Designing and undertaking randomised implementation trials: guide for researchers

Implementation science is the study of methods to promote the systematic uptake of evidence based interventions into practice and policy to improve health. Despite the need for high quality evidence from implementation research, randomised trials of implementation strategies often have serious limitations. These limitations include high risks of bias, limited use of theory, a lack of standard terminology to describe implementation strategies, narrowly focused implementation outcomes, and poor reporting. This paper aims to improve the evidence base in implementation science by providing guidance on the development, conduct, and reporting of randomised trials of implementation strategies. Established randomised trial methods from seminal texts and recent developments in implementation science were consolidated by an international group of researchers, health policy makers, and practitioners. This article provides guidance on the key components of randomised trials of implementation strategies, including articulation of trial aims, trial recruitment and retention strategies, randomised design selection, use of implementation science theory and frameworks, measures, sample size calculations, ethical review, and trial reporting. It also focuses on topics requiring special consideration or adaptation for implementation trials. We propose this guide as a resource for researchers, healthcare and public health policy makers or practitioners, research funders, and journal editors with the goal of advancing rigorous conduct and reporting of randomised trials of implementation strategies

Judicial disagreement need not be political: dissent on the Estonian Supreme Court

I investigate the non-unanimous decisions of judges on the Estonian Supreme Court. I argue that since judges on the court enjoy high de jure independence, dissent frequently, and are integrated in the normal judicial hierarchy, the Estonian Supreme Court is a crucial case for the presumption that judicial disagreement reveals policy preferences. I analyse dissenting opinions using an ideal point response model. Examining the characteristics of cases which discriminated with respect to the recovered dimension, I show that this dimension cannot be interpreted as a meaningful policy dimension, but instead reflects disagreement about the proper scope of constitutional redress

But Not Both:The Exclusive Disjunction in Qualitative Comparative Analysis (QCA)

The application of Boolean logic using Qualitative Comparative Analysis (QCA) is becoming more frequent in political science but is still in its relative infancy. Boolean ‘AND’ and ‘OR’ are used to express and simplify combinations of necessary and sufficient conditions. This paper draws out a distinction overlooked by the QCA literature: the difference between inclusive- and exclusive-or (OR and XOR). It demonstrates that many scholars who have used the Boolean OR in fact mean XOR, discusses the implications of this confusion and explains the applications of XOR to QCA. Although XOR can be expressed in terms of OR and AND, explicit use of XOR has several advantages: it mirrors natural language closely, extends our understanding of equifinality and deals with mutually exclusive clusters of sufficiency conditions. XOR deserves explicit treatment within QCA because it emphasizes precisely the values that make QCA attractive to political scientists: contextualization, confounding variables, and multiple and conjunctural causation

Establishing SARS-CoV-2 membrane protein-specific antibodies as a valuable serological target via high-content microscopy

The prevalence and strength of serological responses mounted toward SARS-CoV-2 proteins other than nucleocapsid (N) and spike (S), which may be of use as additional serological markers, remains underexplored. Using high-content microscopy to assess antibody responses against full-length StrepTagged SARS-CoV-2 proteins, we found that 85% (166/196) of unvaccinated individuals with RT-PCR confirmed SARS-CoV-2 infections and 74% (31/42) of individuals infected after being vaccinated developed detectable IgG against the structural protein M, which is higher than previous estimates. Compared with N antibodies, M IgG displayed a shallower time-dependent decay and greater specificity. Sensitivity for SARS-CoV-2 seroprevalence was enhanced when N and M IgG detection was combined. These findings indicate that screening for M seroconversion may be a good approach for detecting additional vaccine breakthrough infections and highlight the potential to use HCM as a rapidly deployable method to identify the most immunogenic targets of newly emergent pathogens

An introductory view on archaeoastronomy

Archaeoastronomy is still a marginalised topic in academia and is described by the Sophia Centre, the only UK institution offering a broader MA containing this field, as ‘the study of the incorporation of celestial orientation, alignments or symbolism in human monuments and architecture’. By many it is associated with investigating prehistoric monuments such as Stonehenge and combining astronomy and archaeology. The following will show that archaeoastronomy is far more than just an interdisciplinary field linking archaeology and astronomy. It merges aspects of anthropology, ethno-astronomy and even educational research, and is possibly better described as cultural astronomy. In the past decades it has stepped away from its quite speculative beginnings that have led to its complete rejection by the archaeology community. Overcoming these challenges it embraced full heartedly solid scientific and statistical methodology and achieved more credibility. However, in recent times the humanistic influences of a cultural context motivate a new generation of archaeoastronomers that are modernising this subject; and humanists might find it better described as post-modern archaeoastronomy embracing the pluralism of today’s academic approach to landscape and ancient people

Acquisition of Growth-Inhibitory Antibodies against Blood-Stage Plasmodium falciparum

Background: Antibodies that inhibit the growth of blood-stage Plasmodium falciparum may play an important role in acquired and vaccine-induced immunity in humans. However, the acquisition and activity of these antibodies is not well understood. Methods: We tested dialysed serum and purified immunoglobulins from Kenyan children and adults for inhibition of P. falciparum blood-stage growth in vitro using different parasite lines. Serum antibodies were measured by ELISA to bloodstage parasite antigens, extracted from P. falciparum schizonts, and to recombinant merozoite surface protein 1 (42 kDa Cterminal fragment, MSP1-42). Results: Antibodies to blood-stage antigens present in schizont protein extract and to recombinant MSP1-42 significantly increased with age and were highly correlated. In contrast, growth-inhibitory activity was not strongly associated with age and tended to decline marginally with increasing age and exposure, with young children demonstrating the highest inhibitory activity. Comparison of growth-inhibitory activity among samples collected from the same population at different time points suggested that malaria transmission intensity influenced the level of growth-inhibitory antibodies. Antibodies to recombinant MSP1-42 were not associated with growth inhibition and high immunoglobulin G levels were poorly predictive of inhibitory activity. The level of inhibitory activity against different isolates varied. Conclusions: Children can acquire growth-inhibitory antibodies at a young age, but once they are acquired they do not appear to be boosted by on-going exposure. Inhibitory antibodies may play a role in protection from early childhood malaria

Introduction: Toward an Engaged Feminist Heritage Praxis

We advocate a feminist approach to archaeological heritage work in order to transform heritage practice and the production of archaeological knowledge. We use an engaged feminist standpoint and situate intersubjectivity and intersectionality as critical components of this practice. An engaged feminist approach to heritage work allows the discipline to consider women’s, men’s, and gender non-conforming persons’ positions in the field, to reveal their contributions, to develop critical pedagogical approaches, and to rethink forms of representation. Throughout, we emphasize the intellectual labor of women of color, queer and gender non-conforming persons, and early white feminists in archaeology

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Researching COVID to Enhance Recovery (RECOVER) Adult Study Protocol: Rationale, Objectives, and Design

IMPORTANCE: SARS-CoV-2 infection can result in ongoing, relapsing, or new symptoms or other health effects after the acute phase of infection; termed post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID. The characteristics, prevalence, trajectory and mechanisms of PASC are ill-defined. The objectives of the Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC in Adults (RECOVER-Adult) are to: (1) characterize PASC prevalence; (2) characterize the symptoms, organ dysfunction, natural history, and distinct phenotypes of PASC; (3) identify demographic, social and clinical risk factors for PASC onset and recovery; and (4) define the biological mechanisms underlying PASC pathogenesis. METHODS: RECOVER-Adult is a combined prospective/retrospective cohort currently planned to enroll 14,880 adults aged ≥18 years. Eligible participants either must meet WHO criteria for suspected, probable, or confirmed infection; or must have evidence of no prior infection. Recruitment occurs at 86 sites in 33 U.S. states, Washington, DC and Puerto Rico, via facility- and community-based outreach. Participants complete quarterly questionnaires about symptoms, social determinants, vaccination status, and interim SARS-CoV-2 infections. In addition, participants contribute biospecimens and undergo physical and laboratory examinations at approximately 0, 90 and 180 days from infection or negative test date, and yearly thereafter. Some participants undergo additional testing based on specific criteria or random sampling. Patient representatives provide input on all study processes. The primary study outcome is onset of PASC, measured by signs and symptoms. A paradigm for identifying PASC cases will be defined and updated using supervised and unsupervised learning approaches with cross-validation. Logistic regression and proportional hazards regression will be conducted to investigate associations between risk factors, onset, and resolution of PASC symptoms. DISCUSSION: RECOVER-Adult is the first national, prospective, longitudinal cohort of PASC among US adults. Results of this study are intended to inform public health, spur clinical trials, and expand treatment options