Beyond ‘significance’:Principles and practice of the analysis of credibility

The inferential inadequacies of statistical significance testing are now widely recognized. There is, however, no consensus on how to move research into a ‘post p < 0.05’ era. We present a potential route forward via the Analysis of Credibility, a novel methodology that allows researchers to go beyond the simplistic dichotomy of significance testing and extract more insight from new findings. Using standard summary statistics, AnCred assesses the credibility of significant and non-significant findings on the basis of their evidential weight, and in the context of existing knowledge. The outcome is expressed in quantitative terms of direct relevance to the substantive research question, providing greater protection against misinterpretation. Worked examples are given to illustrate how AnCred extracts additional insight from the outcome of typical research study designs. Its ability to cast light on the use of p-values, the interpretation of non-significant findings and the so-called ‘replication crisis’ is also discussed

Variations in HIV Prevention Coverage in Subpopulations of Australian Gay and Bisexual Men, 2017–2021: Implications for Reducing Inequities in the Combination Prevention Era

Using repeated behavioural surveillance data collected from gay and bisexual men (GBM) across Australia, we assessed trends in HIV prevention coverage (the level of ‘safe sex’ achieved in the population by the use of effective prevention methods, including condoms, pre-exposure prophylaxis [PrEP] and having an undetectable viral load). We stratified these trends by age, country of birth/recency of arrival, sexual identity, and the proportion of gay residents in the participant’s suburb. Among 25,865 participants with casual male partners, HIV prevention coverage increased from 69.8% in 2017 to 75.2% in 2021, lower than the UNAIDS target of 95%. Higher levels of coverage were achieved among older GBM (≥ 45 years), non-recently-arrived migrants, and in suburbs with ≥ 10% gay residents. The lowest levels of prevention coverage (and highest levels of HIV risk) were recorded among younger GBM (&lt; 25 years) and bisexual and other-identified participants. Younger, recently-arrived, and bisexual GBM were the most likely to use condoms, while PrEP use was concentrated among gay men, 25–44-year-olds, and in suburbs with more gay residents. The use of undetectable viral load was most common among participants aged ≥ 45 years. Our analysis shows that high HIV prevention coverage can be achieved through a mixture of condom use, PrEP use, and undetectable viral load, or by emphasising PrEP use. In the Australian context, younger, bisexual and other-identified GBM should be prioritised for enhanced access to effective HIV prevention methods. We encourage other jurisdictions to assess the level of coverage achieved by combination prevention, and variations in uptake

Answer changing in multiple choice assessment change that answer when in doubt – and spread the word!

<p>Abstract</p> <p>Background</p> <p>Several studies during the last decades have shown that answer changing in multiple choice examinations is generally beneficial for examinees. In spite of this the common misbelief still prevails that answer changing in multiple choice examinations results in an increased number of wrong answers rather than an improved score. One suggested consequence of newer studies is that examinees should be informed about this misbelief in the hope that this prejudice might be eradicated. This study aims to confirm data from previous studies about the benefits of answer changing as well as pursue the question of whether students informed about the said advantageous effects of answer changing would indeed follow this advice and change significantly more answers. Furthermore a look is cast on how the overall examination performance and mean point increase of these students is affected.</p> <p>Methods</p> <p>The answer sheets to the end of term exams of 79 3^rdyear medical students at the University of Munich were analysed to confirm the benefits of answer changing. Students taking the test were randomized into two groups. Prior to taking the test 41 students were informed about the benefits of changing answers after careful reconsideration while 38 students did not receive such information. Both groups were instructed to mark all answer changes made during the test.</p> <p>Results</p> <p>Answer changes were predominantly from wrong to right in full accordance with existing literature resources. It was shown that students who had been informed about the benefits of answer changing when in doubt changed answers significantly more often than students who had not been informed. Though students instructed on the benefits of changing answers scored higher in their exams than those not instructed, the difference in point increase was not significant.</p> <p>Conclusion</p> <p>Students should be informed about the benefits of changing initial answers to multiple choice questions once when in reasonable doubt about these answers. Furthermore, reconsidering answers should be encouraged as students will heed the advice and change more answers than students not so instructed.</p

Clinical Manifestations and Case Management of Ebola Haemorrhagic Fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008

A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect

The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration

The NF-κB family of transcription factors is a well-established regulator of the immune and inflammatory responses and also plays a key role in other cellular processes, including cell death, proliferation, and migration. Conserved residues in the trans-activation domain of RelA, which can be posttranslationally modified, regulate divergent NF-κB functions in response to different cellular stimuli. Using rela(−/−) mouse embryonic fibroblasts reconstituted with RelA, we find that mutation of the threonine 505 (T505) phospho site to alanine has wide-ranging effects on NF-κB function. These include previously described effects on chemotherapeutic drug-induced apoptosis, as well as new roles for this modification in autophagy, cell proliferation, and migration. This last effect was associated with alterations in the actin cytoskeleton and expression of cellular migration–associated genes such as WAVE3 and α-actinin 4. We also define a new component of cisplatin-induced, RelA T505–dependent apoptosis, involving induction of NOXA gene expression, an effect explained at least in part through induction of the p53 homologue, p73. Therefore, in contrast to other RelA phosphorylation events, which positively regulate NF-κB function, we identified RelA T505 phosphorylation as a negative regulator of its ability to induce diverse cellular processes such as apoptosis, autophagy, proliferation, and migration

The Medicine Tree: Unsettling palaeoecological perceptions of past environments and human activity

In this paper, we consider palaeoecological approaches to past landscapes and reflect upon how these are relevant to archaeological themes concerning concepts of environmental change and the role of past and present human communities in these processes. In particular, we highlight the importance of local context in the perception and understanding of landscape. Utilising a case study from Nepal, we look to ‘unsettle’ a conventional palaeoecological interpretation of a pollen record, originally constructed on western ecological principles, and instead draw on an interpretative perspective rooted in local Buddhist ecological knowledge, or a ‘folk taxonomy’, known as ‘The Medicine Tree’. We discuss how the interpretations of patterns and processes of vegetation change from a pollen record are not necessarily absolute. In particular, we outline how the palaeoecological frame of enquiry and reference is rooted in an essentially Eurocentric, Western scientific paradigm, which, in turn, shapes how we perceive and conceive of past landscapes and the role of ‘anthropogenic impact’ on vegetation. The aim of this is not to suggest that scientific approaches to the ‘reconstruction’ of past landscapes are necessarily invalid, but to illustrate how ‘empirical’ scientific methods and interpretations in archaeological science are contingent upon specific social and cultural frames of reference. We discuss the broader relevance of this, such as how we interpret past human activity and perception of landscape change, the ways in which we might look to mobilise research in the context of contemporary problems, issues concerning ‘degraded landscapes’ and how we incorporate local and archaeological perspectives with palaeoecology within an interconnected and iterative process

Isolated sixth cranial nerve palsy as the presenting symptom of a rapidly expanding ACTH positive pituitary adenoma: a case report

<p>Abstract</p> <p>Background</p> <p>Pituitary adenoma may present with neuro-ophthalmic manifestations and, typically, rapid tumor expansion is the result of apoplexy. Herein, we present the first case of an isolated sixth cranial nerve palsy as initial feature of a rapidly expanding ACTH positive silent tumor without apoplexy.</p> <p>Case Presentation</p> <p>A 44 year old female with a history of sarcoidosis presented with an isolated sixth cranial nerve palsy as the initial clinical feature of a rapidly expanding ACTH positive silent pituitary adenoma. The patient underwent emergent transsphenoidal hypophysectomy for this rapidly progressive tumor and subsequently regained complete vision and ocular motility. Despite tumor extension into the cavernous sinus, the other cranial nerves were spared during the initial presentation.</p> <p>Conclusions</p> <p>This case illustrates the need to consider a rapidly growing pituitary tumor as a possibility when presented with a rapidly progressive ophthalmoplegia.</p

Planetary population synthesis

In stellar astrophysics, the technique of population synthesis has been successfully used for several decades. For planets, it is in contrast still a young method which only became important in recent years because of the rapid increase of the number of known extrasolar planets, and the associated growth of statistical observational constraints. With planetary population synthesis, the theory of planet formation and evolution can be put to the test against these constraints. In this review of planetary population synthesis, we first briefly list key observational constraints. Then, the work flow in the method and its two main components are presented, namely global end-to-end models that predict planetary system properties directly from protoplanetary disk properties and probability distributions for these initial conditions. An overview of various population synthesis models in the literature is given. The sub-models for the physical processes considered in global models are described: the evolution of the protoplanetary disk, the planets' accretion of solids and gas, orbital migration, and N-body interactions among concurrently growing protoplanets. Next, typical population synthesis results are illustrated in the form of new syntheses obtained with the latest generation of the Bern model. Planetary formation tracks, the distribution of planets in the mass-distance and radius-distance plane, the planetary mass function, and the distributions of planetary radii, semimajor axes, and luminosities are shown, linked to underlying physical processes, and compared with their observational counterparts. We finish by highlighting the most important predictions made by population synthesis models and discuss the lessons learned from these predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the 'Handbook of Exoplanets', planet formation section, section editor: Ralph Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed

Factors affecting phage D29 infection: a tool to investigate different growth states of mycobacteria

Bacteriophages D29 and TM4 are able to infect a wide range of mycobacteria, including pathogenic and non pathogenic species. Successful phage infection of both fast- and slow-growing mycobacteria can be rapidly detected using the phage amplification assay. Using this method, the effect of oxygen limitation during culture of mycobacteria on the success of phage infection was studied. Both D29 and TM4 were able to infect cultures of M. smegmatis and Mycobacterium avium subspecies paratuberculosis (MAP) grown in liquid with aeration. However when cultures were grown under oxygen limiting conditions, only TM4 could productively infect the cells. Cell attachment assays showed that D29 could bind to the cells surface but did not complete the lytic cycle. The ability of D29 to productively infect the cells was rapidly recovered (within 1 day) when the cultures were returned to an aerobic environment and this recovery required de novo RNA synthesis. These results indicated that under oxygen limiting conditions the cells are entering a growth state which inhibits phage D29 replication, and this change in host cell biology which can be detected by using both phage D29 and TM4 in the phage amplification assay

Are Bone and Muscle Changes from POWER PE, an 8-month In-school Jumping Intervention, Maintained at Three Years?

Our aim was to determine if the musculoskeletal benefits of a twice-weekly, school-based, jumping regime in healthy adolescent boys and girls were maintained three years later. Subjects of the original POWER PE trial (n = 99) were contacted and asked to undergo retesting three years after cessation of the intervention. All original measures were completed including: sitting height, standing height, weight, calcaneal broadband ultrasound attenuation (BUA), whole body, hip and spine bone mineral content (BMC), lean tissue mass, and fat mass. Physical activity was recorded with the bone-specific physical activity questionnaire (BPAQ) and calcium intake was estimated with a calcium-focussed food questionnaire. Maturity was determined by Tanner staging and estimation of the age of peak height velocity (PHV). Twenty-nine adolescents aged 17.3±0.4 years agreed to participate. Three years after the intervention, there were no differences in subject characteristics between control and intervention groups (p>0.05). Three-year change in weight, lean mass, and fat mass were similar between groups (p>0.05). There were no significant group differences in three-year change in BUA or BMC at any site (p>0.05), although the between-group difference in femoral neck BMC at follow-up exceeded the least significant change. While significant group differences were not observed three years after cessation of the intervention, changes in bone parameters occurred in parallel for intervention and control groups such that the original benefits of the intervention observed within the treatment group were sustained