Collaborative public procurement: Institutional explanations of legitimised resistance

This paper reports on the barriers to regional collaborative procurement developed from an action research study of five UK public authorities in the emergency services sector. Despite political pressure to procure collaboratively, strategic avoidance responses of institutional logics and symbolic tick boxing legitimise stakeholder resistance to isomorphic forces and entrench operational barriers. The prevailing institutional logics are that regional collaborative procurement is unsuitable and risky, derived from procurement's lack of status and the emotive nature of the emergency services. Symbolic tick boxing is seen through collaboration that is limited to high profile spend categories, enabling organisations to demonstrate compliance while simultaneously retaining local decision-making for less visible, but larger areas of spend. The findings expose choice mechanisms in public procurement by exploring tensions arising from collaborative procurement strategies within, and between, organisations. Multiple stakeholders' perspectives add to current thinking on how organisations create institutional logics to avoid institutional pressure to procure collaboratively and how stakeholders legitimise their actions

Mathematical analysis of a two-strain tuberculosis model in Bangladesh

Tuberculosis (TB) is an airborne infectious disease that causes millions of deaths worldwide each year (1.2 million people died in 2019). Alarmingly, several strains of the causative agent, Mycobacterium tuberculosis (MTB)—including drug-susceptible (DS) and drug-resistant (DR) variants—already circulate throughout most developing and developed countries, particularly in Bangladesh, with totally drug-resistant strains starting to emerge. In this study we develop a two-strain DS and DR TB transmission model and perform an analysis of the system properties and solutions. Both analytical and numerical results show that the prevalence of drug-resistant infection increases with an increasing drug use through amplification. Both analytic results and numerical simulations suggest that if the basic reproduction numbers of both DS (R0s) and DR (R0r) TB are less than one, i.e. max[R0s, R0r]max[R0s,1], then DS TB dies out but DR TB persists in the population, and if R0s>max[R0r,1] both DS TB and DR TB persist in the population. Further, sensitivity analysis of the model parameters found that the transmission rate of both strains had the greatest influence on DS and DR TB prevalence. We also investigated the effect of treatment rates and amplification on both DS and DR TB prevalence; results indicate that inadequate or inappropriate treatment makes co-existence more likely and increases the relative abundance of DR TB infections

The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer

IL6-like cytokines are a family of regulators with a complex, pleiotropic role in both the healthy organism, where they regulate immunity and homeostasis, and in different diseases, including cancer. Here we summarise how these cytokines exert their effect through the shared signal transducer IL6ST (gp130) and we review the extensive evidence on the role that different members of this family play in breast cancer. Additionally, we discuss how the different cytokines, their related receptors and downstream effectors, as well as specific polymorphisms in these molecules, can serve as predictive or prognostic biomarkers with the potential for clinical application in breast cancer. Lastly, we also discuss how our increasing understanding of this complex signalling axis presents promising opportunities for the development or repurposing of therapeutic strategies against cancer and, specifically, breast neoplasms

Sport-Related Concussions: Symptom Recurrence After Return to Exercise

Background: Current guidelines dictate a gradual exercise progression after a concussion; however, it is unclear what proportion of athletes experience a recurrence of symptoms once they are symptom free at rest. Estimating the proportion of athletes and predictors of symptom recurrence would help shape return-to-play protocols. Purpose: To determine the proportion and associated risk factors of athletes who have a recurrence of concussion symptoms with exercise after being symptom free at rest. Study Design: Case-control study; Level of evidence, 3. Methods: Between October 1, 2009 and July 31, 2011, we studied patients from a sport concussion clinic located within a tertiary care regional children’s hospital. Patients were queried at every visit using a standardized questionnaire. Our main outcome variable was recurrence of symptoms with exercise after being symptom free at rest at some point in their recovery. Cofactors included age, sex, loss of consciousness with injury, prior concussion (diagnosed and undiagnosed), Post-Concussion Symptom Scale (PCSS) score, time until clinical presentation, and duration of symptoms. Results: Of the 217 patients included, 25 (12%) experienced a return of symptoms. Losing consciousness at the time of injury and a longer duration between injury and clinical presentation were associated with a decreased risk of symptoms recurring with exercise. Conversely, athletes who had sustained previously undiagnosed concussions and had suffered a longer duration of symptoms at rest were at an increased risk of symptom recurrence with exercise. Conclusion: Relatively few athletes who are symptom free at rest after a concussion will have a recurrence of symptoms when they resume exercise. The risk of symptoms recurring with exercise may be greater among those athletes who sustained previously undiagnosed concussions and had a longer period of symptoms at rest. The early identification of athletes who may be at risk of symptom recurrence will help mold treatment guidelines and exercise progression protocols

Understanding how Victoria, Australia gained control of its second COVID-19 wave

During 2020, Victoria was the Australian state hardest hit by COVID-19, but was successful in controlling its second wave through aggressive policy interventions. We calibrated a detailed compartmental model of Victoria's second wave to multiple geographically-structured epidemic time-series indicators. We achieved a good fit overall and for individual health services through a combination of time-varying processes, including case detection, population mobility, school closures, physical distancing and face covering usage. Estimates of the risk of death in those aged ≥75 and of hospitalisation were higher than international estimates, reflecting concentration of cases in high-risk settings. We estimated significant effects for each of the calibrated time-varying processes, with estimates for the individual-level effect of physical distancing of 37.4% (95%CrI 7.2-56.4%) and of face coverings of 45.9% (95%CrI 32.9-55.6%). That the multi-faceted interventions led to the dramatic reversal in the epidemic trajectory is supported by our results, with face coverings likely particularly important

Tissue of origin determines cancer-associated CpG island promoter hypermethylation patterns

ABSTRACT: BACKGROUND: Aberrant CpG island promoter DNA hypermethylation is frequently observed in cancer and is believed to contribute to tumor progression by silencing the expression of tumor suppressor genes. Previously, we observed that promoter hypermethylation in breast cancer reflects cell lineage rather than tumor progression and occurs at genes that are already repressed in a lineage-specific manner. To investigate the generality of our observation we analyzed the methylation profiles of 1,154 cancers from 7 different tissue types. RESULTS: We find that 1,009 genes are prone to hypermethylation in these 7 types of cancer. Nearly half of these genes varied in their susceptibility to hypermethylation between different cancer types. We show that the expression status of hypermethylation prone genes in the originator tissue determines their propensity to become hypermethylated in cancer; specifically, genes that are normally repressed in a tissue are prone to hypermethylation in cancers derived from that tissue. We also show that the promoter regions of hypermethylation-prone genes are depleted of repetitive elements and that DNA sequence around the same promoters is evolutionarily conserved. We propose that these two characteristics reflect tissue-specific gene promoter architecture regulating the expression of these hypermethylation prone genes in normal tissues. CONCLUSIONS: As aberrantly hypermethylated genes are already repressed in pre-cancerous tissue, we suggest that their hypermethylation does not directly contribute to cancer development via silencing. Instead aberrant hypermethylation reflects developmental history and the perturbation of epigenetic mechanisms maintaining these repressed promoters in a hypomethylated state in normal cells.Publisher PDFPeer reviewe