Binary Colloidal Alloy Test-5: Compete

The Binary Colloidal Alloy Test - 5: Compete (BCAT-5-Compete) investigation will photograph andomized colloidal samples onboard the International Space Station (ISS) to determine their resulting structure over time. The use of EarthKAM software and hardware will allow the scientists to capture the kinetics (evolution) of their samples, as well as the final equilibrium state of each sample. BCAT-5-Compete will utilize samples 6 - 8 in the BCAT-5 hardware to study the competition between phase separation and crystallization, which is important in the manufacture of plastics and other materials

HST Fine Guidance Sensor Astrometric Parallaxes for Three Dwarf Novae: SS Aurigae, SS Cygni, and U Geminorum

We report astrometric parallaxes for three well known dwarf novae obtained using the Fine Guidance Sensors on the Hubble Space Telescope. We found a parallax for SS Aurigae of Pi = 5.00 +/- 0.64 mas, for SS Cygni we found Pi = 6.02 +/- 0.46 mas, and for U Geminorum we obtained Pi = 10.37 +/- 0.50 mas. These represent the first true trigonometric parallaxes of any dwarf novae. We briefly compare these results with previous distance estimates. This program demonstrates that with a very modest amount of HST observing time, the Fine Guidance Sensors can deliver parallaxes of unrivaled precision.Comment: 15 pages, 2 Table

A physiological perspective on fisheries-induced evolution

There is increasing evidence that intense fishing pressure is not only depleting fish stocks but also causing evolutionary changes to fish populations. In particular, body size and fecundity in wild fish populations may be altered in response to the high and often size-selective mortality exerted by fisheries. While these effects can have serious consequences for the viability of fish populations, there are also a range of traits not directly related to body size which could also affect susceptibility to capture by fishing gears – and therefore fisheries-induced evolution (FIE) – but which have to date been ignored. For example, overlooked within the context of FIE is the likelihood that variation in physiological traits could make some individuals within species more vulnerable to capture. Specifically, traits related to energy balance (e.g. metabolic rate), swimming performance (e.g. aerobic scope), neuroendocrinology (e.g. stress responsiveness), and sensory physiology (e.g., visual acuity) are especially likely to influence vulnerability to capture through a variety of mechanisms. Selection on these traits could produce major shifts in the physiological traits within populations in response to fishing pressure that are yet to be considered but which could influence population resource requirements, resilience, species’ distributions, and responses to environmental change

Genome-wide association study of multisite chronic pain in UK Biobank

Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype ‘chronic pain grade’, have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual’s overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches

Design, synthesis, and evaluation of curcumin-derived arylheptanoids for glioblastoma and neuroblastoma cytotoxicity

Using an innovative approach toward multiple carbon-carbon bond-formations that relies on the multifaceted catalytic properties of titanocene complexes we constructed a series of C1-C7 analogs of curcumin for evaluation as brain and peripheral nervous system anti-cancer agents. C2-Arylated analogs proved efficacious against neuroblastoma (SK-N-SH & SK-N-FI) and glioblastoma multiforme (U87MG) cell lines. Similar inhibitory activity was also evident in p53 knockdown U87MG GBM cells. Furthermore, lead compounds showed limited growth inhibition in vitro against normal primary human CD34+hematopoietic progenitor cells. Taken together, the present findings indicate that these curcumin analogs are viable lead compounds for the development of new central and peripheral nervous system cancer chemotherapeutics with the potential for little effects on normal hematopoietic progenitor cells

Sex-Stratified Genome-Wide Association Study of Multisite Chronic Pain in UK Biobank

Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception

Site staff perspectives on communicating trial results to participants: Cost and feasibility results from the Show RESPECT cluster randomised, factorial, mixed-methods trial

BACKGROUND/AIMS: Sharing trial results with participants is an ethical imperative but often does not happen. Show RESPECT (ISRCTN96189403) tested ways of sharing results with participants in an ovarian cancer trial (ISRCTN10356387). Sharing results via a printed summary improved patient satisfaction. Little is known about staff experience and the costs of communicating results with participants. We report the costs of communication approaches used in Show RESPECT and the views of site staff on these approaches. METHODS: We allocated 43 hospitals (sites) to share results with trial participants through one of eight intervention combinations (2 × 2 × 2 factorial; enhanced versus basic webpage, printed summary versus no printed summary, email list invitation versus no invitation). Questionnaires elicited data from staff involved in sharing results. Open- and closed-ended questions covered resources used to share results and site staff perspectives on the approaches used. Semi-structured interviews were conducted. Interview and free-text data were analysed thematically. The mean additional site costs per participant from each intervention were estimated jointly as main effects by linear regression. RESULTS: We received questionnaires from 68 staff from 41 sites and interviewed 11 site staff. Sites allocated to the printed summary had mean total site costs of sharing results £13.71/patient higher (95% confidence interval (CI): -3.19, 30.60; p = 0.108) than sites allocated no printed summary. Sites allocated to the enhanced webpage had mean total site costs £1.91/patient higher (95% CI: -14, 18.74; p = 0.819) than sites allocated to the basic webpage. Sites allocated to the email list had costs £2.87/patient lower (95% CI: -19.70, 13.95; p = 0.731) than sites allocated to no email list. Most of these costs were staff time for mailing information and handling patients' queries. Most site staff reported no concerns about how they had shared results (88%) and no challenges (76%). Most (83%) found it easy to answer queries from patients about the results and thought the way they were allocated to share results with participants would be an acceptable standard approach (76%), with 79% saying they would follow the same approach for future trials. There were no significant effects of the randomised interventions on these outcomes. Site staff emphasised the importance of preparing patients to receive the results, including giving opt-in/opt-out options, and the need to offer further support, particularly if the results could confuse or distress some patients. CONCLUSIONS: Adding a printed summary to a webpage (which significantly improved participant satisfaction) may increase costs to sites by ~£14/patient, which is modest in relation to the cost of trials. The Show RESPECT communication interventions were feasible to implement. This information could help future trials ensure they have sufficient resources to share results with participants

A framework for complexity in palliative care: A qualitative study with patients, family carers and professionals

Background:Palliative care patients are often described as complex but evidence on complexity is limited. We need to understand complexity, including at individual patient-level, to define specialist palliative care, characterise palliative care populations and meaningfully compare interventions/outcomes.Aim:To explore palliative care stakeholders’ views on what makes a patient more or less complex and insights on capturing complexity at patient-level.Design:In-depth qualitative interviews, analysed using Framework analysis.Participants/setting:Semi-structured interviews across six UK centres with patients, family, professionals, managers and senior leads, purposively sampled by experience, background, location and setting (hospital, hospice and community).Results:65 participants provided an understanding of complexity, which extended far beyond the commonly used physical, psychological, social and spiritual domains. Complexity included how patients interact with family/professionals, how services’ respond to needs and societal perspectives on care. ‘Pre-existing’, ‘cumulative’ and ‘invisible’ complexity are further important dimensions to delivering effective palliative and end-of-life care. The dynamic nature of illness and needs over time was also profoundly influential. Adapting Bronfenbrenner’s Ecological Systems Theory, we categorised findings into the microsystem (person, needs and characteristics), chronosystem (dynamic influences of time), mesosystem (interactions with family/health professionals), exosystem (palliative care services/systems) and macrosystem (societal influences). Stakeholders found it acceptable to capture complexity at the patient-level, with perceived benefits for improving palliative care resource allocation.Conclusion:Our conceptual framework encompasses additional elements beyond physical, psychological, social and spiritual domains and advances systematic understanding of complexity within the context of palliative care. This framework helps capture patient-level complexity and target resource provision in specialist palliative care

Persistent Leatherback Turtle Migrations Present Opportunities for Conservation

Effective transboundary conservation of highly migratory marine animals requires international management cooperation as well as clear scientific information about habitat use by these species. Populations of leatherback turtles (Dermochelys coriacea) in the eastern Pacific have declined by >90% during the past two decades, primarily due to unsustainable egg harvest and fisheries bycatch mortality. While research and conservation efforts on nesting beaches are ongoing, relatively little is known about this population of leatherbacks' oceanic habitat use and migration pathways. We present the largest multi-year (2004–2005, 2005–2006, and 2007) satellite tracking dataset (12,095 cumulative satellite tracking days) collected for leatherback turtles. Forty-six females were electronically tagged during three field seasons at Playa Grande, Costa Rica, the largest extant nesting colony in the eastern Pacific. After completing nesting, the turtles headed southward, traversing the dynamic equatorial currents with rapid, directed movements. In contrast to the highly varied dispersal patterns seen in many other sea turtle populations, leatherbacks from Playa Grande traveled within a persistent migration corridor from Costa Rica, past the equator, and into the South Pacific Gyre, a vast, low-energy, low-productivity region. We describe the predictable effects of ocean currents on a leatherback migration corridor and characterize long-distance movements by the turtles in the eastern South Pacific. These data from high seas habitats will also elucidate potential areas for mitigating fisheries bycatch interactions. These findings directly inform existing multinational conservation frameworks and provide immediate regions in the migration corridor where conservation can be implemented. We identify high seas locations for focusing future conservation efforts within the leatherback dispersal zone in the South Pacific Gyre