582 research outputs found
Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study
Background: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pound for the completion of postal questionnaires. Methods: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pound to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pound incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results: The response rate following reminders for the historical controls was 78.1% ( 82 of 105) compared with 88.0% ( 389 of 442) for those patients who received the 5 pound payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response ( adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial - the extra cost per additional respondent was almost 50 pound. Conclusion: The direct payment of 5 pound significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study
A Dynamical Analysis of the Suitability of Prehistoric Spheroids from the Cave of Hearths as Thrown Projectiles
Spheroids are ball-shaped stone objects found in African archaeological sites dating from 1.8 million years ago (Early Stone Age) to at least 70,000 years ago (Middle Stone Age). Spheroids are either fabricated or naturally shaped stones selected and transported to places of use making them one of the longest-used technologies on record. Most hypotheses about their use suggest they were percussive tools for shaping or grinding other materials. However, their size and spherical shape make them potentially useful as projectile weapons, a property that, uniquely, humans have been specialised to exploit for millions of years. Here we show (using simulations of projectile motions resulting from human throwing) that 81% of a sample of spheroids from the late Acheulean (Bed 3) at the Cave of Hearths, South Africa afford being thrown so as to inflict worthwhile damage to a medium-sized animal over distances up to 25 m. Most of the objects have weights that produce optimal levels of damage from throwing, rather than simply being as heavy as possible (as would suit other functions). Our results show that these objects were eminently suitable for throwing, and demonstrate how empirical research on behavioural tasks can inform and constrain our theories about prehistoric artefacts
Prime movers : mechanochemistry of mitotic kinesins
Mitotic spindles are self-organizing protein machines that harness teams of multiple force generators to drive chromosome segregation. Kinesins are key members of these force-generating teams. Different kinesins walk directionally along dynamic microtubules, anchor, crosslink, align and sort microtubules into polarized bundles, and influence microtubule dynamics by interacting with microtubule tips. The mechanochemical mechanisms of these kinesins are specialized to enable each type to make a specific contribution to spindle self-organization and chromosome segregation
Occupation of racial grief, loss as a resource : learning from ‘The Combahee River Collective Black Feminist Statement'
The methodology of ‘occupation’ through rereading The Combahee River Collective Black Feminist
Statement (The Combahee River Collective, in: James,
Sharpley-Whiting (eds) The Black Feminist Reader.
Blackwell Publishers Ltd., Oxford, pp 261–270, 1977)
demonstrates the necessity of temporal linkages to historical Black feminist texts and the wisdom of Black feminist
situated knowers. This paper argues that racism produces
grief and loss and as long as there is racism, we all remain
in racial grief and loss. However, in stark contrast to the
configuration of racial grief and loss as something to get
over, perhaps grief and loss can be thought about differently, for example, in terms of racial grief and loss as a
resource. This paper questions Western Eurocentric paternalistic responses to Black women’s ‘talk about their
feelings of craziness… [under] patriarchal rule’ (The
Combahee River Collective 1977: 262) and suggests
alternative ways of thinking about the psychological
impact of grief and loss in the context of racism. In this
paper, a Black feminist occupation of racial grief and loss
includes the act of residing within, and the act of working
with the constituent elements of racial grief and loss. The
proposal is that an occupation of racial grief and loss is a
paradoxical catalyst for building a twenty-first century
global intersectional Black feminist movement
A model of online protection to reduce children's online risk exposure: empirical evidence from Asia
Children are surrounded by a variety of digital media and are exposed to potential risks that come with such easy accessibility. Learning how to be safe online is an important consideration for both children and their caregivers. The present study proposes an integrated model of online safety based on constructs from protection motivation theory and the health belief model, namely perceived severity of (and susceptibility to) risk, online self-efficacy, online privacy concern, and digital literacy. The study comprised a survey conducted among 420 schoolchildren aged 9–16 years. Using partial least squares-structural equation modelling, the results illustrated the presence of a negative effect of ‘perceived severity of online risk’ toward online risks, whereas the effect of ‘digital literacy’ was found to be positive. Children whose perception of online risks was more severe were less exposed to online risks if they had higher ‘online privacy concerns’ than the children with higher ‘digital literacy’ who are more exposed to online risk. Results of the study show that engaging in safe online behaviour requires children to have a high perception regarding severity of online risks as well as knowledge of online privacy concerns. Online risks and opportunities occur in parallel. Consequently, the factors that increase or decrease risk may also increase or decrease the benefits
Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA
Correlations between charged particles in deep inelastic ep scattering have
been studied in the Breit frame with the ZEUS detector at HERA using an
integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in
terms of the angular separation between current-region particles within a cone
centred around the virtual photon axis. Long-range correlations between the
current and target regions have also been measured. The data support
predictions for the scaling behaviour of the angular correlations at high Q2
and for anti-correlations between the current and target regions over a large
range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations
and Monte Carlo models correctly describe the trends of the data at high Q2,
but show quantitative discrepancies. The data show differences between the
correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C
Binding Modes of Peptidomimetics Designed to Inhibit STAT3
STAT3 is a transcription factor that has been found to be constitutively activated in a number of human cancers.
Dimerization of STAT3 via its SH2 domain and the subsequent translocation of the dimer to the nucleus leads to
transcription of anti-apoptotic genes. Prevention of the dimerization is thus an attractive strategy for inhibiting the activity
of STAT3. Phosphotyrosine-based peptidomimetic inhibitors, which mimic pTyr-Xaa-Yaa-Gln motif and have strong to weak
binding affinities, have been previously investigated. It is well-known that structures of protein-inhibitor complexes are
important for understanding the binding interactions and designing stronger inhibitors. Experimental structures of
inhibitors bound to the SH2 domain of STAT3 are, however, unavailable. In this paper we describe a computational study
that combined molecular docking and molecular dynamics to model structures of 12 peptidomimetic inhibitors bound to
the SH2 domain of STAT3. A detailed analysis of the modeled structures was performed to evaluate the characteristics of the
binding interactions. We also estimated the binding affinities of the inhibitors by combining MMPB/GBSA-based energies
and entropic cost of binding. The estimated affinities correlate strongly with the experimentally obtained affinities.
Modeling results show binding modes that are consistent with limited previous modeling studies on binding interactions
involving the SH2 domain and phosphotyrosine(pTyr)-based inhibitors. We also discovered a stable novel binding mode
that involves deformation of two loops of the SH2 domain that subsequently bury the C-terminal end of one of the stronger
inhibitors. The novel binding mode could prove useful for developing more potent inhibitors aimed at preventing
dimerization of cancer target protein STAT3
Dystroglycan versatility in cell adhesion: a tale of multiple motifs
Dystroglycan is a ubiquitously expressed heterodimeric adhesion receptor. The extracellular a-subunit makes connections
with a number of laminin G domain ligands including laminins, agrin and perlecan in the extracellular
matrix and the transmembrane b-subunit makes connections to the actin filament network via cytoskeletal linkers
including dystrophin, utrophin, ezrin and plectin, depending on context. Originally discovered as part of the dystrophin
glycoprotein complex of skeletal muscle, dystroglycan is an important adhesion molecule and signalling scaffold
in a multitude of cell types and tissues and is involved in several diseases. Dystroglycan has emerged as a
multifunctional adhesion platform with many interacting partners associating with its short unstructured cytoplasmic
domain. Two particular hotspots are the cytoplasmic juxtamembrane region and at the very carboxy terminus
of dystroglycan. Regions which between them have several overlapping functions: in the juxtamembrane region; a
nuclear localisation signal, ezrin/radixin/moesin protein, rapsyn and ERK MAP Kinase binding function, and at the C
terminus a regulatory tyrosine governing WW, SH2 and SH3 domain interactions. We will discuss the binding partners
for these motifs and how their interactions and regulation can modulate the involvement of dystroglycan in a
range of different adhesion structures and functions depending on context. Thus dystroglycan presents as a multifunctional
scaffold involved in adhesion and adhesion-mediated signalling with its functions under exquisite spatiotemporal
regulation
Multi-messenger observations of a binary neutron star merger
On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta
Blood Donation and Colorectal Cancer Incidence and Mortality in Men
Background: Although blood donations may reduce body iron stores, to date, prospective data on frequent blood donation and colorectal cancer risk are limited. Methodology/Principal Findings: We tested whether frequent blood donation is associated with a lower risk of colorectal cancer in the Health Professionals Follow-up Study. We prospectively followed 35,121men who provide the information on lifetime number of blood donations in 1992 through 2008. Serum ferritin levels were measured in a random sample of 305 men. Cox proportional hazard regression models were used to calculate the multivariable relative risks (RRs, 95%CIs) after adjusting for age and other established colorectal cancer risk factors. We documented 684 incident colorectal cancer cases and 224 deaths from colorectal cancer. The mean serum ferritin levels varied from 178 µg/L for men who did not donate blood to 98 µg/L for men who had at least 30 donations. Age-adjusted results for both incidence and mortality were essentially the same as the multivariable-adjusted results. Comparing with non-donors, the multivariable RRs (95%CIs) for colorectal cancer incidence were 0.92 (0.77, 1.11) for 1–5 donation, 0.85 (0.64, 1.11) for 6–9 donations, 0.96 (0.73, 1.26) for 10–19 donations, 0.91 (0.63, 1.32) for 20–29 donations, and 0.97 (0.68, 1.38) for at least 30 donations (Ptrend = 0.92). The multivariable RRs for colorectal cancer mortality were 0.99 (0.72, 1.36) for 1–5 donation, 0.93 (0.57, 1.51) for 6–9 donations, 0.85 (0.50, 1.42) for 10–19 donations, and 1.14 (0.72, 1.83) for at least 20 donations (Ptrend = 0.82). The results did not vary by cancer sub-sites, intake levels of total iron, heme iron, or family history of colorectal cancer. Conclusions/Significance: Frequent blood donations were not associated with colorectal cancer incidence and mortality in men. Our results do not support an important role of body iron stores in colorectal carcinogenesis
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