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How social relationships shape moral wrongness judgments
No full textJudgments of whether an action is morally wrong depend on who is involved and the nature of their relationship. But how, when, and why social relationships shape moral judgments is not well understood. We provide evidence to address these questions, measuring cooperative expectations and moral wrongness judgments in the context of common social relationships such as romantic partners, housemates, and siblings. In a pre-registered study of 423 U.S. participants nationally representative for age, race, and gender, we show that people normatively expect different relationships to serve cooperative functions of care, hierarchy, reciprocity, and mating to varying degrees. In a second pre-registered study of 1,320 U.S. participants, these relationship-specific cooperative expectations (i.e., relational norms) enable highly precise out-of-sample predictions about the perceived moral wrongness of actions in the context of particular relationships. In this work, we show that this ‘relational norms’ model better predicts patterns of moral wrongness judgments across relationships than alternative models based on genetic relatedness, social closeness, or interdependence, demonstrating how the perceived morality of actions depends not only on the actions themselves, but also on the relational context in which those actions occur
Decoding visual colour from scalp electroencephalography measurements
No full textRecent advances have made it possible to decode various aspects of visually presented stimuli from patterns of scalp EEG measurements. As of recently, such multivariate methods have been commonly used to decode visual-spatial features such as location, orientation, or spatial frequency. In the current study, we show that it is also possible to track visual colour processing by using Linear Discriminant Analysis on patterns of EEG activity. Building on other recent demonstrations, we show that colour decoding: (1) reflects sensory qualities (as opposed to, for example, verbal labelling) with a prominent contribution from posterior electrodes contralateral to the stimulus, (2) conforms to a parametric coding space, (3) is possible in multi-item displays, and (4) is comparable in magnitude to the decoding of visual stimulus orientation. Through subsampling our data, we also provide an estimate of the approximate number of trials and participants required for robust decoding. Finally, we show that while colour decoding can be sensitive to subtle differences in luminance, our colour decoding results are primarily driven by measured colour differences between stimuli. Colour decoding opens a relevant new dimension in which to track visual processing using scalp EEG measurements, while bypassing potential confounds associated with decoding approaches that focus on spatial features
Results of a national UK physician reported survey of COVID-19 infection in patients with a myeloproliferative neoplasm
No full textPoint-of-care HbA1c testing in an urban primary care diabetes clinic in South Africa – a mixed methods feasibility study
No full textIntroduction:
Monitoring and treatment of type 2 diabetes in South Africa usually takes place in primary care using random blood glucose testing to guide treatment decisions. This study explored the feasibility of using point-of-care haemoglobin A1c (HbA1c) testing in addition to glucose testing in a busy primary care clinic in Cape Town, South Africa.
Subjects:
185 adults aged 19–88 years with type 2 diabetes.
Materials and Methods:
Participants recruited to this mixed methods cohort study received a point-of-care HbA1c test. Doctors were asked to use the point-of-care HbA1c result for clinical decision-making. Qualitative interviews were held with clinical staff.
Results:
Point-of-care HbA1c test results were obtained for 165 participants of whom 109 (65%) had poor glycaemic control (>8% HbA1c, 64 mmol/mol). Medical officers reported using a combination of HbA1c and blood glucose 77% of the time for clinical decision-making. Nurses found the analyser easy to use and doctors valued having the HbA1c result to help with decision-making.
Discussion:
Our results suggest that 30% of patients may have received inappropriate medication or not received necessary additional medication if random blood glucose alone had been used in routine appointments. Clinicians valued having access to the HbA1c test result to help them make treatment decisions
Functional parcellation of human and macaque striatum reveals human-specific connectivity in the dorsal caudate
No full textA wide homology between human and macaque striatum is often assumed as in both the striatum is involved in cognition, emotion and executive functions. However, differences in functional and structural organization between human and macaque striatum may reveal evolutionary divergence and shed light on human vulnerability to neuropsychiatric diseases. For instance, dopaminergic dysfunction of the human striatum is considered to be a pathophysiological underpinning of different disorders, such as Parkinson's disease (PD) and schizophrenia (SCZ). Previous investigations have found a wide similarity in structural connectivity of the striatum between human and macaque, leaving the cross-species comparison of its functional organization unknown. In this study, resting-state functional connectivity (RSFC) derived striatal parcels were compared based on their homologous cortico-striatal connectivity. The goal here was to identify striatal parcels whose connectivity is human-specific compared to macaque parcels. Functional parcellation revealed that the human striatum was split into dorsal, dorsomedial, and rostral caudate and ventral, central, and caudal putamen, while the macaque striatum was divided into dorsal, and rostral caudate and rostral, and caudal putamen. Cross-species comparison indicated dissimilar cortico-striatal RSFC of the topographically similar dorsal caudate. We probed clinical relevance of the striatal clusters by examining differences in their cortico-striatal RSFC and gray matter (GM) volume between patients (with PD and SCZ) and healthy controls. We found abnormal RSFC not only between dorsal caudate, but also between rostral caudate, ventral, central and caudal putamen and widespread cortical regions for both PD and SCZ patients. Also, we observed significant structural atrophy in rostral caudate, ventral and central putamen for both PD and SCZ while atrophy in the dorsal caudate was specific to PD. Taken together, our cross-species comparative results revealed shared and human-specific RSFC of different striatal clusters reinforcing the complex organization and function of the striatum. In addition, we provided a testable hypothesis that abnormalities in a region with human-specific connectivity, i.e., dorsal caudate, might be associated with neuropsychiatric disorders
Continual updating and monitoring of clinical prediction models: time for dynamic prediction systems?
No full textClinical prediction models (CPMs) have become fundamental for risk stratification across healthcare. The CPM pipeline (development, validation, deployment, and impact assessment) is commonly viewed as a one-time activity, with model updating rarely considered and done in a somewhat ad hoc manner. This fails to address the fact that the performance of a CPM worsens over time as natural changes in populations and care pathways occur. CPMs need constant surveillance to maintain adequate predictive performance. Rather than reactively updating a developed CPM once evidence of deteriorated performance accumulates, it is possible to proactively adapt CPMs whenever new data becomes available. Approaches for validation then need to be changed accordingly, making validation a continuous rather than a discrete effort. As such, “living” (dynamic) CPMs represent a paradigm shift, where the analytical methods dynamically generate updated versions of a model through time; one then needs to validate the system rather than each subsequent model revision
SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
No full textAims: The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40–69 years in Europe.
Methods and results: We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65–0.68) to 0.81 (0.76–0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low-risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries.
Conclusion: SCORE2—a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations—enhances the identification of individuals at higher risk of developing CVD across Europe
Being Emmanuel: Matthew's ever-present Jesus?
No full textAmong the New Testament Gospels, Matthew most emphatically stresses the continued presence of Jesus throughout his ministry and with his disciples after Easter. This is despite sensitivity to the challenge of the cross and experiences of absence or deprivation. Structurally, the Gospel develops this affirmation in relation to the narrative of Jesus’ birth and incarnation, to his ministry, to the governance of the Christian community in its apostolic mission to Israel and the nations. Matthew never quite articulates how this continued presence actually works, whether in spatial or sacramental or pneumatological terms. And yet the emphatic correlation of ‘Jesus’ and ‘Emmanuel’ confirms that each is constituted by the other: being ‘God with us’ (Matt 1.23) means precisely to ‘save his people’ (1.21), and vice versa
Germline and somatic genetic variants in the p53 pathway interact to affect cancer risk, progression, and drug response
No full textInsights into oncogenesis derived from cancer susceptibility loci (single nucleotide polymorphisms, SNP) hold the potential to facilitate better cancer management and treatment through precision oncology. However, therapeutic insights have thus far been limited by our current lack of understanding regarding both interactions of these loci with somatic cancer driver mutations and their influence on tumorigenesis. For example, while both germline and somatic genetic variation to the p53 tumor suppressor pathway are known to promote tumorigenesis, little is known about the extent to which such variants cooperate to alter pathway activity. Here we hypothesize that cancer risk-associated germline variants interact with somatic TP53 mutational status to modify cancer risk, progression, and response to therapy. Focusing on a cancer risk SNP (rs78378222) with a well-documented ability to directly influence p53 activity as well as integration of germline datasets relating to cancer susceptibility with tumor data capturing somatically-acquired genetic variation provided supportive evidence for this hypothesis. Integration of germline and somatic genetic data enabled identification of a novel entry point for therapeutic manipulation of p53 activities. A cluster of cancer risk SNPs resulted in increased expression of pro-survival p53 target gene KITLG and attenuation of p53-mediated responses to genotoxic therapies, which were reversed by pharmacological inhibition of the pro-survival c-KIT signal. Together, our results offer evidence of how cancer susceptibility SNPs can interact with cancer driver genes to affect cancer progression and identify novel combinatorial therapies
A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
No full textBackground
Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5′-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health.
Objectives
We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics.
Methods
Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP.
Results
In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers.
Conclusions
We found that 5 different markers, capturing different aspects of vitamin B6–related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors