Initiating Insulin as Part of the Treating To Target in Type 2 Diabetes (4-T) Trial: An interview study of patients' and health professionals' experiences

OBJECTIVE: To explore patients' and health professionals' experiences of initiating insulin as part of the Treating To Target in Type 2 Diabetes (4-T) randomized controlled trial. RESEARCH DESIGN AND METHODS: Interviews were conducted with 45 trial participants and 21 health professionals and thematically analyzed. RESULTS: Patients were generally psychologically insulin receptive when approached to participate in the 4-T trial. Their receptiveness arose largely from their personal experiences observing intensifying prior treatments and deteriorating blood glucose control over time, which led them to engage with and accept the idea that their diabetes was progressive. Health professionals also fostered receptiveness by drawing on their clinical experience to manage patients' anxieties about initiating insulin. CONCLUSIONS: Previous studies may have overemphasized the problem of psychological insulin resistance and overlooked factors and treatment experiences that may promote insulin receptiveness among type 2 patients

Performance of Prototypes and Start up of Series Fabrication of the LHC Arc Quadrupoles

The construction of three prototype arc quadrupoles for the LHC machine has been concluded successfully. These magnets underwent warm and cold magnetic measurements as well as many other tests, both in CEA-Saclay's laboratory and at CERN. Their training qualifies them for use in the LHC machine and their measured field quality points to only very minor corrections. An excellent correlation is found between warm and cold magnetic measurements. The prototype quadrupole design has been fully retained for the series fabrication of the 400 magnets and their cold masses by industry. This paper describes the main tests and measurement results of all three prototypes. It further explains the logistics for the manufacturing of the series of cold masses. These cold masses contain not only the main quadrupole but also different combinations of corrector magnets. Thus, together with variants imposed by the cryogenic configuration of the machine, 40 different types of cold masses have to be fabricated by the firm, to which the contract has been adjudicated

Challenging Social Cognition Models of Adherence:Cycles of Discourse, Historical Bodies, and Interactional Order

Attempts to model individual beliefs as a means of predicting how people follow clinical advice have dominated adherence research, but with limited success. In this article, we challenge assumptions underlying this individualistic philosophy and propose an alternative formulation of context and its relationship with individual actions related to illness. Borrowing from Scollon and Scollon’s three elements of social action – “historical body,” “interaction order,” and “discourses in place” – we construct an alternative set of research methods and demonstrate their application with an example of a person talking about asthma management. We argue that talk- or illness-related behavior, both viewed as forms of social action, manifest themselves as an intersection of cycles of discourse, shifting as individuals move through these cycles across time and space. We finish by discussing how these dynamics of social action can be studied and how clinicians might use this understanding when negotiating treatment with patients

Delay Of Insulin Addition To Oral Combination Therapy Despite Inadequate Glycemic Control: Delay of Insulin Therapy

BACKGROUND: Patients and providers may be reluctant to escalate to insulin therapy despite inadequate glycemic control. OBJECTIVES: To determine the proportion of patients attaining and maintaining glycemic targets after initiating sulfonylurea and metformin oral combination therapy (SU/MET); to assess insulin initiation among patients failing SU/MET; and to estimate the glycemic burden incurred, stratified by whether HbA(1c) goal was attained and maintained. DESIGN: Longitudinal observational cohort study. SUBJECTS: Type 2 diabetes patients, 3,891, who newly initiated SU/MET between 1 January 1996 and 31 December 2000. MEASUREMENTS: Subjects were followed until insulin was added, health plan disenrolment, or until 31 December 2005. We calculated the number of months subjects continued SU/MET therapy alone, in total, and during periods of inadequate glycemic control; the A1C reached during those time periods; and total glycemic burden, defined as the estimated cumulative monthly difference between measured A1C and 8%. RESULTS: During a mean follow-up of 54.6 ± 28.6 months, 41.9% of the subjects added insulin, and 11.8% received maximal doses of both oral agents. Over half of SU/MET patients attained but failed to maintain A1C of 8%, yet continued SU/MET therapy for an average of nearly 3 years, sustaining glycemic burden equivalent to nearly 32 months of A1C levels of 9%. Another 18% of patients never attained the 8% goal with SU/MET, yet continued that therapy for an average of 30 months, reaching mean A1C levels of 10%. CONCLUSIONS: Despite inadequate glycemic control, a minority of patients added insulin or maximized oral agent doses, thus, incurring substantial glycemic burden on SU/MET. Additional studies are needed to examine the benefits of rapid titration to maximum doses and earlier initiation of insulin therapy

Zinc induces temperature-dependent reversible self-assembly of Tau

Tau is an intrinsically disordered microtubule-associated protein that is implicated in several neurodegenerative disorders called tauopathies. In these diseases, Tau is found in the form of intracellular inclusions that consist of aggregated paired helical filaments (PHFs) in neurons. Given the importance of this irreversible PHF formation in neurodegenerative disease, Tau aggregation has been extensively studied. Several different factors, such as mutations or post translational modifications, have been shown to influence the formation of late-stage non-reversible Tau aggregates. It was recently shown that zinc ions accelerated heparin-induced oligomerization of Tau constructs. Indeed, in vitro studies of PHFs have usually been performed in the presence of additional co-factors, such as heparin, in order to accelerate their formation. Using turbidimetry, we investigated the impact of zinc ions on Tau in the absence of heparin and found that zinc is able to induce a temperature-dependent reversible oligomerization of Tau. The obtained oligomers were not amyloid-like and dissociated instantly following zinc chelation or a temperature decrease. Finally, a combination of isothermal titration calorimetry and dynamic light scattering experiments showed zinc binding to a high-affinity binding site and three low-affinity sites on Tau, accompanied by a change in Tau folding. Altogether, our findings stress the importance of zinc in Tau oligomerization. This newly identified Zn-induced oligomerization mechanism may be a part of a pathway different of and concurrent to Tau aggregation cascade leading to PHF formation

Evaluation of major depression in a routine clinical assessment

<p>Abstract</p> <p>Background</p> <p>Major depression is a disorder that significantly worsens a patient's morbidity and mortality. The association of depression and diabetes is well documented and has clinical impact in diabetes treatment's outcome. Patients usually aren't evaluated initially by a psychiatrist, so it is important that non-psychiatrists learn to evaluate major depression and its impact.</p> <p>Conclusions</p> <p>Major depression can and should be evaluated on a routine clinical assessment. Depression's impact on the patients' quality of life, productivity and social interactions is well documented. The initial diagnosis of depression should lead to its prompt treatment, and it has to be emphasized that the incorrect treatment can lead to worsening of the condition, relapses, recurrences or even chronification of major depression.</p

The structure of Chariklo's rings from stellar occultations

Two narrow and dense rings (called C1R and C2R) were discovered around the Centaur object (10199) Chariklo during a stellar occultation observed on 2013 June 3. Following this discovery, we planned observations of several occultations by Chariklo's system in order to better characterize the physical properties of the ring and main body. Here, we use 12 successful occulations by Chariklo observed between 2014 and 2016. They provide ring profiles (physical width, opacity, edge structure) and constraints on the radii and pole position. Our new observations are currently consistent with the circular ring solution and pole position, to within the $\pm 3.3$ km formal uncertainty for the ring radii derived by Braga-Ribas et al. The six resolved C1R profiles reveal significant width variations from $\sim 5$ to 7.5 km. The width of the fainter ring C2R is less constrained, and may vary between 0.1 and 1 km. The inner and outer edges of C1R are consistent with infinitely sharp boundaries, with typical upper limits of one kilometer for the transition zone between the ring and empty space. No constraint on the sharpness of C2R's edges is available. A 1$\sigma$ upper limit of $\sim 20$ m is derived for the equivalent width of narrow (physical width <4 km) rings up to distances of 12,000 km, counted in the ring plane