Hot temperatures and morbidity : a systematic review and meta–analysis

Extreme temperatures have been shown to have a detrimental effect on health. Hot temperatures can increase the risk of mortality, particularly in people suffering from cardiorespiratory diseases. Given the onset of climate change, it is critical that the impact of temperature on health is understood, so that effective public health strategies can correctly identify vulnerable groups within the population. However, while effects on mortality have been extensively studied, temperature–related morbidity has received less attention. This study applied a systematic review and meta–analysis to examine the current literature relating to hot temperatures and morbidity

Exposure to hot and cold temperatures and ambulance attendances in Brisbane, Australia: a time-series study

ABSTRACT Objectives: To investigate the effect of hot and cold temperatures on ambulance attendances. Design: An ecological time series study. Setting and participants: The study was conducted in Brisbane, Australia. We collected information on 783 935 daily ambulance attendances, along with data of associated meteorological variables and air pollutants, for the period of 2000–2007. Outcome measures: The total number of ambulance attendances was examined, along with those related to cardiovascular, respiratory and other non-traumatic conditions. Generalised additive models were used to assess the relationship between daily mean temperature and the number of ambulance attendances. Results: There were statistically significant relationships between mean temperature and ambulance attendances for all categories. Acute heat effects were found with a 1.17% (95% CI: 0.86%, 1.48%) increase in total attendances for 1 °C increase above threshold (0–1 days lag). Cold effects were delayed and longer lasting with a 1.30% (0.87%, 1.73%) increase in total attendances for a 1 °C decrease below the threshold (2–15 days lag). Harvesting was observed following initial acute periods of heat effects, but not for cold effects. Conclusions: This study shows that both hot and cold temperatures led to increases in ambulance attendances for different medical conditions. Our findings support the notion that ambulance attendance records are a valid and timely source of data for use in the development of local weather/health early warning systems

Process economics evaluation of Adeno-associated Viral Vector (AAV) manufacturing

With two products currently approved for gene therapy purposes, adeno-associated virus (AAV) manufacturing has seen consistent pressure to develop scalable strategies, particularly during cell culture and purification. Traditionally, cell culture in adherent mode and gradient density-based polishing steps have been adopted for AAV processing. However, these technologies rely on scale-out strategies to increase capacity in a commercial environment, thereby incurring large costs and facility footprints. This presentation presents insights from an advanced economics analysis using a decisional tool developed at UCL to identify the most cost-effective route for large-scale manufacture of AAV. A cost of goods (COG) comparison will be presented between adherent and suspension cell culture, as well as anion-exchange chromatography versus batch ultracentrifugation at the base case. This provides benchmark COG values, the savings that can be achieved moving to more scalable technologies and the contributions of materials, labour, QC and facility-related costs. A stochastic cost comparison is used to reveal the impact of key input uncertainties (e.g. productivities) on the robustness of each strategy and the likelihood of achieving target COG values. Next, the case study looks at a broad range of USP (e.g. multi-layer cell factories, fixed-bed reactor, single-use stirred tank bioreactor) and DSP (e.g. packed-bed chromatography, batch and continuous ultracentrifugation) technology options and uses an optimisation algorithm to identify the optimal flowsheet for AAV manufacture in terms of both cost-effectiveness and meeting purity targets. This analysis highlights how the optimal flowsheet will change depending on the purity target that needs to be met, with specific focus upon HCPs, DNA and empty capsids Finally, the presentation will highlight how the optimal solutions change for different combinations of demand, batch size and AEX yield, highlighting the trade-off between achieving high yields and purities, whilst opting for scalable technologies. These insights help make better decisions early on in development to facilitate successful commercialisation

Process economics evaluation and optimization of adeno-associated virus downstream processing

Adeno-associated virus (AAV) manufacturing has traditionally focused upon lab-scale techniques to culture and purify vector products, leading to limitations in production capacity. The tool presented in this paper assesses the feasibility of using non-scalable technologies at high AAV demands and identifies optimal flowsheets at large-scale that meet both cost and purity targets. The decisional tool comprises (a) a detailed process economics model with the relevant mass balance, sizing, and costing equations for AAV upstream and downstream technologies, (b) a built-in Monte Carlo simulation to assess uncertainties, and (c) a brute-force optimization algorithm for rapid investigation into the optimal purification combinations. The results overall highlighted that switching to more scalable upstream and downstream processing alternatives is economically advantageous. The base case analysis showed the cost and robustness advantages of utilizing suspension cell culture over adherent, as well as a fully chromatographic purification platform over batch ultracentrifugation. Expanding the set of purification options available gave insights into the optimal combination to satisfy both cost and purity targets. As the purity target increased, the optimal polishing solution moved from the non-capsid purifying multimodal chromatography to anion-exchange chromatography or continuous ultracentrifugation

REDIRECT: reducing older patients' avoidable presentations for emergency care treatment

The project brings together researchers, primary and acute care service providers, and consumers with the primary aim of identifying strategies to reduce avoidable presentations of older patients to Emergency Departments (ED) by redirecting them to primary and community health services. The objectives are to: 1. Understand the journey of older patients who present to ED unnecessarily by analysing four datasets, which include data from regional and national levels, to identify the clinical, social, and health system-related risk factors for ED attendance and re-attendance 2. Identify the appropriate strategies for preventing older patient re-entry from primary health care to sub-acute or acute care 3. Establish the applicability of the proposed interventions at a regional level and the generalisability and feasibility of their implementation in other settings Synopsis Caring for an ageing population raises significant challenges to the health care system, including emergency care. Medicare Locals are charged with the task of reducing avoidable emergency department (ED) attendance partly by improving access to after-hours care. Research shows that increasing numbers of older patients (over 70 years) are attending ED, many over four times per year. To reduce avoidable presentations, we need to improve the options for managing the health care demand of this older age group in primary care and community settings. Accordingly, the project aims to: 1. Better understand the journey of older patients who present to ED unnecessarily and re-enter from primary health care to sub-acute or acute care by analysing four highly relevant datasets: MAGNET (Melbourne East Monash General Practice Database) MMDS (Melbourne Medical Deputising Services) dataset VEMD (Victorian Emergency Minimum Dataset) DYNOPTA (Dynamic Analyses to Optimise Ageing) dataset 2. Determine the appropriate strategies for preventing patient re-entry from primary health care to sub-acute or acute care by conducting a rapid review methodology. 3. Synthesise the above findings and propose alternative care models. Interviews and focus groups will be conducted with key stakeholders and older consumers and their carers to determine the applicability of these models at a local level and the generalisability of our findings to other settings.The research reported in this paper is a project of the Australian Primary Health Care Research Institute which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research Evaluation and Development Strategy

Survey of women׳s experiences of care in a new freestanding midwifery unit in an inner city area of London, England: 2. Specific aspects of care

Objective to describe and compare women׳s experiences of specific aspects of maternity care before and after the opening of the Barkantine Birth Centre, a new freestanding midwifery unit in an inner city area. Design telephone surveys undertaken in late pregnancy and about six weeks after birth. Two separate waves of interviews were conducted, Phase 1 before the birth centre opened and Phase 2 after it had opened. Setting Tower Hamlets, a deprived inner city borough in east London, 2007–2010. Participants 620 women who were resident in Tower Hamlets and who satisfied the Barts and the London Trust’s eligibility criteria for using the birth centre. Of these, 259 women were recruited to Phase 1 and 361 to Phase 2. Measurements and findings the replies women gave show marked differences between the model of care in the birth centre and that at the obstetric unit at the Royal London Hospital with respect to experiences of care and specific practices. Women who initially booked for birth centre care were more likely to attend antenatal classes and find them useful and were less likely to be induced. Women who started labour care at the birth centre in spontaneous labour were more likely to use non-pharmacological methods of pain relief, most notably water and less likely to use pethidine than women who started care at the hospital. They were more likely to be able to move around in labour and less likely to have their membranes ruptured or have continuous CTG. They were more likely to be told to push spontaneously when they needed to rather than under directed pushing and more likely to report that they had been able to choose their position for birth and deliver in places other than the bed, in contrast to the situation at the hospital. The majority of women who had a spontaneous onset of labour delivered vaginally, with 28.6 per cent of women at the birth centre but no one at the hospital delivering in water. Primiparous women who delivered at the birth centre were less likely to have an episiotomy. Most women who delivered at the birth centre reported that they had chosen whether or not to have a physiological third stage, whereas a worrying proportion at the hospital reported that they had not had a choice. A higher proportion of women at the birth centre reported skin to skin contact with their baby in the first two hours after birth. Key conclusions and implications for practice significant differences were reported between the hospital and the birth centre in practices and information given to the women, with lower rates of intervention, more choice and significant differences in women’s experiences. This case study of a single inner-city freestanding midwifery unit, linked to the Birthplace in England Research Programme, indicates that this model of care also leads to greater choice and a better experience for women who opted for it

Graded decomposition numbers for cyclotomic Hecke algebras

In recent joint work with Wang, we have constructed graded Specht modules for cyclotomic Hecke algebras. In this article, we prove a graded version of the Lascoux-Leclerc-Thibon conjecture, describing the decomposition numbers of graded Specht modules over a field of characteristic zero.Comment: 57 pages; final versio

Irreducible projective representations of the symmetric group which remain irreducible in characteristic 2

For any finite group $G$ and any prime $p$ one can ask which ordinary irreducible representations remain irreducible in characteristic $p$. We answer this question for $p=2$ when $G$ is a proper double cover of the symmetric group. Our techniques involve constructing part of the decomposition matrix for a Rouquier block of a double cover, restricting to subgroups using the Brundan--Kleshchev modular branching rules and comparing the dimensions of irreducible representations via the bar-length formula

Irreducible projective representations of the alternating group which remain irreducible in characteristic 2

For any finite group G it is an interesting question to ask which ordinary irreducible representations of G remain irreducible in a given characteristic p. We answer this question for p=2 when G is the proper double cover of the alternating group. As a key ingredient in the proof, we prove a formula for the decomposition numbers in Rouquier blocks of double covers of symmetric groups, in terms of Schur P-functions

Thallium isotopes in early diagenetic pyrite – a paleoredox proxy?

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 75 (2011): 6690-6704, doi:10.1016/j.gca.2011.07.047.This paper presents the first study of Tl isotopes in early diagenetic pyrite. Measurements from two sections deposited during the Toarcian Ocean Anoxic Event (T-OAE, ~183Ma) are compared with data from Late Neogene (<10Ma) pyrite samples from ODP legs 165 and 167 that were deposited in relatively oxic marine environments. The Tl isotope compositions of Late Neogene pyrites are all significantly heavier than seawater, which most likely indicates that Tl in diagenetic pyrite is partially sourced from ferromanganese oxy-hydroxides that are known to display relatively heavy Tl isotope signatures. One of the T-OAE sections from Peniche in Portugal displays pyrite thallium isotope compositions indistinguishable from Late Neogene samples, whereas samples from Yorkshire in the UK are depleted in the heavy isotope of Tl. These lighter compositions are best explained by the lack of ferromanganese precipitation at the sediment–water interface due the sulphidic (euxinic) conditions thought to be prevalent in the Cleveland Basin where the Yorkshire section was deposited. The heavier signatures in the Peniche samples appear to result from an oxic water column that enabled precipitation of ferromanganese oxy-hydroxides at the sediment–water interface. The Tl isotope profile from Yorkshire is also compared with previously published molybdenum isotope ratios determined on the same sedimentary succession. There is a suggestion of an anti-correlation between these two isotope systems, which is consistent with the expected isotope shifts that occur in seawater when marine oxic (ferromanganese minerals) fluxes fluctuate. The results outlined here represent the first evidence that Tl isotopes in early diagenetic pyrite have potential to reveal variations in past ocean oxygenation on a local scale and potentially also for global oceans. However, much more information about Tl isotopes in different marine environments, especially in anoxic/euxinic basins, is needed before Tl isotopes can be confidently utilized as a paleo-redox tracer.SGN is funded by a NERC fellowship