The Ages of Pre-main-sequence Stars

The position of pre-main-sequence or protostars in the Hertzsprung--Russell diagram is often used to determine their mass and age by comparison with pre-main-sequence evolution tracks. On the assumption that the stellar models are accurate, we demonstrate that, if the metallicity is known, the mass obtained is a good estimate. However, the age determination can be very misleading because it is significantly (generally different by a factor of two to five) dependent on the accretion rate and, for ages less than about one million years, the initial state of the star. We present a number of accreting protostellar tracks that can be used to determine age if the initial conditions can be determined and the underlying accretion rate has been constant in the past. Because of the balance established between the Kelvin-Helmholtz, contraction timescale and the accretion timescale a pre-main-sequence star remembers its accretion history. Knowledge of the current accretion rate, together with an H--R-diagram position gives information about the rate of accretion in the past but does not necessarily improve any age estimate. We do not claim that ages obtained by comparison with these particular accreting tracks are likely to be any more reliable than those from comparisons with non-accreting tracks. Instead we stress the unreliability of any such comparisons and use the disparities between various tracks to estimate the likely errors in age and mass estimates. We also show how a set of coeval accreting objects do not appear coeval when compared with non-accreting tracks. Instead accreting pre-main-sequence stars of around a solar mass are likely to appear older than those of either smaller or larger mass.Comment: Accepted by MNRA

Can rapid approaches to qualitative analysis deliver timely, valid findings to clinical leaders? A mixed methods study comparing rapid and thematic analysis

Objectives. This study compares rapid and traditional analyses of a UK health service evaluation dataset to explore differences in researcher time and consistency of outputs. Design. Mixed methods study, quantitatively and qualitatively comparing qualitative methods. Setting. Data from a home birth service evaluation study in a hospital in the English National Health Service, which took place between October and December 2014. Two research teams independently analysed focus group and interview transcript data: one team used a thematic analysis approach using the framework method, and the second used rapid analysis. Participants. Home birth midwives (6), midwifery support workers (4), commissioners (4), managers (6), and community midwives (12) and a patient representative (1) participated in the original study. Primary outcome measures. Time taken to complete analysis in person hours; analysis findings and recommendations matched, partially matched or not matched across the two teams. Results. Rapid analysis data management took less time than thematic analysis (43 hours vs 116.5 hours). Rapid analysis took 100 hours, and thematic analysis took 126.5 hours in total, with interpretation and write up taking much longer in the rapid analysis (52 hours vs 8 hours). Rapid analysis findings overlapped with 79% of thematic analysis findings, and thematic analysis overlapped with 63% of the rapid analysis findings. Rapid analysis recommendations overlapped with 55% of those from the thematic analysis, and thematic analysis overlapped with 59% of the rapid analysis recommendations. Conclusions. Rapid analysis delivered a modest time saving. Excessive time to interpret data in rapid analysis in this study may be due to differences between research teams. There was overlap in outputs between approaches, more in findings than recommendations. Rapid analysis may have the potential to deliver valid, timely findings while taking less time. We recommend further comparisons using additional data sets with more similar research teams

Engaging with History after Macpherson

The Race Relations Amendment Act (2000) identifies a key role for education, and more specifically history, in promoting ‘race equality’ in Britain. In this article Ian Grosvenor and Kevin Myers consider the extent of young people’s current engagement with the history of ‘diversity, change and immigration’ which underpins the commitment to ‘race equality’. Finding that in many of Britain’s schools and universities a singular and exclusionary version of history continues to dominate the curriculum, they go on to consider the reasons for the neglect of multiculturalism. The authors identify the development of an aggressive national identity that depends on the past for its legitimacy and argue that this sense of the past is an important obstacle to future progress

Synthesis and structural characterization of a mimetic membrane-anchored prion protein

During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We demonstrate that PrP coupled to GPIm (PrP-GPIm) inserts into model lipid membranes and that structural information can be obtained from this membrane-anchored PrP. We show that the structure of PrP-GPIm reconstituted in phosphatidylcholine and raft membranes resembles that of PrP, without a GPI anchor, in solution. The results provide experimental evidence in support of previous suggestions that NMR structures of soluble, anchor-free forms of PrP represent the structure of cellular, membrane-anchored PrP. The availability of a lipid-anchored construct of PrP provides a unique model to investigate the effects of different lipid environments on the structure and conversion mechanisms of PrP

Effect of cadence on locomotor–respiratory coupling during upper-body exercise

Introduction: Asynchronous arm-cranking performed at high cadences elicits greater cardiorespiratory responses compared to low cadences. This has been attributed to increased postural demand and locomotor–respiratory coupling (LRC), and yet, this has not been empirically tested. This study aimed to assess the effects of cadence on cardiorespiratory responses and LRC during upper-body exercise. Methods: Eight recreationally-active men performed arm-cranking exercise at moderate and severe intensities that were separated by 10 min of rest. At each intensity, participants exercised for 4 min at each of three cadences (50, 70, and 90 rev min−1) in a random order, with 4 min rest-periods applied in-between cadences. Exercise measures included LRC via whole- and half-integer ratios, cardiorespiratory function, perceptions of effort (RPE and dyspnoea), and diaphragm EMG using an oesophageal catheter. Results: The prevalence of LRC during moderate exercise was highest at 70 vs. 50 rev min−1 (27 ± 10 vs. 13 ± 9%, p = 0.000) and during severe exercise at 90 vs. 50 rev min−1 (24 ± 7 vs. 18 ± 5%, p = 0.034), with a shorter inspiratory time and higher mean inspiratory flow (p < 0.05) at higher cadences. During moderate exercise, (Formula presented.) and fC were higher at 90 rev min−1 (p < 0.05) relative to 70 and 50 rev min−1 ((Formula presented.) 1.19 ± 0.25 vs. 1.05 ± 0.21 vs. 0.97 ± 0.24 L min−1; fC 116 ± 11 vs. 101 ± 13 vs. 101 ± 12 b min−1), with concomitantly elevated dyspnoea. There were no discernible cadence-mediated effects on diaphragm EMG. Conclusion: Participants engage in LRC to a greater extent at moderate-high cadences which, in turn, increase respiratory airflow. Cadence rate should be carefully considered when designing aerobic training programmes involving the upper-limbs

DAF-16 and Δ9 Desaturase Genes Promote Cold Tolerance in Long-Lived Caenorhabditis elegans age-1 Mutants

In Caenorhabditis elegans, mutants of the conserved insulin/IGF-1 signalling (IIS) pathway are long-lived and stress resistant due to the altered expression of DAF-16 target genes such as those involved in cellular defence and metabolism. The three Δ9 desaturase genes, fat-5, fat-6 and fat-7, are included amongst these DAF-16 targets, and it is well established that Δ9 desaturase enzymes play an important role in survival at low temperatures. However, no assessment of cold tolerance has previously been reported for IIS mutants. We demonstrate that long-lived age-1(hx546) mutants are remarkably resilient to low temperature stress relative to wild type worms, and that this is dependent upon daf-16. We also show that cold tolerance following direct transfer to low temperatures is increased in wild type worms during the facultative, daf-16 dependent, dauer stage. Although the cold tolerant phenotype of age-1(hx546) mutants is predominantly due to the Δ9 desaturase genes, additional transcriptional targets of DAF-16 are also involved. Surprisingly, survival of wild type adults following a rapid temperature decline is not dependent upon functional daf-16, and cellular distributions of a DAF-16::GFP fusion protein indicate that DAF-16 is not activated during low temperature stress. This suggests that cold-induced physiological defences are not specifically regulated by the IIS pathway and DAF-16, but expression of DAF-16 target genes in IIS mutants and dauers is sufficient to promote cross tolerance to low temperatures in addition to other forms of stress

Germline Polymorphisms in MGMT Associated With Temozolomide-Related Myelotoxicity Risk in Patients With Glioblastoma Treated on NRG Oncology/RTOG 0825

Background: We sought to identify clinical and genetic predictors of temozolomide-related myelotoxicity among patients receiving therapy for glioblastoma. Methods: Patients (n = 591) receiving therapy on NRG Oncology/RTOG 0825 were included in the analysis. Cases were patients with severe myelotoxicity (grade 3 and higher leukopenia, neutropenia, and/or thrombocytopenia); controls were patients without such toxicity. A risk-prediction model was built and cross-validated by logistic regression using only clinical variables and extended using polymorphisms associated with myelotoxicity. Results: 23% of patients developed myelotoxicity (n = 134). This toxicity was first reported during the concurrent phase of therapy for 56 patients; 30 stopped treatment due to toxicity. Among those who continued therapy (n = 26), 11 experienced myelotoxicity again. The final multivariable clinical factor model included treatment arm, gender, and anticonvulsant status and had low prediction accuracy (area under the curve [AUC] = 0.672). The final extended risk prediction model including four polymorphisms in MGMT had better prediction (AUC = 0.827). Receiving combination chemotherapy (OR, 1.82; 95% CI, 1.02-3.27) and being female (OR, 4.45; 95% CI, 2.45-8.08) significantly increased myelotoxicity risk. For each additional minor allele in the polymorphisms, the risk increased by 64% (OR, 1.64; 95% CI, 1.43-1.89). Conclusions: Myelotoxicity during concurrent chemoradiation with temozolomide is an uncommon but serious event, often leading to treatment cessation. Successful prediction of toxicity may lead to more cost-effective individualized monitoring of at-risk subjects. The addition of genetic factors greatly enhanced our ability to predict toxicity among a group of similarly treated glioblastoma patients