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Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homocysteine during pregnancy, particularly in a folic acid-fortified population.
Data were from the Ottawa and Kingston Birth Cohort of 8085 participants. We used multivariable regression analyses to identify factors associated with maternal homocysteine, adjusted for gestational age at bloodwork. Continuous factors were modelled using restricted cubic splines. A subgroup analysis examined the modifying effect of MTHFR 677C>T genotype on folate, in determining homocysteine concentration.
Participants were recruited in Ottawa and Kingston, Canada, from 2002 to 2009.
Women were recruited when presenting for prenatal care in the early second trimester.
In 7587 participants, factors significantly associated with higher homocysteine concentration were nulliparous, smoking and chronic hypertension, while factors significantly associated with lower homocysteine concentration were non-Caucasian race, history of a placenta-mediated complication and folic acid supplementation. Maternal age and BMI demonstrated U-shaped associations. Folic acid supplementation of >1 mg/d during pregnancy did not substantially increase folate concentration. In the subgroup analysis, MTHFR 677C>T modified the effect of folate status on homocysteine concentration.
We identified determinants of maternal homocysteine relevant to the lowering of homocysteine in the post-folic acid fortification era, characterised by folate-replete populations. A focus on periconceptional folic acid supplementation and improving health status may form an effective approach to lower homocysteine.
This article explores the relationship between Social Quality and income in later life and represents the first application of the concept to a United Kingdom data-set with an explicit focus on older people. In order to undertake this analysis, confirmatory factor analysis models are employed in conjunction with the British Household Panel Survey (BHPS). This enables various dimensions or domains of Social Quality to be measured and then subjected to further scrutiny via regression analysis. Initially, the paper explores links between low income, poverty and older people, prior to outlining the concept of Social Quality and its four conditional factors. Following the methodology, the impact of income on Social Quality domains is explored. We identify that differences in income in older age provide a partial explanation of differences in individual Social Quality. While there is a statistically significant relationship between income and certain aspects of Social Quality such as economic security, altruism, social networks and culture/participation, other factors such as health, identity and time did not have a statistically significant relationship with income. This indicates that improvements in the income of older people are likely to positively impact on aspects of their Social Quality. Finally, some policy implications of the finding are outlined with particular reference to the potential role for pensions in enhancing aspects of Social Quality in retirement.
Health technology assessments (HTA) for combination drug therapies in oncology are increasingly common. Companies face multiple challenges when determining their economic value due to their complexity and high cost, while payers must balance the need for these vital innovations with sensitivity to rising costs. The study objective was to evaluate the current HTA frameworks in Europe and identify the potential barriers/solutions to reimbursement of brand-on-brand (BoB) combination therapy.
A targeted literature review of HTA agency websites was undertaken to identify any literature/guidance relating to HTA decision-making for combination oncology therapies in France, Germany, Sweden, and the UK.
In France and the UK, BoB HTA decisions reflect clinical- and cost-effectiveness. Combination therapies have been accepted for use in France and the UK, for example, dabrafenib plus trametinib, are assessed through standard HTA processes, exemplifying that positive reimbursement is not unattainable where there is an unmet need and high clinical value. Despite this flexibility, many therapies will fail to prove their cost-effectiveness, resulting in delays or arbitrary pricing decisions. Potential solutions are the use of the ‘efficiency frontier’, as typified by the German HTA system, giving more ‘scope‘ to expensive innovations; or the Swedish HTA approach, which applies variable cost-effectiveness thresholds according to therapeutic area, disease severity, and social criteria. Other possibilities include indication-specific pricing, multiple-criteria decision analysis, and net monetary benefit with willingness-to-trade weights. One likely issue to arise is when different companies are involved, necessitating co-operation. In this scenario, a simplistic solution would be arbitration of the division of the combined price, circumventing the need for HTA agencies to make changes to decision-making criteria.
Constructive debates and collaboration between industry and decision-makers are vital to achieve a harmonized HTA process for high-cost combination therapies which offer advanced benefits and improved safety outcomes, whilst satisfying HTA bodies and providing better access for patients.
Health technology assessment (HTA) must adapt to support the changing health system landscapes and improve access to valuable innovation under budgetary constraints. This is exemplified by the pricing and reimbursement of high-cost combination therapies increasingly used in oncology. Variability exists in current HTA practices across different countries, resulting in discrepancies in reimbursement outcomes and patient access. Using Italy as a case study, the objective was to assess the challenges faced by HTA agencies in the negotiation of pricing and reimbursement of combination therapies.
A targeted literature review of Italian HTA agency websites was undertaken to identify any literature/guidance relating to HTA decision-making for combination oncology therapies.
In Italy, there is no fixed cost-effectiveness threshold and decisions are based on multiple criteria. Managed market entry agreements are extensively used; price-volume agreements and drug registries are common. While this framework allows flexibility and avoids the rigidity of incremental cost-effectiveness ratio thresholds, it has raised concerns about transparency and budget impact. Combination therapies are not given specific concessions; however, market access for a combination of a new high-cost drug with an existing one is complex, particularly if the drugs are manufactured by different companies. The added value provided by the new drug in the combination should be rewarded while the older product benefits from the increased volume of use. The price of the older drug cannot be lowered unless the pricing and reimbursement contract is expiring or a new indication/formulation is pending, presenting a challenge to both pharmaceutical companies and HTA agencies.
Combination therapies pose a challenge for HTA agencies. In the Italian system this is partially mitigated by the use of multiple criteria for decision-making and managed access agreements. However, these approaches have also led to concerns about a lack of transparency in decision-making.
Heater-cooler units (HCUs) have been shown to be a source of Mycobacterium chimaera infections. For the past year, weekly water samples have been taken from HCUs used at University Hospitals Birmingham (UHB) NHS Foundation Trust. We report the microbial contamination of the HCUs over a year detailing the decontamination regimes applied at UHB to reduce the microbial load.
UHB is a tertiary referral teaching hospital in Birmingham, United Kingdom, that provides clinical services to nearly 1 million patients every year. The UHB Cardiac department is one of the largest in the United Kingdom and provides treatment for adult patients with a wide range of cardiac diseases.
Water samples taken from HCUs used at UHB for cardiopulmonary bypass surgery were sampled over a year to determine the number of microorganisms by membrane filtration. Various decontamination processes were employed throughout the year.
Varying total viable counts containing a wide variety of microorganisms were obtained from water inside the HCUs. No M. chimaera were isolated after replacement of the HCU internal tubing. Stringent decontamination regimes resulted in degradation of the HCUs and increased TVCs after several months.
More work is required to ensure effective decontamination processes to reduce the microbial load within the HCUs. Our studies indicate that weekly water sampling for TVC will be required indefinitely to monitor the water quality in these units as well as regular replacement of the tubing to control the build-up of biofilm.
Previous research on agriculture in the American Southwest focuses overwhelmingly on archaeological survey methods to discern surface agricultural features, which, in combination with climatological, geological, and geographical variables, are used to create models about agricultural productivity in the past. However, with few exceptions, the role of floodplain irrigation and floodwater farming in ancestral Pueblo agriculture is generally downplayed in scholarly discourse. Using a variety of methods, including Unmanned Aerial Vehicles (UAV), satellite imagery, pedestrian survey, and supervised classification of remotely sensed imagery, we examine this issue through a consideration of how ancestral Ohkay Owingeh (Tewa) people solved the challenges of arid land farming in the lower Rio Chama watershed of New Mexico during the Classic period (A.D. 1350–1598). Based on acreage estimates, our results indicate that runoff and rainwater fields in terrace environments would have been insufficient to supply the nutritional needs of an ancestral Tewa population exceeding 10,000 individuals. Based on these observations, we present a case for the substantial role of subsistence agriculture in the floodplain of the Rio Chama and its associated tributaries.
Peter Townsend argued that poverty could be scientifically measured as a ‘breakpoint’ within the income distribution below which participation collapses. This paper stands on Townsend's shoulders in measuring the level of poverty and participation by: (1) broadening his original measurement of participation; (2) using Structural Equation Modelling (SEM) in conjunction with a new dataset including 40,000 households (Understanding Society, 2011; 2013); and (3) taking into account the multi-cultural/ethnic nature of British society. We find that participation – defined as lack of deprivation, social participation and trust – reduces as income falls but stops doing so among the poorest 30 per cent of individuals. This may be indicating a minimum level of participation, a floor rather than a ‘breakpoint’ as suggested by Townsend, which has to be sustained irrespective of how low income is. Respondents with an ethnic minority background manifest lower levels of participation than white respondents but the relationship has a less linear pattern. Moreover, the floor detected for the overall population is also replicated when combining all respondents from ethnic groups.
The conservation and management of peatlands by practitioners is often assumed to work best when guided by science (e.g. Maltby 1997). However, there are also many excellent peatland management and restoration projects, which have built upon years of practical experience (sometimes through trial and error), undertaken by organisations involved in hands-on peatland conservation. Parry, Holden and Chapman (2014) provide many examples of techniques developed through common sense and ingenuity on the part of practitioners, often with little input from the science community. Often restoration projects have to make progress well before the science is fully understood. Significant investment is being poured into peatland management projects across the world (Parish et al. 2008), and it is important for those investing resources in peatland environments that there is some evaluation of the impacts of such investment. Evaluating the success of peatland management projects may involve the scientific community (e.g. taking measurements of carbon fluxes). In many instances, however, practitioners may involve less stringent measures with success measured by recording some simple visible changes to the landscape. The evaluation of success may indeed be an economic one (Kent 2000) based on cost–benefit analyses (Christie et al. 2011) of, for example, money spent on restoration that has been or will be saved elsewhere through, for instance, improved water quality entering water company treatment works. The observations for measuring peatland conservation success may depend on spatial and temporal scale, geographic settings and project targets, as well as available expertise and funding. There are therefore questions about how we measure success and how scientists, practitioners and policy makers can work closely together to deliver the best outcomes for peatland ecosystem services. Careful attention should be given to the mechanisms for science knowledge exchange between science and practical application so that practical experience and knowledge by those managing peatlands is transferred into the scientific understanding of peatlands. Scientists value the opinions and ideas of the restoration community and there have been recent attempts to move towards improved co-design of research and co-production of knowledge of science and practitioner communities in peatland restoration environments (Reed 2008; Reed et al. 2009).
Taking an ecosystem services approach to peatland conservation means that scientists, practitioners and policy makers have to understand the wider interconnectedness of peatland processes that lead to the provision of goods and services to society.
Gravitational lensing can significantly magnify the images of astrophysical sources, but only if the source lies within the Einstein ring of the lens. In consequence the chance of any Galactic star magnifying a more distant source is extremely small—much less than one in a million. However, the extra light travel time (‘Shapiro delay’) introduced by the presence of a lens can be large even when there is negligible effect on the image magnification, and as the relative positions of source and lens change so does the delay. In this paper we quantify these changes and the corresponding influence on apparent timing properties of pulsars. While the total Shapiro delay can be large, it is the temporal variations in this quantity which are measurable with pulsar timing. We find that the magnitude of the expected delay variations is too small to be detectable except during strong lensing events, which are extremely rare. Even in the case of a high-velocity pulsar in the Galactic Plane, the stochastic Shapiro delay is typically expected not to have a substantial influence on the timing properties. In consequence the viability of a pulsar-based time standard is not adversely affected by gravitational lensing.
The benefits of fetoscopic laser photocoagulation (FLP) for treatment of twin-to-twin transfusion syndrome (TTTS) have been recognized for over a decade, yet access to FLP remains limited in many settings. This means at a population level, the potential benefits of FLP for TTTS are far from being fully realized. In part, this is because there are many centers where the case volume is relatively low. This creates an inevitable tension; on one hand, wanting FLP to be readily accessible to all women who may need it, yet on the other, needing to ensure that a high degree of procedural competence is maintained. Some of the solutions to these apparently competing priorities may be found in novel training solutions to achieve, and maintain, procedural proficiency, and with the increased utilization of ‘competence based’ assessment and credentialing frameworks. We suggest an under-utilized approach is the development of collaborative surgical services, where pooling of personnel and resources can improve timely access to surgery, improve standardized assessment and management of TTTS, minimize the impact of the surgical learning curve, and facilitate audit, education, and research. When deciding which centers should offer laser for TTTS and how we decide, we propose some solutions from a collaborative model.
To examine the association between BMI and folate concentrations in serum and red blood cells (RBC) in pregnant women.
A cross-sectional comparison of folate concentrations in serum and RBC sampled simultaneously from the same individual.
The Ottawa Hospital and Kingston General Hospital, Ontario, Canada.
Pregnant women recruited between 12 and 20 weeks of gestation.
A total of 869 pregnant women recruited from April 2008 to April 2009 were included in the final analysis. Serum folate was inversely associated and RBC folate positively associated with BMI, after adjusting for folic acid supplementation, age, gestational age at blood sample collection, race, maternal education, annual income, smoking and MTHFR 677C→T genotype. In stratified analyses, this differential association was significant in women with the MTHFR CC variant. In women with the CT and TT variants, the differential associations were in the same direction but not significant. Folic acid supplementation during pregnancy did not alter the differential association of BMI with serum and RBC folate concentration. This indicates that the current RBC folate cut-off approach for assessing risk of neural tube defects in obese women may be limited.
BMI is inversely associated with serum folate and positively associated with RBC folate in pregnant women, especially for those with the MTHFR CC variant.
Using Confirmatory Factor Analysis models in conjunction with the British Household Panel Survey (BHPS) this paper reports the first application of the concept of Social Quality to a UK data set. Social Quality is concerned with the quality of society, or social relations, and consists of both a theoretical model and an empirically tested set of measures. Social Quality is explored in relation to the policy issues of low pay and the working poor given the challenges presented by the rising number of households in work and in poverty. This analysis reveals several striking characteristics. In terms of poverty per se poor employees are worse off in terms of economic security, housing, health, human capital, trust, voluntarism, citizenship, knowledge and culture whichever part of the employment structure they belong to. However, in addition, even those in the so-called upper level of the labour market (professional, managerial occupations which require reasonably high levels of skill and motivation) are significantly worse off on these dimensions if they are low paid. Therefore it suggests that measures to raise low pay, such as the living wage, are likely to have considerable implications for Social Quality.
We present the results of an approximately 6 100 deg2 104–196 MHz radio sky survey performed with the Murchison Widefield Array during instrument commissioning between 2012 September and 2012 December: the MWACS. The data were taken as meridian drift scans with two different 32-antenna sub-arrays that were available during the commissioning period. The survey covers approximately 20.5 h < RA < 8.5 h, − 58° < Dec < −14°over three frequency bands centred on 119, 150 and 180 MHz, with image resolutions of 6–3 arcmin. The catalogue has 3 arcmin angular resolution and a typical noise level of 40 mJy beam− 1, with reduced sensitivity near the field boundaries and bright sources. We describe the data reduction strategy, based upon mosaicked snapshots, flux density calibration, and source-finding method. We present a catalogue of flux density and spectral index measurements for 14 110 sources, extracted from the mosaic, 1 247 of which are sub-components of complexes of sources.
Current measures for major depressive disorder focus primarily on the assessment of depressive symptoms, while often omitting other common features. However, the presence of comorbid features in the anxiety spectrum influences outcome and may effect treatment. More comprehensive measures of depression are needed that include the assessment of symptoms in the anxiety–depression spectrum. This study examines the reliability and validity of the Symptoms of Depression Questionnaire (SDQ), which assesses irritability, anger attacks, and anxiety symptoms together with the commonly considered symptoms of depression. Analysis of the factor structure of the SDQ identified 5 subscales, including one in the anxiety–depression spectrum, with adequate internal consistency and concurrent validity. The SDQ may be a valuable new tool to better characterize depression and identify and administer more targeted interventions.
Gyro-phase drift is a guiding center drift that is directly dependent on the charging rate limit of dust grains. The effect of introducing a gyro-phase-dependence on the grain charge leads to two orthogonal components of guiding-center drift. One component, referred to here as grad-q drift, results from the time-varying, gyro-phase angle dependent, in-situ-equilibrium grain charge, assuming that the grain charging is instantaneous. For this component, the grain is assumed to be always in its in-situ-equilibrium charge state and this state gyro-synchronously varies with respect to the grain's average charge state. The other component, referred to here as the gyro-phase drift, arises from any non-instantaneous-charging-induced modification of the diamagnetic drift and points in the direction of -∇RLd (where RLd is the grain gyro-radius), i.e. the direction associated with increasing magnitude of in-situ-equilibrium charge state. For this component, the grain gyro-synchronously undercharges and overcharges with respect to its gyro-synchronously varying, in-situ-equilibrium charge state. These characteristics are illustrated with a single-particle code for predicting grain trajectory that demonstrates how gyro-phase drift magnitude and direction could be exploited, using an extended version of the presented model, as sensitive indicators of the charging time of dust grains because of the cumulative effect of the ever-changing charge state of a grain making repeated excursions in inhomogeneous plasma over many gyro-periods.