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Abstract Background Many people living with cancer are admitted as an emergency, some just prior to diagnosis and others in their last year of life. Factors associated with accessing emergency care for people dying of cancer are complex and not well understood. This can make it difficult to have the resources and staffing in place to best care for individuals in their last year of life and their families. Methods This study uses routinely collected administrative data from people who died of cancer in N. Ireland (NI) during 2015 and explores how personal characteristics (e.g., gender, age) and disease related factors (e.g., tumour site, cancer stage at initial diagnosis) were associated with having an emergency admission to hospital in the last year and the last 28 days of their lives, using multivariate logistic regression. Results Almost three in four people had at least one emergency admission in the last year of life, and over one in three had an emergency admission the last 28 days of life. Patterns were similar for both time outcomes with males, people with haematological, lung or brain cancers, younger persons, those diagnosed with late-stage cancer, and people diagnosed close to time of death, being significantly more likely to have an emergency admission. While there was no significant association between deprivation and emergency admission rates, those living in urban areas were more likely to have an emergency admission in their last month of life compared to rural dwellers. Late diagnosis was evident with 538 people (12.8% of all deaths from cancer) being diagnosed within one month of death and 1242 (29%) within 3 months of death. Conclusion The high level of emergency admissions points to gaps in routine end-of-life care, and the need for additional training for hospital staff including frontline emergency department (ED) staff who are often the ‘gatekeepers’ to emergency inpatient care for people living with cancer. The levels of late diagnosis indicate a need for increased population awareness of cancer symptoms and system change to promote earlier diagnosis.

Background: Nosocomial acquisition of influenza is known to occur but the risk after exposure to a known case and the outcomes after acquisition are poorly defined. Methods: Prospective observational study of patients exposed to influenza from another patient in a multi-site healthcare organisation, with follow-up of 7 days or until discharge, and PCR-confirmation of symptomatic disease. Multivariable analysis was used to investigate association of influenza acquisition with high dependency unit/intensive care unit (HDU/ITU) admission and in-hospital mortality. Results: 23/298 (7.7%) contacts of 11 cases were subsequently symptomatic and tested influenza-positive during follow-up. HDU/ITU admission was significantly higher in these secondary cases (6/23, 26%) compared to flu-negative contacts (20/275, 7.2%; p = 0.002). In-hospital mortality was significantly higher in secondary cases (5/23, 21.7%) compared to flu-negative contacts (11/275, 4%; p

Abstract Introduction The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population‐based cancer registry and pathology report data, 2013–18. Results Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013–18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013–18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013–18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non‐melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential.

Mold and other allergen exposures exacerbate asthma symptoms in sensitized individuals. We evaluated allergen concentrations, skin test sensitivities, and asthma morbidity for 182 children, aged 4–12 years, with moderate to severe asthma, enrolled 18 months after Katrina, from the city of New Orleans and the surrounding parishes that were impacted by the storm, into the Head-off Environmental Asthma in Louisiana (HEAL) observational study. Dust (indoor) and air (indoor and outdoor) samples were collected at baseline of 6 and 12 months. Dust samples were evaluated for dust mite, cockroach, mouse, and Alternaria by immunoassay. Air samples were evaluated for airborne mold spore concentrations. Overall, 89% of the children tested positive to ≥1 indoor allergen, with allergen-specific sensitivities ranging from 18% to 67%. Allergen concentration was associated with skin sensitivity for 1 of 10 environmental triggers analyzed (cat). Asthma symptom days did not differ with skin test sensitivity, and surprisingly, increased symptoms were observed in children whose baseline indoor airborne mold concentrations were below median levels. This association was not observed in follow-up assessments. The lack of relationship among allergen levels (including mold), sensitivities, and asthma symptoms points to the complexity of attempting to assess these associations during rapidly changing social and environmental conditions.

Background Muscle function may be impaired in people with generalised hypermobility, yet prior studies have primarily focused on muscles within the extremities. We aimed to examine changes in lateral abdominal muscle (transversus abdominis (TrA) and the external (EO) and internal abdominal obliques (IO)) thickness and length during contraction between participants with and without hypermobility.Methods This cross-sectional study examined 12 participants with hypermobility and 12 age-matched, sex-matched, height-matched and weight-matched participants without hypermobility. The Beighton and Belavy-Owen-Mitchell score assessed systemic hypermobility. Muscle thickness and length were measured via panoramic ultrasound scans at rest and during contraction.Results When compared with rest across all lumbar levels (L1–L5), contraction produced a lesser increase in TrA thickness (β=0.03, p=0.034) for participants with hypermobility compared with control. No group-by-condition interaction was observed for TrA length across all lumbar levels (L1–L5; p=0.269). Contraction produced a greater decrease in EO thickness (β=0.08, p=0.002) at L3 only for participants with hypermobility compared with control. No group-by-condition interactions were observed for IO thickness.Conclusion Participants with hypermobility had partially impaired lateral abdominal muscle function given a lesser ability to increase TrA muscle thickness during contraction compared with controls.

Boron dipyrromethene (BODIPY) dyes bearing a pyridyl moiety have been used as metal ion sensors, pH sensors, fluorescence probes, and as sensitizers for phototherapy. A comparative study of the properties of the three structural isomers of meso-pyridyl-BODIPYs, their 2,6-dichloro derivatives, and their corresponding methylated cationic pyridinium-BODIPYs was conducted using spectroscopic and electrochemical methods, X-ray analyses, and TD-DFT calculations. Among the neutral derivatives, the 3Py and 4Py isomers showed the highest relative fluorescence quantum yields in organic solvents, which were further enhanced 2-4-fold via the introduction of two chlorines at the 2,6-positions. Among the cationic derivatives, the 2catPy showed the highest relative fluorescence quantum yield in organic solvents, which was further enhanced by the use of a bulky counter anion (PF6−). In water, the quantum yields were greatly reduced for all three isomers but were shown to be enhanced upon introduction of 2,6-dichloro groups. Our results indicate that 2,6-dichloro-meso-(2- and 3-pyridinium)-BODIPYs are the most promising for sensing applications. Furthermore, all pyridinium BODIPYs are highly water-soluble and display low cytotoxicity towards human HEp2 cells.

High-deflection strain gauges show potential as economical and user-friendly sensors for capturing large deformations. The interpretation of these sensors is much more complex than that of conventional strain gauges due to the viscoelastic nature of strain gauges. This research endeavor developed and tested a model for interpreting sensor outputs that includes the time-dependent nature of strain gauges. A model that captures the effect of quasi-static strains was determined by using a conventional approach of fitting an equation to observed data. The dynamic relationship between the strain and the resistance was incorporated by superimposing dynamic components onto the quasi-static model to account for spikes in resistances that accompany each change in sensor strain and subsequent exponential decays. It was shown that the model can be calibrated for a given sensor by taking two data points at known strains. The resulting sensor-specific model was able to interpret strain-gauge electrical signals during a cyclical load to predict strain with an average mean absolute error (MAE) of 1.4% strain, and to determine the strain rate with an average MAE of 0.036 mm/s. The resulting model and tuning procedure may be used in a wide range of applications, such as biomechanical monitoring and analysis.

In Cameroon, in 2019, tuberculosis (TB) treatment coverage was estimated at 53%, indicating that almost half of all people sick with TB were not diagnosed or linked to care. To inform strategies to improve access to TB services, we conducted an evaluation of the alignment between patient-initiated care-seeking behavior and spatial and institutional allocation of TB services. Data sources included the Cameroon Demographic and Health Survey (2018), the Health Facility List (2017), and routinely collected TB surveillance data. Data visualization was performed in Tableau and QGIS. The pathway analysis showed that only an estimated 9% of people attended a health facility providing TB services at initial care-seeking, with access varying from

Background Increased blood pressure (BP) variability and nondipping status seen on 24‐hour ambulatory BP monitoring are often observed in autonomic failure (ATF). Methods and Results We assessed BP variability and nocturnal BP dipping in 273 patients undergoing ambulatory BP monitoring at Southwestern Medical Center between 2010 and 2017. SD, average real variability, and variation independent of mean were calculated from ambulatory BP monitoring. Patients were divided into a discovery cohort (n=201) and a validation cohort (n=72). ATF was confirmed by formal autonomic function test. In the discovery cohort, 24‐hour and nighttime average real variability, SD, and variation independent of mean did not differ significantly between ATF (n=25) and controls (n=176, all P>0.05). However, daytime SD, daytime coefficient of variation, and daytime variation independent of mean of systolic BP (SBP) were all significantly higher in patients with ATF than in controls in both discovery and validation cohorts. Nocturnal BP dipping was more blunted in ATF patients than controls in both cohorts (both P

Leukotoxin (LtxA), from oral pathogen Aggregatibacter actinomycetemcomitans, is a secreted membrane-damaging protein. LtxA is internalized by β2 integrin LFA-1 (CD11a/CD18)-expressing leukocytes and ultimately causes cell death; however, toxin localization in the host cell is poorly understood and these studies fill this void. We investigated LtxA trafficking using multi-fluor confocal imaging, flow cytometry and Rab5a knockdown in human T lymphocyte Jurkat cells. Planar lipid bilayers were used to characterize LtxA pore-forming activity at different pHs. Our results demonstrate that the LtxA/LFA-1 complex gains access to the cytosol of Jurkat cells without evidence of plasma membrane damage, utilizing dynamin-dependent and presumably clathrin-independent mechanisms. Upon internalization, LtxA follows the LFA-1 endocytic trafficking pathways, as identified by co-localization experiments with endosomal and lysosomal markers (Rab5, Rab11A, Rab7, and Lamp1) and CD11a. Knockdown of Rab5a resulted in the loss of susceptibility of Jurkat cells to LtxA cytotoxicity, suggesting that late events of LtxA endocytic trafficking are required for toxicity. Toxin trafficking via the degradative endocytic pathway may culminate in the delivery of the protein to lysosomes or its accumulation in Rab11A-dependent recycling endosomes. The ability of LtxA to form pores at acidic pH may result in permeabilization of the endosomal and lysosomal membranes.

Proteolytic shedding of surface proteins during invasion by apicomplexan parasites is a widespread phenomenon, thought to represent a mechanism by which the parasites disengage adhesin-receptor complexes in order to gain entry into their host cell. Erythrocyte invasion by merozoites of the malaria parasite Plasmodium falciparum requires the shedding of ectodomain components of two essential surface proteins, called MSP1 and AMA1. Both are released by the same merozoite surface "sheddase," but the molecular identity and mode of action of this protease is unknown. Here we identify it as PfSUB2, an integral membrane subtilisin-like protease (subtilase). We show that PfSUB2 is stored in apical secretory organelles called micronemes. Upon merozoite release it is secreted onto the parasite surface and translocates to its posterior pole in an actin-dependent manner, a trafficking pattern predicted of the sheddase. Subtilase propeptides are usually selective inhibitors of their cognate protease, and the PfSUB2 propeptide is no exception; we show that recombinant PfSUB2 propeptide binds specifically to mature parasite-derived PfSUB2 and is a potent, selective inhibitor of MSP1 and AMA1 shedding, directly establishing PfSUB2 as the sheddase. PfSUB2 is a new potential target for drugs designed to prevent erythrocyte invasion by the malaria parasite.

The apical membrane antigen (AMA-1) family of malaria merozoite proteins is characterised by a high degree of inter-species conservation. Evidence that the protein (PK66/AMA-1) from the simian parasite Plasmodium knowlesi was protective in rhesus monkeys suggested that the 83kDa P. falciparum equivalent (PF83/AMA-1) should be investigated for protective effects in humans. Here we briefly review pertinent comparative data, and describe the use of an eukaryotic full length recombinant PF83/AMA-1 molecule to develop a sensitive ELISA for the determination of serological responses in endemic populations. The assay has revealed surprisingly high levels of humoral response to this quantitatively minor antigen. We also show that PK66/AMA-1 inhibitory mAb's are active against merozoites subsequent to release from schizont-infected red cells, further implicating AMA-1 molecules in red cell invasion.