WIMP-nucleus scattering in chiral effective theory

We discuss long-distance QCD corrections to the WIMP-nucleon(s) interactions in the framework of chiral effective theory. For scalar-mediated WIMP-quark interactions, we calculate all the next-to-leading-order corrections to the WIMP-nucleus elastic cross-section, including two-nucleon amplitudes and recoil-energy dependent shifts to the single-nucleon scalar form factors. As a consequence, the scalar-mediated WIMP-nucleus cross-section cannot be parameterized in terms of just two quantities, namely the neutron and proton scalar form factors at zero momentum transfer, but additional parameters appear, depending on the short-distance WIMP-quark interaction. Moreover, multiplicative factorization of the cross-section into particle, nuclear and astro-particle parts is violated. In practice, while the new effects are of the natural size expected by chiral power counting, they become very important in those regions of parameter space where the leading order WIMP-nucleus amplitude is suppressed, including the so-called "isospin-violating dark matter" regime. In these regions of parameter space we find order-of-magnitude corrections to the total scattering rates and qualitative changes to the shape of recoil spectra.Comment: 23 pages, 6 figures, 1 tabl

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Magnetic Fluffy Dark Matter

We explore extensions of inelastic Dark Matter and Magnetic inelastic Dark Matter where the WIMP can scatter to a tower of heavier states. We assume a WIMP mass $m_\chi \sim \mathcal{O}(1-100)$ GeV and a constant splitting between successive states $\delta \sim\mathcal{O}(1 - 100)$ keV. For the spin-independent scattering scenario we find that the direct experiments CDMS and XENON strongly constrain most of the DAMA/LIBRA preferred parameter space, while for WIMPs that interact with nuclei via their magnetic moment a region of parameter space corresponding to $m_{\chi}\sim 11$ GeV and $\delta < 15$ keV is allowed by all the present direct detection constraints.Comment: 16 pages, 6 figures, added comments about magnetic moment form factor to Sec 3.1.2 and results to Sec 3.2.2, final version to be published in JHE

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

Signatures of large composite Dark Matter states

We investigate the interactions of large composite dark matter (DM) states with the Standard Model (SM) sector. Elastic scattering with SM nuclei can be coherently enhanced by factors as large as A^2, where A is the number of constituents in the composite state (there exist models in which DM states of very large A > 10^8 may be realised). This enhancement, for a given direct detection event rate, weakens the expected signals at colliders by up to 1/A. Moreover, the spatially extended nature of the DM states leads to an additional, characteristic, form factor modifying the momentum dependence of scattering processes, altering the recoil energy spectra in direct detection experiments. In particular, energy recoil spectra with peaks and troughs are possible, and such features could be confirmed with only O(50) events, independently of the assumed halo velocity distribution. Large composite states also generically give rise to low-energy collective excitations potentially relevant to direct detection and indirect detection phenomenology. We compute the form factor for a generic class of such excitations - quantised surface modes - finding that they can lead to coherently-enhanced, but generally sub-dominant, inelastic scattering in direct detection experiments. Finally, we study the modifications to capture rates in astrophysical objects that follow from the elastic form factor, as well as the effects of inelastic interactions between DM states once captured. We argue that inelastic interactions may lead to the DM collapsing to a dense configuration at the centre of the object.Comment: 30 pages, 5 figures, v2; references and minor additional comments adde

A metabolomics cell-based approach for anticipating and investigating drug-induced liver injury

In preclinical stages of drug development, anticipating potential adverse drug effects such as toxicity is an important issue for both saving resources and preventing public health risks. Current in vitro cytotoxicity tests are restricted by their predictive potential and their ability to provide mechanistic information. This study aimed to develop a metabolomic mass spectrometry-based approach for the detection and classification of drug-induced hepatotoxicity. To this end, the metabolite profiles of human derived hepatic cells (i.e., HepG2) exposed to different well-known hepatotoxic compounds acting through different mechanisms (i.e., oxidative stress, steatosis, phospholipidosis, and controls) were compared by multivariate data analysis, thus allowing us to decipher both common and mechanism-specific altered biochemical pathways. Briefly, oxidative stress damage markers were found in the three mechanisms, mainly showing altered levels of metabolites associated with glutathione and γ-glutamyl cycle. Phospholipidosis was characterized by a decreased lysophospholipids to phospholipids ratio, suggestive of phospholipid degradation inhibition. Whereas, steatosis led to impaired fatty acids β-oxidation and a subsequent increase in triacylglycerides synthesis. The characteristic metabolomic profiles were used to develop a predictive model aimed not only to discriminate between non-toxic and hepatotoxic drugs, but also to propose potential drug toxicity mechanism(s)

Reduced Serotonin Reuptake Transporter (SERT) Function Causes Insulin Resistance and Hepatic Steatosis Independent of Food Intake

Serotonin reuptake transporter (SERT) is a key regulator of serotonin neurotransmission and a major target of antidepressants. Antidepressants, such as selectively serotonin reuptake inhibitors (SSRIs), that block SERT function are known to affect food intake and body weight. Here, we provide genetic evidence that food intake and metabolism are regulated by separable mechanisms of SERT function. SERT-deficient mice ate less during both normal diet and high fat diet feeding. The reduced food intake was accompanied with markedly elevated plasma leptin levels. Despite reduced food intake, SERT-deficient mice exhibited glucose intolerance and insulin resistance, and progressively developed obesity and hepatic steatosis. Several lines of evidence indicate that the metabolic deficits of SERT-deficient mice are attributable to reduced insulin-sensitivity in peripheral tissues. First, SERT-deficient mice exhibited beta-cell hyperplasia and islet-mass expansion. Second, biochemical analyses revealed constitutively elevated JNK activity and diminished insulin-induced AKT activation in the liver of SERT-deficient mice. SERT-deficient mice exhibited hyper-JNK activity and hyperinsulinemia prior to the development of obesity. Third, enhancing AKT signaling by PTEN deficiency corrected glucose tolerance in SERT-deficient mice. These findings have potential implications for designing selective SERT drugs for weight control and the treatment of metabolic syndromes

Oral bisphosphonate compliance and persistence: a matter of choice?

Compliance to oral bisphosphonates is suboptimal, with negative consequences of increased healthcare utilization and less effective fracture risk reduction. Extending dose interval increased adherence only moderately. We used literature derived from multiple chronic conditions to examine the problem of noncompliance with osteoporosis medication. We reviewed the literature on adherence to osteoporosis medication as well as that across multiple chronic conditions to understand what is known about the cause of the poor adherence. Poor compliance to oral medications is due mostly, not to forgetfulness, but to deliberate choice. Gender differences and style of healthcare management also play a role. Preliminary data suggest psychobehavioral interventions may help to improve motivation. We need to understand better reasons for poor compliance before effective interventions can be developed. Forgetfulness is only a small part of poor compliance. Patient preferences must be considered in medication decision making

Can computerized clinical decision support systems improve practitioners' diagnostic test ordering behavior? A decision-maker-researcher partnership systematic review

<p>Abstract</p> <p>Background</p> <p>Underuse and overuse of diagnostic tests have important implications for health outcomes and costs. Decision support technology purports to optimize the use of diagnostic tests in clinical practice. The objective of this review was to assess whether computerized clinical decision support systems (CCDSSs) are effective at improving ordering of tests for diagnosis, monitoring of disease, or monitoring of treatment. The outcome of interest was effect on the diagnostic test-ordering behavior of practitioners.</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews database, Inspec, and reference lists for eligible articles published up to January 2010. We included randomized controlled trials comparing the use of CCDSSs to usual practice or non-CCDSS controls in clinical care settings. Trials were eligible if at least one component of the CCDSS gave suggestions for ordering or performing a diagnostic procedure. We considered studies 'positive' if they showed a statistically significant improvement in at least 50% of test ordering outcomes.</p> <p>Results</p> <p>Thirty-five studies were identified, with significantly higher methodological quality in those published after the year 2000 (<it>p </it>= 0.002). Thirty-three trials reported evaluable data on diagnostic test ordering, and 55% (18/33) of CCDSSs improved testing behavior overall, including 83% (5/6) for diagnosis, 63% (5/8) for treatment monitoring, 35% (6/17) for disease monitoring, and 100% (3/3) for other purposes. Four of the systems explicitly attempted to reduce test ordering rates and all succeeded. Factors of particular interest to decision makers include costs, user satisfaction, and impact on workflow but were rarely investigated or reported.</p> <p>Conclusions</p> <p>Some CCDSSs can modify practitioner test-ordering behavior. To better inform development and implementation efforts, studies should describe in more detail potentially important factors such as system design, user interface, local context, implementation strategy, and evaluate impact on user satisfaction and workflow, costs, and unintended consequences.</p

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