Estimation of individual beneficial and adverse effects of intensive glucose control for patients with type 2 diabetes

AIMS/HYPOTHESIS: Intensive glucose control reduces the risk of vascular complications while increasing the risk of severe hypoglycaemia at a group level. We sought to estimate individual beneficial and adverse effects of intensive glucose control in patients with type 2 diabetes. METHODS: We performed a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, a randomised controlled trial evaluating standard vs intensive glucose control (HbA1c target ≤6.5% [48 mmol/mol]). In 11,140 participants, we estimated the individual 5 year absolute risk reduction (ARR) for the composite outcome of major micro- and macrovascular events and absolute risk increase (ARI) for severe hypoglycaemia for intensive vs standard glucose control. Predictions were based on competing risks models including clinical characteristics and randomised treatment. RESULTS: Based on these models, 76% of patients had a substantial estimated 5 year ARR for major vascular events (>1%, 5 year number-needed-to-benefit [NNTB5] 200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] 200). When assigning similar or half the weight to severe hypoglycaemia compared with a major vascular event, net benefit was positive in 85% or 99% of patients, respectively. Limiting intensive treatment to the 85% patient subgroup had no significant effect on the overall incidence of major vascular events and severe hypoglycaemia compared with treating all patients. CONCLUSIONS/INTERPRETATION: Taking account of the effects of intensive glucose control on major micro- and macrovascular events and severe hypoglycaemia for individual patients, the estimated net benefit was positive in the majority of the participants in the ADVANCE trial. The estimated individual effects can inform treatment decisions once individual weights assigned to positive and adverse effects have been specified. TRIAL REGISTRATION: ClinicalTrials.gov NCT00145925

How Dysarthric Prosody Impacts Naïve Listeners’ Recognition

The class of speech disorders known as dysarthria arise from disturbances in muscular control over the speech mechanism caused by damage of the central or peripheral nervous system. Dysarthria is typically classified into one of six classes, each corresponding to a different neurological disorder with distinct prosodic cues [3]. The assumption in this classification is that dysarthric speech can be classified implicit on the basis of perception. In this study, we investigate how accurately naïve listeners can recognize stress and intonation in dysarthric speech, and if different neurological disorders impact the ability to convey meaning with these same two cues. To those ends, we collected speech data from Dutch speakers diagnosed with cerebellar lesions (ataxic dysarthria), Parkinson’s Disease (hypokinetic dysarthria), Multiple Sclerosis (mixed classes of dysarthria) and from a healthy control group. Thirteen naïve Dutch listeners participated in the perceptual experiment which targeted recognition of intended realization of four prosodic functions: lexical stress, sentence type, boundary marking and focus. We analyzed recognition accuracy for different groups and performed acoustic analyses to check for fundamental frequency trajectories. Results attest to different accuracy recognition results for different disease groups. The sentence type recognition task was the most sensitive of all tasks for differentiating different diseases both on perceptual and acoustic levels of analysis.</p

Familial paragangliomas

Paragangliomas are rare tumours of the autonomic nervous system and occur in sporadic and hereditary forms. They are usually benign and have a low mortality. However, they cause significant morbidity related to their mass effect. Genetic predisposition can occur within the familial tumour syndromes multiple endocrine neoplasia type 2 (MEN 2), von Hippel-Lindau (VHL) and neurofibromatosis type 1 (NF-1), or be due to mutations in genes specific to the development of paraganglioma only. Compared to sporadic forms, familial paragangliomas tend to present at a younger age and at multiple sites. Tumours should be diagnosed and resected as early as possible, as it has been shown that morbidity is related to tumour size. This article gives an overview of the current literature on the origin of the different forms of paragangliomas, DNA diagnosis, as well as biochemical and radiological screening guidelines

Landmark detection in 2D bioimages for geometric morphometrics: a multi-resolution tree-based approach

The detection of anatomical landmarks in bioimages is a necessary but tedious step for geometric morphometrics studies in many research domains. We propose variants of a multi-resolution tree-based approach to speed-up the detection of landmarks in bioimages. We extensively evaluate our method variants on three different datasets (cephalometric, zebrafish, and drosophila images). We identify the key method parameters (notably the multi-resolution) and report results with respect to human ground truths and existing methods. Our method achieves recognition performances competitive with current existing approaches while being generic and fast. The algorithms are integrated in the open-source Cytomine software and we provide parameter configuration guidelines so that they can be easily exploited by end-users. Finally, datasets are readily available through a Cytomine server to foster future research

Laparoscopic treatment of intestinal malrotation in neonates and infants: retrospective study

Intestinal malrotation in neonates or infants may require urgent surgical treatment, especially when volvulus and vascular compromise of the midgut are suspected. Successful laparoscopic management of malrotation has been described in a number of case reports. It remains unclear, however, whether laparoscopy for the treatment of malrotation has a success rate equal to that of open surgery and what relative risks exist in terms of conversion and redo surgery in larger numbers of patients. This report describes a retrospective analysis of the clinical outcome for 45 children who underwent laparoscopic treatment of intestinal malrotation at the authors' institution. The 45 patients in this series, ages several days to 13 years, underwent a diagnostic laparoscopy for suspected intestinal malrotation. For 37 patients, malrotation with or without volvulus was diagnosed. All these patients underwent laparoscopic derotation and Ladd's procedure. Successful laparoscopic treatment of intestinal malrotation could be performed in 75% of the cases (n = 28), and conversion to an open procedure was necessary in 25% of the cases (n = 9). The median hospital stay was 11 days (range, 2-60 days). Postoperative clinical relapse due to recurrence of malrotation, volvulus, or both occurred for 19% of the laparoscopically treated patients (n = 7). These patients underwent laparoscopic (n = 1) or open (n = 6) redo surgery. Diagnostic laparoscopy is the procedure of choice when intestinal malrotation is suspected. If present, malrotation can be treated adequately with laparoscopic surgery in the majority of cases. Nevertheless, to prevent recurrence of malrotation or volvulus, a low threshold for conversion to an open procedure is mandated

Comparative study of breakwater crown wall – calculation methods

An investigation was undertaken consisting of a state-of-the-art and comparative analysis of currently available methods for calculating the structural stability of wave walls in sloping breakwaters. A total of six design schemes are addressed. The conditions under which the formulations and ranges of validity are explicitly indicated by their authors, are given. The lack of definition in parameters to be used and aspects not taken into account in their investigations are discussed and the results of this analysis are given in a final table

The influence of baseline risk on the relation between HbA1c and risk for new cardiovascular events and mortality in patients with type 2 diabetes and symptomatic cardiovascular disease.

Background Strict glycaemic control in patients with type 2 diabetes has proven to have microvascular benefits while the effects on CVD and mortality are less clear, especially in high risk patients. Whether strict glycaemic control would reduce the risk of future CVD or mortality in patients with type 2 diabetes and pre-existing CVD, is unknown. This study aims to evaluate whether the relation between baseline HbA1c and new cardiovascular events or mortality in patients with type 2 diabetes and pre-existing cardiovascular disease (CVD) is modified by baseline vascular risk. Methods A cohort of 1096 patients with type 2 diabetes and CVD from the Second Manifestations of ARTerial Disease (SMART) study was followed. The relation between HbA1c at baseline and future vascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality was evaluated with Cox proportional hazard analyses in a population that was stratified for baseline risk for vascular events as calculated with the SMART risk score. The mean follow-up duration was 6.9 years for all-cause mortality and 6.4 years for vascular events, in which period 243 and 223 cases were reported, respectively. Results A 1 % increase in HbA1c was associated with a higher risk for all-cause mortality (HR 1.18, 95 % CI 1.06–1.31). This association was also found in the highest SMART risk quartile (HR 1.33, 95 % CI 1.11–1.60). There was no relation between HbA1c and the occurrence of cardiovascular events during follow-up (HR 1.03, 95 % CI 0.91–1.16). The interaction term between HbA1c and SMART risk score was not significantly related to any of the outcomes. Conclusion In patients with type 2 diabetes and CVD, HbA1c is related to the risk of all-cause mortality, but not to the risk of cardiovascular events. The relation between HbA1c and all-cause mortality in patients with type 2 diabetes and vascular disease is not dependent on baseline vascular risk

A Partitioned Finite Element Method for the Structure-Preserving Discretization of Damped Infinite-Dimensional Port-Hamiltonian Systems with Boundary Control

Many boundary controlled and observed Partial Differential Equations can be represented as port-Hamiltonian systems with dissipation, involving a Stokes-Dirac geometrical structure together with constitutive relations. The Partitioned Finite Element Method, introduced in Cardoso-Ribeiro et al. (2018), is a structure preserving numerical method which defines an underlying Dirac structure, and constitutive relations in weak form, leading to finite-dimensional port-Hamiltonian Differential Algebraic systems (pHDAE). Different types of dissipation are examined: internal damping, boundary damping and also diffusion models

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies