Seismic study of stellar convective cores

It has been shown that a discontinuity in the derivatives of the sound speed at the edge of the convective regions inside a star gives rise to a characteristic oscillatory signal in the frequencies of stellar oscillations. This oscillatory signal has been suggested as a means to study the base of the outer convection zone in low mass stars and possibly the outer edge of the convective core in high mass stars. Using stellar models we show that because of a phenomenon similar to aliasing in Fourier transform, it may not be possible to use this signal to detect the convective core. Nevertheless, it may be possible to determine the size of convective cores using the frequency separation \nu_{n+1,l}-\nu_{n,l}.Comment: Accepted for publication in A &

Health Care Delivery Practices in Huntington's Disease Specialty Clinics : An International Survey

The CHDI Foundation, Inc. funds Enroll-HD and the activities of the Enroll-HD Care Improvement Committee, including the present survey. We would like to acknowledge the Enroll-HD and REGISTRY administrative staff that assisted in the recruitment of sites and sites that completed the survey.Peer reviewedPublisher PD

Asteroseismic determination of helium abundance in stellar envelopes

Intermediate degree modes of the solar oscillations have previously been used to determine the solar helium abundance to a high degree of precision. However, we cannot expect to observe such modes in other stars. In this work we investigate whether low degree modes that should be available from space-based asteroseismology missions can be used to determine the helium abundance, Y, in stellar envelopes with sufficient precision. We find that the oscillatory signal in the frequencies caused by the depression in \Gamma_1 in the second helium ionisation zone can be used to determine the envelope helium abundance of low mass main sequence stars. For frequency errors of 1 part in 10^4, we expect errors \sigma_Y in the estimated helium abundance to range from 0.03 for 0.8M_sun stars to 0.01 for 1.2M_sun stars. The task is more complicated in evolved stars, such as subgiants, but is still feasible if the relative errors in the frequencies are less than 10^{-4}.Comment: To appear in MNRAS. 11 pages, 11 figure

A comparison of the prognostic value of composite ratios and cumulative scores in patients with operable rectal cancer

The aim of this study was to directly compare the prognostic value of cumulative scores and composite ratios in patients with operable rectal cancer. Within a single surgical unit preoperative differential blood cell results including neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, as well as CRP (C) and albumin (A) levels were recorded. These results were used to construct a series of composite ratios (NLR, PLR, LMR, CAR) and cumulative scores (NLS, PLS, LMS, NPS, mGPS). The relationship between composite ratios and the cumulative scores and clinicopathological characteristics, cancer specific survival (CSS) and overall survival (OS) were examined. A total of 413 patients were included. When adjusted for TNM stage, surgical approach, time of surgery and margin involvement mGPS (p < 0.05) was associated with CSS. In addition, most composite ratios/scores showed correlations with neoadjuvant therapy (p < 0.001). When a direct comparison between NPS (myeloid) and mGPS (liver) was carried out they showed similar associations with both CSS and OS. Therefore, both composite ratios and cumulative scores have been shown to be prognostic in patients with operable rectal cancer

A phase 1 study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumors.

Background: This study evaluated safety, pharmacokinetics, and clinical activity of intravenous and oral rucaparib, a poly(ADP-ribose) polymerase inhibitor, combined with chemotherapy in patients with advanced solid tumours. Methods: Initially, patients received escalating doses of intravenous rucaparib combined with carboplatin, carboplatin/paclitaxel, cisplatin/pemetrexed, or epirubicin/cyclophosphamide. Subsequently, the study was amended to focus on oral rucaparib (once daily, days 1–14) combined with carboplatin (day 1) in 21-day cycles. Dose-limiting toxicities (DLTs) were assessed in cycle 1 and safety in all cycles. Results: Eighty-five patients were enrolled (22 breast, 15 ovarian/peritoneal, and 48 other primary cancers), with a median of three prior therapies (range, 1–7). Neutropenia (27.1%) and thrombocytopenia (18.8%) were the most common grade greater than or equal to3 toxicities across combinations and were DLTs with the oral rucaparib/carboplatin combination. Maximum tolerated dose for the combination was 240 mg per day oral rucaparib and carboplatin area under the curve 5 mg ml−1 min−1. Oral rucaparib demonstrated dose-proportional kinetics, a long half-life (≈17 h), and good bioavailability (36%). Pharmacokinetics were unchanged by carboplatin coadministration. The rucaparib/carboplatin combination had radiologic antitumour activity, primarily in BRCA1- or BRCA2-mutated breast and ovarian/peritoneal cancers. Conclusions: Oral rucaparib can be safely combined with a clinically relevant dose of carboplatin in patients with advanced solid tumours (Trial registration ID: NCT01009190)

CoRoT/ESTA-TASK 1 and TASK 3 comparison of the internal structure and seismic properties of representative stellar models: Comparisons between the ASTEC, CESAM, CLES, GARSTEC and STAROX codes

We compare stellar models produced by different stellar evolution codes for the CoRoT/ESTA project, comparing their global quantities, their physical structure, and their oscillation properties. We discuss the differences between models and identify the underlying reasons for these differences. The stellar models are representative of potential CoRoT targets. Overall we find very good agreement between the five different codes, but with some significant deviations. We find noticeable discrepancies (though still at the per cent level) that result from the handling of the equation of state, of the opacities and of the convective boundaries. The results of our work will be helpful in interpreting future asteroseismology results from CoRoT.Comment: 26 pages, 21 figures, accepted for publication in Astrophysics and Space Science, CoRoT/ESTA Volum

Fire regimes and carbon in Australian vegetation

Fires regularly affect many of the world\u27s terrestrial ecosystems, and, as a result, fires mediate the exchange of greenhouse gases (GHG) between the land and the atmosphere at a global scale and affect the capacity of terrestrial ecosystems to store carbon (Bowman et al. 2009). Variations in fire -regimes can therefore potentially affect the global, regional and local carbon balance and, potentially, climate change itself (Bonan 2008). Here we examine how variation in fire regimes (Gill 1975; Bradstock et al. 2002) will potentially affect carbon in fire-prone Australian ecosystems via interactions with the stocks and transfers of carbon that are inherent to all terrestrial ecosystems. There are two key reasons why an appreciation of fire regimes is needed to comprehend the fate of terrestrial carbon. First, the status of terrestrial carbon over time will be a function of the balance between losses (emissions) from individual fires (of differing type, season and intensity), which occur as a result of immediate combustion as well as mortality and longerterm decomposition of dead biomass, and carbon that accumulates during regeneration in the intervals between fires. The length of the interval between fires will determine the amount of biomass that accumulates. Second, fire regimes influence the composition and structure of ecosystems and key processes such as plant mortality and recruitment. Hence, alternative trajectories of vegetation composition and structure that result from differing fire regimes will affect carbon dynamics. We explore these themes and summarise the dynamic aspects of carbon stocks and transfers in relation to fire, present conceptual models of carbon dynamics and fire regimes, and review how variation in fire regimes may affect overall storage potential as a function of fireinduced losses and post-fire uptake in two widespread Australian vegetation types. We then appraise future trends under global change and the likely potential for managing fire regimes for carbon \u27benefits\u27, especially with respect to emissions

Role of the repeat expansion size in predicting age of onset and severity in RFC1 disease

RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson's coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multi-variate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset (smaller allele HR=2.06, p<0.001; larger allele HR=1.53, p<0.001) and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR=3.40, p<0.001; larger allele HR=1.71, p=0.002) or loss of independent walking (smaller allele HR=2.78, p<0.001; larger allele HR=1.60; p<0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions (smaller allele: complex neuropathy RR=1.30, p=0.003; CANVAS RR=1.34, p<0.001; larger allele: complex neuropathy RR=1.33, p=0.008; CANVAS RR=1.31, p=0.009). Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I-V β=-1.06, p<0.001; lobules VI-VII β=-0.34, p=?0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype, and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion.Funding: This work was supported by Medical Research Council (MR/T001712/1), Fondazione Cariplo (grant n. 2019-1836), the Inherited Neuropathy Consortium, and Fondazione Regionale per la Ricerca Biomedica (Regione Lombardia, project ID 1751723). R. Currò was supported by the European Academy of Neurology (EAN) Research Fellowship 2021. H. Houlden and M.M. Reilly thank the MRC, the Wellcome Trust, the MDA, MD UK, Ataxia UK, The MSA Trust, the Rosetrees Trust and the NIHR UCLH BRC for grant support. F. Taroni thanks the Fondazione Regionale per la Ricerca Biomedica (CP 20/2018 (Care4NeuroRare) and the Italian Ministry of Health (RC) for grant support. D. Pareyson thanks the Italian Ministry of Health (RRC) for grant support. F.M. Santorelli thanks Ricerca Corrente 2022 Ministero della Salute 5X1000 for grant support. M. Synofzik thanks the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) and the European Joint Programme on Rare Diseases for grant support. P.F. Chinnery the Medical Research Council Mitochondrial Biology Unit, the Medical Research Council (MRC) International Centre for Genomic Medicine in Neuromuscular Disease, the Leverhulme Trust (RPG-2018-408), the Medical Research Council, the Alzheimer's Society Project, and the NIHR Cambridge Biomedical Research for grant support. Acknowledgements: We thank the patients and relatives who participated in this study

Methodology

© The Author(s) 2019. A detailed overview of the methodologies used to develop the 2.0 °C and 1.5 °C scenario presented in this book. Starting with the overall modelling approach, the interaction of seven different models is explained which are used to calculate and developed detailed scenarios for greenhouse gas emission and energy pathways to stay within a 2.0 °C and 1.5 °C global warming limit. The following models are presented: For the non-energy GHG emission pathways, the Generalized Equal Quantile Walk (GQW)method, the land-based sequestration design method and the Carbon cycle and climate (MAGICC) model. For the energy pathways, a renewable energy resources assessment for space constrained environments ([R]E-SPACE, the transport scenario model (TRAEM), the Energy System Model (EM) and the power system model [R]E 24/7. The methodologies of an employment analysis model, and a metal resource assessment tool are outlined. These models have been used to examine the analysis of the energy scenario results