Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes.

BACKGROUND: The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. AIM: To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. METHODS: A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. FINDINGS: In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. CONCLUSION: The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine.

Comparison of 3 ankle braces in reducing ankle inversion in a basketball rebounding task.

Lateral ankle injury incidence rates are very high in the sport of basketball, with a significant proportion occurring during rebounding. Ankle braces are often used as preventative and rehabilitative techniques in the hope of minimizing the likelihood of experiencing excessive ankle inversion. This study aims to evaluate the effect of different ankle braces in preventing ankle inversion during a basketball rebounding task. Sixteen subjects participated in the study (11 males, 5 females; mean age = 26.94 years, SD = 5.32; mean height 1.72 m, SD = 0.08; mean weight 73.95 kg, SD = 13.68). Participants performed a simulated rebounding task in multiple braced conditions: unbraced (UB), Ossur Formfit (OF), Talarmade Ankleguard Air/Gel Stirrup (TAG) and Bauerfeind Malleoloc (BF). Ankle and foot inversion angles, ankle inversion moments and peroneus longus EMG activity were recorded and analysed to determine the effectiveness of each condition to resist inversion. All braced conditions reduced ankle and foot inversion angles compared to UB. In the non-dominant limb, OF showed reduced maximum ankle inversion compared to BF (non-dominant mean difference = 0.630°, p < 0.001) and reduced foot inversion compared to TAG (non-dominant mean difference = 0.966°, p = 0.035). Compared to UB, OF and TAG increased ankle inversion moments in the dominant ankle and showed decreases in the non-dominant ankle. BF reduced mean peak peroneus longus EMG activity compared to all other trials. Whilst statistically significant differences that were demonstrated between several braced conditions are relatively small, they are clinically significant knowing that the maximum barefoot inversion whilst standing is less than 17 degrees.

The effects of wearing an Ankle Stabilizing Orthosis (ASO) Ankle Brace on ankle joints kinetics and kinematics during a basketball rebounding task.

Following an ankle injury, athletes sometimes brace the injured ankle in hopes of minimizing the likelihood of suffering a recurring injury. This study aims to evaluate the effects of wearing an Ankle Stabilizing Orthosis (ASO) ankle brace unilaterally on the dominant side on bilateral ankle joint kinetics and kinematics and peroneus longus EMG activity. Since a significant proportion of ankle injuries in basketball occur during rebounding, data was collected during a simulated rebounding task. Rebounding is defined as the act of retrieving a missed shot attempt. Subjects oftentimes jump vertically to acquire the basketball as it rebounds from the backboard or rim. Sixteen subjects participated in the study (11 males, 5 females; mean age = 26.94 years, SD = 5.32; mean height 1.72 m, SD = 0.08; mean weight 73.95 kg, SD = 13.68). Participants completed the rebounding task in braced (ASO) and unbraced (UB) conditions. Ankle and foot inversion angles, ankle inversion moments and peroneus longus EMG activity were recorded and analysed to determine the effects of wearing an ankle brace unilaterally. In the dominant limb, when compared to UB, ASO reduced ankle and foot inversion, and increased ankle inversion moments. No significant differences were observed in peroneus longus EMG activity. In the non-dominant limb, no significant differences were observed for any of the parameters. These results suggest that wearing an ASO ankle brace on the dominant ankle reduces maximum ankle and foot inversion angles without posing an increased risk to the unbraced leg. However, the increased ankle inversion moments in the braced ankle suggest that there are adjustments regarding force distribution, perhaps due to the restricted range of motion.

Hygienic behaviour selection via freeze-killed honey bee brood not associated with chalkbrood resistance in eastern Australia.

Hygienic behaviour is a social immune response in honey bees shown to help provide resistance to honey bee pests and diseases. A survey of hygienic behaviour and brood diseases was conducted on 649 colonies in eastern Australia to initiate a selective breeding program targeting disease resistance and provide a level of resistance to Varroa (Varroa destructor Anderson and Trueman and V. jacobsoni Oudemans) mites should they become established in Australia. The test population showed a remarkably high baseline level of hygienic behaviour with 17% of colonies meeting or exceeding breeding selection thresholds. Colonies belonging to a breeding program were 5.8 times more likely to be highly hygienic and colonies headed by queens raised from hygienic queen mothers were 2.2 times more likely. Nectar availability (nectar yielding flowering plants within honey bee forage range) influenced hygienic behaviour expression but was not a significant predictor of level of hygienic behaviour. Surprisingly, hygienic behaviour was not a significant predictor of the presence of infection of the honey bee brood disease chalkbrood (Ascosphaera apis) and was not influential in predicting severity of chalkbrood infection in surveyed honey bee colonies. This study, along with reports from commercial beekeepers that chalkbrood infection is on the rise, warrants a deeper exploration of the host-pathogen relationship between Apis mellifera and Ascosphaera apis in Australia.

Reproducibility of the Balance Evaluation Systems Test (BESTest) and the Mini-BESTest in school-aged children.

This study evaluated the intra-rater, inter-rater and test-retest reproducibility of the Full-BESTest and Mini-BESTest when assessing postural control in children. Thirty-four children aged 7-17 years participated in intra-rater and inter-rater evaluation, and 22 children repeated assessment six weeks later for evaluation of test-retest reliability. Postural control was assessed using the Full Balance Evaluation Systems Test (Full-BESTest) and the short-form Mini-BESTest. Intra-rater, inter-rater and test-retest reproducibility were examined using video assessment. Test-retest reproducibility was also assessed in real-time. Reproducibility was examined by agreement and reliability statistics. Agreement was calculated using percentage of agreement, Limits of Agreement and Smallest Detectable Change. Reliability was calculated using Intra-class Correlation Coefficients. Results showed that the reliability of Total Scores was excellent for the Full-BESTest for all conditions (all ICCs>0.82), whereas the Mini-BESTest ranged from fair to excellent (ICC=0.56-0.86). Percentage of Domain Scores with good-excellent reliability (ICCs>0.60) was slightly higher for the Full-BESTest (66%) compared to the Mini-BESTest (59%). Smallest Detectable Change scores were good to excellent for the Full-BESTest (2%-6%) and for the Mini-BESTest (5%-10%) relative to total test scores. Both the Full-BESTest and Mini-BESTest can discriminate postural control abilities within and between days in school-aged children. The Full-BESTest has slightly better reproducibility and a broader range of items, which could be the most useful version for treatment planning. We propose minor modifications to improve reproducibility for children, and indicate the modified version by the title Kids-BESTest. Future psychometric research is recommended for specific paediatric clinical populations.

A first look at relative survival by stage for colorectal and lung cancers in Canada.

Monitoring and reporting on cancer survival provides a mechanism for understanding the effectiveness of Canada's cancer care system. Although 5-year relative survival for colorectal cancer and lung cancer has been previously reported, only recently has pan-Canadian relative survival by stage been analyzed using comprehensive registry data. This article presents a first look at 2-year relative survival by stage for colorectal and lung cancer across 9 provinces. As expected, 2-year age-standardized relative survival ratios (arsrs) for colorectal cancer and lung cancer were higher when the cancer was diagnosed at an earlier stage. The arsrs for stage i colorectal cancer ranged from 92.2% in Nova Scotia [95% confidence interval (ci): 88.6% to 95.1%] to 98.4% in British Columbia (95% ci: 96.2% to 99.3%); for stage iv, they ranged from 24.3% in Prince Edward Island (95% ci: 15.2% to 34.4%) to 38.8% in New Brunswick (95% ci: 33.3% to 44.2%). The arsrs for stage i lung cancer ranged from 66.5% in Prince Edward Island (95% ci: 54.5% to 76.5%) to 84.8% in Ontario (95% ci: 83.5% to 86.0%). By contrast, arsrs for stage iv lung cancer ranged from 7.6% in Manitoba (95% ci: 5.8% to 9.7%) to 13.2% in British Columbia (95% ci: 11.8% to 14.6%). The available stage data are too recent to allow for meaningful comparisons between provinces, but over time, analyzing relative survival by stage can provide further insight into the known differences in 5-year relative survival. As the data mature, they will enable an assessment of the extent to which interprovincial differences in relative survival are influenced by differences in stage distribution or treatment effectiveness (or both), permitting targeted measures to improve population health outcomes to be implemented.

killerFLIP: a novel lytic peptide specifically inducing cancer cell death.

One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killerFLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using electron microscopy demonstrated that killerFLIP-E triggers cell death accompanied by rapid (within minutes) plasma membrane permeabilization. Studies of the structure of the active core of killerFLIP (-E) indicated that it possesses amphiphilic properties and self-assembles into micellar structures in aqueous solution. The biochemical properties of killerFLIP are comparable to those of cationic lytic peptides, which participate in defense against pathogens and have also demonstrated anticancer properties. We show that the pro-cell death effects of killerFLIP are independent of its sequence similarity with c-FLIPL as killerFLIP-induced cell death was largely apoptosis and necroptosis independent. A killerFLIP-E variant containing a scrambled c-FLIPL motif indeed induced similar cell death, suggesting the importance of the c-FLIPL residues but not of their sequence. Thus, we report the discovery of a promising synthetic peptide with novel anticancer activity in vitro and in vivo.

Minimally constrained model of self-organized helical states in reversed-field pinches.

We show that the self-organized single-helical-axis (SHAx) and double-axis (DAx) states in reversed field pinches can be reproduced in a minimally constrained equilibrium model using only five parameters. This is a significant reduction on previous representations of the SHAx which have required an infinite number of constraints. The DAx state, which has a nontrivial topology, has not previously been reproduced using an equilibrium model that preserves this topological structure. We show that both states are a consequence of transport barrier formation in the plasma core, in agreement with experimental results. We take the limit of zero pressure in this work, although the model is also valid for finite pressure.

Cycling of gut mucosal CD4+ T cells decreases after prolonged anti-retroviral therapy and is associated with plasma LPS levels.

The gut mucosa is an important site of HIV immunopathogenesis with severe depletion of CD4+ T cells occurring during acute infection. The effect of prolonged anti-retroviral therapy (ART) on cycling and restoration of T lymphocytes in the gut remains unclear. Colon and terminal ileal biopsies and peripheral blood samples were collected from viremic, untreated, HIV-infected participants, patients treated with prolonged ART (>5 years), and uninfected controls and analyzed by flow cytometry. In the gut, the proportion of cycling T cells decreased and the number of CD4+ T cells normalized in treated patients in parallel with beta 7 expression on CD4+ T cells in blood. Cycling of gut T cells in viremic patients was associated with increased plasma LPS levels, but not colonic HIV-RNA. These data suggest that gut T-cell activation and microbial translocation may be interconnected whereas prolonged ART may decrease activation and restore gut CD4+ T cells.

Contribution of bone microenvironment to leukemogenesis and leukemia progression.

Tumor microenvironment has a major role in cancer progression and resistance to treatment. The bone marrow (BM) is a dynamic network of growth factors, cytokines and stromal cells, providing a permissive environment for leukemogenesis and progression. Both BM stroma and leukemic blasts promote angiogenesis, which is increased in acute lymphoblastic leukemia and acute myeloid leukemia. Growth factors like vascular endothelial growth factor (VEGF), basic fibroblast growth factor and angiopoietins are the main proangiogenic mediators in acute leukemia. Autocrine proleukemic loops have been described for VEGF and angiopoietin in hematopoietic cells. Interactions of stromal cells and extracellular matrix with leukemic blasts can also generate antiapoptotic signals that contribute to neoplastic progression and persistence of treatment-resistant minimal residual disease. High expression of CXC chemokine ligand 4 (CXCR4) by leukemic blasts and activation of the CXCR4-CXCL12 axis is involved in leukemia progression and disruption of normal hematopoiesis. Leukemia-associated bone microenvironment markers could be used as prognostic or predictive indicators of disease progression and/or treatment outcome. Studies related to bone microenvironment would likely provide a better understanding of the treatment resistance associated with leukemia therapy and design of new treatments.

A single-substrate model to interpret intra-annual stable isotope signals in tree-ring cellulose.

The carbon and oxygen stable isotope composition of wood cellulose (delta(13)C(cellulose) and delta(18)O(cellulose), respectively) reveal well-defined seasonal variations that contain valuable records of past climate, leaf gas exchange and carbon allocation dynamics within the trees. Here, we present a single-substrate model for wood growth to interpret seasonal isotopic signals collected in an even-aged maritime pine plantation growing in South-west France, where climate, soil and flux variables were also monitored. Observed seasonal patterns in delta(13)C(cellulose) and delta(18)O(cellulose) were different between years and individuals, and mostly captured by the model, suggesting that the single-substrate hypothesis is a good approximation for tree ring studies on Pinus pinaster, at least for the environmental conditions covered by this study. A sensitivity analysis revealed that the model was mostly affected by five isotopic discrimination factors and two leaf gas-exchange parameters. Modelled early wood signals were also very sensitive to the date when cell wall thickening begins (t(wt)). Our model could therefore be used to reconstruct t(wt) time series and improve our understanding of how climate influences this key parameter of xylogenesis.

Cost-utility of adjuvant hormone therapies with aromatase inhibitors in post-menopausal women with breast cancer: upfront anastrozole, sequential tamoxifen-exemestane and extended tamoxifen-letrozole.

This evaluation adapts a previous Canadian analysis of upfront and sequential adjuvant AI strategies in postmenopausal women with breast cancer to a Belgian perspective and includes an extended aromatase inhibitor (AI) strategy. A Markov model calculated monthly costs and outcomes in a hypothetical cohort of postmenopausal women with early-stage breast cancer. Baseline event rates and hazard ratios were derived from the Arimidex, Tamoxifen Alone or in Combination trial, International Exemestane Study and MA.17 trials. The analysis took a Belgian healthcare payer perspective with a 20-year time horizon. Costs and outcomes were discounted by 3%. Costs are in 2005 Euros. The cost-utility of all three strategies was favourable (<30,000 euros per QALY gained). Based on indirect comparisons using tamoxifen (TAM) alone as a common comparator, sequential TAM-AI was less costly and more effective than upfront or extended strategies. All three AI strategies were cost-effective alternatives to TAM alone, but sequential TAM-AI appears to be the economically preferred strategy.

Cost-utility of adjuvant hormone therapies for breast cancer in post-menopausal women: sequential tamoxifen-exemestane and upfront anastrozole.

BACKGROUND: Adjuvant Anastrozole (ANA) for 5 years and Tamoxifen followed by Exemestane (TAM-EXE) for 2.5 years each have become acceptable alternatives to 5 years of Tamoxifen (TAM) for post-menopausal women with breast cancer. As these newer options are associated with higher drug costs as well as improved outcomes, an economic evaluation was undertaken to compare the cost-utility of ANA and TAM-EXE relative to TAM alone and to each other in terms of cost per quality-adjusted life year (QALY) gained. METHODS: A Markov model was developed to calculate monthly costs and outcomes in a hypothetical cohort of post-menopausal women with early-stage breast cancer. Baseline rates of cancer recurrence and adverse effects with TAM, and hazard ratios associated with ANA and EXE, were derived from the ATAC and IES trials. Patients received hormonal therapy for 5 years and benefit was modeled to persist 5 years beyond treatment. The analysis took a direct payer perspective with a 20-year time horizon. Costs and outcomes were discounted by 3%. Costs are in 2005 Canadian dollars. RESULTS: ANA and TAM-EXE were associated with increased costs and QALYs, though the cost-utility of both relative to TAM alone was strongly favourable (<$50,000/QALY). Based on an indirect comparison of ANA and TAM-EXE, using TAM alone as a common comparator, the cost-utility of ANA relative to TAM-EXE appears unfavourable. CONCLUSIONS: Both upfront and sequential AI options were cost-effective alternatives to TAM alone, but TAM-EXE appears to be the economically preferred AI option based on its more favourable cost-utility versus ANA.

Modeling for cost-effective-adjuvant aromatase inhibitor strategies for postmenopausal women with breast cancer.

BACKGROUND: To determine cost-effective (CE) strategies comparing adjuvant upfront aromatase inhibitor (AI) with sequential tamoxifen (TAM) AI in postmenopausal (PM) women with breast cancer (BC). DESIGN: A Markov model was constructed to calculate cumulative costs and quality-adjusted life year (QALY) gains for upfront AI and TAM-AI in a hypothetical cohort of 60-year-old PM women with BC. Costs, utilities and probabilities were derived from the literature. The hazard ratios (HRs) of AI strategies were applied to a baseline cancer recurrence risk (RR) to determine CE strategies at the $50,000/QALY gain threshold. A direct payer perspective is utilized, and costs and benefits were discounted at 3%. RESULTS: Two-way sensitivity analyses are presented to determine CE strategies across a wide range of HRs and in different clinical scenarios including varying RRs (low, average, high and very high). TAM-AI is the preferred CE strategy at low and average RR, while upfront AI is CE at very high RR. The CE strategy in patients with high RR was dependent on the scenario examined. CONCLUSIONS: This model may help health care providers select CE-adjuvant AI strategies in PM women with BC, until further direct evidence is available from randomized clinical trials.

Wait times for breast cancer care.

Measurement of care time intervals is complex, being influenced by many factors. The definition of the care interval monitored can also bias the detection of changes in waits. The implications of using different care interval definitions to report wait times and identify delays in care provision were examined using a retrospective chart review of 637 women with surgically treated breast cancer who were referred to a cancer centre between September 1999 and 2000 or September 2003 and 2004. Overall waits between detection and adjuvant treatment increased by 12 days over the two periods, but their exact location and cause(s) could not be determined at such a low-resolution interval. At higher resolutions of care intervals, reporting the comprehensive sequence of care events, the prolongation was mainly associated with delayed access to surgery (4 days) and delivery of adjuvant chemotherapy (4 days). The latter went unnoticed when waits were reported at intermediate (referral to adjuvant treatment) and low (detection to adjuvant treatment) resolutions. Disease stage and type of first adjuvant treatment consistently and significantly influenced the length of waits. Comprehensive monitoring of the entire care path is essential to effectively prioritize interventions, assess their outcomes and optimise access to cancer care.

Statistical characterization of the interchange-instability spectrum of a separable ideal-magnetohydrodynamic model system.

A Suydam-unstable circular cylinder of plasma with periodic boundary conditions in the axial direction is studied within the approximation of linearized ideal magnetohydrodynamics (MHD). The normal mode equations are completely separable, so both the toroidal Fourier harmonic index n and the poloidal index m are good quantum numbers. The full spectrum of eigenvalues in the range 1< or = m < or = m(max) is analyzed quantitatively, using asymptotics for large m, numerics for all m, and graphics for qualitative understanding. The density of eigenvalues scales like m(2)(max) as m(max) -->infinity . Because finite-m corrections scale as 1/ m(2)(max) , their inclusion is essential in order to obtain the correct statistics for the distribution of eigenvalues. Near the largest growth rate, only a single radial eigenmode contributes to the spectrum, so the eigenvalues there depend only on m and n as in a two-dimensional system. However, unlike the generic separable two-dimensional system, the statistics of the ideal-MHD spectrum departs somewhat from the Poisson distribution, even for arbitrarily large m(max) . This departure from Poissonian statistics may be understood qualitatively from the nature of the distribution of rational numbers in the rotational transform profile.