659 research outputs found
The Change Up Project : using social norming theory with young people to address domestic abuse and promote healthy relationships
This paper presents the findings of a secondary analysis of data collected during a pilot project, Change Up, which used a social norming approach (SNA) to address domestic violence and abuse (DVA) with young people aged 13â14. A SNA is based upon a well-articulated theory of behavior and evidence-based methodology for addressing social justice issues. This reflects a paradigm shift focusing upon strengths and positives, rather than pathologizing behaviours. Adopting a SNA, the Change Up project comprised a baseline survey followed by the intervention (workshop and peer-to-peer campaign), ending with a post-intervention survey. It was delivered in two high schools in a UK city between 2015 and 16. A secondary analysis of the survey data collected during the surveys and qualitative data collected at the end of each workshop was undertaken and this is reported here. Change Up data illustrates that most young people in the sample thought that DVA is unacceptable. There was, however, a gender difference in the norms held about the social acceptability of girls using physical violence against boys (and vice versa). The analysis of Change Up data indicates that a social norming approach to DVA programs aimed at young people can be successful in promoting attitude and behaviour change. It also highlights a continuing need for young peopleâs education about relationships and gender equality
The microRNA-29 family in cartilage homeostasis and osteoarthritis
MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFÎČ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1ÎČ increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFÎșB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways
Dynamic Regulation of Tgf-B Signaling by Tif1Îł: A Computational Approach
TIF1Îł (Transcriptional Intermediary Factor 1 Îł) has been implicated in
Smad-dependent signaling by Transforming Growth Factor beta (TGF-ÎČ).
Paradoxically, TIF1Îł functions both as a transcriptional repressor or as an
alternative transcription factor that promotes TGF-ÎČ signaling. Using
ordinary differential-equation models, we have investigated the effect of
TIF1Îł on the dynamics of TGF-ÎČ signaling. An integrative model that
includes the formation of transient TIF1Îł-Smad2-Smad4 ternary complexes is
the only one that can account for TGF-ÎČ signaling compatible with the
different observations reported for TIF1Îł. In addition, our model predicts
that varying TIF1Îł/Smad4 ratios play a critical role in the modulation of
the transcriptional signal induced by TGF-ÎČ, especially for short
stimulation times that mediate higher threshold responses. Chromatin
immunoprecipitation analyses and quantification of the expression of TGF-ÎČ
target genes as a function TIF1Îł/Smad4 ratios fully validate this
hypothesis. Our integrative model, which successfully unifies the seemingly
opposite roles of TIF1Îł, also reveals how changing TIF1Îł/Smad4 ratios
affect the cellular response to stimulation by TGF-ÎČ, accounting for a
highly graded determination of cell fate
Acute-Phase-HDL Remodeling by Heparan Sulfate Generates a Novel Lipoprotein with Exceptional Cholesterol Efflux Activity from Macrophages
During episodes of acute-inflammation high-density lipoproteins (HDL), the carrier of so-called good cholesterol, experiences a major change in apolipoprotein composition and becomes acute-phase HDL (AP-HDL). This altered, but physiologically important, HDL has an increased binding affinity for macrophages that is dependent on cell surface heparan sulfate (HS). While exploring the properties of AP-HDLâ¶HS interactions we discovered that HS caused significant remodeling of AP-HDL. The physical nature of this change in structure and its potential importance for cholesterol efflux from cholesterol-loaded macrophages was therefore investigated. In the presence of heparin, or HS, AP-HDL solutions at pH 5.2 became turbid within minutes. Analysis by centrifugation and gel electrophoresis indicated that AP-HDL was remodeled generating novel lipid poor particles composed only of apolipoprotein AI, which we designate ÎČ2. This remodeling is dependent on pH, glycosaminoglycan type, is promoted by Ca2+ and is independent of protease or lipase activity. Compared to HDL and AP-HDL, remodeled AP-HDL (S-HDL-SAA), containing ÎČ2 particles, demonstrated a 3-fold greater cholesterol efflux activity from cholesterol-loaded macrophage. Because the identified conditions causing this change in AP-HDL structure and function can exist physiologically at the surface of the macrophage, or in its endosomes, we postulate that AP-HDL contains latent functionalities that become apparent and active when it associates with macrophage cell surface/endosomal HS. In this way initial steps in the reverse cholesterol transport pathway are focused at sites of injury to mobilize cholesterol from macrophages that are actively participating in the phagocytosis of damaged membranes rich in cholesterol. The mechanism may also be of relevance to aspects of atherogenesis
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Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive
Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinsonâs disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model
Search for CP violation in D+âÏÏ+ and D+sâK0SÏ+ decays
A search for CP violation in D + â ÏÏ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fbâ1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (â0.04 ± 0.14 ± 0.14)% for candidates with K â K + mass within 20 MeV/c 2 of the Ï meson mass. A search for a CP -violating asymmetry that varies across the Ï mass region of the D + â K â K + Ï + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+sâK0SÏ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%
Study of decays to the final state and evidence for the decay
A study of decays is performed for the first time
using data corresponding to an integrated luminosity of 3.0
collected by the LHCb experiment in collisions at centre-of-mass energies
of and TeV. Evidence for the decay
is reported with a significance of 4.0 standard deviations, resulting in the
measurement of
to
be .
Here denotes a branching fraction while and
are the production cross-sections for and mesons.
An indication of weak annihilation is found for the region
, with a significance of
2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html,
link to supplemental material inserted in the reference
Differential branching fraction and angular analysis of decays
The differential branching fraction of the rare decay is measured as a function of , the
square of the dimuon invariant mass. The analysis is performed using
proton-proton collision data, corresponding to an integrated luminosity of 3.0
\mbox{ fb}^{-1}, collected by the LHCb experiment. Evidence of signal is
observed in the region below the square of the mass. Integrating
over 15 < q^{2} < 20 \mbox{ GeV}^2/c^4 the branching fraction is measured as
d\mathcal{B}(\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-)/dq^2 = (1.18 ^{+
0.09} _{-0.08} \pm 0.03 \pm 0.27) \times 10^{-7} ( \mbox{GeV}^{2}/c^{4})^{-1},
where the uncertainties are statistical, systematic and due to the
normalisation mode, , respectively.
In the intervals where the signal is observed, angular distributions are
studied and the forward-backward asymmetries in the dimuon ()
and hadron () systems are measured for the first time. In the
range 15 < q^2 < 20 \mbox{ GeV}^2/c^4 they are found to be A^{l}_{\rm FB} =
-0.05 \pm 0.09 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)} and A^{h}_{\rm FB} =
-0.29 \pm 0.07 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)}.Comment: 27 pages, 10 figures, Erratum adde
Protocol for Pilot Cluster RCT of Project Respect: A school-based intervention to prevent dating and relationship violence and address health inequalities among young people
Background
Dating and relationship violence (DRV) â intimate partner violence during adolescence â encompasses physical, sexual and emotional abuse. DRV is associated with a range of adverse health outcomes including injuries, sexually transmitted infections, adolescent pregnancy and mental health issues. Experiencing DRV also predicts both victimisation and perpetration of partner violence in adulthood.
Prevention targeting early adolescence is important because this is when dating behaviours begin, behavioural norms become established and DRV starts to manifest. Despite high rates of DRV victimisation in England, from 22-48% among girls and 12-27% among boys ages 14-17 who report intimate relationships, no RCTs of DRV prevention programmes have taken place in the UK.
Informed by two school-based interventions that have shown promising results in RCTs in the United States â Safe Dates and Shifting Boundaries â Project Respect aims to optimise and pilot a DRV prevention programme for secondary schools in England.
Methods
Design: Optimisation and pilot cluster RCT. Trial will include a process evaluation and assess the feasibility of conducting a phase III RCT with embedded economic evaluation. Cognitive interviewing will inform survey development.
Participants: Optimisation involves four schools and pilot RCT involves six (four intervention, two control). All are secondary schools in England. Baseline surveys conducted with students in Years 8 and 9 (ages 12-14). Follow-up surveys conducted with the same cohort, 16 months post-baseline.
Optimisation sessions to inform intervention and research methods will involve consultations with stakeholders, including young people.
Intervention: School staff training, including guidance on reviewing school policies and addressing âhotspotsâ for DRV and gender-based harassment; information for parents; informing students of a help-seeking app; and a classroom curriculum for students in years 9 and 10, including a student-led campaign.
Primary Outcome: The primary outcome of the pilot RCT will be whether progression to a phase III RCT is justified. Testing within the pilot will also determine which of two existing scales is optimal for assessing DRV victimisation and perpetration in a phase III RCT.
Discussion
This will be the first RCT of an intervention to prevent DRV in the UK. If findings indicate feasibility and acceptability, we will undertake planning for a phase III RCT of effectiveness.
Trial registration
ISRCTN, ISRCTN 65324176. Registered 8 June 2017, https://doi.org/10.1186/ISRCTN6532417
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