Perspectives on the Self in the Novels of Camilo Castelo Branco (1850-1870)

The aim of this study is to illustrate a thematic inter-dependence between Camilo's life and work, and to establish, upon this basis, the theory that his professional devotion to literature (an idea which is already long established) is based upon an almost total inability to distinguish between real life and the exceptionally vivid world of his own imagination

An Exploration of Just Noticeable Differences in Mid-Air Haptics

Mid-air haptic feedback technology produces tactile sensations that are felt without the need for physical interactions, wearables or controllers. When designing mid-air haptic stimuli, it is important that they are sufficiently different in terms of their perceived sensation.This paper presents the results of two user studies on mid-air haptic feedback technology, with a focus on the sensations of haptic strength and haptic roughness. More specifically, we used the acoustic pressure intensity and the rotation frequency of the mid-air haptic stimulus as proxies to the two sensations of interest and investigated their Just Noticeable Difference (JND) and Weber fractions. Our results indicate statistical significance in the JND for frequency, with a finer resolution compared to intensity. Moreover, correlations are observed in terms of participants' sensitivity to small changes across the different stimuli presented. We conclude that frequency and intensity are mid-air haptic dimensions of depth 5 and 3, respectively, that we can use for the design of distinct stimuli that convey perceptually different tactile information to the user

Distribution and characteristics of newly-defined subgroups of type 2 diabetes in randomised clinical trials : Post hoc cluster assignment analysis of over 12,000 study participants

Publisher Copyright: © 2022Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs). Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration > 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach. Subgroup distribution, characteristics and influencing factors were analysed. Results: In both, pooled and single RCTs, “mild-obesity related diabetes” predominated (45 %) with mean BMI of 35 kg/m2. “Severe insulin-resistant diabetes” was found least often (4.6 %) and prevalence of “mild age-related diabetes” (23.9 %) was mainly influenced by age at onset of diabetes and age cut-offs. Subgroup characteristics were widely comparable to those from real-world cohorts, but all subgroups showed higher frequencies of diabetes-related complications which were associated with longer diabetes duration. A high proportion of “severe insulin-deficient diabetes” (25.4 %) was identified with poor pre-study glycaemic control. Conclusions: Classification of RCT participants into newly-defined diabetes subgroups revealed the existence of a heterogeneous population of T2DM. For future RCTs, subgroup-based randomisation of T2DM will better define the target population and relevance of the outcomes by avoiding clinical heterogeneity.Peer reviewe

Cardiometabolic effects of a novel SIRT1 activator, SRT2104, in people with type 2 diabetes mellitus

Background: The cardiometabolic effects of SRT2104, a novel SIRT1 activator, were investigated in people with type 2 diabetes mellitus (T2DM). Methods: Fifteen adults with T2DM underwent a randomised, double-blind, placebo-controlled cross-over trial and received 28 days of oral SRT2104 (2.0 g/day) or placebo. Forearm vasodilatation (measured during intrabrachial bradykinin, acetylcholine and sodium nitroprusside infusions) as well as markers of glycaemic control, lipid profile, plasma fibrinolytic factors, and markers of platelet-monocyte activation, were measured at baseline and at the end of each treatment period. Results: Lipid profile and platelet-monocyte activation were similar in both treatment arms (p>0.05 for all). Forearm vasodilatation was similar on exposure to acetylcholine and sodium nitroprusside (p>0.05,respectively). Bradykinin-induced vasodilatation was less during treatment with SRT2104 versus placebo (7.753vs9.044, respectively, mean difference=−1.291,(95% CI −2.296 to −0.285, p=0.012)). Estimated net plasminogen activator inhibitor type 1 antigen release was reduced in the SRT2104 arm versus placebo (mean difference=−38.89 ng/100mL tissue/ min, (95%CI −75.47, to –2.305, p=0.038)). There were no differences in other plasma fibrinolytic factors (p>0.05 for all). After 28 days, SRT2104 exposure was associated with weight reduction (−0.93 kg (95% CI −1.72 to −0.15), p=0.0236), and a rise in glycated haemoglobin (5 mmol/ mol or 0.48% (0.26 to 0.70), p=0.004) Conclusions: In people with T2DM, SRT2104 had inconsistent, predominantly neutral effects on endothelial and fibrinolytic function, and no discernible effect on lipids or platelet function. In contrast, weight loss was induced along with deterioration in glycaemic control, suggestive of potentially important metabolic effects. Clinical trial registration: NCT01031108; Results

Effect of hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with and without type 1 diabetes:A prospective, randomised, open-label, blinded endpoint, cross-over study

Abstract Aims This study examined the effect of experimentally‐induced hypoglycaemia on measures of myocardial blood flow and myocardial injury in adults with, and without, type 1 diabetes. Methods In a prospective, randomised, open‐label, blinded, endpoint cross‐over study, 17 young adults with type 1 diabetes with no cardiovascular risk factors, and 10 healthy non‐diabetic volunteers, underwent hyperinsulinaemic‐euglycaemic (blood glucose 4.5–5.5 mmol/L) and hypoglycaemic (2.2–2.5 mmol/L) clamps. Myocardial blood flow was assessed using transthoracic echocardiography Doppler coronary flow reserve (CFR) and myocardial injury using plasma high‐sensitivity cardiac troponin I (hs‐cTnI) concentration. Results During hypoglycaemia, coronary flow reserve trended non‐significantly lower in those with type 1 diabetes than in the non‐diabetic participants (3.54 ± 0.47 vs. 3.89 ± 0.89). A generalised linear mixed‐model analysis examined diabetes status and euglycaemia or hypoglycaemia as factors affecting CFR. No statistically significant difference in CFR was observed for diabetes status (p = .23) or between euglycaemia and hypoglycaemia (p = .31). No changes in hs‐cTnI occurred during hypoglycaemia or in the recovery period (p = .86). Conclusions A small change in CFR was not statistically significant in this study, implying hypoglycaemia may require more than coronary vasomotor dysfunction to cause harm. Further larger studies are required to investigate this putative problem

Diabetes and Driving

Of the nearly 19 million people in the U.S. with diagnosed diabetes (1), a large percentage will seek or currently hold a license to drive. For many, a driver's license is essential to work; taking care of family; securing access to public and private facilities, services, and institutions; interacting with friends; attending classes; and/or performing many other functions of daily life. Indeed, in many communities and areas of the U.S. the use of an automobile is the only (or the only feasible or affordable) means of transportation available. There has been considerable debate whether, and the extent to which, diabetes may be a relevant factor in determining driver ability and eligibility for a license. This position statement addresses such issues in light of current scientific and medical evidence. Sometimes people with a strong interest in road safety, including motor vehicle administrators, pedestrians, drivers, other road users, and employers, associate all diabetes with unsafe driving when in fact most people with diabetes safely operate motor vehicles without creating any meaningful risk of injury to themselves or others. When legitimate questions arise about the medical fitness of a person with diabetes to drive, an individual assessment of that person's diabetes management—with particular emphasis on demonstrated ability to detect and appropriately treat potential hypoglycemia—is necessary in order to determine any appropriate restrictions. The diagnosis of diabetes is not sufficient to make any judgments about individual driver capacity. This document provides an overview of existing licensing rules for people with diabetes, addresses the factors that impact driving for this population, and identifies general guidelines for assessing driver fitness and determining appropriate licensing restrictions

Hydrophilic and lipophilic radiopharmaceuticals as tracers in pharmaceutical development: In vitro – In vivo studies

BACKGROUND: Scintigraphic studies have been performed to assess the release, both in vitro and in vivo, of radiotracers from tablet formulations. Four different tracers with differing physicochemical characteristics have been evaluated to assess their suitability as models for drug delivery. METHODS: In-vitro disintegration and dissolution studies have been performed at pH 1, 4 and 7. In-vivo studies have been performed by scintigraphic imaging in healthy volunteers. Two hydrophilic tracers, ((99m)Tc-DTPA) and ((99m)Tc-MDP), and two lipophilic tracers, ((99m)Tc-ECD) and ((99m)Tc-MIBI), were used as drug models. RESULTS: Dissolution and disintegration profiles, differed depending on the drug model chosen. In vitro dissolution velocity constants indicated a probable retention of the radiotracer in the formulation. In vivo disintegration velocity constants showed important variability for each radiopharmaceutical. Pearson statistical test showed no correlation between in vitro drug release, and in vivo behaviour, for (99m)Tc-DTPA, (99m)Tc-ECD and (99m)Tc-MIBI. High correlation coefficients were found for (99m)Tc-MDP not only for in vitro dissolution and disintegration studies but also for in vivo scintigraphic studies. CONCLUSION: Scintigraphic studies have made a significant contribution to the development of drug delivery systems. It is essential, however, to choose the appropriate radiotracers as models of drug behaviour. This study has demonstrated significant differences in release patterns, depending on the model chosen. It is likely that each formulation would require the development of a specific model, rather than being able to use a generic drug model on the basis of its physicochemical characteristics