The Cosmology of Composite Inelastic Dark Matter

Composite dark matter is a natural setting for implementing inelastic dark matter - the O(100 keV) mass splitting arises from spin-spin interactions of constituent fermions. In models where the constituents are charged under an axial U(1) gauge symmetry that also couples to the Standard Model quarks, dark matter scatters inelastically off Standard Model nuclei and can explain the DAMA/LIBRA annual modulation signal. This article describes the early Universe cosmology of a minimal implementation of a composite inelastic dark matter model where the dark matter is a meson composed of a light and a heavy quark. The synthesis of the constituent quarks into dark mesons and baryons results in several qualitatively different configurations of the resulting dark matter hadrons depending on the relative mass scales in the system.Comment: 31 pages, 4 figures; references added, typos correcte

Interventions designed to improve the quality and efficiency of medication use in managed care: A critical review of the literature – 2001–2007

<p>Abstract</p> <p>Background</p> <p>Managed care organizations use a variety of strategies to reduce the cost and improve the quality of medication use. The effectiveness of such policies is not well understood. The objective of this research was to update a previous systematic review of interventions, published between 1966 and 2001, to improve the quality and efficiency of medication use in the US managed care setting.</p> <p>Methods</p> <p>We searched MEDLINE and EMBASE for publications from July 2001 to January 2007 describing interventions targeting drug use conducted in the US managed care setting. We categorized studies by intervention type and adequacy of research design using commonly accepted criteria. We summarized the outcomes of well-controlled strategies and documented the significance and magnitude of effects for key study outcomes.</p> <p>Results</p> <p>We identified 164 papers published during the six-year period. Predominant strategies were: educational interventions (n = 20, including dissemination of educational materials, and group or one-to-one educational outreach); monitoring and feedback (n = 22, including audit/feedback and computerized monitoring); formulary interventions (n = 66, including tiered formulary and patient copayment); collaborative care involving pharmacists (n = 15); and disease management with pharmacotherapy as a primary focus (n = 41, including care for depression, asthma, and peptic ulcer disease). Overall, 51 studies met minimum criteria for methodological adequacy. Effective interventions included one-to-one academic detailing, computerized alerts and reminders, pharmacist-led collaborative care, and multifaceted disease management. Further, changes in formulary tier-design and related increases in copayments were associated with reductions in medication use and increased out-of-pocket spending by patients. The dissemination of educational materials alone had little or no impact, while the impact of group education was inconclusive.</p> <p>Conclusion</p> <p>There is good evidence for the effectiveness of several strategies in changing drug use in the managed care environment. However, little is known about the cost-effectiveness of these interventions. Computerized alerts showed promise in improving short-term outcomes but little is known about longer-term outcomes. Few well-designed, published studies have assessed the potential negative clinical effects of formulary-related interventions despite their widespread use. However, some evidence suggests increases in cost sharing reduce access to essential medicines for chronic illness.</p

Provider payments and patient charges as policy tools for cost-containment: How successful are they in high-income countries?

In this paper, we focus on those policy instruments with monetary incentives that are used to contain public health expenditure in high-income countries. First, a schematic view of the main cost-containment methods and the variables in the health system they intend to influence is presented. Two types of instruments to control the level and growth of public health expenditure are considered: (i) provider payment methods that influence the price and quantity of health care, and (ii) cost-containment measures that influence the behaviour of patients. Belonging to the first type of instruments, we have: fee-for-service, per diem payment, case payment, capitation, salaries and budgets. The second type of instruments consists of patient charges and reference price systems for pharmaceuticals. Secondly, we provide an overview of experience in high-income countries that use or have used these particular instruments. Finally, the paper assesses the overall potential of these instruments in cost-containment policies

The different stratospheric influence on cold-extremes in Eurasia and North America

The stratospheric polar vortex can influence the tropospheric circulation and thereby winter weather in the mid-latitudes. Weak vortex states, often associated with sudden stratospheric warmings (SSW), have been shown to increase the risk of cold-spells especially over Eurasia, but its role for North American winters is less clear. Using cluster analysis, we show that there are two dominant patterns of increased polar cap heights in the lower stratosphere. Both patterns represent a weak polar vortex but they are associated with different wave mechanisms and different regional tropospheric impacts. The first pattern is zonally symmetric and associated with absorbed upward-propagating wave activity, leading to a negative phase of the North Atlantic Oscillation (NAO) and cold-air outbreaks over northern Eurasia. This coupling mechanism is well-documented in the literature and is consistent with the downward migration of the northern annular mode (NAM). The second pattern is zonally asymmetric and linked to downward reflected planetary waves over Canada followed by a negative phase of the Western Pacific Oscillation (WPO) and cold-spells in Central Canada and the Great Lakes region. Causal effect network (CEN) analyses confirm the atmospheric pathways associated with this asymmetric pattern. Moreover, our findings suggest the reflective mechanism to be sensitive to the exact region of upward wave-activity fluxes and to be state-dependent on the strength of the vortex. Identifying the causal pathways that operate on weekly to monthly timescales can pave the way for improved sub-seasonal to seasonal forecasting of cold spells in the mid-latitudes

Dark Matter in 3D

We discuss the relevance of directional detection experiments in the post-discovery era and propose a method to extract the local dark matter phase space distribution from directional data. The first feature of this method is a parameterization of the dark matter distribution function in terms of integrals of motion, which can be analytically extended to infer properties of the global distribution if certain equilibrium conditions hold. The second feature of our method is a decomposition of the distribution function in moments of a model independent basis, with minimal reliance on the ansatz for its functional form. We illustrate our method using the Via Lactea II N-body simulation as well as an analytical model for the dark matter halo. We conclude that O(1000) events are necessary to measure deviations from the Standard Halo Model and constrain or measure the presence of anisotropies.Comment: 36 pages, 13 figure

Computerized clinical decision support systems for drug prescribing and management: A decision-maker-researcher partnership systematic review

<p>Abstract</p> <p>Background</p> <p>Computerized clinical decision support systems (CCDSSs) for drug therapy management are designed to promote safe and effective medication use. Evidence documenting the effectiveness of CCDSSs for improving drug therapy is necessary for informed adoption decisions. The objective of this review was to systematically review randomized controlled trials assessing the effects of CCDSSs for drug therapy management on process of care and patient outcomes. We also sought to identify system and study characteristics that predicted benefit.</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. We updated our earlier reviews (1998, 2005) by searching MEDLINE, EMBASE, EBM Reviews, Inspec, and other databases, and consulting reference lists through January 2010. Authors of 82% of included studies confirmed or supplemented extracted data. We included only randomized controlled trials that evaluated the effect on process of care or patient outcomes of a CCDSS for drug therapy management compared to care provided without a CCDSS. A study was considered to have a positive effect (<it>i.e.</it>, CCDSS showed improvement) if at least 50% of the relevant study outcomes were statistically significantly positive.</p> <p>Results</p> <p>Sixty-five studies met our inclusion criteria, including 41 new studies since our previous review. Methodological quality was generally high and unchanged with time. CCDSSs improved process of care performance in 37 of the 59 studies assessing this type of outcome (64%, 57% of all studies). Twenty-nine trials assessed patient outcomes, of which six trials (21%, 9% of all trials) reported improvements.</p> <p>Conclusions</p> <p>CCDSSs inconsistently improved process of care measures and seldomly improved patient outcomes. Lack of clear patient benefit and lack of data on harms and costs preclude a recommendation to adopt CCDSSs for drug therapy management.</p

Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However, its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of early, diet-related, liver injury and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE−/−) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r = 0.520, p < 0.0001). Conclusion: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted. Keywords: Non-alcoholic fatty liver disease, Glyoxalase, Methylglyoxal, Proteomics, iTRA