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Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
Methods:
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Results:
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
Conclusions:
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Cardiovascular risk prediction tools are important for cardiovascular disease (CVD) prevention, however, which algorithms are appropriate for people with severe mental illness (SMI) is unclear.
Objectives/aims
To determine the cost-effectiveness using the net monetary benefit (NMB) approach of two bespoke SMI-specific risk algorithms compared to standard risk algorithms for primary CVD prevention in those with SMI, from an NHS perspective.
Methods
A microsimulation model was populated with 1000 individuals with SMI from The Health Improvement Network Database, aged 30–74 years without CVD. Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those high-risk (> 10%) were assumed to be prescribed statin therapy, others received usual care. Individuals entered the model in a ‘healthy’ free of CVD health state and with each year could retain their current health state, have cardiovascular events (non-fatal/fatal) or die from other causes according to transition probabilities.
Results
The SMI-specific BMI and general population lipid algorithms had the highest NMB of the four algorithms resulting in 12 additional QALYs and a cost saving of approximately £37,000 (US$ 58,000) per 1000 patients with SMI over 10 years.
Conclusions
The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of a SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
A cementitious backfill has been proposed in many geological disposal concepts for intermediate-level waste and low-level waste in the UK and elsewhere. In this paper, the main features of the chemical evolution of backfill and the associated changes in the near-field pH are illustratedwith results from recent work. For example, interaction of the groundwater with calcium silicate hydrate (C-S-H) phases in a backfill is expected to play an important role in the long-term pH-buffering behaviour. Existing experimental data for the dissolution of C-S-H gels are compared withrecent experimental results from leach tests on gels of a lower calcium to silicon ratio (C/S) to provide a consistent set of data across the full C/S range. The results confirm that a congruent dissolution point around C/S = 0.8 is approached by leaching from below (i.e. for gels with 0.29< C/S < 0.8), as well as from above, as reported elsewhere. In addition, a spreadsheet model has been developed to calculate the volume of backfill required at the vault scale to meet specified pH performance criteria. This model includes the major reactions of the backfill with thegroundwater, waste encapsulants and waste components. It can also consider the effects of specific waste packages on local pH performance to allow comparison with the vault-scale calculations.
In the United Kingdom, disposal of radioactive waste may involve packages of grouted waste being placed in a geological disposal facility (GDF) and surrounded by a cementitious backfill. This paper describes modelling that has been carried out to develop an understanding of the possible spatial and temporal evolution within the GDF.
A single waste package is assumed to be filled with an encapsulation grout, placed in an underground vault and surrounded by a cementitious backfill. Groundwater from the host rock flows into the vault and through the backfill. A simplified model system examines the interactions between groundwater, cementitious backfill and grout.
In most cases the model predicts a reduction in the backfill porosity due to precipitation and dissolution reactions, particularly at the upstream edge of the vault. The degree to which this occurs depends on the groundwater composition. The model also predicts precipitation and dissolution reactions would occur in the grouts close to their interface with the backfill, reducing the local porosity significantly which may isolate the grouts from the backfill, so that the pH within the grouts would be unchanged over an extended period.
This study aimed to monitor the microbiological effect of cleaning near-patient sites over a 48-hour period with a novel disinfectant, electrolyzed water.
Setting.
One ward dedicated to acute care of the elderly population in a district general hospital in Scotland.
Methods.
Lockers, left and right cotsides, and overbed tables in 30 bed spaces were screened for aerobic colony count (ACC), methicillin-susceptible Staphylococcus aureus (MSSA), and methicillin-resistant S. aureus (MRSA) before cleaning with electrolyzed water. Sites were rescreened at varying intervals from 1 to 48 hours after cleaning. Microbial growth was quantified as colony-forming units (CFUs) per square centimeter and presence or absence of MSSA and MRSA at each site. The study was repeated 3 times at monthly intervals.
Results.
There was an early and significant reduction in average ACC (360 sampled sites) from a before-cleaning level of 4.3 to 1.65 CFU/cm2 at 1 hour after disinfectant cleaning (P <.0001). Average counts then increased to 3.53 CFU/cm2 at 24 hours and 3.68 CFU/cm2 at 48 hours. Total MSSA/MRSA (34 isolates) decreased by 71% at 4 hours after cleaning but then increased to 155% (53 isolates) of precleaning levels at 24 hours.
Conclusions.
Cleaning with electrolyzed water reduced ACC and staphylococci on surfaces beside patients. ACC remained below precleaning levels at 48 hours, but MSSA/MRSA counts exceeded original levels at 24 hours after cleaning. Although disinfectant cleaning quickly reduces bioburden, additional investigation is required to clarify the reasons for rebound contamination of pathogens at near-patient sites.
Infect Control Hosp Epidemiol 2014;35(12):1505–1510
The prevention of depression is a key public health policy priority. PredictD is the first risk algorithm for the prediction of the onset of major depression. Our aim in this study was to model the cost-effectiveness of PredictD in depression prevention in general practice (GP).
Method
A decision analytical model was developed to determine the cost-effectiveness of two approaches, each of which was compared to treatment as usual (TAU) over 12 months: (1) the PredictD risk algorithm plus a low-intensity depression prevention programme; and (2) a universal prevention programme in which there was no initial identification of those at risk. The model simulates the incidence of depression and disease progression over 12 months and calculates the net monetary benefit (NMB) from the National Health Service (NHS) perspective.
Results
Providing patients with PredictD and a depression prevention programme prevented 15 (17%) cases of depression in a cohort of 1000 patients over 12 months and had the highest probability of being the optimal choice at a willingness to pay (WTP) of £20 000 for a quality-adjusted life year (QALY). Universal prevention was strongly dominated by PredictD plus a depression prevention programme in that universal prevention resulted in less QALYs than PredictD plus prevention for a greater cost.
Conclusions
Using PredictD to identify primary-care patients at high risk of depression and providing them with a low-intensity prevention programme is potentially cost-effective at a WTP of £20 000 per QALY.
E. coli O157 can be transmitted to humans by three primary (foodborne, environmental, waterborne) and one secondary (person-to-person transmission) pathways. A regression model and quantitative microbiological risk assessments (QMRAs) were applied to determine the relative importance of the primary transmission pathways in NE Scotland. Both approaches indicated that waterborne infection was the least important but it was unclear whether food or the environment was the main source of infection. The QMRAs over-predicted the number of cases by a factor of 30 and this could be because all E. coli O157 strains may not be equally infective and/or the level of infectivity in the dose–response model was too high. The efficacy of potential risk mitigation strategies to reduce human exposure to E. coli O157 using QMRAs was simulated. Risk mitigation strategies focusing on food and environment are likely to have the biggest impact on infection figures.
We present a preliminary large-scale, neutral Hydrogen emission map of structure around dwarf irregular (dIm) galaxy NGC 1569. These data were taken earlier this year with the Robert C. Byrd Green Bank Telescope (GBT). Our primary objective was to search for HI structure potentially connecting NGC 1569 with IC 342 as an explanation for the starburst and peculiar kinematics prevalent in NGC 1569.
The objective of the present study was to evaluate the influence of heat stress on bovine oocyte maturation. Both nuclear stage and distribution of cortical granules (CG) were simultaneously evaluated in each oocyte. Oocyte overmaturation under standard conditions of culture was also evaluated. For this purpose, logistic regression procedures were used to evaluate possible effects of factors such as heat stress, overmaturation, replicate, CG distribution and metaphase II (MII) morphology on oocyte maturation. Based on the odds ratio, oocytes on heat stressed (HSO) and overmaturated (OMO) oocyte group were, respectively, 14.5 and 5.4 times more likely to show anomalous MII morphology than those matured under control conditions (CO). The likelihood for an oocyte of showing the CG distribution pattern IV (aging oocyte) was 6.3 and 9.3 times higher for HSO and OMO groups, respectively, than for the CO group. The risk of undergoing anomalous oocyte maturation, considering both nuclear stage and distribution of CG was 17.1 and 18 times greater in oocytes cultured in HSO and OMO groups, respectively, than those in the CO group. In conclusion, heat stress proved to be valuable in aging oocytes. Heat stress advanced age for nuclear and cytoplasmic processes in a similar form to that of oocyte overmaturation.