737 research outputs found
Heterotic strings on G_2 orbifolds
We study compactification of heterotic strings to three dimensions on
orbifolds of G_2 holonomy. We consider the standard embedding and show that the
gauge group is broken from E_8 x E_8 or SO(32) to F_4 x E_8 or SO(25)
respectively. We also compute the spectrum of massless states and compare with
the results obtained from reduction of the 10-dimensional fields. Non-standard
embeddings are discussed briefly. For type II compactifications we verify that
IIB and IIA have equal massless spectrum.Comment: LaTex, 21 page
PROPEL: implementation of an evidence based pelvic floor muscle training intervention for women with pelvic organ prolapse: a realist evaluation and outcomes study protocol
Abstract Background Pelvic Organ Prolapse (POP) is estimated to affect 41%–50% of women aged over 40. Findings from the multi-centre randomised controlled “Pelvic Organ Prolapse PhysiotherapY” (POPPY) trial showed that individualised pelvic floor muscle training (PFMT) was effective in reducing symptoms of prolapse, improved quality of life and showed clear potential to be cost-effective. However, provision of PFMT for prolapse continues to vary across the UK, with limited numbers of women’s health physiotherapists specialising in its delivery. Implementation of this robust evidence from the POPPY trial will require attention to different models of delivery (e.g. staff skill mix) to fit with differing care environments. Methods A Realist Evaluation (RE) of implementation and outcomes of PFMT delivery in contrasting NHS settings will be conducted using multiple case study sites. Involving substantial local stakeholder engagement will permit a detailed exploration of how local sites make decisions on how to deliver PFMT and how these lead to service change. The RE will track how implementation is working; identify what influences outcomes; and, guided by the RE-AIM framework, will collect robust outcomes data. This will require mixed methods data collection and analysis. Qualitative data will be collected at four time-points across each site to understand local contexts and decisions regarding options for intervention delivery and to monitor implementation, uptake, adherence and outcomes. Patient outcome data will be collected at baseline, six months and one year follow-up for 120 women. Primary outcome will be the Pelvic Organ Prolapse Symptom Score (POP-SS). An economic evaluation will assess the costs and benefits associated with different delivery models taking account of further health care resource use by the women. Cost data will be combined with the primary outcome in a cost effectiveness analysis, and the EQ-5D-5L data in a cost utility analysis for each of the different models of delivery. Discussion Study of the implementation of varying models of service delivery of PFMT across contrasting sites combined with outcomes data and a cost effectiveness analysis will provide insight into the implementation and value of different models of PFMT service delivery and the cost benefits to the NHS in the longer term
Women’s experiences of receiving care for pelvic organ prolapse: a qualitative study
Background Pelvic organ prolapse is a common urogenital condition affecting 41–50% of women over the age of 40. To achieve early diagnosis and appropriate treatment, it is important that care is sensitive to and meets women’s needs, throughout their patient journey. This study explored women’s experiences of seeking diagnosis and treatment for prolapse and their needs and priorities for improving person-centred care. Methods Twenty-two women receiving prolapse care through urogynaecology services across three purposefully selected NHS UK sites took part in three focus groups and four telephone interviews. A topic guide facilitated discussions about women’s experiences of prolapse, diagnosis, treatment, follow-up, interactions with healthcare professionals, overall service delivery, and ideals for future services to meet their needs. Data were analysed thematically. Results Three themes emerged relating to women’s experiences of a) Evaluating what is normal b) Hobson’s choice of treatment decisions, and c) The trial and error of treatment and technique. Women often delayed seeking help for their symptoms due to lack of awareness, embarrassment and stigma. When presented to GPs, their symptoms were often dismissed and unaddressed until they became more severe. Women reported receiving little or no choice in treatment decisions. Choices were often influenced by health professionals’ preferences which were subtly reflected through the framing of the offer. Women’s embodied knowledge of their condition and treatment was largely unheeded, resulting in decisions that were inconsistent with women’s preferences and needs. Physiotherapy based interventions were reported as helping women regain control over their symptoms and life. A need for greater awareness of prolapse and physiotherapy interventions among women, GPs and consultants was identified alongside greater focus on prevention, early diagnosis and regular follow-up. Greater choice and involvement in treatment decision making was desired. Conclusions As prolapse treatment options expand to include more conservative choices, greater awareness and education is needed among women and professionals about these as a first line treatment and preventive measure, alongside a multi-professional team approach to treatment decision making. Women presenting with prolapse symptoms need to be listened to by the health care team, offered better information about treatment choices, and supported to make a decision that is right for them
Para- and Ortho-Substitutions Are Key Determinants of Polybrominated Diphenyl Ether Activity toward Ryanodine Receptors and Neurotoxicity
BackgroundPolybrominated diphenyl ethers (PBDEs) are widely used flame retardants that bioaccumulate in human tissues. Their neurotoxicity involves dysregulation of calcium ion (Ca(2+))signaling; however, specific mechanisms have yet to be defined.ObjectiveWe aimed to define the structure-activity relationship (SAR) for PBDEs and their metabolites toward ryanodine receptors type 1 (RyR1) and type 2 (RyR2) and to determine whether it predicts neurotoxicity.MethodsWe analyzed [3H]ryanodine binding, microsomal Ca(2+) fluxes, cellular measurements of Ca(2+) homeostasis, and neurotoxicity to define mechanisms and specificity of PBDE-mediated Ca(2+) dysregulation.ResultsPBDEs possessing two ortho-bromine substituents and lacking at least one para-bromine substituent (e.g., BDE-49) activate RyR1 and RyR2 with greater efficacy than corresponding congeners with two para-bromine substitutions (e.g., BDE-47). Addition of a methoxy group in the free para position reduces the activity of parent PBDEs. The hydroxylated BDEs 6-OH-BDE-47 and 4´-OH-BDE-49 are biphasic RyR modulators. Pretreatment of HEK293 cells (derived from human embryonic kidney cells) expressing either RyR1 or RyR2 with BDE-49 (250 nM) sensitized Ca2+ flux triggered by RyR agonists, whereas BDE-47 (250 nM) had negligible activity. The divergent activity of BDE-49, BDE-47, and 6-OH-BDE-47 toward RyRs predicted neurotoxicity in cultures of cortical neurons.ConclusionsWe found that PBDEs are potent modulators of RyR1 and RyR2. A stringent SAR at the ortho and para position determined whether a congener enhanced, inhibited, or exerted nonmonotonic actions toward RyRs. These results identify a convergent molecular target of PBDEs previously identified for noncoplanar polychlorinated biphenyls (PCBs) that predicts their cellular neurotoxicity and therefore could be a useful tool in risk assessment of PBDEs and related compounds
Decoupling property of the supersymmetric Higgs sector with four doublets
In supersymmetric standard models with multi Higgs doublet fields,
selfcoupling constants in the Higgs potential come only from the D-terms at the
tree level. We investigate the decoupling property of additional two heavier
Higgs doublet fields in the supersymmetric standard model with four Higgs
doublets. In particular, we study how they can modify the predictions on the
quantities well predicted in the minimal supersymmetric standard model (MSSM),
when the extra doublet fields are rather heavy to be measured at collider
experiments. The B-term mixing between these extra heavy Higgs bosons and the
relatively light MSSM-like Higgs bosons can significantly change the
predictions in the MSSM such as on the masses of MSSM-like Higgs bosons as well
as the mixing angle for the two light CP-even scalar states. We first give
formulae for deviations in the observables of the MSSM in the decoupling region
for the extra two doublet fields. We then examine possible deviations in the
Higgs sector numerically, and discuss their phenomenological implications.Comment: 26 pages, 24 figures, text sligtly modified,version to appear in
Journal of High Energy Physic
The Drosophila Zinc Finger Protein Trade Embargo Is Required for Double Strand Break Formation in Meiosis
Homologous recombination in meiosis is initiated by the programmed induction of double strand breaks (DSBs). Although the Drosophila Spo11 ortholog Mei-W68 is required for the induction of DSBs during meiotic prophase, only one other protein (Mei-P22) has been shown to be required for Mei-W68 to exert this function. We show here that the chromatin-associated protein Trade Embargo (Trem), a C2H2 zinc finger protein, is required to localize Mei-P22 to discrete foci on meiotic chromosomes, and thus to promote the formation of DSBs, making Trem the earliest known function in the process of DSB formation in Drosophila oocytes. We speculate that Trem may act by either directing the binding of Mei-P22 to preferred sites of DSB formation or by altering chromatin structure in a manner that allows Mei-P22 to form foci
Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders
Personality is influenced by genetic and environmental factors1
and associated with mental health. However, the underlying
genetic determinants are largely unknown. We identified six
genetic loci, including five novel loci2,3, significantly associated
with personality traits in a meta-analysis of genome-wide
association studies (N = 123,132–260,861). Of these genomewide
significant loci, extraversion was associated with variants
in WSCD2 and near PCDH15, and neuroticism with variants
on chromosome 8p23.1 and in L3MBTL2. We performed a
principal component analysis to extract major dimensions
underlying genetic variations among five personality traits
and six psychiatric disorders (N = 5,422–18,759). The first
genetic dimension separated personality traits and psychiatric
disorders, except that neuroticism and openness to experience
were clustered with the disorders. High genetic correlations
were found between extraversion and attention-deficit–
hyperactivity disorder (ADHD) and between openness and
schizophrenia and bipolar disorder. The second genetic
dimension was closely aligned with extraversion–introversion
and grouped neuroticism with internalizing psychopathology
(e.g., depression or anxiety)
Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)
Background: The English National Health Service has made a major investment in nine partnerships between
higher education institutions and local health services called Collaborations for Leadership in Applied Health
Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and
implement research through sustained interactions between academics and health services. CLAHRCs provide a
natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery.
This protocol describes an externally funded evaluation that focuses on implementation mechanisms and
processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances.
Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which
deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see
it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual
framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to
Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth
comparative case studies of research implementation using multiple data collection methods including
interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of
data collection. We will test the wider applicability of emerging findings with a wider community using an
interpretative forum.
Discussion: The idea that collaboration between academics and services might lead to more applicable health
research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is
limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for
implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g.,
Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge
translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts
particularly with respect to integrated stakeholder involvement
Optical pump rectification emission: route to terahertz free-standing surface potential diagnostics
We introduce a method for diagnosing the electric surface potential of a semiconductor based on THz surface generation. In our scheme, that we name Optical Pump Rectification Emission, a THz field is generated directly on the surface via surface optical rectification of an ultrashort pulse after which the DC surface potential is screened with a second optical pump pulse. As the THz generation directly relates to the surface potential arising from the surface states, we can then observe the temporal dynamics of the static surface field induced by the screening effect of the photo-carriers. Such an approach is potentially insensitive to bulk carrier dynamics and does not require special illumination geometries
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