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A conceptual framework has been developed specifically for cost-related nonadherence (CRNA) that differs from models proposed for general medication nonadherence.This study aimed to demonstrate that CRNA studies are best explained by a conceptual framework developed for general medication nonadherence.A systematic literature review was conducted using MEDLINE via PubMed, CINAHL, ScienceDirect, and Google Scholar databases from 2008 to 2020. Articles were considered for inclusion if they were research studies, used a self-reported measure for CRNA, and provided self-reported data on factors associated with CRNA.A total of 58 studies were identified and included in the review. Factors related to financial pressures were consistently associated with CRNA corresponding to conceptual frameworks for both CRNA and general medication nonadherence. However, noneconomic factors, classified as moderators in the CRNA framework (i.e., patient factors, disease factors, clinician factors), consistently demonstrated independent effects, often with similar strength of association compared with economic factors. Overall, the pattern of risk factors identified in CRNA studies was consistent with general nonadherence except for indicators of poor health. Poor health was often associated with an increased risk of CRNA, whereas the inverse association is generally observed in general nonadherence studies (i.e., nonadherence higher in primary prevention vs. secondary prevention). However, the apparent disagreement was likely caused by the general population studied rather than a unique causal pathway for CRNA.Financial difficulties are extremely common among people who take prescription medications. However, current evidence is insufficient to support a conceptual framework that differs from general medication nonadherence.

BACKGROUND: Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null-null) or impaired (non-null) LDL-receptor activity. Loss-of-function variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS: In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS: The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of -49.0 percentage points (95% confidence interval [CI], -65.0 to -33.1; P

Shenzhen Yao,1 Lisa Lix,2 Gary Teare,3 Charity Evans,1 David Blackburn1 1College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; 2Department of Community Health Sciences of Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; 3Program Program Knowledge, Evidence and Innovation, Provincial Population and Public Health, Alberta Health Services, Calgary, Alberta, CanadaCorrespondence: David BlackburnCollege of Pharmacy and Nutrition, University of Saskatchewan, 2A20.01 Health Sciences Building, 107 Wiggins Road, Saskatoon, Saskatchewan, S7N5E5, CanadaTel +1 306 966 2081Fax +1 306 966 6377Email d.blackburn@usask.caPurpose: Age or sex concordance (same sex or same age range) may also be associated with medication adherence but was not fully investigated. We aim to quantify the impact of age and sex concordance on optimal adherence to statin medications.Patients and Methods: A retrospective cohort study was conducted using population-based health administrative data from Saskatchewan, Canada. Participants were individuals newly initiated on statin medications between January 1, 2012, and December 31, 2017. The outcome was optimal adherence (proportion of days covered ≥ 80%) measured at one year after the first statin claim. The independent variables were sex and age concordance (age within five years) between patients and prescribers. The association between adherence outcome and sex/age concordance was analyzed by multivariable logistic regression models using generalized estimating equations controlled by a package of potential confounding factors.Results: Among 51,874 new statin users, 20.6% (n = 10,710) were age concordant with prescriber. The vast majority of age concordance occurred in patients younger than 66 years (88.6%, 9,486/10,710). Sex concordance was observed in 62.8% (n = 32,551) of patients and age-sex combined concordance in 13.2% (n = 6,856). Among patients younger than 66 years (n = 36,641/51,874, 70.6%), age concordance did not have a significant impact on optimal adherence [adjusted OR (aOR) = 1.02, 95% CI 0.97 to 1.07]. Weak association between sex concordance (aOR = 1.05, 95% CI 1.00 to 1.11), and age-sex combined concordance (aOR = 1.05, 95% CI 0.99 to 1.12) was observed.Conclusion: Age and sex concordance were not statistically significant predictors of optimal statin adherence. However, a weak association was detected for sex concordance. Future studies should examine this factor in different health care settings.Keywords: medication adherence, age concordance, sex concordance, statin, observational study, cohort

Organisms’ body size is an important biological trait that is related to the environment and constrained by physiology. It is also one of few biological characteristics that can be inferred from fossil specimens. Variation in body size both within and across fossil communities can provide insight into their response to past climatic events, as well as morphological or ecological evolution in specific taxa. Among vertebrates, frogs and toads (Anura) are of particular interest given their sensitivity to environmental variation. Here, we propose a method for estimating body size in toads, one of the most ecologically and taxonomically diverse frog families (Bufonidae) that is cosmopolitan in distribution and contains aquatic, terrestrial, arboreal, and fossorial species. We used computed tomography scans (CT-scans) of 36 living species of toads to digitally segment five bones that are frequently found as fossil (ilium, sacrum, urostyle, humerus, and radioulna). We took nine different measurements on those bones to be used as proxies for body size and for each specimen collected a measurement of body size, snout–urostyle length (SUL). We used ordinary least square regression analysis (OLS) with 95% confidence and prediction intervals to determine if those measurements are useful to estimate body size from isolated bones and in the fossil record. Our regression analyses indicate that these measurements can serve as proxies to estimate body size in bufonids (with coefficients of determination between 0.80–0.95). The measurements with the highest coefficient of determinations are those of the ilium and humeri, both of which are abundant in the fossil record and taxonomically informative. Last, we tested our method on examples of living and fossils toads of North and South America. Our method is the first quantitative approach to estimate size in toads based on isolated bones and enables us to continue to explore the correlation between size and ecology in toads in the past.

Objectives Continuity of care (COC) is considered an important determinant of medication adherence based on measures such as the usual provider continuity index (UPCI) that are derived exclusively from physician visit claims. This study aimed to: a) determine if high UPCI values predict physicians who deliver different clinical services; and b) compare UPCI with an integrated COC measure capturing physician visits, prescribing, and a complete medical examination in a multivariable model of patients receiving statin medications. Methods This was a retrospective cohort study of new statin users between 2012 and 2017 in Saskatchewan, Canada. We calculated sensitivity/specificity of a high UPCI value for predicting physicians who were prescribers of statins and/or providers of complete medical examinations. Next, we used logistic regression models to test two measures of COC (high UPCI value or an integrated COC measure) on the outcome of optimal statin adherence (proportion of days covered ≥80%). The DeLong test was used to compare predictive performance of the two models. Results Among 55,144 new statin users, a high UPCI was neither a sensitive or specific marker of physicians who prescribed statins or performed a complete medical examination. The integrated COC measure had a stronger association with optimal adherence [adjusted odds ratio (OR) = 1.56, 95% confidence interval (CI) 1.50 to 1.63] than UPCI (adjusted OR = 1.23, 95% CI 1.19 to 1.28), and improved predictive performance of the adherence model. Conclusion The number of physician visits alone appears to be insufficient to represent COC. An integrated measure improves predictive performance for optimal medication adherence in patients initiating statins.

Current safety standards for automated driving recommend the development of a safety case. This case aims to justify and critically evaluate, by means of an explicit argument and evidence, how the safety claims concerning the intended functionality of an automated driving feature are supported. However, little guidance exists on how such an argument could be developed. In this paper, the MISRA consortium proposes a state machine on which an argument concerning the safety of the intended functionality could be structured. By systematically covering the activation status of the automated driving feature within and outside the operational design domain, this state machine helps in exploring the conditions, and asserting the corresponding safety claims, under which hazardous events could be caused by the intended functionality. MISRA uses a Traffic Jam Drive feature to illustrate the application of this approach.

Natural history collections (NHCs) are the foundation of historical baselines for assessing anthropogenic impacts on biodiversity. Along these lines, the online mobilization of specimens via digitization–the conversion of specimen data into accessible digital content–has greatly expanded the use of NHC collections across a diversity of disciplines. We broaden the current vision of digitization (Digitization 1.0)–whereby specimens are digitized within NHCs–to include new approaches that rely on digitized products rather than the physical specimen (Digitization 2.0). Digitization 2.0 builds upon the data, workflows, and infrastructure produced by Digitization 1.0 to create digital-only workflows that facilitate digitization, curation, and data linkages, thus returning value to physical specimens by creating new layers of annotation, empowering a global community, and developing automated approaches to advance biodiversity discovery and conservation. These efforts will transform large-scale biodiversity assessments to address fundamental questions including those pertaining to critical modern issues of global change.

Poor knowledge about immunosuppressive (IS) medications remains a major problem for patients in the posttransplant setting. Therefore, more effective educational strategies in the pretransplant setting are being considered as a possible method to improve knowledge and readiness for the challenges of posttransplant care. However, the most effective/relevant content of a pretransplant educational program is yet to be determined.To identify pretransplant education topics from the posttransplant patient perspective.A focus group meeting was conducted among 7 high-functioning, stable adult kidney transplant recipients recruited from the Saskatchewan Transplant Program. Demographic information including age, gender, occupation, background/ethnicity, and time since transplant were recorded. A moderator, assistant moderator, and research assistant facilitated the 90-minute focus group meeting using a predetermined semistructured interview guide. The session was audio recorded and transcribed verbatim. Nvivo software was used to code the data and identify emerging themes exploring views of participants relating to the educational information required for pretransplant patients.Patients were satisfied with the education they had received. Ideas were classified into the following major themes-patient satisfaction, transplant waitlist, surgery, medications, posttransplant complications, lifestyle and monitoring, knowledge acquisition, illusion of control, and life changes posttransplant. Knowledge gaps were identified in all areas of the transplantation process and were not exclusive to IS medications.Misconceptions regarding transplantation were identified by a group of high-functioning, stable adult recipients who were satisfied with their clinical care. Future educational strategies should aim to address the entire transplantation process and not be limited to medications.

In this paper, we examine the impacts of casual copying in the market for goods that have strong network externalities and/or are strong complements with goods in another market. By allowing casual copying to occur, the monopolist triggers two effects. The ""copying effect"" reduces demand (and thus profits) due the introduction of a better outside alternative to consumers. However, a ""network augmenting"" effect works to increase demand through the larger size of a network that allows copying. We find that if the marginal network externality is large enough, the monopolist will find it profitable to allow some level of casual copying to occur among non-purchasers of the good. And in a simplified dynamic setting, we find that as time passes and the good’s network becomes more mature, the monopolist will seek higher and higher levels of copy protection. This implies that firms in newly formed markets should be more willing to allow copying to occur than those in established markets. ", En este artículo, se examinan los impactos de una copia casual en el mercado de bienes, donde estos tienen una red con fuertes externalidades y/o fuertes complementos con bienes de otros mercados. Permitiendo la copia casual gatillar dos efectos en el monopolista, un efecto copia que reduce la demanda (las ganancias) a través de permitir el acceso a una mejor alternativa a los consumidores, como también, un efecto de “aumento de difusión” que incrementa la demanda a través del tamaño de la red que permite la copia, por ende, si la externalidad marginal de la red es suficientemente grande, entonces el monopolista encontrará beneficioso permitir algún grado de copia casual entre los no compradores del bien. En un planteamiento dinámico simple, se encuentra que en la medida que el tiempo transcurre y la red de bienes madura el monopolista buscará niveles más altos de protección a la copia, es decir, las firmas en mercados recién formados deberían permitir un mayor grado de copia que en aquellos mercados establecidos.

Input shaping is an effective method for reducing motion-induced vibration. The majority of input-shaping theory is based on linear analysis; however, input shaping has proven effective on moderately nonlinear systems. This work investigates the effect of nonlinear crane dynamics on the performance of input shaping. Typical bridge cranes are driven using Cartesian motions and behave nearly linearly. The rotational structure of a tower crane makes nonlinearities more apparent. Nonlinear equations of motion are presented and experimentally verified. Novel command-shaping algorithms are then proposed for reducing vibration during the nonlinear slewing motions of tower cranes.

A 2005 national study surveyed 2,103 Troops to Teachers (T3) program completers and their school administrators using 21 research-based instructional practices and four effective classroom management strategies associated with increased student achievement to determine whether T3s were more effective in the classroom than traditionally prepared teachers with comparable years of teaching experience. Sixty-one percent returned completed surveys. Principals overwhelmingly (more than 90%) reported that T3s are more effective in classroom instruction and classroom management/student discipline—and have a more positive impact on student achievement—than traditionally prepared teachers. Moreover, T3s teach in high-poverty schools, teach high-demand subjects (special education, math, science), plan to remain in teaching, and increase the teaching pool's diversity.

Microhylidae is a large, cosmopolitan anuran family. Recent molecular analyses have demonstrated the monophyly of the family—a conclusion that is supported by the larval morphology, coupled with the unique mode of tongue protrusion in adults, and a suite of osteological and myological characters seemingly associated with this innovation in feeding. Despite this functional constraint, osteological diversity probably exceeds that of any other anuran family, and this diversity is especially evident in the New World microhylids that comprise two clades, Gastrophryninae and Otophryninae. To facilitate comparisons among these clades, we describe the larval chondrocranium, skeletal development, and adult osteology of Gastrophryne carolinensis. We provide a phylogenetic context for these comparisons through a novel phylogenetic analysis of 45 microhylid genera based on data for one mitochondrial and three nuclear loci from previously published studies. Nearly all relationships within the monophyletic Gastrophryninae are resolved with robust support. Based on these results, we found that the larval chondrocrania of gastrophrynines share morphological features that distinguish them from Otophryne and other anurans. Among the adults, all gastrophrynines show evidence of an anterior shift of the jaws that is correlated with specializations in the otic region, and with the alignment of the planum antorbitale, the cartilage wall separating the nasal capsule from the orbits. The larval infrarostral and the adult mandibles lack a typical anuran mandibular symphysis, and the mentomeckelian bone of the adult is modified with a special process. The most variable part of the skull is the palate in which a neopalatine usually is absent and the vomer may be single or divided. The posteromedial processes of the hyoids of gastrophynines tend to be elaborated, and some taxa bear a peculiar transverse slit in the posterior part of the hyoid corpus. The anterior zonal elements of the pectoral girdle are reduced or absent, and the posterior parts enlarged and shifted posteriorly. Most taxa have eight presacral vertebrae; depending on the taxon the last presacral is amphicoelous or procoelous.

Despite the prominence of “tree-thinking” among contemporary systematists and evolutionary biologists, the biological meaning of different mathematical representations of phylogenies may still be muddled. We compare two basic kinds of discrete mathematical models used to portray phylogenetic relationships among species and higher taxa: stem-based trees and node-based trees. Each model is a tree in the sense that is commonly used in mathematics; the difference between them lies in the biological interpretation of their vertices and edges. Stem-based and node-based trees carry exactly the same information and the biological interpretation of each is similar. Translation between these two kinds of trees can be accomplished by a simple algorithm, which we provide. With the mathematical representation of stem-based and node-based trees clarified, we argue for a distinction between types of trees and types of names. Node-based and stem-based trees contain exactly the same information for naming clades. However, evolutionary concepts, such as monophyly, are represented as different mathematical substructures in the two models. For a given stem-based tree, one should employ stem-based names, whereas for a given node-based tree, one should use node-based names, but applying a node-based name to a stem-based tree is not logical because node-based names cannot exist on a stem-based tree and visa versa. Authors might use node-based and stem-based concepts of monophyly for the same representation of a phylogeny, yet, if so, they must recognize that such a representation differs from the graphical models used for computing in phylogenetic systematics.

Purpose. Assess whether a convenient care clinic (CCC) medical weight-loss program can promote weight loss. Design. Prospective cohort study with follow-up at 10 weeks. Setting. A CCC (Lindora Health Clinic) weight-loss program (Lean for Life) based in a retail pharmacy (Rite Aid Pharmacy) in Costa Mesa, California. Subjects. The first 100 people to purchase the weight-loss program. Intervention. A 10-week, $465 medical weight-loss program with individual counseling sessions; a hypocaloric diet of 900 to 1200 kcal/day (25%–30% carbohydrates, 40% protein, 25% fat); and adjunctive pharmacologic treatment, if necessary. Measures. We collected data on age, height, weight, visits per week, medication use, comorbid conditions, and weight change. Analysis. Data were analyzed based on length of enrollment and mean percent weight loss. Statistical tests used were t-test and Spearman rank correlation test. Results. Eighty-six subjects had valid data entries for weight change over the 10-week period. Average age was 51.6 years; mean starting body mass index was 30.3. Thirty patients participated for 0 to 4 weeks, 30 for 4 to 9 weeks, and 26 for 10 weeks. Mean percent weight changes for the 0 to 4, 5 to 9, and 10-week groups were −1.6, −6.0, and −8.1, respectively. Forty-five (45%) of the patients achieved medically significant weight loss (≥ 5%). Conclusion. The study shows that a medical weight-loss program offered at a CCC in a retail pharmacy can produce medically significant weight loss of ≥5%. Further research of collaborations between the retail and medical weight-loss industries is warranted. Study design limitations included selection bias and confounding variables other than the weight-loss program.

A new conduction calibration apparatus has been designed to deliver heat fluxes up to a maximum of 100 kW/m2 with an established goal of ± 5 % precision. This system will provide a close to purely diffusive (as opposed to radiative) heat flux boundary condition and, when compared to the gauge’s response in the National Institute of Standards and Technology (NIST) radiative calibration facility, act as a check on the sensitivity of a heat flux gauge to the mode of heat transfer. A platinum-plated copper block heated electrically with 2 kW power is designed to produce uniform temperatures up to 750 K across its face. A cold plate will be maintained around 290 K through pool boiling using a liquid refrigerant and a remote condenser. A 1 mm wide helium filled gap between the hot plate and the sensing surface of a cooled heat flux gauge will provide the high conductive fluxes desired (while limiting radiation to a few per cent and avoiding the uncertainties associated with contact resistance). Detailed numerical modeling of the device is being used to identify limitations and evaluate alternatives in the design, and to analyze the level of uncertainty associated with the facility. A description of the apparatus and the results of preliminary modeling are reported.

The concept of the physical unit is key to the understanding of physics, for it is the link between the theoretical relationships which describe physical quantities and the measurements which confirm or confound their predictions. No topic can be more suitable for treatment in a special issue of Metrologia, for the journal's field is measurement: fine measurements, measurements of fundamental quantities, the relationships between measurements, the processes and conventions which allow measurements to be exchanged, duplicated and confirmed. And if physical quantities are to be measured, reference must be made to the units in which they are expressed. Units, in turn, serve no function in isolation. Used individually, units can convey only the simplest of ideas. When organized, however, so that they are part of a system which is logically coherent, which permits the transfer of measurements from one place to another or from one area of science to another and is recognized universally by those whose work depends on unambiguous statements of quantity, they represent a tool of remarkable power with which to express quantities in a concise and consistent way. This issue describes the units of the Systeme International d'Unites (SI). It does this in a series of essays, each of which treats the SI in a way which reflects the personal interests and viewpoint of the author. Individual articles deal with the definition and description of units, their historical development and their application in scientific, legal, business, regional and international affairs. There is no pretence that this is a textbook on the SI, for the topic is not covered exhaustively, completely or even uniformly: the purpose of these essays is to show that the SI is ubiquitous, touching many aspects of human endeavour; that it is useful, serving the interests of science, technology and commerce; and that it is not closed, the underlying principles of how to describe, select, define and disseminate the base and derived units of physics still being open to debate. Giving weight and coherence to this issue is the collective experience of the authors. Individually, they have made important contributions to measurement, have taken part in the operations of national standards laboratories and in the work in which such laboratories collaborate. They are members of the committees which negotiate terms for the use and recognition, at national, regional and international level, of the units which industrial laboratories maintain. Just under half of them are members of the Comite Consultatif des Unites (CCU), the committee to which the Comite International des Poids et Mesures (CIPM), itself turns when it looks for advice on issues affecting the use of units. This issue deals with topics which are central to the decisions of the CIPM. This is an appropriate place, therefore, to mention the close interest which two members of the Comite International have taken in Metrologia and the unfailing support they have given it: Professor Dieter Kind and Professor Jan de Boer. As President of the Comite International, Professor Kind greatly influenced the decision that the Bureau International des Poids et Mesures should purchase Metrologia and did much to create the spirit of independent commentary in which the journal operates. Now that his retirement from his principal post as President of the Physikalisch-Technische Bundesanstalt, Braunschweig, approaches, I take this opportunity, on behalf of Metrologia, its readers and its Editorial Board, to wish him a happy retirement and hope that in the future he will still find time to take an interest in the affairs of the journal. Professor de Boer's contribution to measurement is long and distinguished. His membership of the CIPM began in 1954 and he was its Secretary from 1962 to 1989. He thus took part in the debate which resulted in the decision to launch Metrologia in 1965. As the sole person to hold office as President of the CCU, he writes with unique authority in the article which opens this issue. He was a contributor to the first volume of Metrologia, and I hope that his most recent contribution marks the beginning of a new and distinguished series.

I would respectfully disagree with the decision to exclude medication adherence from the position statement on performance measures for adults with coronary artery disease and hypertension ([1][1]). After reviewing the reasons outlined by the writing committee, I am concerned that this decision may

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