A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

A faint type of supernova from a white dwarf with a helium-rich companion.

Supernovae are thought to arise from two different physical processes. The cores of massive, short-lived stars undergo gravitational core collapse and typically eject a few solar masses during their explosion. These are thought to appear as type Ib/c and type II supernovae, and are associated with young stellar populations. In contrast, the thermonuclear detonation of a carbon-oxygen white dwarf, whose mass approaches the Chandrasekhar limit, is thought to produce type Ia supernovae. Such supernovae are observed in both young and old stellar environments. Here we report a faint type Ib supernova, SN 2005E, in the halo of the nearby isolated galaxy, NGC 1032. The 'old' environment near the supernova location, and the very low derived ejected mass ( approximately 0.3 solar masses), argue strongly against a core-collapse origin. Spectroscopic observations and analysis reveal high ejecta velocities, dominated by helium-burning products, probably excluding this as a subluminous or a regular type Ia supernova. We conclude that it arises from a low-mass, old progenitor, likely to have been a helium-accreting white dwarf in a binary. The ejecta contain more calcium than observed in other types of supernovae and probably large amounts of radioactive (44)Ti.

Newly formed dust within the circumstellar environment of SN Ia-CSM 2018evt.

Dust associated with various stellar sources in galaxies at all cosmic epochs remains a controversial topic, particularly whether supernovae play an important role in dust production. We report evidence of dust formation in the cold, dense shell behind the ejecta-circumstellar medium (CSM) interaction in the Type Ia-CSM supernova (SN) 2018evt three years after the explosion, characterized by a rise in mid-infrared emission accompanied by an accelerated decline in the optical radiation of the SN. Such a dust-formation picture is also corroborated by the concurrent evolution of the profiles of the Hα emission line. Our model suggests enhanced CSM dust concentration at increasing distances from the SN as compared to what can be expected from the density profile of the mass loss from a steady stellar wind. By the time of the last mid-infrared observations at day +1,041, a total amount of 1.2 ± 0.2 × 10-2 M⊙ of new dust has been formed by SN 2018evt, making SN 2018evt one of the most prolific dust factories among supernovae with evidence of dust formation. The unprecedented witness of the intense production procedure of dust may shed light on the perceptions of dust formation in cosmic history.

Performance demonstration of vacuum microwave components critical for the operation of the ITER low-field side reflectometer.

Final design studies in preparation for manufacturing have been performed for functional components of the vacuum portion of the ITER Low-Field Side Reflectometer (LFSR). These components consist of an antenna array, electron cyclotron heating (ECH) protection mirrors, phase calibration mirrors, and vacuum windows. Evaluation of these components was conducted at the LFSR test facility and DIII-D. The antenna array consists of six corrugated-waveguide antennas for simultaneous profile, fluctuation, and Doppler measurements. A diffraction grating, incorporated into the plasma-facing miter bend, provides protection of sensitive components from stray ECH at 170 GHz. For in situ phase calibration of the LFSR profile reflectometer, an embossed mirror is incorporated into the adjacent miter bend. Measurements of the radiated beam profile indicate that these components have a small, acceptable effect on mode conversion and beam quality. Baseline transmission characteristics of the dual-disk vacuum window are obtained and are used to guide ongoing developments. Preliminary simulations indicate that a surface-relief structure on the window surfaces can greatly improve transmission. The workability of real-time phase measurements was demonstrated on the DIII-D profile reflectometer. The new automated real-time analysis agrees well with the standard post-processing routine.

Confidence matters: a Self-Determination Theory study of factors determining engagement in self-management support practices of UK clinicians.

Within a national quality improvement programme for self-management of long-term conditions, we surveyed clinicians working with patients with diabetes, chronic obstructive pulmonary disease, musculoskeletal pain and depression. We applied the Self-Determination Theory framework to explore what factors can facilitate and impede the clinicians' engagement in clinical self-management support (SMS), patient centredness and organizational support for self-management. We also investigated whether attending professional training for clinicians in the practice of self-management (SM) increases motivation to support SM and reported use of SM practices. The study included 482 clinicians who were surveyed once (cross-sectional design) and 114 clinicians who were surveyed before and after training (longitudinal cohort). We found that the high level of satisfaction of competence need predicts practising SMS in all three areas (clinical SMS: beta coefficient = 0.21; p < 0.0001; patient centredness: beta coefficient = 0.50; p < 0.001; organizational SMS: coefficient = 0.20; p < 0.0001). Internalized regulation to support SMS increases engagement in clinical and organizational SMS. Upon comparing the two samples we explored the possible predictors of clinicians' self-referring to attend the training. Clinicians who volunteer to attend the training spend more time working directly with patients with long-term conditions (chi(2) = 4.8; df = 1; p = 0.02), had less previous relevant training (chi(2) = 4.77; df = 1; p = 0.02), and they have less autonomy to support SM (t = 5.0; df = 476; p < 0.0001). However, they report more engagement in patient-centred practices (t = 1.9; df = 585; p = 0.05). These factors are a good fit with the aims of the programme. We confirmed that attending the training had a significant, positive impact on clinicians' engagement in clinical SMS and patient centredness, as well as their overall confidence to support SM. We conclude that to facilitate clinicians to practice SMS it is very important to provide relevant professional training, professional support and incentives to foster clinicians' perceptions of their competence in relation to these practices. Organizations should develop a culture that values SMS, offer training to clinicians to enhance their sense of competence to effectively deliver SMS and support clinicians in finding their own way of supporting SM; in other words to create an optimal context to internalize regulation to support SM.

Aldrin and dieldrin: loss under sterile conditions.

After their application to sterile nutrient agar, both aldrin and dieldrin disappeared rather rapidly from the agar in glass-covered petri dishes. In most instances this disappearance was considerably retarded from agar inoculated with either fungi or bacteria. In the presence of microorganisms, aldrin was also epoxidized into dieldrin. Half of the applied aldrin volatilized from the agar during the first day of incubation; dieldrin volatilized more slowly and at a constant rate.

Initial description of the human NLRP3 promoter.

Mutations in NLRP3 (CIAS1) are identified in a continuum of related inflammatory disorders, known as cryopyrinopathies since NLRP3 codes for the protein cryopyrin. Approximately 40% of patients with classic presentation lack mutations in the coding region of NLRP3 suggesting heterogeneity or epigenetic factors. Cryopyrin is a key regulator of proinflammatory cytokine release. Therefore, variations in the NLRP3 promoter sequence may have effects on disease state in patients with cryopyrinopathies and other inflammatory diseases. In this report, we confirmed three 5'-untranslated region splice forms with two separate transcriptional start sites, and identified potential promoter regions and six new DNA promoter variants. One variant is unique to a mutation negative cryopyrinopathy patient and increases in vitro gene expression. Additional studies can now be performed to further characterize the NLRP3 promoter and sequence variants, which will lead to better understanding of the regulation of NLRP3 expression and its role in disease.

Tribo-mechanical properties of thin boron coatings deposited on polished cobalt alloy surfaces for orthopedic applications.

This paper presents experimental evidence that thin (< approximately 200 nm) boron coatings, deposited with a (vacuum) cathodic arc technique on pre-polished Co-Cr-Mo surfaces, could potentially extend the life of metal-on-polymer orthopedic devices using cast Co-Cr-Mo alloy for the metal component. The primary tribological test used a linear, reciprocating pin-on-disc arrangement, with pins made of ultra-high molecular weight polyethylene. The disks were cast Co-Cr-Mo samples that were metallographically polished and then coated with boron at a substrate bias of 500 V and at about 100 degrees C. The wear tests were carried out in a saline solution to simulate the biological environment. The improvements were manifested by the absence of a detectable wear track scar on the coated metal component, while significant polymer transfer film was detected on the uncoated (control) samples tested under the same conditions. The polymer transfer track was characterized with both profilometry and Rutherford Backscattering Spectroscopy. Mechanical characterization of the thin films included nano-indentation, as well as additional pin-on-disk tests with a steel ball to demonstrate adhesion, using ultra-high frequency acoustic microscopy to probe for any void occurrence at the coating-substrate interface.

Evaluation of the validity of the Quality of Well-being Scale in Trinidad and Tobago.

Both developing countries in the Caribbean and developed countries face resource allocation challenges. However, cost-effectiveness analysis instruments that may assist in allocation of resources have not been tested in Caribbean countries. Trinidad and Tobago is an advantageous location to test an instrument for potential use in the Caribbean. It has a single payer healthcare system and a literate population. Due to historical and current migration from other Caribbean countries, the population might be a fair representation of English-speaking Caribbean nations. We tested the validity of the Quality of Well-being Scale (QWB) on a sample of the non-institutionalized general population in Trinidad. The survey included reports of chronic conditions and items from the Trinidad and Tobago National Health Interview Survey. Data were analyzed using a multivariable regression model. One adult from each of 235 households consented to the interview. The results are consistent with results obtained in the United States of America. Being older female, more chronic conditions and more symptoms/problems were significantly associated with lower mean QWB scores. These results suggest that the QWB with US-derived weights show evidence of validity in Trinidad and Tobago. Thus, health decision makers can use the QWB to compare the effects of different health conditions and health interventions. In addition, investigators can make cross-cultural comparisons of QWB scores for diseases or health conditions.

Fine mapping of a genetic locus for Peutz-Jeghers syndrome on chromosome 19p.

Peutz-Jeghers syndrome (PJS) was recently mapped in a single report to the telomeric region of chromosome 19p (A. Hemminki et al., Nat. Genet., 15: 87-90, 1997). Our studies confirm this location and provide further localization of the PJS locus. In the five families examined, there were no recombinants with the marker D19S886. The multipoint log odds score at D19S886 is 7.52, and we found no evidence for genetic heterogeneity. We also found that all carriers expressed the PJS phenotype and no noncarriers displayed PJS sequellae, indicating complete penetrance with no sporadic cases.

Relationship of general advance directive instructions to specific life-sustaining treatment preferences in patients with serious illness.

OBJECTIVE: To determine whether brief general instructions in a typical proxy-instruction advance directive (California Durable Power of Attorney for Health Care [DPAHC]) provide interpretable information about patient requests to limit life-saving treatments, and to determine whether patient treatment preferences are stable over time. DESIGN: Prospective structured interviews. SETTING: University of California, San Diego Medical Center and Veterans Affairs Medical Center, La Jolla. PATIENTS: One hundred four patients (from a randomly chosen sample of 185) with a 5-year life expectancy of no better than 50% as judged by their physicians. MAIN OUTCOME MEASURES: Patients completed the California DPAHC, a proxy-instruction advance directive, at entry and at 1 year. The patients also completed a questionnaire at entry, after 6 months, and after 1 year, indicating their preferences on a five-point Likert-format comparative rating scale for cardiopulmonary resuscitation, mechanical ventilation, artificial nutrition, and hospitalization for pneumonia. RESULTS: Sixty-eight percent of the subjects executed the DPAHC. Most patients wished treatments to be limited or withheld under certain conditions of reduced quality of life. Although general instructions noted on the DPAHC and preferences regarding specific procedures were stable over the course of a year, the advance directive's general instructions were often inconsistent with, and poor predictors of, specific procedure preferences. CONCLUSIONS: The brief general instruction component of the California DPAHC is not helpful in communicating patient wishes regarding specific life-saving procedures.

Effects of offering advance directives on quality adjusted life expectancy and psychological well-being among ill adults.

Two hundred and four patients from various clinical services at the San Diego Veterans' Administration Medical Center and the University of California, San Diego Medical Center were randomly assigned to either experimental (offered the opportunity to execute an Advance Directive regarding the level of care they wanted to receive if incapacitated) or control (no Advance Directive offered) conditions. Patients were given a baseline interview and re-interviewed at specific intervals (3 months, 6 months, 1 year and 2 years after baseline, and every 6 months thereafter). Outcome measures included the Qualitty of Well-being Scale, a measure of health status, and the General Well-being Index, a measure of psychological well-being. All differences between the health status and psychological well-being of experimental and control groups 3.5 years after the randomization were non-significant. Methodological implications of including mortality as part of the outcomes are discussed.

Internal Consistency Analysis: a method for studying the accuracy of function assessment for health outcome and quality of life evaluation.

Social, mental and physical function are major components of health outcomes and health related life quality, but the accuracy of function measurement is difficult to study rigorously. Internal Consistency Analysis (ICA) uses multiple sources of evidence from a survey interview to study the accuracy of a classification. It was developed to study function classifications for a general health outcome measure, the Quality of Well-being (QWB) scale. ICA is described and evidence of its utility in improving the classifications needed for the QWB is presented.

Comparison of the Quality of Well-being Scale and the SF-36 results among two samples of ill adults: AIDS and other illnesses.

PURPOSE: To compare results of using the SF-36 Short Form 36 (SF-36) and the Quality of Well-being Scale (QWB) in characterizing health outcomes over time in patients having serious illnesses, including cancer and AIDS. BACKGROUND: The SF-36 and the QWB are alternative measures of health-related quality of life. The SF-36 is a morbidity measure that features a profile of nine dimensions. The QWB is a preference-based measure that combines morbidity and mortality into a single number. However, the QWB can also be scored and used as a profile. We compare SF-36 and QWB scores with different scoring methods to assess validity and sensitivity to change over time in health outcomes for adult patients with HIV infection, cancer, and other serious illnesses. SUBJECTS: 201 adults with serious illnesses, including 99 with AIDS and 102 with cancer or other illnesses. PROCEDURE: All subjects received both measures at baseline and at 6-month intervals thereafter, over a period of 21/2 years. RESULTS: In the profile mode, the QWB captured outcomes that characterize the AIDS syndrome. The SF-36 differentiated between the AIDS and other illnesses patients on some scales, but without consistent direction. However, the overall QWB showed a decrease in quality of life over time for both the AIDS and other illnesses patients while the SF-36 did not. This is because many patients died and these were counted as outcomes by the QWB and as missing data by the SF-36. CONCLUSIONS: The QWB appears to be better able to capture outcomes of serious illness over time than does the SF-36.

Alzheimer's disease-associated reduction of polysomal mRNA translation.

Polysomes from the frontal cortices of individuals who had histopathologically confirmed Alzheimer's disease were compared with polysomes from individuals who exhibited no neuropathological conditions. The cytosolic polysome yield from Alzheimer's disease frontal cortex was reduced 40% compared with that obtained from control frontal cortex. The translational activity per unit polysome of the Alzheimer's disease polysomes was only 50% of control in a reticulocyte lysate in vitro translation assay in which human polysomes do not undergo reinitiation. These differences exhibited brain region specificity in that polysomes isolated from Alzheimer's disease cerebellum were not different from control cerebellar polysomes. Thus, the disruptions are not due to a secondary and general response of the entire brain to the disease. These reductions were reflected by similar decreases in the translation of the mRNA for high molecular weight neurofilament polypeptide. Thus, the inhibition of polysomal mRNA translation is a mechanism by which gene expression is impaired in pathologically involved brain regions of individuals afflicted by Alzheimer's disease.

A possible mechanism of action of the neurotoxic agent iminodipropionitrile (IDPN): a selective aggregation of the medium and heavy neurofilament polypeptides (NF-M and NF-H)

Juvenile male rats treated acutely with the neurotoxic agent, iminodipropionitrile showed no changes in the levels of total neurofilament subunit mRNA or protein for up to 28 days. However, the drug promoted aggregation of the neurofilaments, both spontaneously upon isolation and in an in vitro reassembly assay. This observation correlated with a basic pI shift of the heavy neurofilament subunit, due to a yet to be identified modification. Because of the crucial involvement of this neurofilament subunit in axonal integrity, it is likely that iminodipropionitrile produces a major portion of its neurotoxicity through this mechanism.

Insulin influences astroglial morphology and glial fibrillary acidic protein (GFAP) expression in organotypic cultures.

Variations in the levels and timing of exposure to insulin-related peptides influence the phenotypic appearance of astroglia present in organotypic cultures of the E17 mouse cerebellum as well as the expression of glial fibrillary acidic protein (GFAP) mRNA and its encoded protein. The morphology of GFAP-immunoreactive cells was influenced by the levels of insulin added in an age-specific manner. Fetal radial glia were selectively and significantly (P less than 0.001) increased by high (10 micrograms/ml) insulin levels, comprising the majority of the GFAP-positive cells seen. In contrast, there was an almost complete reversal of this pattern elicited by low (10 pg/ml) insulin levels, where GFAP-positive cells appeared undifferentiated and epithelioid (P less than 0.001). In newborn cultures, on the other hand, the morphological responses to both high and low levels of insulin were considerably attenuated and involved radial glia primarily, whose numbers were significantly increased by the high insulin levels. Exposure to high levels of insulin was accompanied by an increase in GFAP mRNA expression, as determined by non-isotopic (biotin) in situ hybridization histochemistry, and intense GFAP immunoreactivity, while low insulin levels elicited minimal expression of both message and protein product. In view of the critical interdependence of developing neurons and radial glia with respect to neuronal migration and the differentiation of neurons and astroglia, the responses observed suggest developmentally regulated mechanisms by which insulin-related peptides themselves may influence directly and indirectly both neuronal and astroglial differentiation.

Binding of vascular heparan sulfate proteoglycan to Alzheimer's amyloid precursor protein is mediated in part by the N-terminal region of A4 peptide.

The exact mechanisms of deposition and accumulation of amyloid in senile plaques and in blood vessels in Alzheimer's disease remain unknown. Heparan sulfate proteoglycans may play an important role in amyloid deposition in Alzheimer's disease. Previous investigations have demonstrated high affinity binding between heparan sulfate proteoglycans and the amyloid precursor, as well as with the A4 peptide. In the current studies, a specific vascular heparan sulfate proteoglycan found in senile plaques bound with high affinity to two amyloid protein precursors (APP695 and APP770). Vascular heparan sulfate proteoglycan also bound the Alzheimer's amyloid A4 peptide, and not other amyloid protein precursor regions studied, with high affinity. Both heparan sulfate glycosaminoglycan chains and chemically deglycosylated vascular heparan sulfate proteoglycan protein core bound to A4. High affinity interactions between vascular heparan sulfate proteoglycan and the A4 peptide may play a role in the process of amyloidogenesis in Alzheimer's disease, by localizing the site of deposition of A4, protecting A4 from further proteolysis, or by promoting aggregation and fibril formation.

Quality of life and policy analysis in arthritis.

Problems in the American health care system have stimulated interest in cost-effectiveness methodologies. However, there is little consensus on how to define a common unit of health outcome. Many measures used in policy studies consider only mortality and do not fully capture the significant impact of disease-related dysfunction. The impact of conditions, such as osteoarthritis, that have little impact on mortality rates but substantial impact on functioning and well-being may be underestimated in these analyses. In this article, we propose a measurement and policy model that is based on a theoretical conceptualization of health outcome. The model considers the impact of disease and its treatment in terms of both morbidity and mortality. The value of the model for clinical trials, population assessments, and policy analysis is reviewed. A public policy application of the model in Oregon is briefly described.