Restorative sleep predicts the resolution of chronic widespread pain: results from the EPIFUND study

PublishedJournal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tVersion of record of article published in Rheumatology (Oxford). 2008 Dec; 47(12): 1809–1813. Published online 2008 Oct 7. doi: 10.1093/rheumatology/ken389OBJECTIVES: Poor sleep is associated with chronic widespread pain (CWP). Conversely, good-quality sleep may play a role in the resolution of pain symptoms. Sleep is a multidimensional construct, comprising a number of diverse components. The aims of the current study were to examine the hypotheses that: (i) good sleep quality would predict the resolution of CWP, (ii) restorative sleep would predict the resolution of CWP and (iii) that these relationships would be independent of confounding psychological factors. METHODS: Subjects in a population-based prospective study completed a pain questionnaire at baseline from which subjects with CWP were identified. Baseline sleep was measured using the Estimation of Sleep Problems Scale which measures sleep onset, maintenance, early wakening and restorative sleep. The questionnaire also contained scales examining psychosocial status. Subjects were followed up 15 months later and pain status was assessed. RESULTS: A total of 1061 subjects reported CWP at baseline of whom 679 (75% of eligible subjects) responded at follow-up. Of those, a total of 300 (44%) no longer satisfied criteria for CWP. Univariate analysis revealed that three of the four sleep components were associated with the resolution of CWP: rapid sleep onset, odds ratio (OR) = 1.7, 95% CI 1.2, 2.5; absence of early wakening, OR = 1.6, 95% CI 1.1, 2.4; and restorative sleep, OR = 2.7, 95% CI 1.5, 4.8. After adjusting for the effect of psychosocial factors, which may have confounded the relationship, only restorative sleep (OR = 2.0, 95% CI 1.02, 3.8) was associated. CONCLUSIONS: Self-reported restorative sleep was independently associated with the resolution of CWP and return to musculoskeletal health.This study was funded by the Arthritis Research Campaign, Grant number: 1755

General Gauge Mediation with Gauge Messengers

We generalize the General Gauge Mediation formalism to allow for the possibility of gauge messengers. Gauge messengers occur when charged matter fields of the susy-breaking sector have non-zero F-terms, which leads to tree-level, susy-breaking mass splittings in the gauge fields. A classic example is that SU(5) / SU(3) x SU(2) x U(1) gauge fields could be gauge messengers. We give a completely general, model independent, current-algebra based analysis of gauge messenger mediation of susy-breaking to the visible sector. Characteristic aspects of gauge messengers include enhanced contributions to gaugino masses, (tachyonic) sfermion mass-squareds generated already at one loop, and also at two loops, and significant one-loop A-terms, already at the messenger scale.Comment: 79 pages, 5 figure

Global Symmetries and D-Terms in Supersymmetric Field Theories

We study the role of D-terms in supersymmetry (SUSY) breaking. By carefully analyzing the SUSY multiplets containing various conserved currents in theories with global symmetries, we obtain a number of constraints on the renormalization group flow in supersymmetric field theories. Under broad assumptions, these results imply that there are no SUSY-breaking vacua, not even metastable ones, with parametrically large D-terms. This explains the absence of such D-terms in models of dynamical SUSY-breaking. There is, however, a rich class of calculable models which generate comparable D-terms and F-terms through a variety of non-perturbative effects; these D-terms can be non-abelian. We give several explicit examples of such models, one of which is a new calculable limit of the 3-2 model.Comment: 34 pages, 2 figures; reference added, minor change

Dynamical completions of generalized O'Raifeartaigh models

We present gauge theory completions of Wess-Zumino models admitting supersymmetry breaking vacua with spontaneously broken R-symmetry. Our models are simple deformations of generalized ITIY models, a supersymmetric theory with gauge group Sp(N), N+1 flavors plus singlets, with a modified tree level superpotential which explicitly breaks (part of) the global symmetry. Depending on the nature of the deformation, we obtain effective O'Raifeartaigh-like models whose pseudomoduli space is locally stable in a neighborhood of the origin of field space, or in a region not including it. Hence, once embedded in direct gauge mediation scenarios, our models can give low energy spectra with either suppressed or unsuppressed gaugino mass.Comment: 21 pages, 1 figure; v3: reference adde

A Bound on the Superpotential

We prove a general bound on the superpotential in theories with broken supersymmetry and broken R-symmetry, 2|W|< f_a F, where f_a and F are the R-axion and Goldstino decay constants, respectively. The bound holds for weakly coupled as well as strongly coupled theories, thereby providing an exact result in theories with broken supersymmetry. We briefly discuss several possible applications.Comment: 20 page

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

&lt;p&gt;Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.&lt;/p&gt; &lt;p&gt;Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.&lt;/p&gt; &lt;p&gt;Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.&lt;/p&gt; &lt;p&gt;Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.&lt;/p&gt

Tree Level Metastability and Gauge Mediation in Baryon Deformed SQCD

We investigate supersymmetric QCD with gauge group SU(2) and a baryon deformation to the superpotential. The existence of an uplifted vacuum at the origin with tree level metastability is demonstrated. When this model is implemented in a direct gauge mediation scenario we therefore find gaugino masses which are comparable to sfermion masses and parameterised by an effective number of messengers 1/8. All deformations are well motivated by appealing to the electric theory and an R-symmetry. This R-symmetry is explicitly broken by the same term responsible for supersymmetry breaking. Moreover, the model does not suffer from the Landau pole problem and we find that it can be described in terms of just two scales: the weak scale and a high scale like the Planck or GUT scale. The model can be tested by searching for new particles at the TeV scale charged under the visible sector gauge group.Comment: 17 pages, 7 figures, updated reference

Condensate cosmology in O'Raifeartaigh models

Flat directions charged under an R-symmetry are a generic feature of O'Raifeartaigh models. Non-topological solitons associated with this symmetry, R-balls, are likely to form through the fragmentation of a condensate, itself created by soft terms induced during inflation. In gravity mediated SUSY breaking R-balls decay to gravitinos, reheating the universe. For gauge mediation R-balls can provide a good dark matter candidate. Alternatively they can decay, either reheating or cooling the universe. Conserved R-symmetry permits decay to gravitinos or gauginos, whereas spontaneously broken R-symmetry results in decay to visible sector gauge bosons.Comment: 29 pages, 5 figures. Comments and references added, accepted for publication in JHE

Mitochondrial phylogeography and demographic history of the Vicuña: implications for conservation

The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275 000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22°S) dry Andes 14–12 000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29°S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81