Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia

Objectives To assess the cost effectiveness of strategies to screen for and treat familial hypercholesterolaemia. Design Cost effectiveness analysis. A care pathway for each patient was delineated and the associated probabilities, benefits, and costs were calculated. Participants Simulated population aged 16­54 years in England and Wales. Interventions Identification and treatment of patients with familial hypercholesterolaemia by universal screening, opportunistic screening in primary care, screening of people admitted to hospital with premature myocardial infarction, or tracing family members of affected patients. Main outcome measure Cost effectiveness calculated as cost per life year gained (extension of life expectancy resulting from intervention) including estimated costs of screening and treatment. Results Tracing of family members was the most cost effective strategy (£3097 (&5066, $4479) per life year gained) as 2.6 individuals need to be screened to identify one case at a cost of £133 per case detected. If the genetic mutation was known within the family then the cost per life year gained (£4914) was only slightly increased by genetic confirmation of the diagnosis. Universal population screening was least cost effective (£13 029 per life year gained) as 1365 individuals need to be screened at a cost of £9754 per case detected. For each strategy it was more cost effective to screen younger people and women. Targeted strategies were more expensive per person screened, but the cost per case detected was lower. Population screening of 16 year olds only was as cost effective as family tracing (£2777 with a clinical confirmation). Conclusions Screening family members of people with familial hypercholesterolaemia is the most cost effective option for detecting cases across the whole population

1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine

Intestinal absorption of phosphate is stimulated by 1,25(OH)2 vitamin D3. At least two distinct mechanisms underlie phosphate absorption in the gut, an active transcellular transport requiring the Na+/phosphate cotransporter NaPi‐IIb/Slc34a2, and a poorly characterized paracellular passive pathway. 1,25(OH)2 vitamin D3 stimulates NaPi‐IIb expression and function, and loss of NaPi‐IIb reduces intestinal phosphate absorption. However, it is remains unknown whether NaPi‐IIb is the only target for hormonal regulation by 1,25(OH)2 vitamin D3. Here we compared the effects of intraperitoneal administration of 1,25(OH)2 vitamin D3 (2 days, once per day) in wild‐type and intestinal‐specific Slc34a2‐deficient mice, and analysed trans‐ vs. paracellular routes of phosphate absorption. We found that treatment stimulated active transport of phosphate only in jejunum of wild‐type mice, though NaPi‐IIb protein expression was upregulated in jejunum and ileum. In contrast, 1,25(OH)2 vitamin D3 administration had no effect in Slc34a2‐deficient mice, suggesting that the hormone specifically regulates NaPi‐IIb expression. In both groups, 1,25(OH)2 vitamin D3 elicited the expected increase of plasma fibroblast growth factor 23 (FGF23) and reduction of parathyroid hormone (PTH). Treatment resulted in hyperphosphaturia (and hypercalciuria) in both genotypes, though mice remained normophosphataemic. While increased intestinal absorption and higher FGF23 can trigger the hyperphosphaturic response in wild types, only higher FGF23 can explain the renal response in Slc34a2‐deficient mice. Thus, 1,25(OH)2 vitamin D3 stimulates intestinal phosphate absorption by acting on the active transcellular pathway mostly mediated by NaPi‐IIb while the paracellular pathway appears not to be affected

Is the distant globular cluster Pal 14 in a deep-freeze?

We investigate the velocity dispersion of Pal 14, an outer Milky-Way globular cluster at Galactocentric distance of 71 kpc with a very low stellar density (central density 0.1-0.2 Msun/pc^3). Due to this low stellar density the binary population of Pal 14 is likely to be close to the primordial binary population. Artificial clusters are generated with the observed properties of Pal 14 and the velocity dispersion within these clusters is measured as Jordi et al. (2009) have done with 17 observed stars of Pal 14. We discuss the effect of the binary population on these measurements and find that the small velocity dispersion of 0.38 km/s which has been found by Jordi et al. (2009) would imply a binary fraction of less than 0.1, even though from the stellar density of Pal 14 we would expect a binary fraction of more than 0.5. We also discuss the effect of mass segregation on the velocity dispersion as possible explanation for this discrepancy, but find that it would increase the velocity dispersion further. Thus, either Pal 14 has a very unusual stellar population and its birth process was significantly different than we see in today's star forming regions, or the binary population is regular and we would have to correct the observed 0.38 km/s for binarity. In this case the true velocity dispersion of Pal 14 would be much smaller than this value and the cluster would have to be considered as "kinematically frigid", thereby possibly posing a challenge for Newtonian dynamics but in the opposite sense to MOND.Comment: 8 pages, 4 figures, accepted for publication in Ap

The water consumption of energy production: an international comparison

Producing energy resources requires significant quantities of fresh water. As an energy sector changes or expands, the mix of technologies deployed to produce fuels and electricity determines the associated burden on regional water resources. Many reports have identified the water consumption of various energy production technologies. This paper synthesizes and expands upon this previous work by exploring the geographic distribution of water use by national energy portfolios. By defining and calculating an indicator to compare the water consumption of energy production for over 150 countries, we estimate that approximately 52 billion cubic meters of fresh water is consumed annually for global energy production. Further, in consolidating the data, it became clear that both the quality of the data and global reporting standards should be improved to track this important variable at the global scale. By introducing a consistent indicator to empirically assess coupled water–energy systems, it is hoped that this research will provide greater visibility into the magnitude of water use for energy production at the national and global scales

Traps of multi-level governance. Lessons from the implementation of the Water Framework Directive in Italy

During recent decades, different patterns of multi-level governance (MLG) have spread across Europe as a consequence of Europeanisation of public policies, which have increasingly adopted decentralized and participatory procedures conceived as a tool of more effective and accountable policy-making. It appears, however, that the implementation of operational designs based on MLG may be rather problematic and it does not necessarily bring to the expected performance improvements. Referring to the case of the EU Water Framework Directive (2000/60/EC), which conceives the creation of new multi-level institutional settings as a key tool for enacting a new holistic approach to water management and protection, this article explores the difficulties that the implementation of such settings has brought in Italy, despite some favorable pre-conditions existing in the country. Evidence is provided that along with institutional and agency variables, the implementation effectiveness of MLG arrangements promoted by the EU can be challenged by their inherent characteristics

Multiple metrics for quantifying the intensity of water consumption of energy production

Discussion of the environmental implications of worldwide energy demand is currently dominated by the effects of carbon dioxide (CO[subscript 2]) emissions on global climate. At the regional scale, however, water resource challenges associated with energy systems are a growing concern. This paper, based on an inventory of national energy portfolios, posits an indicator-based framework for characterizing regional energy portfolios' relative water intensity. These calculations extend upon a previous paper that established a method for calculating the national water consumption of energy production (WCEP) at the global level. Intensity indicators are based on normalizing the WCEP results with a set of additional indicators (including population, gross domestic product, total energy production, and regional water availability). The results show great variability in water consumption across nations, as well as across the various water intensity measures that were applied. Therefore, it is best to apply this full suite of indicators to each country to develop an integrated understanding of the intensity of water use for energy across countries

Ab-initio theory of NMR chemical shifts in solids and liquids

We present a theory for the ab-initio computation of NMR chemical shifts (sigma) in condensed matter systems, using periodic boundary conditions. Our approach can be applied to periodic systems such as crystals, surfaces, or polymers and, with a super-cell technique, to non-periodic systems such as amorphous materials, liquids, or solids with defects. We have computed the hydrogen sigma for a set of free molecules, for an ionic crystal, LiH, and for a H-bonded crystal, HF, using density functional theory in the local density approximation. The results are in excellent agreement with experimental data.Comment: to appear in Physical Review Letter

Vegetation and Topographic Control of Wind-blown Snow Distributions in Distributed and Aggregated Simulations for an Arctic Tundra Basin

In the Pacific Northwest (PNW), concern about the impacts of climate and land cover change on water resources and flood-generating processes emphasizes the need for a mechanistic understanding of the interactions between forest canopies and hydrologic processes. Detailed measurements during the 1999 and 2000 hydrologic years were used to modify the Simultaneous Heat and Water (SHAW) model for application in forested systems. Major changes to the model include improved representation of rainfall interception and stomatal conductance dynamics. The model was developed for the 1999 hydrologic year and tested for the 2000 hydrologic year without modification of the site parameters. The model effectively simulated throughfall, soil water content profiles, and shallow soil temperatures for both years. The largest discrepancies between soil moisture and temperature were observed during periods of discontinuous snow cover due to spatial variability that was not explicitly simulated by the model. Soil warming at bare locations was delayed until most of the snow cover ablated because of the large heat sink associated with the residual snow patches. During the summer, simulated transpiration decreased from a maximum monthly mean of 2.2 mm day⁻¹ in July to 1.3 mm day⁻¹ in September as a result of decreasing soil moisture and declining net radiation. The results indicate that a relatively simple representation of the vegetation canopy can accurately simulate seasonal hydrologic fluxes in this environment, except during periods of discontinuous snow cover

An efficient Fredholm method for calculation of highly excited states of billiards

A numerically efficient Fredholm formulation of the billiard problem is presented. The standard solution in the framework of the boundary integral method in terms of a search for roots of a secular determinant is reviewed first. We next reformulate the singularity condition in terms of a flow in the space of an auxiliary one-parameter family of eigenproblems and argue that the eigenvalues and eigenfunctions are analytic functions within a certain domain. Based on this analytic behavior we present a numerical algorithm to compute a range of billiard eigenvalues and associated eigenvectors by only two diagonalizations.Comment: 15 pages, 10 figures; included systematic study of accuracy with 2 new figures, movie to Fig. 4, http://www.quantumchaos.de/Media/0703030media.av

A Mixed-Methods Evaluation of a Community-Based Glaucoma Check Service in Hackney, London, UK.

: To evaluate the uptake, feasibility and acceptability of a general practice-based optometrist-led glaucoma check service. The service targeted people of black Caribbean and black African descent aged 40-65 years, resident in Hackney, London, United Kingdom. : The study used a mixed-method design, including analysis of service data, prospective audit of secondary care referrals patient survey, cost-consequence analysis, and interviews with staff involved in developing and implementing the service. : A total of 3040 patients were invited to undergo the free check; 595 (19.6%) booked an appointment and 461 (15.2%) attended. Overall, 31 patients (6.8%) were referred to secondary care, of whom 22 attended and were assessed for glaucoma. Four were diagnosed with glaucoma and eight with suspected glaucoma, i.e. 2.6% of patients who underwent the check. The cost per patient identified with suspected or confirmed glaucoma was £9,013. Staff who were interviewed suggested that patients who attended might be those who routinely attended optometrist appointments, however only 62.4% of survey respondents reported having had an eye examination in the previous two years, and 11.4% of women and 16.0% of men reported never having had an eye examination. : This study represents one possible configuration for a glaucoma case-finding service, and it contributes to a wider debate about whether screening, targeted or otherwise, should be offered in the UK. Our findings suggest that general practice is an acceptable setting and that such a service may reach some people not previously engaged with primary eye care services.<br/