Evaluating emergency service response to COVID-19: A scoping review.

Introduction: The issue of how emergency services (police, fire, ambulance, local authorities) respond to pandemics has received greater research focus recently in relation to the COVID-19 outbreak, which saw agencies going beyond usual roles to support communities for prolonged periods. A critical appraisal is needed of this published evidence to take stock of what is known about the effectiveness of emergency service response to Covid-19.

Method: A scoping review of scientific and grey literature identified 17 qualitative (N = 9), quantitative (N = 6), or mixed methods (N = 2) studies from across the UK and internationally that focus on the effectiveness of emergency service response to the Covid-19 outbreak.

Totality of evidence of the effectiveness of repurposed therapies for COVID-19: Can we use real-world studies alongside randomized controlled trials?

Rapid and robust strategies to evaluate the efficacy and effectiveness of novel and existing pharmacotherapeutic interventions (repurposed treatments) in future pandemics are required. Observational "real-world studies" (RWS) can report more quickly than randomized controlled trials (RCTs) and would have value were they to yield reliable results. Both RCTs and RWS were deployed during the coronavirus disease 2019 (COVID-19) pandemic.

NKG2D Fine-Tunes the Local Inflammatory Response in Colorectal Cancer.

Treating colorectal cancer (CRC) is a major challenge due to the heterogeneous immunological, clinical and pathological landscapes. Immunotherapy has so far only proven effective in a very limited subgroup of CRC patients. To better define the immune landscape, we examined the immune gene expression profile in various subsets of CRC patients and used a mouse model of intestinal tumors to dissect immune functions.

Chemotherapy-induced COX-2 upregulation by cancer cells defines their inflammatory properties and limits the efficacy of chemoimmunotherapy combinations.

Cytotoxic therapies, besides directly inducing cancer cell death, can stimulate immune-dependent tumor growth control or paradoxically accelerate tumor progression. The underlying mechanisms dictating these opposing outcomes are poorly defined. Here, we show that cytotoxic therapy acutely upregulates cyclooxygenase (COX)-2 expression and prostaglandin E (PGE) production in cancer cells with pre-existing COX-2 activity.

Tissue-resident FOLR2 macrophages associate with CD8 T cell infiltration in human breast cancer.

Macrophage infiltration is a hallmark of solid cancers, and overall macrophage infiltration correlates with lower patient survival and resistance to therapy. Tumor-associated macrophages, however, are phenotypically and functionally heterogeneous. Specific subsets of tumor-associated macrophage might be endowed with distinct roles on cancer progression and antitumor immunity.

RNA sensing via the RIG-I-like receptor LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency.

RNA editing by the adenosine deaminase ADAR1 prevents innate immune responses to endogenous RNAs. In ADAR1-deficient cells, unedited self RNAs form base-paired structures that resemble viral RNAs and inadvertently activate the cytosolic RIG-I-like receptor (RLR) MDA5, leading to an antiviral type I interferon (IFN) response. Mutations in ADAR1 cause Aicardi-Goutières Syndrome (AGS), an autoinflammatory syndrome characterized by chronic type I IFN production.

Maximizing the Potential of Mini-Grants to Promote Policy, Systems, and Environmental Changes: Outcomes and Challenges.

Purpose And Objectives: This article describes the implementation and evaluation of a chronic disease mini-grant initiative, coordinated by a state health department in collaboration with multiple stakeholders. Braided funding from federal and state sources was used to build and implement the initiative.

Intervention Approach: Mini-grants, facilitated by five different facilitating organizations, were funded to promote implementation of policy, systems, and environmental (PSE) changes at the local level.

Optimising recruitment in habitat creation for the native European oyster (Ostrea edulis): Implications of temporal and spatial variability in larval abundance.

European oyster (Ostrea edulis) restoration often requires the timely deployment of shell habitat for larval settlement. To inform this increasingly popular process, the present study investigated temporal and spatial abundance patterns of O. edulis larvae in a rare commercial fishery (Loch Ryan, Scotland, UK).

Anti-Inflammatory Drugs Remodel the Tumor Immune Environment to Enhance Immune Checkpoint Blockade Efficacy.

Identifying strategies to improve the efficacy of immune checkpoint blockade (ICB) remains a major clinical need. Here, we show that therapeutically targeting the COX2/PGE/EP2-4 pathway with widely used nonsteroidal and steroidal anti-inflammatory drugs synergized with ICB in mouse cancer models. We exploited a bilateral surgery model to distinguish responders from nonresponders shortly after treatment and identified acute IFNγ-driven transcriptional remodeling in responder mice, which was also associated with patient benefit to ICB.

DNGR-1 limits Flt3L-mediated antitumor immunity by restraining tumor-infiltrating type I conventional dendritic cells.

Background: Conventional type 1 dendritic cells (cDC1s) are central to antitumor immunity and their presence in the tumor microenvironment associates with improved outcomes in patients with cancer. DNGR-1 (CLEC9A) is a dead cell-sensing receptor highly restricted to cDC1s. DNGR-1 has been involved in both cross-presentation of dead cell-associated antigens and processes of disease tolerance, but its role in antitumor immunity has not been clarified yet.

Artificial Intelligence Applied to Gene Expression Testing (IVIGET) to Predict Trivalent Inactivated Influenza Vaccine Immunogenicity in HIV Infected Children.

The number of patients affected by chronic diseases with special vaccination needs is burgeoning. In this scenario, predictive markers of immunogenicity, as well as signatures of immune responses are typically missing even though it would especially improve the identification of personalized immunization practices in these populations. We aimed to develop a predictive score of immunogenicity to Influenza Trivalent Inactivated Vaccination (TIV) by applying deep machine learning algorithms using transcriptional data from sort-purified lymphocyte subsets after stimulation.

Tissue-Scale Mechanical Coupling Reduces Morphogenetic Noise to Ensure Precision during Epithelial Folding.

Morphological constancy is universal in developing systems. It is unclear whether precise morphogenesis stems from faithful mechanical interpretation of gene expression patterns. We investigate the formation of the cephalic furrow, an epithelial fold that is precisely positioned with a linear morphology.

Open science: The open clinical trials data journey.

Open data sharing and access has the potential to promote transparency and reproducibility in research, contribute to education and training, and prompt innovative secondary research. Yet, there are many reasons why researchers don't share their data. These include, among others, time and resource constraints, patient data privacy issues, lack of access to appropriate funding, insufficient recognition of the data originators' contribution, and the concern that commercial or academic competitors may benefit from analyses based on shared data.

BET 1: Oseltamivir use for quicker alleviation of symptoms, fewer hospital admissions and lower mortality in adult patients with influenza B.

A short cut review was carried out to establish whether Oseltamivir leads to faster alleviation of symptoms, fewer hospital admissions and lower mortality in adult patients with confirmed influenza B presenting to the Emergency Department. Two studies were directly relevant to the question using the described search methodology on Ovid Medline and Embase. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated.

Allostatic load as a predictor of all-cause and cause-specific mortality in the general population: Evidence from the Scottish Health Survey.

Allostatic load is a multiple biomarker measure of physiological 'wear and tear' that has shown some promise as marker of overall physiological health, but its power as a risk predictor for mortality and morbidity is less well known. This study has used data from the 2003 Scottish Health Survey (SHeS) (nationally representative sample of Scottish population) linked to mortality records to assess how well allostatic load predicts all-cause and cause-specific mortality. From the sample, data from 4,488 men and women were available with mortality status at 5 and 9.

Two tales of cardiovascular risksmiddle-aged women living in Sweden and Scotland: a cross-sectional comparative study.

Objectives: To compare cardiovascular risk factors as well as rates of cardiovascular diseases in middle-aged women from urban areas in Scotland and Sweden.

Design: Comparative cross-sectional study.

Setting: Data from the general population in urban areas of Scotland and the general population in two major Swedish cities in southeast Sweden, south of Stockholm.

Obesity in Scotland: a persistent inequality.

Background: Obesity is a health problem in its own right and a risk factor for other conditions such as cardiovascular disease. The prevalence of overweight and obesity increased in Scotland between 1995 and 2008 with socio-economic inequalities persisting in adults over time and increasing in children. This paper explores changes in the underlying distribution of body mass index (BMI) which is less well understood.

Socio-economic differences in diet, physical activity and leisure-time screen use among Scottish children in 2006 and 2010: are we closing the gap?

Objective: To investigate socio-economic differences in children's diet, activity and inactivity and changes in these differences over 4 years during which new policies on food in schools were introduced.

Design: Two cross-sectional surveys in which diet was assessed by FFQ and physical activity and inactivity were assessed by interviewer-administered questionnaire. Socio-economic status was assessed by the area-based Scottish Index of Multiple Deprivation.

A Bayesian cluster analysis method for single-molecule localization microscopy data.

Cell function is regulated by the spatiotemporal organization of the signaling machinery, and a key facet of this is molecular clustering. Here, we present a protocol for the analysis of clustering in data generated by 2D single-molecule localization microscopy (SMLM)-for example, photoactivated localization microscopy (PALM) or stochastic optical reconstruction microscopy (STORM). Three features of such data can cause standard cluster analysis approaches to be ineffective: (i) the data take the form of a list of points rather than a pixel array; (ii) there is a non-negligible unclustered background density of points that must be accounted for; and (iii) each localization has an associated uncertainty in regard to its position.

A Case of a Chronic Pancreatic Pseudocyst Causing Atraumatic Splenic Rupture without Evidence of Acute Pancreatitis.

Atraumatic splenic rupture is a rare complication of a pancreatic pseudocyst (PP), described in the setting of chronic pancreatitis. There is common understanding, within the literature, that an inflammatory process at the tail of the pancreas may disrupt the spleen and result in such splenic complications. The authors present a case report of a 29-year-old male with a PP, associated with chronic pancreatitis.

Seven key investments for health equity across the lifecourse: Scotland versus the rest of the UK.

While widespread lip service is given in the UK to the social determinants of health (SDoH), there are few published comparisons of how the UK's devolved jurisdictions 'stack up', in terms of implementing SDoH-based policies and programmes, to improve health equity over the life-course. Based on recent SDoH publications, seven key societal-level investments are suggested, across the life-course, for increasing health equity by socioeconomic position (SEP). We present hard-to-find comparable analyses of routinely collected data to gauge the relative extent to which these investments have been pursued and achieved expected goals in Scotland, as compared with England and Wales, in recent decades.

A single and rapid calcium wave at egg activation in Drosophila.

Activation is an essential process that accompanies fertilisation in all animals and heralds major cellular changes, most notably, resumption of the cell cycle. While activation involves wave-like oscillations in intracellular Ca(2+) concentration in mammals, ascidians and polychaete worms and a single Ca(2+) peak in fish and frogs, in insects, such as Drosophila, to date, it has not been shown what changes in intracellular Ca(2+) levels occur. Here, we utilise ratiometric imaging of Ca(2+) indicator dyes and genetically encoded Ca(2+) indicator proteins to identify and characterise a single, rapid, transient wave of Ca(2+) in the Drosophila egg at activation.

Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells.