This contemporary, international, evidence-informed guidance aims to achieve the greatest good for the greatest number of people with familial hypercholesterolaemia (FH) across different countries. ...FH, a family of monogenic defects in the hepatic LDL clearance pathway, is a preventable cause of premature coronary artery disease and death. Worldwide, 35 million people have FH, but most remain undiagnosed or undertreated. Current FH care is guided by a useful and diverse group of evidence-based guidelines, with some primarily directed at cholesterol management and some that are country-specific. However, none of these guidelines provides a comprehensive overview of FH care that includes both the lifelong components of clinical practice and strategies for implementation. Therefore, a group of international experts systematically developed this guidance to compile clinical strategies from existing evidence-based guidelines for the detection (screening, diagnosis, genetic testing and counselling) and management (risk stratification, treatment of adults or children with heterozygous or homozygous FH, therapy during pregnancy and use of apheresis) of patients with FH, update evidence-informed clinical recommendations, and develop and integrate consensus-based implementation strategies at the patient, provider and health-care system levels, with the aim of maximizing the potential benefit for at-risk patients and their families worldwide.
Abstract
We demonstrate the determination of anharmonic acoustic phonon properties via second-order Raman scattering exemplarily on copper iodide single crystals. The origin of multi-phonon features ...from the second-order Raman spectra was assigned by the support of the calculated 2-phonon density of states. In this way, the temperature dependence of acoustic phonons was determined down to 10 K. To determine independently the harmonic contributions of respective acoustic phonons, density functional theory in quasi-harmonic approximation was used. Finally, the anharmonic contributions were determined. The results are in agreement with earlier publications and extend CuI’s determined acoustic phonon properties to lower temperatures with higher accuracy. This approach demonstrates that it is possible to characterize the acoustic anharmonicities via Raman scattering down to zero-temperature renormalization constants of at least 0.1 cm
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Familial hypercholesterolemia (FH) is an inherited lipid disorder that confers high risk for premature cardiovascular disease but remains undertreated. Causes are multifactorial and multilevel, ...ranging from underprescribing (at the clinician-level) to medication nonadherence (at the patient-level). We evaluated patient and clinician stakeholder barriers and facilitators for treatment of FH to explore possible solutions to the problem.
Semi-structured interviews and focus groups guided by the Practical, Robust, Implementation and Sustainability Model (PRISM), were conducted with 33 patients and 17 clinician stakeholders across three healthcare systems. A total of14 patients and 9 clinician stakeholders participated in on-site focus groups and the remainder were individual interviews. Transcripts were coded using an iterative process to create a static codebook. We characterized patient and clinician stakeholder barriers into three categories: medical care-, medication-, and life-related. Feasibility of brainstormed solutions varied and was not always representative of the needs of all stakeholders. Patients suggested a need for childhood screening for FH and doctors being persistent about the importance of treating FH, creation of a patient peer group, data transparency, advocacy, and policy changes that would enable patients to receive better treatment. Clinician stakeholders suggested the need for clinical champions. Both groups of stakeholders discussed the need for education about FH.
Proposed solutions to improve treatment of FH proffered by participants in this study included resources for both patients and clinician stakeholders that clarify cardiovascular disease risks from FH, develop programs to screen for and identify FH at younger ages, and foster open conversations between patients and clinicians about treatment.
Circulating tumor cells (CTCs) and circulating clusters of cancer and stromal cells have been identified in the blood of patients with malignant cancer and can be used as a diagnostic for disease ...severity, assess the efficacy of different treatment strategies and possibly determine the eventual location of metastatic invasions for possible treatment. There is thus a critical need to isolate, propagate and characterize viable CTCs and clusters of cancer cells with their associated stroma cells. Here, we present a microfluidic device for mL/min flow rate, continuous-flow capture of viable CTCs from blood using deterministic lateral displacement (DLD) arrays. We show here that a DLD array device can isolate CTCs from blood with capture efficiency greater than 85% CTCs at volumetric flow rates of up to 10 mL/min with no effect on cell viability.
Damage significantly influences response of a strain sensor only if it occurs in the proximity of the sensor. Thus, two-dimensional (2D) sensing sheets covering large areas offer reliable early-stage ...damage detection for structural health monitoring (SHM) applications. This paper presents a scalable sensing sheet design consisting of a dense array of thin-film resistive strain sensors. The sensing sheet is fabricated using flexible printed circuit board (Flex-PCB) manufacturing process which enables low-cost and high-volume sensors that can cover large areas. The lab tests on an aluminum beam showed the sheet has a gauge factor of 2.1 and has a low drift of 1.5 μ ϵ / d a y . The field test on a pedestrian bridge showed the sheet is sensitive enough to track strain induced by the bridge's temperature variations. The strain measured by the sheet had a root-mean-square (RMS) error of 7 μ ϵ r m s compared to a reference strain on the surface, extrapolated from fiber-optic sensors embedded within the bridge structure. The field tests on an existing crack showed that the sensing sheet can track the early-stage damage growth, where it sensed 600 μ ϵ peak strain, whereas the nearby sensors on a damage-free surface did not observe significant strain change.
Health care delivery is increasingly influenced by the emerging concepts of precision health and the learning health care system. Although not synonymous with precision health, genomics is a key ...enabler of individualized care. Delivering patient-centered, genomics-informed care based on individual-level data in the current national landscape of health care delivery is a daunting challenge. Problems to overcome include data generation, analysis, storage, and transfer; knowledge management and representation for patients and providers at the point of care; process management; and outcomes definition, collection, and analysis. Development, testing, and implementation of a genomics-informed program requires multidisciplinary collaboration and building the concepts of precision health into a multilevel implementation framework. Using the principles of a learning health care system provides a promising solution. This article describes the implementation of population-based genomic medicine in an integrated learning health care system-a working example of a precision health program.
Stable water isotopes have been measured in a wide range of climate archives, with the purpose of reconstructing regional climate variations. Yet the common assumption that the isotopic signal is a ...direct indicator of temperature proves to be misleading under certain circumstances, since its relationship with temperature also depends on e.g. atmospheric circulation and precipitation seasonality. Here we introduce the principles, benefits and caveats of using climate models with embedded water isotopes as a support for the interpretation of isotopic climate archives. A short overview of the limitations of empirical calibrations of isotopic proxy records is presented. In some cases, the underlying hypotheses are not fulfilled and the calibration contradicts the physical interpretation of isotopic fractionation. The simulation of climate and its associated isotopic signal, despite difficulties related to downscaling and intrinsic atmospheric variability, can provide a "transfer function" between the isotopic signal and the considered climate variable. The relationship between modelled temperature and isotopic signal is analysed under present-day, pre-industrial and mid-Holocene conditions. The linear regression relationship is statistically more significant for precipitation-weighted annual temperature than mean annual temperature, yet the regression slope varies greatly between the time-slice experiments. Temperature reconstructions that do not account for the slope variations will in this case underestimate the low-frequency variability and overestimate high-frequency variability from the isotopic proxy record. The spatial variability of the simulated δ18O-temperature slope further indicates that the isotopic signal is primarily controlled by synoptic atmospheric circulation rather than local temperature.
Here we present a general approach for the description for the frequency dependent dielectric tensor coefficients for optically anisotropic materials. Based on symmetry arguments we show that the ...components of the dielectric tensor are in general not independent of each other. For each excitation there exists an eigensystem, where its contribution to the dielectric tensor can be described by a diagonal susceptibility tensor. From the orientation of the eigensystem and the relative magnitude of the tensor elements, the dipole interaction distribution in real space can be deduced. In the limiting cases, the oriented dipole approach as well as the tensor of isotropic and uniaxial materials are obtained. The application of this model is demonstrated exemplarily on triclinic K2Cr2O7 and the orientation and directional distribution of the corresponding dipole moments in real space are determined.
The successful design of nanofluidic devices for the manipulation of biopolymers requires an understanding of how the predictions of soft condensed matter physics scale with device dimensions. Here ...we present measurements of DNA extended in nanochannels and show that below a critical width roughly twice the persistence length there is a crossover in the polymer physics.
The classical SiO2/Si interface, which is the basis of integrated circuit technology, is prepared by thermal oxidation followed by high temperature (>800 °C) annealing. Here we show that an interface ...synthesized between titanium dioxide (TiO2) and hydrogen-terminated silicon (H:Si) is a highly efficient solar cell heterojunction that can be prepared under typical laboratory conditions from a simple organometallic precursor. A thin film of TiO2 is grown on the surface of H:Si through a sequence of vapor deposition of titanium tetra(tert-butoxide) (1) and heating to 100 °C. The TiO2 film serves as a hole-blocking layer in a TiO2/Si heterojunction solar cell. Further heating to 250 °C and then treating with a dilute solution of 1 yields a hole surface recombination velocity of 16 cm/s, which is comparable to the best values reported for the classical SiO2/Si interface. The outstanding performance of this heterojunction is attributed to Si–O–Ti bonding at the TiO2/Si interface, which was probed by angle-resolved X-ray photoelectron spectroscopy. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) showed that Si–H bonds remain even after annealing at 250 °C. The ease and scalability of the synthetic route employed and the quality of the interface it provides suggest that this surface chemistry has the potential to enable fundamentally new, efficient silicon solar cell devices.
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