Bayesian versus frequentist statistical inference for investigating a one-off cancer cluster reported to a health department

Background. The problem of silent multiple comparisons is one of the most difficult statistical problems faced by scientists. It is a particular problem for investigating a one-off cancer cluster reported to a health department because any one of hundreds, or possibly thousands, of neighbourhoods, schools, or workplaces could have reported a cluster, which could have been for any one of several types of cancer or any one of several time periods. Methods. This paper contrasts the frequentist approach with a Bayesian approach for dealing with silent multiple comparisons in the context of a one-off cluster reported to a health department. Two published cluster investigations were re-analysed using the Dunn-Sidak method to adjust frequentist p-values and confidence intervals for silent multiple comparisons. Bayesian methods were based on the Gamma distribution. Results. Bayesian analysis with non-informative priors produced results similar to the frequentist analysis, and suggested that both clusters represented a statistical excess. In the frequentist framework, the statistical significance of both clusters was extremely sensitive to the number of silent multiple comparisons, which can only ever be a subjective "guesstimate". The Bayesian approach is also subjective: whether there is an apparent statistical excess depends on the specified prior. Conclusion. In cluster investigations, the frequentist approach is just as subjective as the Bayesian approach, but the Bayesian approach is less ambitious in that it treats the analysis as a synthesis of data and personal judgements (possibly poor ones), rather than objective reality. Bayesian analysis is (arguably) a useful tool to support complicated decision-making, because it makes the uncertainty associated with silent multiple comparisons explicit

A Multisite Preregistered Paradigmatic Test of the Ego-Depletion Effect

We conducted a preregistered multilaboratory project (k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result (d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect (d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Spectropolarimetry of high-redshift obscured and red quasars

Spectropolarimetry is a powerful technique that has provided critical support for the geometric unification model of local active galactic nuclei. In this paper, we present optical (rest-frame UV) Keck spectropolarimetry of five luminous obscured (Type 2) and extremely red quasars (ERQs) at z~2.5. Three objects reach polarization fractions of >10% in the continuum. We propose a model in which dust scattering is the dominant scattering and polarization mechanism in our targets, though electron scattering cannot be completely excluded. Emission lines are polarized at a lower level than is the continuum. This suggests that the emission-line region exists on similar spatial scales as the scattering region. In three objects we detect an intriguing 90 degree swing in the polarization position angle as a function of line-of-sight velocity in the emission lines of Ly-alpha, CIV and NV. We interpret this phenomenon in the framework of a geometric model with an equatorial dusty scattering region in which the material is outflowing at several thousand km/sec. Emission lines may also be scattered by dust or resonantly. This model explains several salient features of observations by scattering on scales of a few tens of pc. Our observations provide a tantalizing view of the inner region geometry and kinematics of high-redshift obscured and extremely red quasars. Our data and modeling lend strong support for toroidal obscuration and powerful outflows on the scales of the UV emission-line region, in addition to the larger scale outflows inferred previously from the optical emission-line kinematics.Comment: 26 pages, MNRAS, in pres

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Impact of hospital-wide process redesign on clinical outcomes: A comparative study of internally versus externally led intervention

Introduction: In response to increasing demand for hospital beds, institution-wide clinical process redesign has been advocated for improving efficiency

An ovine model for investigation of the microenvironment of the male mammary gland

Publication status: PublishedFunder: Anatomical Society PhD Studentship; doi: http://dx.doi.org/10.13039/100012070AbstractThe specific biology of the male breast remains relatively unexplored in spite of the increasing global prevalence of male breast cancer. Delineation of the microenvironment of the male breast is restricted by the low availability of human samples and a lack of characterisation of appropriate animal models. Unlike the mouse, the male ovine gland persists postnatally. We suggest that the male ovine mammary gland constitutes a promising adjunctive model for the male breast. In this study, we evaluate the male ovine mammary gland microenvironment, comparing intact and neutered males. Assessment of the glandular histo‐anatomy highlights the resemblance of the male gland to that of neonatal female sheep and confirms the presence of rudimentary terminal duct lobular units. Irrespective of neutered status, cell proliferation in epithelial and stromal compartments is similarly low in males, and cell proliferation in epithelial cells and in the intralobular stroma is significantly lower than in pubertal female sheep. Between 42% and 72% of the luminal mammary epithelial cells in the male gland express the androgen receptor and expression is significantly reduced by neutering. Luminal epithelial cells within the intact and neutered male gland also express oestrogen receptor alpha, but minimal progesterone receptor expression is observed. The distribution of leukocytes within the ducts and stroma is similar to the mammary gland of female sheep and females of other species. Both macrophages and T lymphocytes are intercalated in the epithelial bilayer and are more abundant in the intralobular stroma than the interlobular stroma, suggesting that they may have a protective immunological function within the vestigial glandular tissue of the male sheep. Mast cells are also observed within the stroma. These cells cluster near the glandular tissue and are frequently located adjacent to blood vessels. The abundance of mast cells is significantly higher in intact males compared to neutered males, suggesting that hormone signalling may impact mast cell recruitment. In this study, we demonstrate the utility of the male ovine mammary gland as a model for furthering our knowledge of postnatal male mammary biology.</jats:p

B cell receptor repertoire kinetics after SARS-CoV-2 infection and vaccination.

Funder: Medical Research CouncilFunder: National Institute for Health Research (NIHR)B cells are important in immunity to both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and vaccination, but B cell receptor (BCR) repertoire development in these contexts has not been compared. We analyze serial samples from 171 SARS-CoV-2-infected individuals and 63 vaccine recipients and find the global BCR repertoire differs between them. Following infection, immunoglobulin (Ig)G1/3 and IgA1 BCRs increase, somatic hypermutation (SHM) decreases, and, in severe disease, IgM and IgA clones are expanded. In contrast, after vaccination, the proportion of IgD/M BCRs increase, SHM is unchanged, and expansion of IgG clones is prominent. VH1-24, which targets the N-terminal domain (NTD) and contributes to neutralization, is expanded post infection except in the most severe disease. Infection generates a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein, while a more focused response after vaccination mainly targets the spike's receptor-binding domain. Thus, the nature of SARS-CoV-2 exposure differentially affects BCR repertoire development, potentially informing vaccine strategies

A Multisite Preregistered Paradigmatic Test of the Ego-Depletion Effect

We conducted a preregistered multilaboratory project (k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result (d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (delta = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect (d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation