Search

Abstract Background The purpose of this study was to understand the healthcare provider (HCP) perspective on the extent of suboptimal insulin dosing in people with diabetes (PwD), as well as specific challenges and solutions to insulin management. Methods An online survey of general practitioners and specialists (N = 640) who treat PwD in Germany, Spain, the United Kingdom, and the United States was conducted. Responses regarding HCP background and their patients, HCP perceptions of suboptimal insulin use, and challenges associated with optimal insulin use were collected. Categorical summary statistics were presented. Results Overall, for type 1 diabetes (T1D) and type 2 diabetes (T2D), most physicians indicated

Virginia Bellido,1 Natalia Duque,2 Rachel S Newson,3 Esther Artime,2 Erik Spaepen,4 Miriam Rubio de Santos,2 Jennifer Redondo-Antón,2 Silvia Díaz-Cerezo,2 Jorge Navarro5 1Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla, Spain; 2Medical Department, Medical Affairs, Eli Lilly and Company, Madrid, Spain; 3NAPAC Real World Evidence, Medical Affairs, Eli Lilly and Company, Sydney, NSW, Australia; 4Statistics, HaaPACS GmbH, Schriesheim, Germany; 5Department of Medicine, University of Valencia, Valencia, SpainCorrespondence: Natalia Duque, Eli Lilly and Company, Alcobendas, Madrid, Spain, Email duque_natalia@lilly.comBackground: This study aimed to determine physicians’ perceptions of the extent of suboptimal insulin dosing and the barriers and solutions to optimal dosing in people with diabetes (PwD) treated with insulin.Methods: A cross-sectional online survey was conducted in four countries with primary care physicians and endocrinologists treating PwD using insulin pens, which included 53 questions on physicians’ characteristics and their perceptions of the behaviors of PwD in relation to insulin dosing routines, unmet needs and potential solutions. Analyses were descriptive.Results: Of the 160 physicians (80 primary care physicians, 80 specialists) surveyed in Spain, 58.1% were male and 88.8% had been qualified to practice for more than five years. Most physicians (> 65%) indicated that 0– 30% of PwD missed or skipped, mistimed, or miscalculated an insulin dose in the last 30 days. Common reasons for these actions were that PwD forgot, were out of their normal routine, were too busy or distracted, or were unsure of how much insulin to take. To optimize insulin dosing, over 75% of physicians considered it very helpful for PwD to have real-time insulin dosing calculation guidance, mobile app reminders, a device automatically recording glucose measurements and/or insulin, having insulin and glucose data in one place, and having the time for more meaningful conversations about insulin dosing routines.Conclusion: According to physicians’ perspectives, suboptimal insulin dosing remains common among PwD. This survey highlights the need for integrated and automated insulin dosing support to manage the complexity of insulin treatment, improve communications between PwD and physicians, and ultimately improve outcomes for PwD.Plain Language Summary: In Spain, more than 50% of people with diabetes (PwD) do not reach glycemic targets (glycated hemoglobin [HbA1C] under 7%). While there are many innovations in insulin therapy and device technology, treatment adherence is often poor.This study presents results from an online survey of physicians’ perceptions of insulin dosing and the barriers and solutions to optimal insulin dosing in Spain. Most physicians indicated that PwD missed or skipped, mistimed, or miscalculated an insulin dose. Common reasons included PwD being out of their normal routine, being too busy or distracted, or being unsure of how much insulin to take. To improve insulin dosing, physicians suggested real-time insulin dosing calculation guidance, mobile app reminders, and a device that automatically records glucose measurements and insulin. Furthermore, having time for more meaningful conversations about insulin dosing routines was found as a solution to improve insulin dosing.There is a need for integrated and automated insulin dosing support to manage insulin treatment, improve communications between PwD and physicians, and improve outcomes for PwD.Keywords: diabetes mellitus, type 1 diabetes mellitus, type 2 diabetes mellitus, insulin dosing, physicians, Spain, barriers, solutions

Abstract The severe difficulty to resolve simultaneously both the macroscopic deformation process and the dislocation dynamics on the atomic scale limits our understanding of crystal plasticity. Here we use colloidal crystals, imaged on the single particle level by high-speed three-dimensional (3D) confocal microscopy, and resolve in real-time both the relaxation of the epitaxial misfit strain and the accompanying evolution of dislocations. We show how dislocation interactions give rise to the formation of complex dislocation networks in 3D and to unexpectedly sharp plastic relaxation. The sharp relaxation is facilitated by attractive interactions that promote the formation of new dislocations that are more efficient in mediating strain. Dislocation networks form fragmented structures, as dislocation growth is blocked by either attractive interactions, which result in the formation of sessile dislocation junctions, or by repulsion from perpendicular segments. The strength of these blocking mechanisms decreases with the thickness of the crystal film. These results reveal the critical role of dislocation interactions in plastic deformation of thin films and can be readily generalized from the colloidal to the atomic scale.

ABSTRACT: Supplementation of a combination of lysolecithin, a synthetic emulsifier, and monoglycerides (LEX) in liquid and dry form to broiler diets with different energy levels was investigated to determine their effect on performance, litter quality and subsequent occurrence of footpad lesions. One thousand two hundred and forty-eight-day-old Ross 308 broilers were assigned to 1 of 6 treatments for a 42-day study: a basal diet with a normal energy content (NE); NE + 300 g/t LEX in liquid form (LEL); NE + 500 g/t LEX in dry form (LED); a basal diet with low energy (LE, −90 kcal/kg starter, −100 kcal/kg grower, finisher), LE + 300 g/t LEL and a LE + 500 g/t LED. Each treatment consisted of 13 pens of 16 birds each. Diets were fed in 3 phases (starter d 0–10, grower d 11–21, finisher d 22–42). Feed intake and weight were measured on d 0, 10, 21, and 42. On d 42 a litter sample was collected from each pen and 2 birds per pen were assessed for footpad lesions and breast scald. Data were analyzed using JMP 16, with means separation achieved using Tukey's HSD; significance was assumed at P < 0.05. Results showed a higher (P < 0.05) cumulative bodyweight gain with LEX supplementation (NE CON = 2,718 g, NE+LED = 2,829, NE+LEL = 2,895, LE CON = 2,722, LE+LED = 2,787, LE+LEL = 2,893; P = 0.0027). An increased feed intake was observed for the LE diets, however cumulative FCR of LE+LED and LE+LEL remained equal to the NE control (1.657 NE CON, 1.657 LE+LED, 1.623 LE+LEL; P > 0.05), suggesting LEX enabled the birds to compensate for the energy gap. Litter dry matter was significantly improved with both LED and LEL supplementation compared to the control groups, and resulted in lower (P < 0.05) occurrence and severity of footpad lesions and breast scalds. Considering the income over feed cost (IOFC) of the NE treatment as the reference point for comparison, all other treatments improved profitability, with NE+LEL and LE+LEL achieving the greatest IOFC with 154.58 and 175.96 €/1,000 birds respectively. In conclusion, feeding broilers a combination of lysophospholipids, a synthetic emulsifier and monoglycerides resulted in improved bird performance. The use of the LEX also improved litter quality and footpad health, therefore improving animal welfare indicators such as breast scald and footpad measurements.

Human languages, signed and spoken, can be characterized by the structural patterns they use to associate communicative "forms" with "meanings." One such pattern is paradigmatic morphology, where complex words are built from the systematic use "and re-use" of sub-lexical units. Here, we provide evidence of emergent paradigmatic morphology akin to number inflection in a communication system developed without input from a conventional language, "homesign." We study the communication systems of four deaf child homesigners (mean age 8;02). Although these idiosyncratic systems vary from one another, we nevertheless find that all four children use handshape and movement devices productively to express cardinal and non-cardinal number information, and that their number expressions are consistent in both form and meaning. Our study shows, for the first time, that all four homesigners not only incorporate number devices into representational devices used as predicates, but also into gestures functioning as nominals, including deictic gestures. In other words, the homesigners express number by systematically combining "and re-combining" additive markers for number ("qua" inflectional morphemes) with representational and deictic gestures ("qua" bases). The creation of new, complex forms with predictable meanings across gesture types and linguistic functions constitutes evidence for an inflectional morphological "paradigm" in homesign and expands our understanding of the structural patterns of language that are, and are not, dependent on linguistic input.

Abstract Introduction Insulin lispro 100 units/mL Jr KwikPen is the first prefilled, disposable, half‐unit insulin pen that delivers 0.5–30 units in increments of 0.5 units for the treatment of patients with diabetes. This study describes the profile of patients in Spain who initiated insulin therapy with Jr KwikPen in a real‐world setting. Methods This retrospective, observational study based on IQVIA's electronic medical records database included patients with Type 1 (T1D) or Type 2 (T2D) diabetes who initiated therapy with Jr KwikPen between May 2018 and December 2020. Sociodemographic, clinical, and treatment characteristics at treatment initiation were analysed descriptively. Results A total of 416 patients were included. The main characteristics of the T1D/T2D groups (N = 326/90), respectively were as follows: female sex, 61.7%/65.6%; mean age (standard deviation [SD]), 32.5 (20.7)/55.5 (16.6) years; body mass index, 20.9 (4.2)/25.2 (4.6) kg/m2 (N = 239/77); HbA1c, 7.8 (1.7)%/8.0 (1.5)% (N = 141/64); and presence of diabetes‐associated comorbidities, 27.9%/64.4%. Only 32.8% of patients with T1D were

Abstract Background FDG-PET/CT has a high negative predictive value to detect residual nodal disease in patients with locally advanced squamous cell head and neck cancer after completing concurrent chemoradiotherapy (CCRT). However, the positive predictive value remains suboptimal due to inflammation after radiotherapy, generating unnecessary further investigations and possibly even surgery. We report the results of a preplanned secondary end point of the ECLYPS study regarding the potential advantages of dual time point FDG-PET/CT imaging (DTPI) in this setting. Standardized dedicated head and neck FDG-PET/CT images were obtained 12 weeks after CCRT at 60 and 120 min after tracer administration. We performed a semiquantitative assessment of lymph nodes, and the retention index (RI) was explored to optimize diagnostic performance. The reference standard was histology, negative FDG-PET/CT at 1 year, or > 2 years of clinical follow-up. The time-dependent area under the receiver operator characteristics (AUROC) curves was calculated. Results In total, 102 subjects were eligible for analysis. SUV values increased in malignant nodes (median SUV1 = 2.6 vs. SUV2 = 2.7; P = 0.04) but not in benign nodes (median SUV1 = 1.8 vs. SUV2 = 1.7; P = 0.28). In benign nodes, RI was negative although highly variable (median RI = − 2.6; IQR 21.2), while in malignant nodes RI was positive (median RI = 12.3; IQR 37.2) and significantly higher (P = 0.018) compared to benign nodes. A combined threshold (SUV1 ≥ 2.2 + RI ≥ 3%) significantly reduced the amount of false-positive cases by 53% (P = 0.02) resulting in an increased specificity (90.8% vs. 80.5%) and PPV (52.9% vs. 37.0%), while sensitivity (60.0% vs. 66.7%) and NPV remained comparably high (92.9% vs. 93.3%). However, AUROC, as overall measure of benefit in diagnostic accuracy, did not significantly improve (P = 0.62). In HPV-related disease (n = 32), there was no significant difference between SUV1, SUV2, and RI in malignant and benign nodes, yet this subgroup was small. Conclusions DTPI did not improve the overall diagnostic accuracy of FDG-PET/CT to detect residual disease 12 weeks after chemoradiation. Due to differences in tracer kinetics between malignant and benign nodes, DTPI improved the specificity, but at the expense of a loss in sensitivity, albeit minimal. Since false negatives at the 12 weeks PET/CT are mainly due to minimal residual disease, DTPI is not able to significantly improve sensitivity, but repeat scanning at a later time (e.g. after 12 months) could possibly solve this problem. Further study is required in HPV-associated disease.

A key debate in computer science education is whether and how computational thinking (CT) is used within disciplines other than computer science. Broad definitions provide many avenues for developing integrated instruction, as practices within existing activities can simply be reframed in terms of CT. But such general use of the term CT may confuse its meaning and dilute its power as a tool for bringing CS to all. In this paper, we take the viewpoint that mathematical thinking and computational thinking share common practices, such as using repetition to accomplish tasks, but these shared ideas may develop differently in mathematics and computer science. We use document analysis to analyze the K-5 Common Core State Standards for Mathematics for the presence of these common practices and describe the specific ways they develop in mathematics. We compare these elements of mathematical thinking to related elements of CT to identify synergies and differences between CT and mathematical thinking. We argue that these synergies and differences have implications for the development of integrated instruction designed to bring CS to all.

When asked to explain their solutions to a problem, children often gesture and, at times, these gestures convey information that is different from the information conveyed in speech. Children who produce these gesture-speech "mismatches" on a particular task have been found to profit from instruction on that task. We have recently found that some children produce gesture-speech mismatches when identifying numbers at the cusp of their knowledge, for example, a child incorrectly labels a set of two objects with the word "three" and simultaneously holds up two fingers. These mismatches differ from previously studied mismatches (where the information conveyed in gesture has the potential to be integrated with the information conveyed in speech) in that the gestured response contradicts the spoken response. Here, we ask whether these contradictory number mismatches predict which learners will profit from number-word instruction. We used the Give-a-Number task to measure number knowledge in 47 children (M[subscript age] = 4.1 years, SD = 0.58), and used the "What's on this Card" task to assess whether children produced gesture-speech mismatches above their knower level. Children who were early in their number learning trajectories ("one-knowers" and "two-knowers") were then randomly assigned, within knower level, to one of two training conditions: a Counting condition in which children practiced counting objects; or an Enriched Number Talk condition containing counting, labeling set sizes, spatial alignment of neighboring sets, and comparison of these sets. Controlling for counting ability, we found that children were more likely to learn the meaning of new number words in the Enriched Number Talk condition than in the Counting condition, but only if they had produced gesture-speech mismatches at pretest. The findings suggest that numerical gesture-speech mismatches are a reliable signal that a child is ready to profit from rich number instruction and provide evidence, for the first time, that cardinal number gestures have a role to play in number-learning.

ABSTRACT Plant roots are colonized by microorganisms from the surrounding soil that belong to different kingdoms and form a multikingdom microbial community called the root microbiota. Despite their importance for plant growth, the relationship between soil management, the root microbiota, and plant performance remains unknown. Here, we characterize the maize root-associated bacterial, fungal, and oomycetal communities during the vegetative and reproductive growth stages of four maize inbred lines and the pht1;6 phosphate transporter mutant. These plants were grown in two long-term experimental fields under four contrasting soil managements, including phosphate-deficient and -sufficient conditions. We showed that the maize root-associated microbiota is influenced by soil management and changes during host growth stages. We identified stable bacterial and fungal root-associated taxa that persist throughout the host life cycle. These taxa were accompanied by dynamic members that covary with changes in root metabolites. We observed an inverse stable-to-dynamic ratio between root-associated bacterial and fungal communities. We also found a host footprint on the soil biota, characterized by a convergence between soil, rhizosphere, and root bacterial communities during reproductive maize growth. Our study reveals the spatiotemporal dynamics of the maize root-associated microbiota and suggests that the fungal assemblage is less responsive to changes in root metabolites than the bacterial community. IMPORTANCE Plant roots are inhabited by microbial communities called the root microbiota, which supports plant growth and health. We show in a maize field study that the root microbiota consists of stable and dynamic members. The dynamics of the microbial community appear to be driven by changes in the metabolic state of the roots over the life cycle of maize.

The multinational CRASH study found that substantive recommendations from health care providers were predictive of actions taken by people with diabetes during and after a severe hypoglycemic event, which highlights the importance of equipping people with actionable strategies to prevent and treat severe hypoglycemia should a severe hypoglycemic event arise.