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The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Abstract Introduction Understanding interactions between sleep and emotion in isolated, confined, extreme environments (ICEs) is relevant to multiple populations (e.g., military personnel, off-shore workers, astronauts). Little is known about risk and resilience factors affecting sleep in these environments; however conditions (e.g., loss of natural light, communication delays) are conducive to sleep, circadian, and emotional disturbances. This study assesses sleep, neurobehavioral and emotion regulation factors in the Human Exploration Research Analog (HERA), a highly controlled, 3-story analog, simulating human exploration into space. Methods Sixteen participants (9 male) aged 29–52 (M=36.38, SD=7.11) completed a 30-day mission in HERA. Actigraphy data was collected continuously, including 11 days pre-mission. Subjective sleep complaints (Sleep Self-Assessment Scale; pre-mission, mission day 7 (D7), and D14), neurobehavioral symptoms (Neurobehavioral Checklist [NBCL]; pre-mission, D4, D11, D18), and pre-mission emotion regulation (including Anxiety Sensitivity Index and Difficulties in Emotion Regulation Scale) were also measured. Analyses included data from D0-D24, after which a sleep manipulation occurred. Results Pre-mission, positive adaptation was negatively associated with subjective sleep complaints (rt= -.47, p=.02). Variability in total sleep time (TST) was negatively associated with emotion regulation difficulties (rt= -.494, p=.02) and poor self-regulation (rt=-.55, p=.02), whilst individuals with higher anxiety sensitivity showed increased sleep percentage (rt=.45, p=.04) and decreased wake after sleep onset (rt= -.43, p=.05). During mission, TST increased, with a significant overall change from pre-mission to D18 (F(2.26, 27.16)=8.91, p=.001, η2partial=.45). Early in the mission (D1-D4), subjective sleep complaints were positively associated with poor self-regulation (rt=.56, p=.005). During D1-D4, sleep onset latency (SOL) was negatively associated with anxious apprehension (rt=-.46, p=.02) and marginally associated with poor self-regulation (rt=-.31, p=.11). In subsequent mission days (D4-D11 and D11-18) the negative association between poor self-regulation and SOL was maintained (rt=-.47, p=.02 and rt=-.47, p=.01 respectively). Conclusion Associations identified between emotional functioning and sleep provide potential indicators of individual risk and resilience patterns within ICEs. Such findings await replication in larger samples and across different environmental conditions.

We present a new catalogue of 5,106 infrared bubbles created through visual classification via the online citizen science website 'The Milky Way Project'. Bubbles in the new catalogue have been independently measured by at least 5 individuals, producing consensus parameters for their position, radius, thickness, eccentricity and position angle. Citizen scientists - volunteers recruited online and taking part in this research - have independently rediscovered the locations of at least 86% of three widely-used catalogues of bubbles and H ii regions whilst finding an order of magnitude more objects. 29% of the Milky Way Project catalogue bubbles lie on the rim of a larger bubble, or have smaller bubbles located within them, opening up the possibility of better statistical studies of triggered star formation. Also outlined is the creation of a 'heat map' of star-formation activity in the Galactic plane. This online resource provides a crowd-sourced map of bubbles and arcs in the Milky Way, and will enable better statistical analysis of Galactic star-formation sites., Comment: 19 pages, 20 figures, submitted to MNRAS

We propose an evolutionary path for prestellar cores on the radius-mass diagram, which is analogous to stellar evolutionary paths on the Hertzsprung-Russell Diagram. Using James Clerk Maxwell Telescope (JCMT) observations of L1688 in the Ophiuchus star-forming complex, we analyse the HCO+ (J=4\rightarrow3) spectral line profiles of prestellar cores. We find that of the 58 cores observed, 14 show signs of infall in the form of a blue-asymmetric double-peaked line profile. These 14 cores all lie beyond the Jeans mass line for the region on a radius-mass plot. Furthermore another 10 cores showing tentative signs of infall, in their spectral line profile shapes, appear on or just over the Jeans mass line. We therefore propose the manner in which a prestellar core evolves across this diagram. We hypothesise that a core is formed in the low-mass, low-radius region of the plot. It then accretes quasistatically, increasing in both mass and radius. When it crosses the limit of gravitational instability it begins to collapse, decreasing in radius, towards the region of the diagram where protostellar cores are seen., 42 pages, 11 figures (+58 in appendix), Accepted for publication in MNRAS

As part of a JCMT Legacy Survey of star formation in the Gould Belt, we present early science results for Taurus. CO J=3-2 maps have been secured along the north-west ridge and bowl, collectively known as L 1495, along with deep 13CO and C18O J=3-2 maps in two sub-regions. With these data we search for molecular outflows, and use the distribution of flows, HH objects and shocked H2 line emission features, together with the population of young stars, protostellar cores and starless condensations to map star formation across this extensive region. In total 21 outflows are identified. It is clear that the bowl is more evolved than the ridge, harbouring a greater population of T Tauri stars and a more diffuse, more turbulent ambient medium. By comparison, the ridge contains a much younger, less widely distributed population of protostars which, in turn, is associated with a greater number of molecular outflows. We estimate the ratio of the numbers of prestellar to protostellar cores in L 1495 to be ~ 1.3-2.3, and of gravitationally unbound starless cores to (gravitationally bound) prestellar cores to be ~ 1. If we take previous estimates of the protostellar lifetime of ~ 5 x 10^5 yrs, this indicates a prestellar lifetime of 9(+/-3) x 10^5 yrs. From the number of outflows we also crudely estimate the star formation efficiency in L 1495, finding it to be compatible with a canonical value of 10-15 %. We note that molecular outflow-driving sources have redder near-IR colours than their HH jet-driving counterparts. We also find that the smaller, denser cores are associated with the more massive outflows, as one might expect if mass build-up in the flow increases with the collapse and contraction of the protostellar envelope., Accepted by MNRAS; 20 pages, 14 figures; paper with higher-resolution colour images available from http://www.jach.hawaii.edu/~cdavis

Ventricular premature complexes (PVCs) on a 2-minute electrocardiogram (ECG) are a common, largely asymptomatic finding, associated with increased risk of coronary heart disease (CHD) and death. They may reflect atherosclerosis or other pathogenic pathways that predispose to arrhythmias and stroke.

The Gould Belt Legacy Survey (GBS) on the JCMT has observed a region of 260 square arcminutes in 12CO J=3--2 emission, and a 190 square arcminute subset of this in 13CO and C18O towards the Serpens molecular cloud. We examine the global velocity structure of the non-outflowing gas, and calculate excitation temperatures and opacities. The large scale mass and energetics of the region are evaluated, with special consideration for high velocity gas. We find the cloud to have a mass of 203 solar masses, and to be gravitationally bound, and that the kinetic energy of the outflowing gas is approximately seventy percent of the turbulent kinetic energy of the cloud. We identify compact outflows towards some of the submillimetre Class 0/I sources in the region, Comment: 17 Pages, accepted by MNRAS

In this article I present some special astronomical scripts created for Google Earth, Google Sky and Twitter. These 'hacks' are examples of the ways in which such tools can be used either alone, in on conjunction with online services. The result of a combination of multiple, online services to form a new facility is called a mash-up. Some of what follows falls into that definition. As we move into an era of online data and tools, it is the network as a whole that becomes important. Tools emerging from this network can be capable of more than the sum of their parts., Comment: 15 pages, conference" Astronomy: Networked Astronomy and the New Media", 2009, edited by R. J. Simpson, D. Ward-Thompson

In this article I present some special astronomical scripts created for Google Earth, Google Sky and Twitter. These 'hacks' are examples of the ways in which such tools can be used either alone, in on conjunction with online services. The result of a combination of multiple, online services to form a new facility is called a mash-up. Some of what follows falls into that definition. As we move into an era of online data and tools, it is the network as a whole that becomes important. Tools emerging from this network can be capable of more than the sum of their parts., 15 pages, conference" Astronomy: Networked Astronomy and the New Media", 2009, edited by R. J. Simpson, D. Ward-Thompson

Using a scientific measurement without an estimate of its error is like lending money to a stranger. Given the explosion in nucleic acid and protein sequence and structural data, what risks are the scientific and medical communities running in using these databases. Is there an 'ombudsman' who speaks for the users of the data? CODATA, the Committee on Data for Science and Technology of the International Council of Scientific Unions was established to improve the quality, reliability, processing, management, and accessibility of data for science and technology. The CODATA Task Group on Biological Macromolecules has surveyed quality control procedures of archival databanks in molecular biology. Our role is 'to advise, to be consulted, and to warn.' This report describes the kinds and extents of errors that may appear in nucleic acid and protein databases, and presents an agenda for future work to improve the quality of these databases. The results of the survey appear on the webhttp://www.codata.org/codata/tgreports/ tg_reps.html.

The receptor gp130 is used by the interleukin-6 (IL-6)-type cytokines, which include IL-6 and leukaemia-inhibitory factor (LIF). To investigate the role of the three extracellular membrane-proximal fibronectin-type-III-like (FNIII) modules of gp130 and the related receptor for granulocyte colony-stimulating factor (G-CSFR) in cytokine signal transduction we have transfected into murine myeloid M1-UR21 cells the chimaera (GR-FNIII)gp130, which contains the membrane-proximal FNIII modules of the G-CSFR on a gp130 backbone, and its complement, the chimaera (gp130-FNIII)GR. Whereas the binding affinities of (125)I-labelled IL-6 to (GR-FNIII)gp130, or of (125)I-Tyr1,3-G-CSF to (gp130-FNIII)GR, were similar to wild-type gp130 and wild-type G-CSFR, respectively, (125)I-LIF failed to bind with high affinity to (GR-FNIII)gp130. In assays measuring differentiation the (gp130-FNIII)GR cells were fully responsive to G-CSF, whereas the (GR-FNIII)gp130 cells responded fully to the agonistic anti-gp130 monoclonal antibody (mAb) B-S12, but not to IL-6 or LIF. Neutralizing mAbs that recognize the membrane-proximal FNIII modules of gp130 or the G-CSFR differentially interfered with signalling by B-S12, LIF and G-CSF. The data suggest that B-S12 and G-CSF induce the correct orientation or conformation for signalling by the wild-type and chimaeric homodimeric receptors, that the membrane-proximal region of gp130 is important for the correct formation of the signalling IL-6-IL-6 receptor-gp130 complex and that this region is also involved in LIF-dependent receptor heterodimerization and signalling.

Three defensin-like peptides (DLPs) were isolated from platypus venom and sequenced. One of these peptides, DLP-1, was synthesized chemically and its three-dimensional structure was determined using NMR spectroscopy. The main structural elements of this 42-residue peptide were an anti-parallel beta-sheet comprising residues 15-18 and 37-40 and a small 3(10) helix spanning residues 10-12. The overall three-dimensional fold is similar to that of beta-defensin-12, and similar to the sodium-channel neurotoxin ShI (Stichodactyla helianthus neurotoxin I). However, the side chains known to be functionally important in beta-defensin-12 and ShI are not conserved in DLP-1, suggesting that it has a different biological function. Consistent with this contention, we showed that DLP-1 possesses no anti-microbial properties and has no observable activity on rat dorsal-root-ganglion sodium-channel currents.

The clinical syndrome of benign prostatic hyperplasia reflects a complex interplay between benign prostatic enlargement, which will affect almost all men by the age of 80, and the resulting outlet obstruction and lower urinary tract symptoms. The disease is now known to adversely affect the quality of life of around one man in three over the age of 50. New medical treatments and new surgical interventions are challenging the previous standard treatment of transurethral resection of prostate, which continues to have a morbidity of 17% and some mortality. Primary care will be increasingly involved in shared care with particular emphasis on monitoring of patients on watchful waiting medical therapy- and following operative intervention.

BACKGROUND: Panic disorder, with and without agoraphobia, is a prevalent condition which presents primarily in general practice. Previous clinical outcome studies have been conducted mainly in specialist university departments or hospital settings, and have tended to employ complex rating scales that are not well suited for use as outcome measures in primary care. AIM: To evaluate the outcome, in a primary care setting, of fluvoxamine versus cognitive behaviour therapy, each used alone and in combination in a double-blind placebo-controlled framework, balanced for therapist contact. METHOD: A total of 149 patients satisfying DSMIII-R criteria for panic disorder were randomly allocated to receive one of the following: fluvoxamine, placebo, fluvoxamine plus cognitive behaviour therapy, placebo plus cognitive behaviour therapy, and cognitive behaviour therapy alone. These five treatment groups represent the minimum number acceptable for such a comparison to be made. All patients received an identical schedule of contact over 13 weeks. Measures of symptom severity, general health and social disruption were taken at entry point and end point; measures of change in symptoms were taken at end point only. Outcome was reported in terms of brief global ratings of severity of illness and change in symptoms, and of ratings of general health and social disruption that are suitable for use in general practice. RESULTS: All active treatment groups showed statistically significant advantages over placebo over a range of outcome ratings. The groups employing cognitive behaviour therapy showed the most robust and consistent response. CONCLUSION: The brief global measures reported here proved adequate to the task of assessing treatment outcome. Results indicate that treatments including cognitive behaviour therapy can be effective in the treatment of panic disorder and agoraphobia in primary care.

Proceedings of the International Offshore and Polar Engineering Conference, Volume 1995-June, 1995, Pages 346-352 © 1995 by The International Society of Offshore and Polar Engineers. This paper presents the development and application of reliability based inspection planning techniques for floaters. Based on previous experience from jacket structure applications optimised inspection planning (OIP) techniques for floaters are developed The differences between floaters and jacket structures in relation to fatigue damage, redundancy levels and inspection practice are examined and reflected in the proposed methodology. The application and benefits of these techniques is demonstrated through representative analyses and important trends are highlighted through the results of a parametric sensitivity study.

BACKGROUND. The Stirling benign prostatic hyperplasia natural history group have previously reported a prevalence of this condition of 255 per 1000 in a community study of 1610 men aged 40-79 years. AIM. It was decided to examine the consultation patterns of men with benign prostatic hyperplasia in greater detail. METHOD. All participating men were invited to complete a previously validated lifestyle questionnaire including questions on consultations with their general practitioner during the previous year and previous history of prostatic problems. The men who had a urinary symptom score greater than 11, or who had a urinary flow rate of less than 15 ml per second were examined by transurethral ultrasonography for prostate size. RESULTS. Of 364 men with benign prostatic hyperplasia, 89% had not consulted their doctor about urinary symptoms in the year prior to the study. Men with moderate to severe urinary symptoms were six times more likely to have consulted their doctor than those with mild symptoms. Moderate to severe symptoms and greater interference with daily living activities were both associated with a greater likelihood of consultation, independent of age. Of all the men in the study referred to the specialist clinic for assessment of prostate size by transurethral ultrasonography, two thirds were referred because of low urinary flow rate and one third because of high urinary symptom scores. The reported consultation data showed a reverse ratio of one third of those consulting having a low urinary flow rate and approximately two thirds having urinary symptoms. CONCLUSION. While mass screening is unjustified, there is a need for patient education about benign prostatic hyperplasia in general and the recognition of declining strength of urinary flow as a symptom of benign prostatic hyperplasia and not of ageing alone. Furthermore, evaluation of primary care use of urinary flowmeters and the development of local protocols are suggested as elements of a case finding strategy for benign prostatic hyperplasia based on patient led consultation.

BACKGROUND. Increased general practice attendance rates have been associated with the diagnosis of mental illness but panic disorder has not been specifically investigated in this respect. In addition, studies have failed adequately to assess type and frequency of secondary care referral and patterns of psychotropic prescription in patients with panic disorder in relation to matched controls. AIM. This study set out to compare subjects with panic disorder with age and sex matched controls on measures of general practice consultation rate; psychotropic and non-psychotropic drug use; referral to secondary care, laboratory and radiological tests and hospital admissions; history of illness and complaints; and psychiatric comorbidity. METHOD. The study was carried out in nine practices in the Forth Valley area. One hundred patients with panic disorder, previously diagnosed using DSM III-R criteria, were identified and matched by age and sex with controls. Data were collected by review of general practice case notes. RESULTS. Subjects with panic disorder had significantly higher rates of general practice consultation over the 10 year period prior to DSM III-R diagnosis of panic disorder than controls. Subjects with panic disorder had also been prescribed a significantly greater number of psychotropic and non-psychotropic medications over this period, had had more secondary care investigations and had higher rates of mainly minor illness and related complaints than controls. High comorbidity of panic disorder with depression which had been diagnosed over the 10 year period prior to DSM III-R diagnosis of panic disorder was found. CONCLUSION. The results of this study describe a population of subjects with panic disorder who are long-term heavy users of primary care services. The results also suggest an association between panic disorder and both minor illness and psychiatric comorbidity over the 10 year period prior to DSM III-R diagnosis of panic disorder.

From three general practices, served by 11 principals, 205 long-term benzodiazepine users were identified and matched for age and sex with controls. Benzodiazepine users had significantly higher rates of previous physical illness, consultation and non-psychotropic drug consumption than controls. The characteristics of those receiving prescriptions for benzodiazepine hypnotics alone, anxiolytics alone and anxiolytics plus hypnotics were also investigated. Significant differences emerged between these three groups. Patients receiving hypnotics only were older, had a history of more physical illness and had received more non-psychotropic medication than patients receiving anxiolytics only. The anxiolytic plus hypnotic group had previously received more hypnotics and were currently receiving more medication than the group receiving anxiolytics alone. The results are discussed in relation to current concerns about benzodiazepine dependence and withdrawal.

Studies were performed on the binding of tritiated adenosine and its analogues, 5'-N-ethylcarboxamide adenosine (NECA) and N6-phenylisopropyladenosine (PIA), to human peripheral blood lymphocytes. These revealed binding only of adenosine (Kd, 1-10 microM, 14,000 binding sites/cell), which was abolished by dipyridamole, a specific adenosine transport inhibitor, suggesting that the binding is to the nucleoside transporter. The absence of high affinity (Kd less than or equal to 1 microM) binding of adenosine or of the two analogues. NECA and PIA suggests that the previously reported effects of adenosine on cAMP formation are not mediated by cell surface specific nucleoside receptors. Binding of adenosine to the carrier in lymphocytes from patients with common variable immunodeficiency was similar to those from control subjects.

We previously reported the purification and partial amino acid sequence of a novel murine cytokine designated CP-10, which has chemotactic activity for murine polymorphonuclear cells (PMN) and macrophages. The complete cDNA encoding an 88-amino acid polypeptide has been isolated and the sequence is presented here. Transient transfection of CP-10 cDNA into CV-1 cells confirmed the chemotactic activity of rCP-10 for murine PMN. CP-10 has sequence homology with members of the S100 family of Ca(2+)-binding proteins with pronounced amino acid sequence similarities within the putative N- and C-terminal Ca(2+)-binding sites, but differences within their connecting hinge and C-terminal regions. We have confirmed the hypothesis of Kligman and Hilt that functional specificity of individual members of the S100 protein family may reside in the hinge region. A synthetic peptide corresponding to the hinge region of CP-10 (CP-10(42-55) was compared with native CP-10 in chemotaxis and skin test assays. Native CP-10 had potent activity for phagocytic cells, but not lymphocytes, in vitro (optimal activity, 10(-11) to 10(-13) M) and elicited a sustained recruitment of neutrophils and mononuclear cells over 24 h in vivo. The hinge-region peptide had strong chemotactic activity for murine phagocytic cells (optimal activity, 10(-10) - 10(-11) M) but elicited only a transient infiltration of neutrophils over 4 to 8 h after intradermal injection. Results indicate that although the hinge region contributes significantly to the functional specificity of the S100 protein CP-10, sustained cellular recruitment typical of a delayed type hypersensitivity response is apparently dependent on the structural integrity of the protein.

The ex vivo expansion of tumor-associated-antigen (TAA)- specific cytotoxic T-cells (CTLs) from healthy donors for adoptive transfer to cancer patients is now providing additional treatment options for patients. Many studies have shown that adoptive transfer of expanded CTLs can reduce the risk of relapse in cancer patients following hematopoietic stem cell transplantation (HSCT). However, the procedure can be limited by difficulties in priming and expanding sufficient numbers of TAA-specific-CTLs. Because acute dynamic exercise mobilizes large numbers of T-cells to peripheral blood, we hypothesized that a single bout of exercise would augment the ex vivo expansion of TAA-specific-CTLs.We therefore collected lymphocytes from blood donated by healthy adults at rest and after brief maximal dynamic exercise. TAA-specific CTLs were expanded using autologous monocyte-derived-dendritic cells pulsed with melanoma-associated antigen 4 (MAGE-A4), with preferentially expressed antigen in melanoma (PRAME), and with Wilms' tumor protein (WT-1). Post exercise, 84% of the participants had a greater number of CTLs specific for at least one of the three TAA.Cells expanded from post exercise blood yielded a greater number of MAGE-A4 and PRAME-specific-cells in 70% and 61% of participants, respectively. In the 'exercise-responsive' participants (defined as participants with at least a 10% increase in TAA-specific-CTLs post-exercise), MAGEA4- and PRAME-specific-CTLs increased 3.4-fold and 6.2- fold respectively. Moreover, expanded TAA-specific CTLs retained their antigen-specific cytotoxic activity. No phenotype differences were observed between expanded cells donated at rest and postexercise. We conclude that exercise can enhance the ex vivo expansion of TAA-specific-CTLs from healthy adults without compromising cytotoxic function. Hence, this study has implications for immunotherapy using adoptive T-cell transfer of donor-derived T-cells after allogeneic HSCT.

The murine plasma cell alloantigen PC-1 is selectively expressed on B lymphocytes in their terminal phase of differentiation into antibody-secreting cells. Previous work on an analytical scale has shown that PC-1 consists of two apparently identical disulfide-bonded polypeptides, each of Mr 115,000. In this paper, we describe the generation of a monoclonal antibody to PC-1 and its use in the preparative isolation of PC-1 by affinity chromatography. Final purification to apparent homogeneity was achieved by preparative polyacrylamide gel electrophoresis. It was estimated that NS-1 myeloma cells possess 1 to 4 X 10(5) PC-1 monomers per cell on their surface. The yield of PC-1 after purification was approximately 10(5) monomers per cell. Purified PC-1 was digested with trypsin, and the resulting peptides were separated by reversed-phase high-performance liquid chromatography. Purified peptides were sequenced with a gas-phase sequencer.