Cognitive Performance Across the Life Course of Bolivian Forager-Farmers With Limited Schooling

Cognitive performance is characterized by at least two distinct life course trajectories. Many cognitive abilities (e.g. “effortful processing” abilities including fluid reasoning, and processing speed) improve throughout early adolescence and start declining in early adulthood, while other abilities (e.g. “crystallized” abilities like vocabulary breadth) improve throughout adult life, remaining robust even at late ages. Although schooling may impact performance and cognitive “reserve”, it has been argued that these age patterns of cognitive performance are human universals. Here we examine age patterns of cognitive performance among Tsimane forager-horticulturalists of Bolivia, and test whether schooling is related to differences in cognitive performance over the life course to assess models of active vs. passive cognitive reserve. We used a battery of eight tasks to assess a range of latent cognitive traits reflecting attention, processing speed, verbal declarative memory and semantic fluency (n=919 individuals, 49.9% female). Tsimane cognitive abilities show similar age-related differences as observed in industrialized populations: higher throughout adolescence and only slightly lower in later adulthood for semantic fluency, but substantially lower performance beginning in early adulthood for all other abilities. Schooling is associated with greater cognitive abilities at all ages controlling for sex, but has no attenuating effect on cognitive performance in late adulthood, consistent with models of passive cognitive reserve. We interpret the minimal attenuation of semantic fluency late in life in light of evolutionary theories of post-reproductive lifespan, which emphasize indirect fitness contributions of older adults through the transfer of information, labor and food to descendant kin

Sources of marine debris for Seychelles and other remote islands in the western Indian Ocean

Vast quantities of debris are beaching at remote islands in the western Indian Ocean. We carry out marine dispersal simulations incorporating currents, waves, winds, beaching, and sinking, for both terrestrial and marine sources of debris, to predict where this debris comes from. Our results show that most terrestrial debris beaching at these remote western Indian Ocean islands drifts from Indonesia, India, and Sri Lanka. Debris associated with fisheries and shipping also poses a major risk. Debris accumulation at Seychelles is likely seasonal, peaking during February–April. This pattern is driven by monsoonal winds and may be amplified during positive Indian Ocean Dipole and El-Niño events. Our results underline the vulnerability of small island states to marine plastic pollution, and are a crucial step towards improved management of the issue. The trajectories used in this study are available for download, and our analyses can be rerun under different parameter choices.journal articl

The Tsimane Health and Life History Project: Integrating Anthropology and Biomedicine

The Tsimane Health and Life History Project, an integrated bio-behavioral study of the human life course, is designed to test competing hypotheses of human life-history evolution. One aim is to understand the bidirectional connections between life history and social behavior in a highfertility, kin-based context lacking amenities of modern urban life (e.g. sanitation, banks, electricity). Another aim is to understand how a high pathogen burden influences health and well-being during development and adulthood. A third aim addresses how modernization shapes human life histories and sociality. Here we outline the project’s goals, history, and main findings since its inception in 2002. We reflect on the implications of current findings and highlight the need for more coordinated ethnographic and biomedical study of contemporary nonindustrial populations to address broad questions that can situate evolutionary anthropology in a key position within the social and life sciences

Transcriptional profiling of mycobacterial antigen-induced responses in infants vaccinated with BCG at birth

BACKGROUND: Novel tuberculosis (TB) vaccines recently tested in humans have been designed to boost immunity induced by the current vaccine, Mycobacterium bovis Bacille Calmette-Guérin (BCG). Because BCG vaccination is used extensively in infants, this population group is likely to be the first in which efficacy trials of new vaccines will be conducted. However, our understanding of the complexity of immunity to BCG in infants is inadequate, making interpretation of vaccine-induced immune responses difficult. METHODS: To better understand BCG-induced immunity, we performed gene expression profiling in five 10-week old infants routinely vaccinated with BCG at birth. RNA was extracted from 12 hour BCG-stimulated or purified protein derivative of tuberculin (PPD)-stimulated PBMC, isolated from neonatal blood collected 10 weeks after vaccination. RNA was hybridised to the Sentrix(R) HumanRef-8 Expression BeadChip (Illumina) to measure expression of >16,000 genes. RESULTS: We found that ex vivo stimulation of PBMC with PPD and BCG induced largely similar gene expression profiles, except that BCG induced greater macrophage activation. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, including PPAR-gamma, involved in activation of the alternative, anti-inflammatory macrophage response was down-regulated following stimulation with both antigens. In contrast, up-regulation of genes associated with the classic, pro-inflammatory macrophage response was noted. Further analysis revealed a decrease in the expression of cell adhesion molecules (CAMs), including integrin alpha M (ITGAM), which is known to be important for entry of mycobacteria into the macrophage. Interestingly, more leukocyte genes were down-regulated than up-regulated. CONCLUSION: Our results suggest that a combination of suppressed and up-regulated genes may be key in determining development of protective immunity to TB induced by vaccination with BCG

Once a feminist: Lynne Segal on Grace Paley’s The Little Disturbances of Man

The following contributions came in response to a request, sent to a number of key figures in feminism today, to write on a text that had been formative for their thinking as feminists. The chosen text could be a theory, a novel, an artwork, a performance, a poem: one that had stimulated, or even revolutionised, their ideas. As we hoped, this project has created a selection of texts central to our many and different experiences as feminists. I used to say that Margaret Drabble's The Garrick Year was the story of my life, in my early twenties, as if I was just a creature of time and circumstance. I read The Garrick Year sometime between October 1965, when my first child was born, and the end of 1967, before my marriage disintegrated. Like the heroine Emma Evans, I married a successful actor, had a child, and followed his career—which in the novel led Emma to Hereford for a summer season of plays

More Than Provocative, Less Than Scientific: A Commentary on the Editorial Decision to Publish Cofnas (2020)

We are addressing this letter to the editors of Philosophical Psychology after reading an article they decided to publish in the recent vol. 33, issue 1. The article is by Nathan Cofnas and is entitled “Research on group differences in intelligence: A defense of free inquiry” (2020). The purpose of our letter is not to invite Cofnas’s contribution into a broader dialogue, but to respectfully voice our concerns about the decision to publish the manuscript, which, in our opinion, fails to meet a range of academic quality standards usually expected of academic publications

Diagnostic Performance of a Machine Learning Algorithm (Asthma/Chronic Obstructive Pulmonary Disease [COPD] Differentiation Classification) Tool Versus Primary Care Physicians and Pulmonologists in Asthma, COPD, and Asthma/COPD Overlap

Funding The study was funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States. Acknowledgement The studies were funded by Novartis Pharmaceuticals Corporation, East Hanover, NJ, United States. Under the direction of authors, Rabi Panigrahy, Preethi B and Ian Wright (professional medical writers; Novartis) assisted in the preparation of this article in accordance with the third edition of Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3)Peer reviewedPublisher PD

Molecular selection of therapy in metastatic colorectal cancer: the FOCUS4 molecularly stratified RCT

Complex trials with innovative designs are becoming increasingly common and offer the potential to improve patient outcomes in a shorter time frame. There is evidence that patients with colorectal cancer fall into different subgroups with varying responsiveness to therapy, and that this variation is linked to genetic biomarkers. To the best of our knowledge, FOCUS4 was the first molecularly stratified trial in metastatic colorectal cancer and remains one of the first umbrella trial designs to be launched globally. Objectives To identify novel therapies that improve disease control within the molecular subgroup of metastatic colorectal cancer in which the novel therapies were expected to be most effective. Design This was a Phase II/III molecularly stratified umbrella trial that used adaptive statistical methodology to decide which subtrial should close early; new subtrials were added as protocol amendments. Setting The maintenance setting following 16 weeks of first-line combination chemotherapy. Participants Patients with newly diagnosed metastatic colorectal cancer were registered, and central laboratory testing was used to stratify their tumour into molecular subtypes. Following 16 weeks of first-line therapy, patients with stable or responding disease were eligible for randomisation into either a molecularly stratified subtrial or the non-stratified FOCUS4-N trial. Interventions Of the 20 drug combinations that were explored for inclusion in the platform trial, three molecularly targeted subtrials were activated: FOCUS4-B (PIK3CA mutation or PTEN overexpression) – aspirin versus placebo; FOCUS4-C (TP53 and RAS mutation) – adavosertib (AstraZeneca Ltd, Cambridge, UK) versus active monitoring; and FOCUS4-D (BRAF-PIK3CA-RAS wild type) – AZD8931 versus placebo. A non-stratified subtrial was also carried out: FOCUS4-N – capecitabine versus active monitoring. Main outcome measures The main outcome measure was progression-free survival from the time of randomisation to progression, comparing the intervention with active monitoring/placebo. Toxicity and overall survival data were collected in all randomised patients, and quality of life (using EuroQol-5 Dimensions) data were collected in FOCUS4-N only. Results Between January 2014 and October 2020, 1434 patients were registered from 88 hospitals in the UK. Successful biomarker testing was completed in 1291 out of 1382 samples (93%), and 908 out of 1315 patients (69%) completing 16 weeks of first-line therapy were eligible for randomisation, with 361 randomly allocated to a subtrial. FOCUS4-B evaluated aspirin versus placebo in the PIK3CA-mutant/ PTEN -loss subgroup, but recruited only six patients, so was closed for futility. FOCUS4-C evaluated adavosertib versus active monitoring in 67 patients in the RAS + TP53 double-mutant subgroup and met its primary end point, showing an improvement in progression-free survival (median 3.61 vs. 1.87 months; hazard ratio 0.35, 95% confidence interval 0.18 to 0.68; p = 0022). FOCUS4-D evaluated AZD8931 in 32 patients in the BRAF-PIK3CA-RAS wild-type subgroup and showed no benefit, so was discontinued after the first interim analysis. FOCUS4-N evaluated capecitabine monotherapy versus active monitoring in 254 patients and met its primary end point, showing improvement in progression-free survival (hazard ratio 0.40, 95% confidence interval 0.21 to 0.75; p < 0.0001). Limitations FOCUS4-C and FOCUS4-N were closed early owing to COVID-19, so did not accrue their planned recruitment numbers. Conclusions Adaptive stratified medicine studies are feasible in common cancers but present challenges. Capecitabine monotherapy is an effective maintenance therapy. Wee1 inhibition using adavosertib shows significant clinical activity, notably in left-sided colorectal cancer. Trial registration This trial was registered as ISRCTN90061546. Funding This project was jointly funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership, and Cancer Research UK. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 9. See the NIHR Journals Library website for further project information