Application of the PM6 method to modeling the solid state

The applicability of the recently developed PM6 method for modeling various properties of a wide range of organic and inorganic crystalline solids has been investigated. Although the geometries of most systems examined were reproduced with good accuracy, severe errors were found in the predicted structures of a small number of solids. The origin of these errors was investigated, and a strategy for improving the method proposed

Postpandemic rebound of adeno-associated virus type 2 (AAV2) infections temporally associated with an outbreak of unexplained severe acute hepatitis in children in the United Kingdom

Over 1000 cases of unexplained severe acute hepatitis in children have been reported to date worldwide. An association with adeno-associated virus type 2 (AAV2) infection, a human parvovirus, prompted us to investigate the epidemiology of AAV in the United Kingdom. Three hundred pediatric respiratory samples collected before (April 03, 2009–April 03, 2013) and during (April 03, 2022) the COVID-19 pandemic were obtained. Wastewater samples were collected from 50 locations in London (August 2021–March 2022). Samples were tested for AAV using real-time polymerase chain reaction followed by sequencing. Selected adenovirus (AdV)-positive samples were also sequenced. The detection frequency of AAV2 was a sevenfold higher in 2022 samples compared with 2009–2013 samples (10% vs. 1.4%) and highest in AdV-positive samples compared with negatives (10/37, 27% vs. 5/94, 5.3%, respectively). AAV2-positive samples displayed high genetic diversity. AAV2 sequences were either very low or absent in wastewater collected in 2021 but increased in January 2022 and peaked in March 2022. AAV2 was detected in children in association with AdV of species C, with a highest frequency in 2022. Our findings are consistent with the expansion of the population of children unexposed to AAV2, leading to greater spread of the virus once distancing restrictions were lifted

Synchronisation of egg hatching of brown hairstreak (Thecla betulae) and budburst of blackthorn (Prunus spinosa) in a warmer future

Synchronisation of the phenology of insect herbivores and their larval food plant is essential for the herbivores’ fitness. The monophagous brown hairstreak (Thecla betulae) lays its eggs during summer, hibernates as an egg, and hatches in April or May in the Netherlands. Its main larval food plant blackthorn (Prunus spinosa) flowers in early spring, just before the leaves appear. As soon as the Blackthorn opens its buds, and this varies with spring temperatures, food becomes available for the brown hairstreak. However, the suitability of the leaves as food for the young caterpillars is expected to decrease rapidly. Therefore, the timing of egg hatch is an important factor for larval growth. This study evaluates food availability for brown hairstreak at different temperatures. Egg hatch and budburst were monitored from 2004 to 2008 at different sites in the Netherlands. Results showed ample food availability at all monitored temperatures and sites but the degree of synchrony varied strongly with spring temperatures. To further study the effect of temperature on synchronisation, an experiment using normal temperatures of a reference year (T) and temperatures of T + 5°C was carried out in climate chambers. At T + 5°C, both budburst and egg hatch took place about 20 days earlier and thus, on average, elevated temperature did not affect synchrony. However, the total period of budburst was 11 days longer, whereas the period of egg hatching was 3 days shorter. The implications for larval growth by the brown hairstreak under a warmer climate are considered.

A new scheme to calculate isotope effects

We present a new scheme to calculate isotope effects. Only selected frequencies at the target level of theory are calculated. The frequencies are selected by an analysis of the Hessian from a lower level of theory. We obtain accurate isotope effects without calculating the full Hessian at the target level of theory. The calculated frequencies are very accurate. The scheme converges to the correct isotope effect

Three applications of path integrals: equilibrium and kinetic isotope effects, and the temperature dependence of the rate constant of the [1,5] sigmatropic hydrogen shift in (Z)-1,3-pentadiene

Recent experiments have confirmed the importance of nuclear quantum effects even in large biomolecules at physiological temperature. Here we describe how the path integral formalism can be used to describe rigorously the nuclear quantum effects on equilibrium and kinetic properties of molecules. Specifically, we explain how path integrals can be employed to evaluate the equilibrium (EIE) and kinetic (KIE) isotope effects, and the temperature dependence of the rate constant. The methodology is applied to the [1,5] sigmatropic hydrogen shift in pentadiene. Both the KIE and the temperature dependence of the rate constant confirm the importance of tunneling and other nuclear quantum effects as well as of the anharmonicity of the potential energy surface. Moreover, previous results on the KIE were improved by using a combination of a high level electronic structure calculation within the harmonic approximation with a path integral anharmonicity correction using a lower level method.Comment: 9 pages, 4 figure

Complete mitochondrial DNA sequences provide new insights into the Polynesian motif and the peopling of Madagascar

More than a decade of mitochondrial DNA (mtDNA) studies have given the 'Polynesian motif' renowned status as a marker for tracing the late-Holocene expansion of Austronesian speaking populations. Despite considerable research on the Polynesian motif in Oceania, there has been little equivalent work on the western edge of its expansion - leaving major issues unresolved regarding the motif's evolutionary history. This has also led to considerable uncertainty regarding the settlement of Madagascar. In this study, we assess mtDNA variation in 266 individuals from three Malagasy ethnic groups: the Mikea, Vezo, and Merina. Complete mtDNA genome sequencing reveals a new variant of the Polynesian motif in Madagascar; two coding region mutations define a Malagasy-specific sub-branch. This newly defined 'Malagasy motif' occurs at high frequency in all three ethnic groups (13-50%), and its phylogenetic position, geographic distribution, and estimated age all support a recent origin, but without conclusively identifying a specific source region. Nevertheless, the haplotype's limited diversity, similar to those of other mtDNA haplogroups found in our Malagasy groups, best supports a small number of initial settlers arriving to Madagascar through the same migratory process. Finally, the discovery of this lineage provides a set of new polymorphic positions to help localize the Austronesian ancestors of the Malagasy, as well as uncover the origin and evolution of the Polynesian motif itself

Parameter identification problems in the modelling of cell motility

We present a novel parameter identification algorithm for the estimation of parameters in models of cell motility using imaging data of migrating cells. Two alternative formulations of the objective functional that measures the difference between the computed and observed data are proposed and the parameter identification problem is formulated as a minimisation problem of nonlinear least squares type. A Levenberg–Marquardt based optimisation method is applied to the solution of the minimisation problem and the details of the implementation are discussed. A number of numerical experiments are presented which illustrate the robustness of the algorithm to parameter identification in the presence of large deformations and noisy data and parameter identification in three dimensional models of cell motility. An application to experimental data is also presented in which we seek to identify parameters in a model for the monopolar growth of fission yeast cells using experimental imaging data. Our numerical tests allow us to compare the method with the two different formulations of the objective functional and we conclude that the results with both objective functionals seem to agree

Radiotherapy following breast-conserving surgery for screen-detected ductal carcinoma in situ: indications and utilisation in the UK. Interim findings from the Sloane Project

Use of radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) varies according to country, precedent and prejudice. Results from a preliminary analysis of the data available within the UK Sloane Project can be appreciated in the context of the uncertainty concerning the selection of adjuvant RT following BCS for DCIS. There was a marked geographical variation in the use of RT within the United Kingdom. However, overall, patients with DCIS treated with BCS were significantly more likely to have RT planned (and given) if they had large (⩾15 mm), intermediate or high-grade tumours or if central comedo-type necrosis was present. Unexpectedly, margin width did not appear to have a significant effect on the decision-making process. However, the Van Nuys Prognostic Index did significantly affect the chances of getting planned RT in the univariate analysis, suggesting that clinicians may be starting to use this scoring system in routine practice to assist in decision making

Talking in primary care (TIP): protocol for a cluster-randomised controlled trial in UK primary care to assess clinical and cost-effectiveness of communication skills e-learning for practitioners on patients' musculoskeletal pain and enablement.

INTRODUCTION: Effective communication can help optimise healthcare interactions and patient outcomes. However, few interventions have been tested clinically, subjected to cost-effectiveness analysis or are sufficiently brief and well-described for implementation in primary care. This paper presents the protocol for determining the effectiveness and cost-effectiveness of a rigorously developed brief eLearning tool, EMPathicO, among patients with and without musculoskeletal pain. METHODS AND ANALYSIS: A cluster randomised controlled trial in general practitioner (GP) surgeries in England and Wales serving patients from diverse geographic, socioeconomic and ethnic backgrounds. GP surgeries are randomised (1:1) to receive EMPathicO e-learning immediately, or at trial end. Eligible practitioners (eg, GPs, physiotherapists and nurse practitioners) are involved in managing primary care patients with musculoskeletal pain. Patient recruitment is managed by practice staff and researchers. Target recruitment is 840 adults with and 840 without musculoskeletal pain consulting face-to-face, by telephone or video. Patients complete web-based questionnaires at preconsultation baseline, 1 week and 1, 3 and 6 months later. There are two patient-reported primary outcomes: pain intensity and patient enablement. Cost-effectiveness is considered from the National Health Service and societal perspectives. Secondary and process measures include practitioner patterns of use of EMPathicO, practitioner-reported self-efficacy and intentions, patient-reported symptom severity, quality of life, satisfaction, perceptions of practitioner empathy and optimism, treatment expectancies, anxiety, depression and continuity of care. Purposive subsamples of patients, practitioners and practice staff take part in up to two qualitative, semistructured interviews. ETHICS APPROVAL AND DISSEMINATION: Approved by the South Central Hampshire B Research Ethics Committee on 1 July 2022 and the Health Research Authority and Health and Care Research Wales on 6 July 2022 (REC reference 22/SC/0145; IRAS project ID 312208). Results will be disseminated via peer-reviewed academic publications, conference presentations and patient and practitioner outlets. If successful, EMPathicO could quickly be made available at a low cost to primary care practices across the country. TRIAL REGISTRATION NUMBER: ISRCTN18010240