
Determining the evolutionary relationships between fossil hominid groups such as Neanderthals and modern humans has been a question of enduring interest in human evolutionary genetics. Here we ...present a new method for addressing whether archaic human groups contributed to the modern gene pool (called ancient admixture), using the patterns of variation in contemporary human populations. Our method improves on previous work by explicitly accounting for recent population history before performing the analyses. Using sequence data from the Environmental Genome Project, we find strong evidence for ancient admixture in both a European and a West African population (p approximately 10(-7)), with contributions to the modern gene pool of at least 5%. While Neanderthals form an obvious archaic source population candidate in Europe, there is not yet a clear source population candidate in West Africa.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The origin of contemporary Europeans remains contentious. We obtained a genome sequence from Kostenki 14 in European Russia dating from 38,700 to 36,200 years ago, one of the oldest fossils of ...anatomically modern humans from Europe. We find that Kostenki 14 shares a close ancestry with the 24,000-year-old Mal'ta boy from central Siberia, European Mesolithic hunter-gatherers, some contemporary western Siberians, and many Europeans, but not eastern Asians. Additionally, the Kostenki 14 genome shows evidence of shared ancestry with a population basal to all Eurasians that also relates to later European Neolithic farmers. We find that Kostenki 14 contains more Neandertal DNA that is contained in longer tracts than present Europeans. Our findings reveal the timing of divergence of western Eurasians and East Asians to be more than 36,200 years ago and that European genomic structure today dates back to the Upper Paleolithic and derives from a metapopulation that at times stretched from Europe to central Asia.
Instances in which natural selection maintains genetic variation in a population over millions of years are thought to be extremely rare. We conducted a genome-wide scan for long-lived balancing ...selection by looking for combinations of SNPs shared between humans and chimpanzees. In addition to the major histocompatibility complex, we identified 125 regions in which the same haplotypes are segregating in the two species, all but two of which are noncoding. In six cases, there is evidence for an ancestral polymorphism that persisted to the present in humans and chimpanzees. Regions with shared haplotypes are significantly enriched for membrane glycoproteins, and a similar trend is seen among shared coding polymorphisms. These findings indicate that ancient balancing selection has shaped human variation and point to genes involved in host-pathogen interactions as common targets.
Adoptive cellular therapy with chimeric antigen receptor T cells (car-ts) has recently received approval from Health Canada and the U.S. Food and Drug Administration after remarkable and durable ...remissions were seen in children with recurrent or refractory leukemia and adults with non-Hodgkin lymphoma-responses that were so impressive that a shift in the paradigm of care has now occurred for children with acute lymphoblastic leukemia. The concept behind car-t immunotherapy is that modification of a patient's own T cells to facilitate their localization to the cancer cell, with subsequent activation of the T cell effector mechanism and proliferation, will result in targeted killing of cancer cells. The car-ts are a novel drug in that the starting material for the manufacture of the car-t product comes from the patient, whose viable T cells are then genetically modified. Thus, collaboration is needed between the pharmaceutical companies, which must meet good manufacturing standards for each patient's unique product, and the treating sites. For regulators and health authorities, this new class of drugs requires new paradigms for assessment and approval. Treatments with car-ts require that institutions address unique logistics requirements and management of novel toxicities. The Hospital for Sick Children has had early experience with both the licensing of clinical trials and the introduction of the first commercial product. Here, we provide an overview of basic concepts and treatment, with caveats drawn from what we have learned thus far in bringing this new therapy to the clinical front line.
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