Variation in Glycemic Outcomes in Focal Forms of Congenital Hyperinsulinism - The UK Perspective

Context: In focal congenital hyperinsulinism (CHI), localized clonal expansion of pancreatic β-cells causes excess insulin secretion and severe hypoglycemia. Surgery is curative, but not all lesions are amenable to surgery. Objective: We describe surgical and nonsurgical outcomes of focal CHI in a national cohort. Methods: Patients with focal CHI were retrospectively reviewed at 2 specialist centers, 2003-2018. Results: Of 59 patients with focal CHI, 57 had heterozygous mutations in ABCC8/KCNJ11 (51 paternally inherited, 6 de novo). Fluorine-18 L-3,4 dihydroxyphenylalanine positron emission tomography computed tomography scan identified focal lesions in 51 patients. In 5 patients, imaging was inconclusive; the diagnosis was established by frozen section histopathology in 3 patients, a lesion was not identified in 1 patient, and 1 declined surgery. Most patients (n = 56) were unresponsive to diazoxide, of whom 33 were unresponsive or partially responsive to somatostatin receptor analog (SSRA) therapy. Fifty-five patients underwent surgery: 40 had immediate resolution of CHI, 10 had persistent hypoglycemia and a focus was not identified on biopsy in 5. In the 10 patients with persistent hypoglycemia, 7 underwent further surgery with resolution in 4 and ongoing hypoglycemia requiring SSRA in 3. Nine (15% of cohort) patients (1 complex surgical access; 4 biopsy negative; 4 declined surgery) were managed conservatively; medication was discontinued in 8 children at a median (range) age 2.4 (1.5-7.7) years and 1 remains on SSRA at 16 years with improved fasting tolerance and reduction in SSRA dose. Conclusion: Despite a unifying genetic basis of disease, we report inherent heterogeneity in focal CHI patients impacting outcomes of both surgical and medical management

Explosive Nucleosynthesis: What we learned and what we still do not understand

This review touches on historical aspects, going back to the early days of nuclear astrophysics, initiated by B$^2$FH and Cameron, discusses (i) the required nuclear input from reaction rates and decay properties up to the nuclear equation of state, continues (ii) with the tools to perform nucleosynthesis calculations and (iii) early parametrized nucleosynthesis studies, before (iv) reliable stellar models became available for the late stages of stellar evolution. It passes then through (v) explosive environments from core-collapse supernovae to explosive events in binary systems (including type Ia supernovae and compact binary mergers), and finally (vi) discusses the role of all these nucleosynthesis production sites in the evolution of galaxies. The focus is put on the comparison of early ideas and present, very recent, understanding.Comment: 11 pages, to appear in Springer Proceedings in Physics (Proc. of Intl. Conf. "Nuclei in the Cosmos XV", LNGS Assergi, Italy, June 2018

Prediction of preterm birth with and without preeclampsia using mid-pregnancy immune and growth-related molecular factors and maternal characteristics.

OBJECTIVE:To evaluate if mid-pregnancy immune and growth-related molecular factors predict preterm birth (PTB) with and without (±) preeclampsia. STUDY DESIGN:Included were 400 women with singleton deliveries in California in 2009-2010 (200 PTB and 200 term) divided into training and testing samples at a 2:1 ratio. Sixty-three markers were tested in 15-20 serum samples using multiplex technology. Linear discriminate analysis was used to create a discriminate function. Model performance was assessed using area under the receiver operating characteristic curve (AUC). RESULTS:Twenty-five serum biomarkers along with maternal age <34 years and poverty status identified >80% of women with PTB ± preeclampsia with best performance in women with preterm preeclampsia (AUC = 0.889, 95% confidence interval (0.822-0.959) training; 0.883 (0.804-0.963) testing). CONCLUSION:Together with maternal age and poverty status, mid-pregnancy immune and growth factors reliably identified most women who went on to have a PTB ± preeclampsia

A new, large-bodied omnivorous bat (Noctilionoidea: Mystacinidae) reveals lost morphological and ecological diversity since the Miocene in New Zealand

A new genus and species of fossil bat is described from New Zealand's only pre-Pleistocene Cenozoic terrestrial fauna, the early Miocene St Bathans Fauna of Central Otago, South Island. Bayesian total evidence phylogenetic analysis places this new Southern Hemisphere taxon among the burrowing bats (mystacinids) of New Zealand and Australia, although its lower dentition also resembles Africa's endemic sucker-footed bats (myzopodids). As the first new bat genus to be added to New Zealand's fauna in more than 150 years, it provides new insight into the original diversity of chiropterans in Australasia. It also underscores the significant decline in morphological diversity that has taken place in the highly distinctive, semi-terrestrial bat family Mystacinidae since the Miocene. This bat was relatively large, with an estimated body mass of ~40 g, and its dentition suggests it had an omnivorous diet. Its striking dental autapomorphies, including development of a large hypocone, signal a shift of diet compared with other mystacinids, and may provide evidence of an adaptive radiation in feeding strategy in this group of noctilionoid bats

Clinical practice: Drug desensitization in children

Immediate type allergic reactions to medication are potentially life threatening and can hamper drug therapy of several medical conditions. Exact incidence and prevalence data for these reactions in children are lacking. If no alternative drug treatment is available, a desensitization procedure may secure the continuation of necessary therapy. Desensitization is only appropriate in case of a strong suspicion of an IgE-mediated allergic reaction. It should be performed by trained clinicians (allergy specialists) in a hospital setting where treatment of a potential anaphylactic reaction can be done without any delay. In this article, literature describing desensitization procedures for several antibiotics, antineoplastic agents, and vaccines in children is reviewed. In general, desensitization schemes for children differ only in final dose from schemes for adults. Contradictory data were found regarding the protective effects of premedication with antihistamines and glucocorticoids

Characteristics of outdoor falls among older people: A qualitative study

Background Falls are a major threat to older people’s health and wellbeing. Approximately half of falls occur in outdoor environments but little is known about the circumstances in which they occur. We conducted a qualitative study to explore older people’s experiences of outdoor falls to develop understanding of how they may be prevented. Methods We conducted nine focus groups across the UK (England, Wales, and Scotland). Our sample was from urban and rural settings and different environmental landscapes. Participants were aged 65+ and had at least one outdoor fall in the past year. We analysed the data using framework and content analyses. Results Forty-four adults aged 65 – 92 took part and reported their experience of 88 outdoor falls. Outdoor falls occurred in a variety of contexts, though reports suggested the following scenarios may have been more frequent: when crossing a road, in a familiar area, when bystanders were around, and with an unreported or unknown attribution. Most frequently, falls resulted in either minor or moderate injury, feeling embarrassed at the time of the fall, and anxiety about falling again. Ten falls resulted in fracture, but no strong pattern emerged in regard to the contexts of these falls. Anxiety about falling again appeared more prevalent among those that fell in urban settings and who made more visits into their neighbourhood in a typical week. Conclusions This exploratory study has highlighted several aspects of the outdoor environment that may represent risk factors for outdoor falls and associated fear of falling. Health professionals are recommended to consider outdoor environments as well as the home setting when working to prevent falls and increase mobility among older people

Checklists in the operating room: Help or hurdle? A qualitative study on health workers' experiences

<p>Abstract</p> <p>Background</p> <p>Checklists have been used extensively as a cognitive aid in aviation; now, they are being introduced in many areas of medicine. Although few would dispute the positive effects of checklists, little is known about the process of introducing this tool into the health care environment. In 2008, a pre-induction checklist was implemented in our anaesthetic department; in this study, we explored the nurses' and physicians' acceptance and experiences with this checklist.</p> <p>Method</p> <p>Focus group interviews were conducted with a purposeful sample of checklist users (nurses and physicians) from the Department of Anaesthesia and Intensive Care in a tertiary teaching hospital. The interviews were analysed qualitatively using systematic text condensation.</p> <p>Results</p> <p>Users reported that checklist use could divert attention away from the patient and that it influenced workflow and doctor-nurse cooperation. They described senior consultants as both sceptical and supportive; a head physician with a positive attitude was considered crucial for successful implementation. The checklist improved confidence in unfamiliar contexts and was used in some situations for which it was not intended. It also revealed insufficient equipment standardisation.</p> <p>Conclusion</p> <p>Our findings suggest several issues and actions that may be important to consider during checklist use and implementation.</p

Late Gadolinium Enhancement Cardiovascular Magnetic Resonance Assessment of Substrate for Ventricular Tachycardia With Hemodynamic Compromise.

Background: The majority of data regarding tissue substrate for post myocardial infarction (MI) VT has been collected during hemodynamically tolerated VT, which may be distinct from the substrate responsible for VT with hemodynamic compromise (VT-HC). This study aimed to characterize tissue at diastolic locations of VT-HC in a porcine model. Methods: Late Gadolinium Enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging was performed in eight pigs with healed antero-septal infarcts. Seven pigs underwent electrophysiology study with venous arterial-extra corporeal membrane oxygenation (VA-ECMO) support. Tissue thickness, scar and heterogeneous tissue (HT) transmurality were calculated at the location of the diastolic electrograms of mapped VT-HC. Results: Diastolic locations had median scar transmurality of 33.1% and a median HT transmurality 7.6%. Diastolic activation was found within areas of non-transmural scar in 80.1% of cases. Tissue activated during the diastolic component of VT circuits was thinner than healthy tissue (median thickness: 5.5 mm vs. 8.2 mm healthy tissue, p < 0.0001) and closer to HT (median distance diastolic tissue: 2.8 mm vs. 11.4 mm healthy tissue, p < 0.0001). Non-scarred regions with diastolic activation were closer to steep gradients in thickness than non-scarred locations with normal EGMs (diastolic locations distance = 1.19 mm vs. 9.67 mm for non-diastolic locations, p < 0.0001). Sites activated late in diastole were closest to steep gradients in tissue thickness. Conclusions: Non-transmural scar, mildly decreased tissue thickness, and steep gradients in tissue thickness represent the structural characteristics of the diastolic component of reentrant circuits in VT-HC in this porcine model and could form the basis for imaging criteria to define ablation targets in future trials