Blind estimation of reverberation time in classrooms and hospital wards

This paper investigates blind Reverberation Time (RT) estimation in occupied classrooms and hospital wards. Measurements are usually made while these spaces are unoccupied for logistical reasons. However, occupancy can have a significant impact on the rate of reverberant decay. Recent work has developed a Maximum Likelihood Estimation (MLE) method which utilises only passively recorded speech and music signals, this enables measurements to be made while the room is in use. In this paper the MLE method is applied to recordings made in classrooms during lessons. Classroom occupancy levels differ for each lesson, therefore a model is developed using blind estimates to predict the RT for any occupancy level to within ±0.07s for the mid-frequency octave bands. The model is also able to predict the effective room and per person absorption area. Ambient sound recordings were also carried out in a number of rooms in two hospitals for a week. Hospital measurements are more challenging as the occurrence of free reverberant decay is rarer than in schools and the acoustic conditions may be non-stationary. However, by gaining recordings over a period of a week, estimates can be gained within ±0.07 s. These estimates are representative of the times when the room contains the highest acoustic absorption. In other words when curtains are drawn, there are many visitors or perhaps a window may be open

Structural and magnetic properties of Pr-alloyed MnBi nanostructures

The structural and magnetic properties of Pr-alloyed MnBi (short MnBi-Pr) nanostructures with a range of Pr concentrations have been investigated. The nanostructures include thin films having Pr concentrations 0, 2, 3, 5 and 9 atomic percent and melt-spun ribbons having Pr concentrations 0, 2, 4 and 6 percent respectively. Addition of Pr into the MnBi lattice has produced a significant change in the magnetic properties of these nanostructures including an increase in coercivity and structural phase transition temperature, and a decrease in saturation magnetization and anisotropy energy. The highest value of coercivity measured in the films is 23 kOe and in the ribbons is 5.6 kOe. The observed magnetic properties are explained as the consequences of competing ferromagnetic and antiferromagnetic interactions

Hyperinsulinism-hyperammonaemia syndrome: novel mutations in the GLUD1 gene and genotype-phenotype correlations

Background: Activating mutations in the GLUD1 gene (which encodes for the intra-mitochondrial enzyme glutamate dehydrogenase, GDH) cause the hyperinsulinism–hyperammonaemia (HI/HA) syndrome. Patients present with HA and leucine-sensitive hypoglycaemia. GDH is regulated by another intra-mitochondrial enzyme sirtuin 4 (SIRT4). Sirt4 knockout mice demonstrate activation of GDH with increased amino acid-stimulated insulin secretion. Objectives: To study the genotype–phenotype correlations in patients with GLUD1 mutations. To report the phenotype and functional analysis of a novel mutation (P436L) in the GLUD1 gene associated with the absence of HA. Patients and methods: Twenty patients with HI from 16 families had mutational analysis of the GLUD1 gene in view of HA (n=19) or leucine sensitivity (n=1). Patients negative for a GLUD1 mutation had sequence analysis of the SIRT4 gene. Functional analysis of the novel P436L GLUD1 mutation was performed. Results: Heterozygous missense mutations were detected in 15 patients with HI/HA, 2 of which are novel (N410D and D451V). In addition, a patient with a normal serum ammonia concentration (21 µmol/l) was heterozygous for a novel missense mutation P436L. Functional analysis of this mutation confirms that it is associated with a loss of GTP inhibition. Seizure disorder was common (43%) in our cohort of patients with a GLUD1 mutation. No mutations in the SIRT4 gene were identified. Conclusion: Patients with HI due to mutations in the GLUD1 gene may have normal serum ammonia concentrations. Hence, GLUD1 mutational analysis may be indicated in patients with leucine sensitivity; even in the absence of HA. A high frequency of epilepsy (43%) was observed in our patients with GLUD1 mutations

Diazoxide-responsive hyperinsulinemic hypoglycemia caused by HNF4A gene mutations

Objective: The phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH). Subjects and methods: We sequenced the ABCC8, KCNJ11, GCK, GLUD1, and/or HNF4A genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype. Results: A genetic diagnosis was possible for 59/220 (27%) patients. KATP channel mutations were most common (15%) followed by GLUD1 mutations causing hyperinsulinism with hyperammonemia (5.9%), and HNF4A mutations (5%). Seven of the 11 probands with a heterozygous HNF4A mutation did not have a parent affected with diabetes, and four de novo mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years. Conclusions: In this large series, HNF4A mutations are the third most common cause of diazoxide responsive HH. We recommend that HNF4A sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once KATP channel mutations have been excluded

A study of volatile compounds in the breath of children with type 1 diabetes

A pilot study of exhaled volatile compounds and their correlation with blood glucose levels in eight children with type 1 diabetes is reported. Five paired blood and breath samples were obtained from each child over a 6 hour period. The blood glucose concentration ranged from 41.4 to 435.6 mg/dL. Breath samples were collected in Tedlar bags and immediately evacuated through thermal desorption tubes packed with Carbopack B and C. The VOCs were later recovered by thermal desorption and analysed using gas chromatography mass spectrometry. The study identified 74 volatile compounds present in at least 10% of the patient samples. Of these 74 volatiles 36 were found in all patient samples tested. Further analysis of the 36 compounds found that none showed significant overall correlation with blood glucose levels. Isoprene showed a weak negative correlation with blood glucose levels. Acetone was found to have no correlation with blood glucose levels for the patients studied. Some patients showed significant individual correlation between the relative peak areas of certain compounds and blood glucose levels. However, there was no consistent pattern observed within these results across all 8 patients. Additional breath samples were collected in Tedlar bags and analysed using SIFTMS for 3 of the patients and a healthy control. The levels of 24 volatiles are reported and were found to be generally consistent with previously reported SIFT-MS data. In agreement with the GCMS data, no compounds exhibited a significant overall correlation with blood glucose level

Clinical and Molecular Characterisation Of Hyperinsulinaemic Hypoglycaemia In Infants Born Small-For-Gestational Age

OBJECTIVE: To characterise the phenotype and genotype of neonates born small-for-gestational age (SGA; birth weight <10th centile) who developed hyperinsulinaemic hypoglycaemia (HH). METHODS: Clinical information was prospectively collected on 27 SGA neonates with HH, followed by sequencing of KCNJ11 and ABCC8. RESULTS: There was no correlation between the maximum glucose requirement and serum insulin levels. Serum insulin level was undetectable in five infants (19%) during hypoglycaemia. Six infants (22%) required diazoxide treatment >6 months. Normoglycaemia on diazoxide <5 mg/kg/day was a safe predictor of resolved HH. Sequencing of KCNJ11/ABCC8 did not identify any mutations. CONCLUSIONS: Serum insulin levels during hypoglycaemia taken in isolation can miss the diagnosis of HH. SGA infants may continue to have hypofattyacidaemic hypoketotic HH beyond the first few weeks of life. Recognition and treatment of this group of patients are important and may have important implications for neurodevelopmental outcome of these patients

The Tangible Common Denominator of Substance Use Disorders: A Reply to Commentaries to Rehm et al. (2013a)

In response to our suggestion to define substance use disorders via ‘heavy use over time', theoretical and conceptual issues, measurement problems and implications for stigma and clinical practice were raised. With respect to theoretical and conceptual issues, no other criterion has been shown, which would improve the definition. Moreover, heavy use over time is shown to be highly correlated with number of criteria in current DSM-5. Measurement of heavy use over time is simple and while there will be some underestimation or misrepresentation of actual levels in clinical practice, this is not different from the status quo and measurement of current criteria. As regards to stigma, research has shown that a truly dimensional concept can help reduce stigma. In conclusion, ‘heavy use over time' as a tangible common denominator should be seriously considered as definition for substance use disorde

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Optimizing the bioenergy water footprint by selecting SRC willow canopy phenotypes: regional scenario simulations

© The Author(s) 2019. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Background and Aims: Bioenergy is central for the future energy mix to mitigate climate change impacts; however, its intricate link with the water cycle calls for an evaluation of the carbon–water nexus in biomass production. The great challenge is to optimize trade-offs between carbon harvest and water use by choosing cultivars that combine low water use with high productivity. Methods: Regional scenarios were simulated over a range of willow genotype × environment interactions for the major UK soil × climate variations with the process-based model LUCASS. Soil available water capacity (SAWC) ranged from 51 to 251 mm and weather represented the north-west (wet, cool), north-east (dry, cool), south-west (wet, warm) and south-east (dry, warm) of the UK. Scenario simulations were evaluated for small/open narrow-leaf (NL) versus large/closed broad-leaf (BL) willow canopy phenotypes using baseline (1965–89) and warmer recent (1990–2014) weather data. Key Results: The low productivity under baseline climate in the north could be compensated by choosing BL cultivars (e.g. ‘Endurance’). Recent warmer climate increased average productivity by 0.5–2.5 t ha−1, especially in the north. The modern NL cultivar ‘Resolution’ had the smallest and most efficient water use. On marginal soils (SAWC <100 mm), yields remained below an economic threshold of 9 t ha−1 more frequently under baseline than recent climate. In the drought-prone south-east, ‘Endurance’ yielded less than ‘Resolution’, which consumed on average 17 mm year−1 less water. Assuming a planting area of 10 000 ha, in droughty years between 1.3 and 4.5 × 106 m3 of water could be saved, with a small yield penalty, for ‘Resolution’. Conclusions: With an increase in air temperature and occasional water scarcities expected with climate change, high-yielding NL cultivars should be the preferred choice for sustainable use of marginal lands and reduced competition with agricultural food crops.Peer reviewedFinal Published versio

The breadth of primary care: a systematic literature review of its core dimensions

Background: Even though there is general agreement that primary care is the linchpin of effective health care delivery, to date no efforts have been made to systematically review the scientific evidence supporting this supposition. The aim of this study was to examine the breadth of primary care by identifying its core dimensions and to assess the evidence for their interrelations and their relevance to outcomes at (primary) health system level. Methods: A systematic review of the primary care literature was carried out, restricted to English language journals reporting original research or systematic reviews. Studies published between 2003 and July 2008 were searched in MEDLINE, Embase, Cochrane Library, CINAHL, King's Fund Database, IDEAS Database, and EconLit. Results: Eighty-five studies were identified. This review was able to provide insight in the complexity of primary care as a multidimensional system, by identifying ten core dimensions that constitute a primary care system. The structure of a primary care system consists of three dimensions: 1. governance; 2. economic conditions; and 3. workforce development. The primary care process is determined by four dimensions: 4. access; 5. continuity of care; 6. coordination of care; and 7. comprehensiveness of care. The outcome of a primary care system includes three dimensions: 8. quality of care; 9. efficiency care; and 10. equity in health. There is a considerable evidence base showing that primary care contributes through its dimensions to overall health system performance and health. Conclusions: A primary care system can be defined and approached as a multidimensional system contributing to overall health system performance and health