Designing implementation strategies to improve identification, cascade testing, and management of families with familial hypercholesterolemia: An intervention mapping approach

INTRODUCTION: Familial hypercholesterolemia (FH) is a common inherited cholesterol disorder that, without early intervention, leads to premature cardiovascular disease. Multilevel strategies that target all components of FH care including identification, cascade testing, and management are needed to address gaps that exist in FH care. We utilized intervention mapping, a systematic implementation science approach, to identify and match strategies to existing barriers and develop programs to improve FH care. METHODS: Data were collected utilizing two methods: a scoping review of published literature, related to any component of FH care, and a parallel mixed method study using interviews and surveys. The scientific literature was searched using key words including barriers or facilitators and familial hypercholesterolemia from inception to December 1, 2021. The parallel mixed method study recruited individuals and families with FH to participate in either dyadic interviews ( RESULTS: In steps 1-3, a needs assessment found barriers to FH care included underdiagnosis of the condition which led to suboptimal management due to a myriad of determinants including knowledge gaps, negative attitudes, and risk misperceptions by individuals with FH and clinicians. Literature review highlighted barriers to FH care at the health system level, notably the relative lack of genetic testing resources and infrastructure needed to support FH diagnosis and treatment. Examples of strategies to overcome identified barriers included development of multidisciplinary care teams and educational programs. In steps 4-6, an NHLBI-funded study, the Collaborative Approach to Reach Everyone with FH (CARE-FH), deployed strategies that focused on improving identification of FH in primary care settings. The CARE-FH study is used as an example to describe program development, implementation, and evaluation techniques of implementation strategies. CONCLUSION: The development and deployment of evidence-based implementation strategies that address barriers to FH care are important next steps to improve identification, cascade testing, and management

Predictions in SU(5) Supergravity Grand Unification with Proton Stability and Relic Density Constraints

It is shown that in the physically interesting domain of the parameter space of SU(5) supergravity GUT, the Higgs and the Z poles dominate the LSP annihilation. Here the naive analyses on thermal averaging breaks down and formulae are derived which give a rigorous treatment over the poles. These results are then used to show that there exist significant domains in the parameter space where the constraints of proton stability and cosmology are simultaneously satisfied. New upper limits on light particle masses are obtained.Comment: (An error in the reheating factor is corrected, strengthening the conclusions, i.e. the region in parameter space where the relic density constraints are satisfied is enlarged.

Implementation strategies to improve statin utilization in individuals with hypercholesterolemia: A systematic review and meta-analysis

BACKGROUND: Numerous implementation strategies to improve utilization of statins in patients with hypercholesterolemia have been utilized, with varying degrees of success. The aim of this systematic review is to determine the state of evidence of implementation strategies on the uptake of statins. METHODS AND RESULTS: This systematic review identified and categorized implementation strategies, according to the Expert Recommendations for Implementing Change (ERIC) compilation, used in studies to improve statin use. We searched Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov from inception to October 2018. All included studies were reported in English and had at least one strategy to promote statin uptake that could be categorized using the ERIC compilation. Data extraction was completed independently, in duplicate, and disagreements were resolved by consensus. We extracted LDL-C (concentration and target achievement), statin prescribing, and statin adherence (percentage and target achievement). A total of 258 strategies were used across 86 trials. The median number of strategies used was 3 (SD 2.2, range 1-13). Implementation strategy descriptions often did not include key defining characteristics: temporality was reported in 59%, dose in 52%, affected outcome in 9%, and justification in 6%. Thirty-one trials reported at least 1 of the 3 outcomes of interest: significantly reduced LDL-C (standardized mean difference [SMD] - 0.17, 95% CI - 0.27 to - 0.07, p = 0.0006; odds ratio [OR] 1.33, 95% CI 1.13 to 1.58, p = 0.0008), increased rates of statin prescribing (OR 2.21, 95% CI 1.60 to 3.06, p \u3c 0.0001), and improved statin adherence (SMD 0.13, 95% CI 0.06 to 0.19; p = 0.0002; OR 1.30, 95% CI 1.04 to 1.63, p = 0.023). The number of implementation strategies used per study positively influenced the efficacy outcomes. CONCLUSION: Although studies demonstrated improved statin prescribing, statin adherence, and reduced LDL-C, no single strategy or group of strategies consistently improved outcomes. TRIAL REGISTRATION: PROSPERO CRD42018114952

Supercollider Signatures of Supergravity Models with Yukawa Unification

We study the predictions of the simplest SU(5) grand unified model within the framework of minimal supergravity, including constraints from the radiative breaking of electroweak symmetry. As a consequence of the unification of the $b$-quark and $\tau$-lepton Yukawa couplings, the top quark mass is predicted to be close to its fixed point value. We delineate the regions of the supergravity parameter space allowed by constraints from the non-observation of proton decay and from the requirement that the LSP does not overclose the universe. These constraints lead to a definite pattern of sparticle masses: the feature unique to Yukawa unified models is that some of the third generation squarks are much lighter than those of the first two generations. Despite the fact that all sparticle masses and mixings are determined by just four SUSY parameters at the GUT scale (in addition to $m_t$), we find that the signals for sparticle production can vary substantially over the allowed parameter space. We identify six representative scenarios and study the signals from sparticle production at the LHC. We find that by studying the signal in various channels, these scenarios may be distinguished from one another, and also from usually studied ``minimal models'' where squarks and sleptons are taken to be degenerate. In particular, our studies allow us to infer that some third generation squarks are lighter than other squarks---a feature that could provide the first direct evidence of supergravity grand unification.Comment: 28 pages Revtex files with 5 PS figures available from [email protected], Preprint nos. FSU-HEP-940311, KEK-TH-392, MAD/PH/825, UH-511-785-9

Pleural Mesothelioma in New Caledonia: Associations with Environmental Risk Factors

International audienceBackground: High incidences of malignant mesothelioma (MM) have been observed in New Caledonia. Previous work has shown an association between MM and soil containing serpentinite. Objectives: We studied the spatial and temporal variation of MM and its association with environmental factors. Methods: We investigated the 109 MM cases recorded in the Cancer Registry of New Caledonia between 1984 and 2008 and performed spatial, temporal, and space-time cluster analyses. We conducted an ecological analysis involving 100 tribes over a large area including those with the highest incidence rates. Associations with environmental factors were assessed using logistic and Poisson regression analyses. Results: The highest incidence was observed in the Houaïlou area with a world age-standardized rate of 128.7 per 100,000 person-years [95% confidence interval (CI), 70.41-137.84]. A significant spatial cluster grouped 18 tribes (31 observed cases vs. 8 expected cases; p = 0.001), but no significant temporal clusters were identified. The ecological analyses identified serpentinite on roads as the greatest environmental risk factor (odds ratio = 495.0; 95% CI, 46.2-4679.7; multivariate incidence rate ratio = 13.0; 95% CI, 10.2-16.6). The risk increased with serpentinite surface, proximity to serpentinite quarries and distance to the peridotite massif. The association with serpentines was stronger than with amphiboles. Living on a slope and close to dense vegetation appeared protective. The use of whitewash, previously suggested to be a risk factor, was not associated with MM incidence. Conclusions: Presence of serpentinite on roads is a major environmental risk factor for mesothelioma in New Caledonia

Biases in the perceived timing of perisaccadic perceptual and motor events

Subjects typically experience the temporal interval immediately following a saccade as longer than a comparable control interval. One explanation of this effect is that the brain antedates the perceptual onset of a saccade target to around the time of saccade initiation. This could explain the apparent continuity of visual perception across eye movements. Thisantedating account was tested in three experiments in which subjects made saccades of differing extents and then judged either the duration or the temporal order of key events. Postsaccadic stimuli underwent subjective temporal lengthening and had early perceived onsets. A temporally advanced awareness of saccade completion was also found, independently of antedating effects. These results provide convergent evidence supporting antedating and differentiating it from other temporal biases

Anomaly-Free Gauged R-Symmetry

We review the gauging of an R-symmetry in local and global susy. We then construct the first anomaly-free models. We break the R-symmetry and susy at the Planck scale and discuss the low-energy effects. We include a solution to the mu-problem, and the prediction of observable effects at HERA. The models also nicely allow for GUT-scale baryogenesis and R-parity violation without the sphaleron interactions erasing the baryon-asymmetry.Comment: 6 pages, latex, no figures. Talk presented at SUSY-95. Work done in collaboration with A. Chamseddin

The Neutralino Relic Density in Minimal N=1 Supergravity

We compute the cosmic relic (dark matter) density of the lightest supersymmetric particle (LSP) in the framework of minimal $N=1$ Supergravity models with radiative breaking of the electroweak gauge symmetry. To this end, we re--calculate the cross sections for all possible annihilation processes for a general, mixed neutralino state with arbitrary mass. Our analysis includes effects of all Yukawa couplings of third generation fermions, and allows for a fairly general set of soft SUSY breaking parameters at the Planck scale. We find that a cosmologically interesting relic density emerges naturally over wide regions of parameter space. However, the requirement that relic neutralinos do not overclose the universe does not lead to upper bounds on SUSY breaking parameters that are strictly valid for all combinations of parameters and of interest for existing or planned collider experiments; in particular, gluino and squark masses in excess of 5 TeV cannot strictly be excluded. On the other hand, in the ``generic'' case of a gaugino--like neutralino whose annihilation cross sections are not ``accidentally'' enhanced by a nearby Higgs or $Z$ pole, all sparticles should lie within the reach of the proposed $pp$ and $e^+e^-$ supercolliders. We also find that requiring the LSP to provide all dark matter predicted by inflationary models imposes a strict lower bound of 40 GeV on the common scalar mass $m$ at the Planck scale, while the lightest sleptons would have to be heavierComment: 53 pages(8figs are not included), Latex file; DESY 92-101, SLAC-PUB-586

Leptonic CP Violation in Supersymmetric Standard Model

We point out the possibility of spontaneous and hard CP-violation in the scalar potential of R-parity broken supersymmetric Standard Model. The existence of spontaneous CP-violation depends crucially on the R-parity breaking terms in the superpotential and, in addition, on the choice of the soft supersymmetry breaking terms. Unlike in theories with R-parity conservation, it is natural, in the context of the present model, for the sneutrinos to acquire (complex) vacuum expectation values. In the context of this model we examine here the global implications, like the strength of the CP-violating interactions and the neutrino masses.Comment: REVTEX, 15 page