Wearable activity technology and action-planning (WATAAP) to promote physical activity in cancer survivors: Randomised controlled trial protocol

Background/Objective: Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour, warranting a feasible intervention to increase physical activity. The Health Action Process Approach (HAPA) is a promising theoretical frame-work for health behaviour change, and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors. Method: Sixty-eight survivors of colorectal and gynecologic cancer will be randomised into 12- week intervention and control groups. Intervention group participants will receive: a Fitbit AltaTM to monitor physical activity, HAPA-based group sessions, booklet, and support phone-call. Participants in the control group will only receive the HAPA-based booklet. Physical activity (using accelerometers), blood pressure, BMI, and HAPA constructs will be assessed at baseline, 12-weeks (post-intervention) and 24-weeks (follow-up). Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis. Conclusions: Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors

Validation of Risk Prediction Models to Inform Clinical Decisions After Acute Kidney Injury

Wellcome Trust Research Training Fellowship: 102729/Z/13/Z Academy of Medical Sciences Starter Grant for Clinical Lecturers: SGL020\1076 We acknowledge the support of the Grampian Data Safe Haven (DaSH) facility within the Aberdeen Centre for Health Data Science and the associated financial support of the University of Aberdeen, and NHS Research Scotland (through NHS Grampian investment in DaSH). More information is available at the DaSH website: http://www.abdn.ac.uk/iahs/facilities/grampian-data-safe-haven.phpPeer reviewedPublisher PD

Conservation and Diversity of Influenza A H1N1 HLA-Restricted T Cell Epitope Candidates for Epitope-Based Vaccines

Background: The immune-related evolution of influenza viruses is exceedingly complex and current vaccines against influenza must be reformulated for each influenza season because of the high degree of antigenic drift among circulating influenza strains. Delay in vaccine production is a serious problem in responding to a pandemic situation, such as that of the current H1N1 strain. Immune escape is generally attributed to reduced antibody recognition of the viral hemagglutinin and neuraminidase proteins whose rate of mutation is much greater than that of the internal non-structural proteins. As a possible alternative, vaccines directed at T cell epitope domains of internal influenza proteins, that are less susceptible to antigenic variation, have been investigated. Methodology/Principal Findings: HLA transgenic mouse strains expressing HLA class I A*0201, A*2402, and B*0702, and class II DRB1*1501, DRB1*0301 and DRB1*0401 were immunized with 196 influenza H1N1 peptides that contained residues of highly conserved proteome sequences of the human H1N1, H3N2, H1N2, H5N1, and avian influenza A strains. Fifty-four (54) peptides that elicited 63 HLA-restricted peptide-specific T cell epitope responses were identified by IFN-γ ELISpot assay. The 54 peptides were compared to the 2007-2009 human H1N1 sequences for selection of sequences in the design of a new candidate H1N1 vaccine, specifically targeted to highly-conserved HLA-restricted T cell epitopes. Conclusions/Significance: Seventeen (17) T cell epitopes in PB1, PB2, and M1 were selected as vaccine targets based on sequence conservation over the past 30 years, high functional avidity, non-identity to human peptides, clustered localization, and promiscuity to multiple HLA alleles. These candidate vaccine antigen sequences may be applicable to any avian or human influenza A virus. © 2010 Tan et al

Raman spectroscopy of a single ion coupled to a high-finesse cavity

We describe an ion-based cavity-QED system in which the internal dynamics of an atom is coupled to the modes of an optical cavity by vacuum-stimulated Raman transitions. We observe Raman spectra for different excitation polarizations and find quantitative agreement with theoretical simulations. Residual motion of the ion introduces motional sidebands in the Raman spectrum and leads to ion delocalization. The system offers prospects for cavity-assisted resolved-sideband ground-state cooling and coherent manipulation of ions and photons.Comment: 8 pages, 6 figure

Wearable activity technology and action-planning (WATAAP) to promote physical activity in cancer survivors: Randomised controlled trial protocol

FUNDAMENTOS/OBJETIVO: Los sobrevivientes de cáncer colorrectal y ginecológico corren riesgo cardiovascular debido a las comorbilidades y al comportamiento sedentario, lo que justifica una intervención factible para aumentar la actividad física. El Enfoque del Proceso de Acción Sanitaria (HAPA) es un marco teórico prometedor para el cambio de comportamiento en materia de salud, y los rastreadores de actividad física que se pueden llevar puestos ofrecen un medio novedoso de autocontrol de la actividad física para los supervivientes de cáncer. MÉTODO: Sesenta y ocho sobrevivientes de cáncer colorrectal y ginecológico serán asignados al azar a grupos de intervención y control de 12 semanas. Los participantes del grupo de intervención recibirán: un Fitbit AltaTM para monitorear la actividad física, sesiones de grupo basadas en HAPA, un folleto y una llamada telefónica de apoyo. Los participantes del grupo de control sólo recibirán el folleto basado en HAPA. La actividad física (utilizando acelerómetros), la presión sanguínea, el IMC y las construcciones HAPA se evaluarán en la línea de base, a las 12 semanas (después de la intervención) y a las 24 semanas (seguimiento). El análisis de los datos utilizará la interacción Grupo x Tiempo de un análisis de Modelo Mixto Lineal General. CONCLUSIONES: Las intervenciones de actividad física que son aceptables y que tienen sólidos fundamentos teóricos son prometedoras para mejorar la salud de los sobrevivientes de cáncer.BACKGROUND/OBJECTIVE: Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour, warranting a feasible intervention to increase physical activity. The Health Action Process Approach (HAPA) is a promising theoretical framework for health behaviour change, and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors. METHOD: Sixty-eight survivors of colorectal and gynecologic cancer will be randomised into 12-week intervention and control groups. Intervention group participants will receive: a Fitbit AltaTM to monitor physical activity, HAPA-based group sessions, booklet, and support phonecall. Participants in the control group will only receive the HAPA-based booklet. Physical activity (using accelerometers), blood pressure, BMI, and HAPA constructs will be assessed at baseline, 12-weeks (post-intervention) and 24-weeks (follow-up). Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis. CONCLUSIONS: Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors.• The Tonkinson Colorectal Cancer Research. Subvención 57838 • St. John of God Gynecologic Oncology Research Group (Western Australia). AyudapeerReviewe

Measurement of the 58Ni(α, γ) 62Zn reaction and its astrophysical impact

Funding Details: PHY 08-22648, NSF, National Science Foundation; PHY 0969058, NSF, National Science Foundation; PHY 1102511, NSF, National Science FoundationCross section measurements of the 58Ni(α,γ)62Zn reaction were performed in the energy range Eα=5.5to9.5 MeV at the Nuclear Science Laboratory of the University of Notre Dame, using the NSCL Summing NaI(Tl) detector and the γ-summing technique. The measurements are compared to predictions in the statistical Hauser-Feshbach model of nuclear reactions using the SMARAGD code. It is found that the energy dependence of the cross section is reproduced well but the absolute value is overestimated by the prediction. This can be remedied by rescaling the α width by a factor of 0.45. Stellar reactivities were calculated with the rescaled α width and their impact on nucleosynthesis in type Ia supernovae has been studied. It is found that the resulting abundances change by up to 5% when using the new reactivities. © 2014 American Physical Society.Peer reviewe

The dystrotelin, dystrophin and dystrobrevin superfamily: new paralogues and old isoforms

BACKGROUND: Dystrophins and dystrobrevins are distantly related proteins with important but poorly understood roles in the function of metazoan muscular and neuronal tissues. Defects in them and their associated proteins cause a range of neuromuscular disorders. Members of this superfamily have been discovered in a relatively serendipitous way; we set out to compile a comprehensive description of dystrophin- and dystrobrevin-related sequences from available metazoan genome sequences, validated in representative organisms by RT-PCR, or acquired de novo from key species. RESULTS: Features of the superfamily revealed by our survey include: a) Dystrotelin, an entirely novel branch of the superfamily, present in most vertebrates examined. Dystrotelin is expressed in the central nervous system, and is a possible orthologue of Drosophila DAH. We describe the preliminary characterisation of its function, evolution and expression. b) A novel vertebrate member of the dystrobrevin family, γ-dystrobrevin, an ancient branch now extant only in fish, but probably present in our own ancestors. Like dystrophin, zebrafish γ-dystrobrevin mRNA is localised to myosepta. c) The extent of conservation of alternative splicing and alternative promoter use in the dystrophin and dystrobrevin genes; alternative splicing of dystrophin exons 73 and 78 and α-dystrobrevin exon 13 are conserved across vertebrates, as are the use of the Dp116, Dp71 and G-utrophin promoters; the Dp260 and Dp140 promoters are tetrapod innovations. d) The evolution of the unique N-terminus of DRP2 and its relationship to Dp116 and G-utrophin. e) A C-terminally truncated common ancestor of dystrophin and utrophin in cyclostomes. f) A severely restricted repertoire of dystrophin complex components in ascidians. CONCLUSION: We have refined our understanding of the evolutionary history and isoform diversity of the five previously reported vertebrate superfamily members and describe two novel members, dystrotelin and γ-dystrobrevin. Dystrotelins, dystrophins and dystrobrevins are roughly equally related to each other. Vertebrates therefore have a repertoire of seven superfamily members (three dystrophins, three dystrobevins, and one dystrotelin), with one lost in tetrapods. Most invertebrates studied have one member from each branch. Although the basic shared function which is implied by the common architecture of these distantly related proteins remains unclear, it clearly permeates metazoan biology

Ligand-Independent Adenosine A 2B Receptor Constitutive Activity as a Promoter of Prostate Cancer Cell Proliferation s

ABSTRACT Aberrant ligand-independent G protein-coupled receptor constitutive activity has been implicated in the pathophysiology of a number of cancers. The adenosine A 2B receptor (A 2B AR) is dynamically upregulated under pathologic conditions associated with a hypoxic microenvironment, including solid tumors. This, in turn, may amplify ligand-independent A 2B AR signal transduction. The contribution of A 2B AR constitutive activity to disease progression is currently unknown yet of fundamental importance, as the preferred therapeutic modality for drugs designed to reduce A 2B AR constitutive activity would be inverse agonism as opposed to neutral antagonism. The current study investigated A 2B AR constitutive activity in a heterologous expression system and a native 22Rv1 human prostate cancer cell line exposed to hypoxic conditions (2% O 2 ). (4-chlorophenyl)piperazide-1-sulfonyl)phenyl)-1-propylxanthine), mediated a concentration-dependent decrease in baseline cAMP levels in both cellular systems. Proliferation of multiple prostate cancer cell lines was also attenuated in the presence of PSB-603. Importantly, both the decrease in baseline cAMP accumulation and the reduction of proliferation were not influenced by the addition of adenosine deaminase, demonstrating that these effects are not dependent on stimulation of A 2B ARs by the endogenous agonist adenosine. Our study is the first to reveal that wild-type human A 2B ARs have high constitutive activity in both model and native cells. Furthermore, our findings demonstrate that this ligand-independent A 2B AR constitutive activity is sufficient to promote prostate cancer cell proliferation in vitro. More broadly, A 2B AR constitutive activity may have wider, currently unappreciated implications in pathologic conditions associated with a hypoxic microenvironment

Population Structure Shapes Copy Number Variation in Malaria Parasites.

If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size (Ne) than from populations with a small Ne. Malaria parasites (Plasmodium falciparum) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from <500 bp to 59 kb, as well as 10,107 flanking, biallelic single-nucleotide polymorphisms. Overall, CNVs were rare, small, and skewed toward low frequency variants, consistent with the deleterious model. Relative to African and South East Asian populations, CNVs were significantly more common in South America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an FST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1, and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen