Solid–liquid interfacial free energy of ice Ih, ice Ic, and ice 0 within a mono-atomic model of water via the capillary wave method

We apply the capillarywave method, based on measurements of fluctuations in a ribbon-like interfacial geometry, to determine the solid–liquid interfacial free energy for both polytypes of ice I and the recently proposed ice 0 within a mono-atomic model of water. We discuss various choices for the molecular order parameter, which distinguishes solid from liquid, and demonstrate the influence of this choice on the interfacial stiffness. We quantify the influence of discretisation error when sampling the interfacial profile and the limits on accuracy imposed by the assumption of quasi onedimensional geometry. The interfacial free energies of the two ice I polytypes are indistinguishable to within achievable statistical error and the small ambiguity which arises from the choice of order parameter. In the case of ice 0, we find that the large surface unit cell for low index interfaces constrains the width of the interfacial ribbon such that the accuracy of results is reduced. Nevertheless, we establish that the interfacial free energy of ice 0 at its melting temperature is similar to that of ice I under the same conditions. The rationality of a core–shell model for the nucleation of ice I within ice 0 is questioned within the context of our results. © 2017 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). [http://dx.doi.org/10.1063/1.4975776

An Improved Implementation and Abstract Interface for Hybrid

Hybrid is a formal theory implemented in Isabelle/HOL that provides an interface for representing and reasoning about object languages using higher-order abstract syntax (HOAS). This interface is built around an HOAS variable-binding operator that is constructed definitionally from a de Bruijn index representation. In this paper we make a variety of improvements to Hybrid, culminating in an abstract interface that on one hand makes Hybrid a more mathematically satisfactory theory, and on the other hand has important practical benefits. We start with a modification of Hybrid's type of terms that better hides its implementation in terms of de Bruijn indices, by excluding at the type level terms with dangling indices. We present an improved set of definitions, and a series of new lemmas that provide a complete characterization of Hybrid's primitives in terms of properties stated at the HOAS level. Benefits of this new package include a new proof of adequacy and improvements to reasoning about object logics. Such proofs are carried out at the higher level with no involvement of the lower level de Bruijn syntax.Comment: In Proceedings LFMTP 2011, arXiv:1110.668

The neurological assessment in young children treated with artesunate monotherapy or artesunate-mefloquine combination therapy for uncomplicated Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p>Mefloquine and artesunate combination therapy is the recommended first-line treatment for uncomplicated malaria throughout much of south-east Asia. Concerns have been raised about the potential central nervous system (CNS) effects of both drug components and there are no detailed reports in very young children.</p> <p>Methods</p> <p>Children, aged between three months and five years, with acute uncomplicated <it>Plasmodium falciparum </it>malaria were randomized to either 7 days of artesunate monotherapy or the same schedule of artesunate plus mefloquine on day 7 and 8. Neurological testing targeting coordination and behaviour was carried out at day 0, 7, 9, 10, 14 and 28. Non-febrile healthy control children from the same population were tested on days 0, 7, 14 and 28.</p> <p>Results</p> <p>From December 1994 to July 1997, 91 children with uncomplicated <it>P. falciparum</it>, 45 treated with artesunate monotherapy, 46 treated with mefloquine and artesunate combination therapy and 36 non-febrile controls, underwent neurological testing. Malaria and fever had a significant negative impact on testing performance. By contrast, the anti-malarial treatments were not associated with worsening performances in the various components of the test. Artesunate and mefloquine do not appear to have a significant influence on coordination and behaviour. Children treated with mefloquine were significantly less likely to suffer recurrent malaria infection during follow-up compared to those treated with artesunate alone (P = 0.033).</p> <p>Conclusion</p> <p>In keeping with the results of randomized controlled trials in adults, mefloquine was not associated with a decrease in specific items of neurological performance. Likewise, children treated with artesunate did not perform significantly differently to control children. This study does not exclude subtle or rare treatment CNS effects of artesunate or mefloquine. Treatment of acute uncomplicated malaria results in a significant improvement on items of neurological performance.</p

Clinical and cost-effectiveness of an adapted intervention for preschoolers with moderate to severe intellectual disabilities displaying behaviours that challenge: the EPICC-ID RCT

BACKGROUND: Stepping Stones Triple P is an adapted intervention for parents of young children with developmental disabilities who display behaviours that challenge, aiming at teaching positive parenting techniques and promoting a positive parent-child relationship. OBJECTIVE: To evaluate the clinical and cost-effectiveness of level 4 Stepping Stones Triple P in reducing behaviours that challenge in children with moderate to severe intellectual disabilities. DESIGN, SETTING, PARTICIPANTS: A parallel two-arm pragmatic multisite single-blind randomised controlled trial recruited a total of 261 dyads (parent and child). The children were aged 30-59 months and had moderate to severe intellectual disabilities. Participants were randomised, using a 3 : 2 allocation ratio, into the intervention arm (Stepping Stones Triple P; n = 155) or treatment as usual arm (n = 106). Participants were recruited from four study sites in Blackpool, North and South London and Newcastle. INTERVENTION: Level 4 Stepping Stones Triple P consists of six group sessions and three individual phone or face-to-face contacts over 9 weeks. These were changed to remote sessions after 16 March 2020 due to the coronavirus disease 2019 pandemic. MAIN OUTCOME MEASURE: The primary outcome measure was the parent-reported Child Behaviour Checklist, which assesses the severity of behaviours that challenge. RESULTS: We found a small non-significant difference in the mean Child Behaviour Checklist scores (-4.23, 95% CI -9.98 to 1.52, p = 0.146) in the intervention arm compared to treatment as usual at 12 months. Per protocol and complier average causal effect sensitivity analyses, which took into consideration the number of sessions attended, showed the Child Behaviour Checklist mean score difference at 12 months was lower in the intervention arm by -10.77 (95% CI -19.12 to -2.42, p = 0.014) and -11.53 (95% CI -26.97 to 3.91, p = 0.143), respectively. The Child Behaviour Checklist mean score difference between participants who were recruited before and after the coronavirus disease 2019 pandemic was estimated as -7.12 (95% CI -13.44 to -0.81) and 7.61 (95% CI -5.43 to 20.64), respectively (p = 0.046), suggesting that any effect pre-pandemic may have reversed during the pandemic. There were no differences in all secondary measures. Stepping Stones Triple P is probably value for money to deliver (-£1057.88; 95% CI -£3218.6 to -£46.67), but decisions to roll this out as an alternative to existing parenting interventions or treatment as usual may be dependent on policymaker willingness to invest in early interventions to reduce behaviours that challenge. Parents reported the intervention boosted their confidence and skills, and the group format enabled them to learn from others and benefit from peer support. There were 20 serious adverse events reported during the study, but none were associated with the intervention. LIMITATIONS: There were low attendance rates in the Stepping Stones Triple P arm, as well as the coronavirus disease 2019-related challenges with recruitment and delivery of the intervention. CONCLUSIONS: Level 4 Stepping Stones Triple P did not reduce early onset behaviours that challenge in very young children with moderate to severe intellectual disabilities. However, there was an effect on child behaviours for those who received a sufficient dose of the intervention. There is a high probability of Stepping Stones Triple P being at least cost neutral and therefore worth considering as an early therapeutic option given the long-term consequences of behaviours that challenge on people and their social networks. FUTURE WORK: Further research should investigate the implementation of parenting groups for behaviours that challenge in this population, as well as the optimal mode of delivery to maximise engagement and subsequent outcomes. STUDY REGISTRATION: This study is registered as NCT03086876 (https://www.clinicaltrials.gov/ct2/show/NCT03086876?term=Hassiotis±Angela&draw=1&rank=1). FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: HTA 15/162/02) and is published in full in Health Technology Assessment; Vol. 28, No. 6. See the NIHR Funding and Awards website for further award information

The effects of cancer therapies on physical fitness before oesophagogastric cancer surgery: a prospective, blinded, multi-centre, observational, cohort study [version 1; peer review: 2 approved]

Background: Neoadjuvant cancer treatment is associated with improved survival following major oesophagogastric cancer surgery. The impact of neoadjuvant chemo/chemoradiotherapy on physical fitness and operative outcomes is however unclear. This study aims to investigate the impact of neoadjuvant chemo/chemoradiotherapy on fitness and post-operative mortality. Methods: Patients with oesophagogastric cancer scheduled for chemo/chemoradiotherapy and surgery were recruited to a prospective, blinded, multi-centre, observational cohort study. Primary outcomes were changes in fitness with chemo/chemoradiotherapy, measured using cardiopulmonary exercise testing and its association with mortality one-year after surgery. Patients were followed up for re-admission at 30-days, in-hospital morbidity and quality of life (exploratory outcomes). Results: In total, 384 patients were screened, 217 met the inclusion criteria, 160 consented and 159 were included (72% male, mean age 65 years). A total of 132 patients (83%) underwent chemo/chemoradiotherapy, 109 (71%) underwent chemo/chemoradiotherapy and two exercise tests, 100 (63%) completed surgery and follow-up. A significant decline in oxygen uptake at anaerobic threshold and oxygen uptake peak was observed following chemo/chemoradiotherapy: -1.25ml.kg-1.min-1 (-1.80 to -0.69) and -3.02ml.kg-1.min-1 (-3.85 to -2.20); p<0.0001).  Baseline chemo/chemoradiotherapy anaerobic threshold and peak were associated with one-year mortality (HR=0.72, 95%CI 0.59 to 0.88; p=0.001 and HR=0.85, 0.76 to 0.95; p=0.005). The change in physical fitness was not associated with one-year mortality. Conclusion: Chemo/chemoradiotherapy prior to oesophagogastric cancer surgery reduced physical fitness. Lower baseline fitness was associated with reduced overall survival at one-year. Careful consideration of fitness prior to chemo/chemoradiotherapy and surgery is urgently needed

Indoor comfort and adaptation in low-income and middle-income residential buildings in a Nigerian city during a dry season

This paper investigates occupants' comfort, adaptation and their responses during the dry season in low-income to middle-income residential buildings in Abuja, Nigeria. The study aims to provide empirical data on occupants' comfort through evaluating 171 households in four different locations in Abuja. The study considered a combination of different research methods for data collection. Post-occupancy surveys were used to evaluate the buildings and residents' adaptation within the thermal environment. Thermal comfort surveys were also carried out in eight low-income residential households to assess occupants' perception of the thermal environment. Based on the short duration of the physical measurements, building simulation was also used to examine thermal comfort of occupants for an extended period. The Post Occupancy Evaluation (POE) results revealed over 70% of the occupants were dissatisfied with their thermal environment. The comfort surveys reported similar results with over 65% of the responses revealed being ‘uncomfortably warm’. The results showed an overall mean temperature of all the measured case studies to be 31.7 °C and the average temperature (predicted) of 30.7 °C. The neutral temperatures were in a range of 28°C–30.4 °C compared to the preferred temperature range of 27.5°C–29.4 °C. The prevalence of thermal discomfort highlights the need to explore the possibilities of reducing internal temperatures, particularly by passive means (fabric, shading, insulation etc.) given the need to avoid or reduce the need for air conditioning to make the buildings energy-efficient for low to middle income groups

Spectroscopic and Mechanistic Studies of Heterodimetallic Forms of Metallo-β-lactamase NDM-1

In an effort to characterize the roles of each metal ion in metallo-β-lactamase NDM-1, heterodimetallic analogues (CoCo-, ZnCo-, and CoCd-) of the enzyme were generated and characterized. UV–vis, 1H NMR, EPR, and EXAFS spectroscopies were used to confirm the fidelity of the metal substitutions, including the presence of a homogeneous, heterodimetallic cluster, with a single-atom bridge. This marks the first preparation of a metallo-β-lactamase selectively substituted with a paramagnetic metal ion, Co(II), either in the Zn1 (CoCd-NDM-1) or in the Zn2 site (ZnCo-NDM-1), as well as both (CoCo-NDM-1). We then used these metal-substituted forms of the enzyme to probe the reaction mechanism, using steady-state and stopped-flow kinetics, stopped-flow fluorescence, and rapid-freeze-quench EPR. Both metal sites show significant effects on the kinetic constants, and both paramagnetic variants (CoCd- and ZnCo-NDM-1) showed significant structural changes on reaction with substrate. These changes are discussed in terms of a minimal kinetic mechanism that incorporates all of the data