A large oxygen-dominated core from the seismic cartography of a pulsating white dwarf.

White-dwarf stars are the end product of stellar evolution for most stars in the Universe. Their interiors bear the imprint of fundamental mechanisms that occur during stellar evolution. Moreover, they are important chronometers for dating galactic stellar populations, and their mergers with other white dwarfs now appear to be responsible for producing the type Ia supernovae that are used as standard cosmological candles. However, the internal structure of white-dwarf stars-in particular their oxygen content and the stratification of their cores-is still poorly known, because of remaining uncertainties in the physics involved in stellar modelling codes. Here we report a measurement of the radial chemical stratification (of oxygen, carbon and helium) in the hydrogen-deficient white-dwarf star KIC08626021 (J192904.6+444708), independently of stellar-evolution calculations. We use archival data coupled with asteroseismic sounding techniques to determine the internal constitution of this star. We find that the oxygen content and extent of its core exceed the predictions of existing models of stellar evolution. The central homogeneous core has a mass of 0.45 solar masses, and is composed of about 86 per cent oxygen by mass. These values are respectively 40 per cent and 15 per cent greater than those expected from typical white-dwarf models. These findings challenge present theories of stellar evolution and their constitutive physics, and open up an avenue for calibrating white-dwarf cosmochronology.

Compositionality in visual perception.

Quilty-Dunn et al.'s wide-ranging defense of the Language of Thought Hypothesis (LoTH) argues that vision traffics in abstract, structured representational formats. We agree: Vision, like language, is compositional - just as words compose into phrases, many visual representations contain discrete constituents that combine in systematic ways. Here, we amass evidence extending this proposal, and explore its implications for how vision interfaces with the rest of the mind.

Caregiver self-efficacy to talk about sex predicts conversations about HIV transmission risk with perinatally infected young people in Zimbabwe.

Given advances in care and treatment for HIV, perinatally infected young people are surviving into adolescence. These young people are making decisions about engaging in sexual relationships and it is critical to ensure they have the information they need to engage responsibly in sexual activity, particularly in an era where adherence to treatment could make their virus undetectable. The main objective of this analysis was to examine whether an HIV-positive young person's knowledge about forward transmission is associated with caregiver self-efficacy to talk about sex and general caregiver communication. Using data from a 12-month prospective cohort of caregivers of HIV-positive children aged 9-15 on ART and pre-ART in rural Zimbabwe, we found that caregiver self-efficacy to talk about sex predicted whether conversations about HIV transmission would occur between caregiver and the young person. However, by the end of 12-months, nearly two-thirds of caregivers of HIV-positive teenagers in our sample had still not explained how their adolescents could spread the virus to others despite these caregivers saying their adolescent should know this information at baseline. We discuss the implications for designing sexual and reproductive health (SRH) programs among populations of young people perinatally infected with HIV to ensure that this breakthrough generation receives the SRH support they need.

The face of postural tachycardia syndrome - insights from a large cross-sectional online community-based survey.

BACKGROUND: Patients with postural tachycardia syndrome (POTS) experience chronic symptoms of orthostatic intolerance. There are minimal data detailing the demographics, clinical features and clinical course of this condition. This online, community-based survey highlights patients' experience with POTS. It consists of the largest sample of POTS patients reported to date. OBJECTIVES: To describe the demographics, past medical history, medications, treatments and diagnostic journey for patients living with POTS. METHODS: Postural tachycardia syndrome patients completed an online, community-based, cross-sectional survey. Participants were excluded if they had not received a diagnosis of POTS from a physician. The questions focused on the patient experience and journey, rather than physiological responses. RESULTS: The final analysis included 4835 participants. POTS predominantly affects white (93%) females (94%) of childbearing age, with approximately half developing symptoms in adolescence (mode 14 years). POTS is a chronic multisystem disorder involving a broad array of symptoms, with many patients diagnosed with comorbidities in addition to POTS. POTS patients often experience lengthy delays [median (interquartile range) 24 (6-72) months] and misdiagnosis, but the diagnostic delay is improving. POTS patients can present with a myriad of symptoms most commonly including lightheadedness (99%), tachycardia (97%), presyncope (94%), headache (94%) and difficulty concentrating (94%). CONCLUSIONS: These data provide important insights into the background, clinical features and diagnostic journey of patients suffering from POTS. These data should serve as an essential step for moving forward with future studies aimed at early and accurate diagnoses of these patients leading to appropriate treatments for their symptoms.

Precision Health: Bringing Oral Health into the Context of Overall Health.

Unprecedented advances in genomics, data science, and biotechnology have ushered in a new era of health care in which interventions are increasingly tailored to individual patients. Precision-based approaches extend to oral health, which is essential to overall health. Harnessing the full potential of precision oral health will depend on research to more fully understand the factors that underlie health and contribute to disease-including the human genome, microbiome, epigenome, proteome, and others.

Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer.

Background: Selection of resistance mutations may play a major role in the development of endocrine resistance. ESR1 mutations are rare in primary breast cancer but have high prevalence in patients treated with aromatase inhibitors (AI) for advanced breast cancer. We investigated the evolution of genetic resistance to the first-line AI therapy using sequential ctDNA sampling in patients with advanced breast cancer. Patients and methods: Eighty-three patients on the first-line AI therapy for metastatic breast cancer were enrolled in a prospective study. Plasma samples were collected every 3 months to disease progression and ctDNA analysed by digital droplet PCR and enhanced tagged-amplicon sequencing (eTAm-Seq). Mutations identified in progression samples by sequencing were tracked back through samples before progression to study the evolution of mutations on therapy. The frequency of novel mutations was validated in an independent cohort of available baseline plasma samples in the Study of Faslodex versus Exemestane with or without Arimidex (SoFEA) trial, which enrolled patients with prior sensitivity to AI. Results: Of the 39 patients who progressed on the first-line AI, 56.4% (22/39) had ESR1 mutations detectable at progression, which were polyclonal in 40.9% (9/22) patients. In serial tracking, ESR1 mutations were detectable median 6.7 months (95% confidence interval 3.7-NA) before clinical progression. Utilising eTAm-Seq ctDNA sequencing of progression plasma, ESR1 mutations were demonstrated to be sub-clonal in 72.2% (13/18) patients. Mutations in RAS genes were identified in 15.4% (6/39) of progressing patients (4 KRAS, 1 HRAS, 1 NRAS). In SoFEA, KRAS mutations were detected in 21.2% (24/113) patients although there was no evidence that KRAS mutation status was prognostic for progression free or overall survival. Conclusions: Cancers progressing on the first-line AI show high levels of genetic heterogeneity, with frequent sub-clonal mutations. Sub-clonal KRAS mutations are found at high frequency. The genetic diversity of AI resistant cancers may limit subsequent targeted therapy approaches.

Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder.

This corrects the article DOI: 10.1038/mp.2015.165.

Osimertinib benefit in EGFR-mutant NSCLC patients with T790M-mutation detected by circulating tumour DNA.

Background: Approximately 50% of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitors (TKIs) will acquire resistance by the T790M mutation. Osimertinib is the standard of care in this situation. The present study assesses the efficacy of osimertinib when T790M status is determined in circulating cell-free tumour DNA (ctDNA) from blood samples in progressing advanced EGFR-mutant NSCLC patients. Material and methods: ctDNA T790M mutational status was assessed by Inivata InVision™ (eTAm-Seq™) assay in 48 EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKIs without a tissue biopsy between April 2015 and April 2016. Progressing T790M-positive NSCLC patients received osimertinib (80 mg daily). The objectives were to assess the response rate to osimertinib according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, the progression-free survival (PFS) on osimertinib, and the percentage of T790M positive in ctDNA. Results: The ctDNA T790M mutation was detected in 50% of NSCLC patients. Among assessable patients, osimertinib gave a partial response rate of 62.5% and a stable disease rate of 37.5%. All responses were confirmed responses. After median follow up of 8 months, median PFS by RECIST criteria was not achieved (95% CI: 4-NA), with 6- and 12-months PFS of 66.7% and 52%, respectively. Conclusion(s): ctDNA from liquid biopsy can be used as a surrogate marker for T790M in tumour tissue.

Nuclear Magnetic Resonance Signature of the Spin-Nematic Phase in LiCuVO_{4} at High Magnetic Fields.

We report a ^{51}V nuclear magnetic resonance investigation of the frustrated spin-1/2 chain compound LiCuVO_{4}, performed in pulsed magnetic fields and focused on high-field phases up to 56 T. For the crystal orientations H∥c and H∥b, we find a narrow field region just below the magnetic saturation where the local magnetization remains uniform and homogeneous, while its value is field dependent. This behavior is the first microscopic signature of the spin-nematic state, breaking spin-rotation symmetry without generating any transverse dipolar order, and is consistent with theoretical predictions for the LiCuVO_{4} compound.

Entropy Evolution in the Magnetic Phases of Partially Frustrated CePdAl.

In the heavy-fermion metal CePdAl, long-range antiferromagnetic order coexists with geometric frustration of one-third of the Ce moments. At low temperatures, the Kondo effect tends to screen the frustrated moments. We use magnetic fields B to suppress the Kondo screening and study the magnetic phase diagram and the evolution of the entropy with B employing thermodynamic probes. We estimate the frustration by introducing a definition of the frustration parameter based on the enhanced entropy, a fundamental feature of frustrated systems. In the field range where the Kondo screening is suppressed, the liberated moments tend to maximize the magnetic entropy and strongly enhance the frustration. Based on our experiments, this field range may be a promising candidate to search for a quantum spin liquid.

Copy number variation in bipolar disorder.

Large (>100 kb), rare (<1% in the population) copy number variants (CNVs) have been shown to confer risk for schizophrenia (SZ), but the findings for bipolar disorder (BD) are less clear. In a new BD sample from the United Kingdom (n=2591), we have examined the occurrence of CNVs and compared this with previously reported samples of 6882 SZ and 8842 control subjects. When combined with previous data, we find evidence for a contribution to BD for three SZ-associated CNV loci: duplications at 1q21.1 (P=0.022), deletions at 3q29 (P=0.03) and duplications at 16p11.2 (P=2.3 × 10(-4)). The latter survives multiple-testing correction for the number of recurrent large CNV loci in the genome. Genes in 20 regions (total of 55 genes) were enriched for rare exonic CNVs among BD cases, but none of these survives correction for multiple testing. Finally, our data provide strong support for the hypothesis of a lesser contribution of very large (>500 kb) CNVs in BD compared with SZ, most notably for deletions >1 Mb (P=9 × 10(-4)).

Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder.

Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P=2.74 × 10(-8)). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants ('SNP heritability') as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD.

A compact system of small planets around a former red-giant star.

Planets that orbit their parent star at less than about one astronomical unit (1 AU is the Earth-Sun distance) are expected to be engulfed when the star becomes a red giant. Previous observations have revealed the existence of post-red-giant host stars with giant planets orbiting as close as 0.116 AU or with brown dwarf companions in tight orbits, showing that these bodies can survive engulfment. What has remained unclear is whether planets can be dragged deeper into the red-giant envelope without being disrupted and whether the evolution of the parent star itself could be affected. Here we report the presence of two nearly Earth-sized bodies orbiting the post-red-giant, hot B subdwarf star KIC 05807616 at distances of 0.0060 and 0.0076 AU, with orbital periods of 5.7625 and 8.2293 hours, respectively. These bodies probably survived deep immersion in the former red-giant envelope. They may be the dense cores of evaporated giant planets that were transported closer to the star during the engulfment and triggered the mass loss necessary for the formation of the hot B subdwarf, which might also explain how some stars of this type did not form in binary systems.

Exercise for people with cancer: a systematic review.

BACKGROUND: This systematic review was completed by the Exercise for People with Cancer Guideline Development Group, a group organized by Cancer Care Ontario's Program in Evidence-Based Care (pebc). It provides background and guidance for clinicians with respect to exercise for people living with cancer in active and post treatment. It focuses on the benefits of specific types of exercise, pre-screening requirements for new referrals, safety concerns, and delivery models. METHODS: Using the pebc's standardized approach, medline and embase were systematically searched for existing guidelines, systematic reviews, and primary literature. RESULTS: The search identified two guidelines, eighteen systematic reviews, and twenty-nine randomized controlled trials with relevance to the topic. The present review provides conclusions about the duration, frequency, and intensity of exercise appropriate for people living with cancer. CONCLUSIONS: The evidence shows that exercise is safe and provides benefit in quality of life and in muscular and aerobic fitness for people with cancer both during and after treatment. The evidence is sufficient to support the promotion of exercise for adults with cancer, and some evidence supports the promotion of exercise in group or supervised settings and for a long period of time to improve quality of life and muscular and aerobic fitness. Exercise at moderate intensities could also be sustainable for longer periods and could encourage exercise to be continued over an individual's lifetime. It is important that a pre-screening assessment be conducted to evaluate the effects of disease, treatments, and comorbidities.

Exercise for people with cancer: a clinical practice guideline.

BACKGROUND: Development of this guideline was undertaken by the Exercise for People with Cancer Guideline Development Group, a group organized by Cancer Care Ontario's Program in Evidence-Based Care (pebc). The purpose of the guideline was to provide guidance for clinicians with respect to exercise for patients living with cancer, focusing on the benefits of specific types of exercise, recommendations about screening requirements for new referrals, and safety concerns. METHODS: Consistent with the pebc's standardized approach, a systematic search was conducted for existing guidelines, and systematic literature searches were performed in medline and embase for both systematic reviews and primary literature. Content and methodology experts performed an internal review, which was followed by an external review by targeted experts and intended users. RESULTS: The search identified three guidelines, eighteen systematic reviews, and twenty-nine randomized controlled trials with relevance to the topic. The present guideline provides recommendations for the duration, frequency, and intensity of exercise appropriate for people living with cancer. It also provides recommendations for pre-exercise assessment, safety concerns, and delivery models. CONCLUSIONS: There is sufficient evidence to show that exercise provides benefits in quality of life and muscular and aerobic fitness for people with cancer both during and after treatment, and that it does not cause harm. The present guideline is intended to support the Canadian Society for Exercise Physiology's Canadian physical activity guidelines. The recommendations are intended for clinicians and institutions treating cancer patients in Ontario, and for policymakers and program planners involved in the delivery of exercise programs for cancer patients.

Acute care hospitalization near the end of life for cancer patients who die in hospital in Canada.

Acute care hospitals have a role in managing the health care needs of people affected by cancer when they are at the end of life. However, there is a need to provide end-of-life care in other settings, including at home or in hospice, when such settings are more appropriate. Using data from 9 provinces, we examined indicators that describe the current landscape of acute care hospital use at the end of life for patients who died of cancer in hospital in Canada. Interprovincial variation was observed in acute care hospital deaths, length of stay in hospital, readmission to hospital, and intensive care unit use at the end of life. High rates of acute care hospital use near the end of life might suggest that community and home-based end-of-life care might not be suiting patient needs.

Fractional Quantum Hall States in a Ge Quantum Well.

Measurements of the Hall and dissipative conductivity of a strained Ge quantum well on a SiGe/(001)Si substrate in the quantum Hall regime are reported. We analyze the results in terms of thermally activated quantum tunneling of carriers from one internal edge state to another across saddle points in the long-range impurity potential. This shows that the gaps for different filling fractions closely follow the dependence predicted by theory. We also find that the estimates of the separation of the edge states at the saddle are in line with the expectations of an electrostatic model in the lowest spin-polarized Landau level (LL), but not in the spin-reversed LL where the density of quasiparticle states is not high enough to accommodate the carriers required.

A multi-method review of home-based chemotherapy.

This study summarises research- and practice-based evidence on home-based chemotherapy, and explores existing delivery models. A three-pronged investigation was conducted consisting of a literature review and synthesis of 54 papers, a review of seven home-based chemotherapy programmes spanning four countries, and two case studies within the Canadian province of Ontario. The results support the provision of home-based chemotherapy as a safe and patient-centred alternative to hospital- and outpatient-based service. This paper consolidates information on home-based chemotherapy programmes including services and drugs offered, patient eligibility criteria, patient views and experiences, delivery structures and processes, and common challenges. Fourteen recommendations are also provided for improving the delivery of chemotherapy in patients' homes by prioritising patient-centredness, provider training and teamwork, safety and quality of care, and programme management. The results of this study can be used to inform the development of an evidence-informed model for the delivery of chemotherapy and related care, such as symptom management, in patients' homes.

Special care dentistry: how prepared are we?

AIM: To assess and evaluate the confidence of the undergraduate dental team in Irish dental schools regarding their training in the field of special care dentistry (SCD). METHOD: A questionnaire was distributed amongst the undergraduate dental teams within Cork University Dental School and Hospital (CUDSH) and Dublin Dental University Hospital (DDUH). The data were analysed to assess for differences between the median responses of the various groups. RESULTS: A total of 139 students participated in the study; 82 from DDUH (59 dental science students, seven dental hygiene students and 16 dental nursing students) and 57 from CUDSH (43 dental science students and 14 dental hygiene students). Twenty-two per cent (n = 30) of respondents agreed that their training had been sufficient in providing treatment or assistance for patients requiring SCD. Seventy-five per cent agreed that more emphasis should be placed on clinical training in SCD (n = 76). Thirty-one per cent of students anticipated a high level of confidence in treating patients requiring SCD upon graduation (n = 43), with dental science students feeling the least prepared amongst the dental team. CONCLUSION: Confidence levels of the undergraduate dental team were low with regard to SCD. The existing hands-on clinical training in SCD was deemed insufficient by the respondents. Students believed more emphasis should be placed on SCD training in the undergraduate curriculum.

Patient-reported outcomes in routine cancer clinical practice: a scoping review of use, impact on health outcomes, and implementation factors.

BACKGROUND: This review focused on the identification of patient-reported outcome measures (PROMs) used in routine cancer clinical practice, the impact on patient, provider, and system outcomes, and the implementation factors influencing uptake. METHODS: A scoping review of the published health literature was conducted using empirical databases, namely, Ovid Medline (2003 to September 2013), CINAHL (2003-2013) and PsycINFO (2003-2013). Scoping reviews are systematic literature reviews in a broad topic area that provide relevant and quantified results about the knowledge available on a particular topic and aim to rapidly map and synthesize the evidence to emphasize what is known. RESULTS: From a total of 2447 unique publications, 30 articles that met eligibility criteria were reviewed. PRO use appears to be acceptable to patients, enables earlier detection of symptoms and may improve communication between clinicians and patients. However, the impact of routine PROMs collection on health outcomes is less clear and high-quality research is still warranted. CONCLUSION: PROMs use in routine cancer clinical practice is growing with improvements on essential care processes shown but a number of implementation barriers must still be addressed. The lack of standardization in PROMs used in cancer organizations may make it difficult to use these data for quality monitoring in the future.