509 research outputs found
Developing a digital intervention for cancer survivors: an evidence-, theory- and person-based approach
This paper illustrates a rigorous approach to developing digital interventions using an evidence-, theory- and person-based approach. Intervention planning included a rapid scoping review which identified cancer survivorsâ needs, including barriers and facilitators to intervention success. Review evidence (N=49 papers) informed the interventionâs Guiding Principles, theory-based behavioural analysis and logic model. The intervention was optimised based on feedback on a prototype intervention through interviews (N=96) with cancer survivors and focus groups with NHS staff and cancer charity workers (N=31). Interviews with cancer survivors highlighted barriers to engagement, such as concerns about physical activity worsening fatigue. Focus groups highlighted concerns about support appointment length and how to support distressed participants. Feedback informed intervention modifications, to maximise acceptability, feasibility and likelihood of behaviour change. Our systematic method for understanding user views enabled us to anticipate and address important barriers to engagement. This methodology may be useful to others developing digital interventions
Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory
Data from the Sudbury Neutrino Observatory have been used to constrain the
lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The
analysis was based on a search for gamma-rays from the de-excitation of the
residual nucleus that would result from the disappearance of either a proton or
neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90%
confidence for either neutron or proton decay modes. This is about an order of
magnitude more stringent than previous constraints on invisible proton decay
modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of
2) Submitted to Physical Review Letter
First Neutrino Observations from the Sudbury Neutrino Observatory
The first neutrino observations from the Sudbury Neutrino Observatory are
presented from preliminary analyses. Based on energy, direction and location,
the data in the region of interest appear to be dominated by 8B solar
neutrinos, detected by the charged current reaction on deuterium and elastic
scattering from electrons, with very little background. Measurements of
radioactive backgrounds indicate that the measurement of all active neutrino
types via the neutral current reaction on deuterium will be possible with small
systematic uncertainties. Quantitative results for the fluxes observed with
these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000
Conference, Sudbury, Canada, June 16-21, 2000 to be published in the
Proceeding
Advancing clinical trials for inherited retinal diseases: Recommendations from the second monaciano symposium
Major advances in the study of inherited retinal diseases (IRDs) have placed efforts to develop treatments for these blinding conditions at the forefront of the emerging field of precision medicine. As a result, the growth of clinical trials for IRDs has increased rapidly over the past decade and is expected to further accelerate as more therapeutic possibilities emerge and qualified participants are identified. Although guided by established principles, these specialized trials, requiring analysis of novel outcome measures and endpoints in small patient populations, present multiple challenges relative to study design and ethical considerations. This position paper reviews recent accomplishments and existing challenges in clinical trials for IRDs and presents a set of recommendations aimed at rapidly advancing future progress. The goal is to stimulate discussions among researchers, funding agencies, industry, and policy makers that will further the design, conduct, and analysis of clinical trials needed to accelerate the approval of effective treatments for IRDs, while promoting advocacy and ensuring patient safety
Gravitational waves from single neutron stars: an advanced detector era survey
With the doors beginning to swing open on the new gravitational wave
astronomy, this review provides an up-to-date survey of the most important
physical mechanisms that could lead to emission of potentially detectable
gravitational radiation from isolated and accreting neutron stars. In
particular we discuss the gravitational wave-driven instability and
asteroseismology formalism of the f- and r-modes, the different ways that a
neutron star could form and sustain a non-axisymmetric quadrupolar "mountain"
deformation, the excitation of oscillations during magnetar flares and the
possible gravitational wave signature of pulsar glitches. We focus on progress
made in the recent years in each topic, make a fresh assessment of the
gravitational wave detectability of each mechanism and, finally, highlight key
problems and desiderata for future work.Comment: 39 pages, 12 figures, 2 tables. Chapter of the book "Physics and
Astrophysics of Neutron Stars", NewCompStar COST Action 1304. Minor
corrections to match published versio
Cucurbitacin I Inhibits Cell Motility by Indirectly Interfering with Actin Dynamics
Cucurbitacins are plant natural products that inhibit activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway by an unknown mechanism. They are also known to cause changes in the organization of the actin cytoskeleton. actin depolymerization experiments, cucurbitacin I had no effect on the rate of actin filament disassembly at the nanomolar concentrations that inhibit cell migration. At elevated concentrations, the depolymerization rate was also unaffected, although there was a delay in the initiation of depolymerization. Therefore, cucurbitacin I targets some factor involved in cellular actin dynamics other than actin itself. Two candidate proteins that play roles in actin depolymerization are the actin-severing proteins cofilin and gelsolin. Cucurbitacin I possesses electrophilic reactivity that may lead to chemical modification of its target protein, as suggested by structure-activity relationship data. However, mass spectrometry revealed no evidence for modification of purified cofilin or gelsolin by cucurbitacin I.Cucurbitacin I results in accumulation of actin filaments in cells by a unique indirect mechanism. Furthermore, the proximal target of cucurbitacin I relevant to cell migration is unlikely to be the same one involved in activation of the JAK2/STAT3 pathway
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at â s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fbâ1 of â s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus
Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 Ă 10â7), SMARCC1 (p = 8.15 Ă 10â10), and PTCH1 (p = 1.06 Ă 10â6). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 Ă 10â4). Together, these probands account for âŒ10% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications
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