4,382 research outputs found
Individuals with low back pain: how do they view physical activity?
Background. Recent guidelines for those with acute low back pain have advocated early resumption of normal activity and increased physical activity. Little is known about the relationship between low back pain and physical activity, and on the impact of that relationship on the promotion of increased levels of physical activity within a general practice population.
Objectives. We aimed to explore associations between factors that influence changes in physical activity and the way individuals perceive and behave with their low back pain, and the impact of those perceptions and behaviour on physical activity.
Methods. Twenty-seven informants were chosen using a purposive sample from a larger group of individuals who, because of their low back trouble, had been referred by their GPs to a community-based, single-blind, randomized controlled trial (RCT) at the University of York, which is evaluating the effectiveness and cost-effectiveness of a progressive exercise programme. Fifty-four interviews were conducted with this subgroup of the RCT; four informants were interviewed once, 19 twice and four of them three times. Interviews were transcribed and analysed using manual and computer-aided approaches.
Results. Physical activity was perceived as (i) activities of daily living, (ii) activities causing breathlessness that they went out of the way to do and (iii) more competitive-type activity. The avoidance of physical activity and fear of pain returning were the two main factors directly associated with informants' backs and changes in physical activity. These two factors hindered increases in physical activity, even though the majority of informants believed strongly that being physically active helped ease their low back pain.
Conclusions. When advocating that individuals with acute low back pain return to or increase physical activity, it is important that clinicians identify avoidance of physical activity and/or fear of pain at the earliest stage in order to tailor advice and reassurance appropriately. If avoidance of activity and fear of pain is identified and clinicians want to encourage patients to take up and sustain increased physical activity, they should explore issues of fear of pain, and avoidance of and confidence to do physical activities, in addition to other factors influencing physical activity
Ras/Raf-1/MAPK pathway mediates response to tamoxifen but not chemotherapy in breast cancer patients
<b>Purpose</b>: The expression and activation of the Ras/Raf-1/mitogen-activated protein kinase (MAPK) pathway plays an important role in the development and progression of cancer, and may influence response to treatments such as tamoxifen and chemotherapy. In this study we investigated whether the expression and activation of the key components of this pathway influenced clinical outcome, to test the hypothesis that activation of the MAPK pathway drives resistance to tamoxifen and chemotherapy in women with breast cancer.
<b>Experimental Design</b>: Breast tumors from patients at the Glasgow Royal Infirmary and others treated within the BR9601 trial were analyzed for expression of the three Ras isoforms, total Raf-1, active and inactive forms of Raf-1 [pRaf(ser338) and pRaf(ser259), respectively], MAPK, and phospho-MAPK using an immunohistochemical approach. Analyses were done with respect to disease free-survival and overall survival.
<b>Results</b>: Expression and activation of the Ras pathway was associated with loss of benefit from treatment with tamoxifen but not chemotherapy. Overexpression of pRaf(ser338) was associated with shortened disease-free and overall survival time in univariate analyses. Multivariate analysis suggested pRaf(ser338) was independent of known prognostic markers in predicting outcome following tamoxifen treatment (<i>P</i>=0.03).
<b>Conclusion</b>: This study suggests that activation of the Ras pathway predicts for poor outcome on tamoxifen but not chemotherapy, and identifies pRaf(ser338) as a potential marker of resistance to estrogen receptor–targeted therapy. In addition, it suggests that expression of pRaf(ser338) could identify patients for whom tamoxifen alone is insufficient adjuvant systemic therapy, but for whom the addition of chemotherapy may be of benefit
Sustained signalling by PTH modulates IP3 accumulation and IP3 receptors through cyclic AMP junctions.
Parathyroid hormone (PTH) stimulates adenylyl cyclase through type 1 PTH receptors (PTH1R) and potentiates the Ca(2+) signals evoked by carbachol, which stimulates formation of inositol 1,4,5-trisphosphate (IP3). We confirmed that in HEK cells expressing PTH1R, acute stimulation with PTH(1-34) potentiated carbachol-evoked Ca(2+) release. This was mediated by locally delivered cyclic AMP (cAMP), but unaffected by inhibition of protein kinase A (PKA), exchange proteins activated by cAMP, cAMP phosphodiesterases (PDEs) or substantial inhibition of adenylyl cyclase. Sustained stimulation with PTH(1-34) causes internalization of PTH1R-adenylyl cyclase signalling complexes, but the consequences for delivery of cAMP to IP3R within cAMP signalling junctions are unknown. Here, we show that sustained stimulation with PTH(1-34) or with PTH analogues that do not evoke receptor internalization reduced the potentiated Ca(2+) signals and attenuated carbachol-evoked increases in cytosolic IP3. Similar results were obtained after sustained stimulation with NKH477 to directly activate adenylyl cyclase, or with the membrane-permeant analogue of cAMP, 8-Br-cAMP. These responses were independent of PKA and unaffected by substantial inhibition of adenylyl cyclase. During prolonged stimulation with PTH(1-34), hyperactive cAMP signalling junctions, within which cAMP is delivered directly and at saturating concentrations to its targets, mediate sensitization of IP3R and a more slowly developing inhibition of IP3 accumulation.Supported by the Wellcome Trust (101844) and the Biotechnology and Biological Sciences Research Council (L000075). AM was supported in part by the Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow, India.This is the final version of the article. It first appeared from the Company of Biologists via //http://jcs.biologists.org/content/128/2/408
Directed Random Markets: Connectivity determines Money
Boltzmann-Gibbs distribution arises as the statistical equilibrium
probability distribution of money among the agents of a closed economic system
where random and undirected exchanges are allowed. When considering a model
with uniform savings in the exchanges, the final distribution is close to the
gamma family. In this work, we implement these exchange rules on networks and
we find that these stationary probability distributions are robust and they are
not affected by the topology of the underlying network. We introduce a new
family of interactions: random but directed ones. In this case, it is found the
topology to be determinant and the mean money per economic agent is related to
the degree of the node representing the agent in the network. The relation
between the mean money per economic agent and its degree is shown to be linear.Comment: 14 pages, 6 figure
Supersymmetric particle mass measurement with invariant mass correlations
The kinematic end-point technique for measuring the masses of supersymmetric
particles in R-Parity conserving models at hadron colliders is re-examined with
a focus on exploiting additional constraints arising from correlations in
invariant mass observables. The use of such correlations is shown to
potentially resolve the ambiguity in the interpretation of quark+lepton
end-points and enable discrimination between sequential two-body and three-body
lepton-producing decays. The use of these techniques is shown to improve the
SUSY particle mass measurement precision for the SPS1a benchmark model by at
least 20-30% compared to the conventional end-point technique.Comment: 29 pages, 23 .eps figures, JHEP3 style; v2 adds some references and
small clarifications to text; v3 adds some more clarifications to the tex
Rapid recycling of Ca2+ between IP3-sensitive stores and lysosomes.
Inositol 1,4,5-trisphosphate (IP3) evokes release of Ca2+ from the endoplasmic reticulum (ER), but the resulting Ca2+ signals are shaped by interactions with additional intracellular organelles. Bafilomycin A1, which prevents lysosomal Ca2+ uptake by inhibiting H+ pumping into lysosomes, increased the amplitude of the initial Ca2+ signals evoked by carbachol in human embryonic kidney (HEK) cells. Carbachol alone and carbachol in combination with parathyroid hormone (PTH) evoke Ca2+ release from distinct IP3-sensitive Ca2+ stores in HEK cells stably expressing human type 1 PTH receptors. Bafilomycin A1 similarly exaggerated the Ca2+ signals evoked by carbachol or carbachol with PTH, indicating that Ca2+ released from distinct IP3-sensitive Ca2+ stores is sequestered by lysosomes. The Ca2+ signals resulting from store-operated Ca2+ entry, whether evoked by thapsigargin or carbachol, were unaffected by bafilomycin A1. Using Gd3+ (1 mM) to inhibit both Ca2+ entry and Ca2+ extrusion, HEK cells were repetitively stimulated with carbachol to assess the effectiveness of Ca2+ recycling to the ER after IP3-evoked Ca2+ release. Blocking lysosomal Ca2+ uptake with bafilomycin A1 increased the amplitude of each carbachol-evoked Ca2+ signal without affecting the rate of Ca2+ recycling to the ER. This suggests that Ca2+ accumulated by lysosomes is rapidly returned to the ER. We conclude that lysosomes rapidly, reversibly and selectively accumulate the Ca2+ released by IP3 receptors residing within distinct Ca2+ stores, but not the Ca2+ entering cells via receptor-regulated, store-operated Ca2+ entry pathways.Wellcome Trust (101844)
Caica Galicia Foundation, Spain (studentship to CILS)
Obra Social La Caixa, Spain (studentship to CILS)This is thefinal published version. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111275
Scheduling Bidirectional Traffic on a Path
We study the fundamental problem of scheduling bidirectional traffic along a
path composed of multiple segments. The main feature of the problem is that
jobs traveling in the same direction can be scheduled in quick succession on a
segment, while jobs in opposing directions cannot cross a segment at the same
time. We show that this tradeoff makes the problem significantly harder than
the related flow shop problem, by proving that it is NP-hard even for identical
jobs. We complement this result with a PTAS for a single segment and
non-identical jobs. If we allow some pairs of jobs traveling in different
directions to cross a segment concurrently, the problem becomes APX-hard even
on a single segment and with identical jobs. We give polynomial algorithms for
the setting with restricted compatibilities between jobs on a single and any
constant number of segments, respectively
Domestic ventilation rates, indoor humidity and dust mite allergens : are our homes causing the asthma pandemic?
This paper is concerned with historical changes in domestic ventilation rates, relative humidity and the associated risk of house dust mite colonization. A controlled trial evaluated allergen and water vapour control measures on the level of house dust mite (HDM) Der p1 allergen and indoor humidity, concurrently with changes in lung function in 54 subjects who completed the protocol. Mechanical heat recovery ventilation units significantly reduced moisture content in the active group, while HDM allergen reservoirs in carpets and beds were reduced by circa 96%. Self reported health status confirmed a significant clinical improvement in the active group. The study can form the basis for assessing minimum winter ventilation rates that can suppress RH below the critical ambient equilibrium humidity of 60% and thus inhibit dust mite colonization and activity in temperate and maritime in' uenced climatic regions
AAV Serotype Influences Gene Transfer in Corneal Stroma \u3cem\u3ein vivo\u3c/em\u3e
This study evaluated the cellular tropism and relative transduction efficiency of three AAV serotypes, AAV6, AAV8 and AAV9, for corneal gene delivery using mouse cornea in vivo and donor human cornea ex vivo. The AAV6, AAV8 and AAV9 serotypes having AAV2 plasmid encoding for alkaline phosphatase (AP) gene were generated by transfecting HEK293 cell line with pHelper, pARAP4 and pRep/Cap plasmids. Viral vectors (109 vg/μl) were topically applied onto mouse cornea in vivo and human cornea ex vivo after removing the epithelium. Human corneas were processed for transgene delivery at day 5 after viral vector application. Mouse corneas were harvested at 4, 14 and 30 days after vector application for AP staining. Transduction efficiency was calculated by quantifying pixels of AP-stained area using Image J software and also confirmed by functional AP enzyme activity in the corneal lysates. Cellular toxicity of the three AAV serotypes was tested with TUNEL assay. Inflammatory response was detected by immunostaining for CD11b and F4/80. All three AAV serotypes successfully transduced mouse and human corneas. The order of transduction efficiency was AAV9\u3eAAV8\u3eAAV6. The transduction efficiency of AAV9 was 1.1–1.4 fold higher (p\u3e0.05) as compared to AAV8 and 3.5–5.5 fold higher (p\u3c0.01) as compared to AAV6. The level of transgene expression for all the three serotypes was greater at 14 days compared to 4 days and this high level of transgene expression was maintained up to the tested time point of 30 days. Corneas exposed to any of the three AAV serotypes did not show significant TUNEL positive cells or any inflammatory response as tested by CD11b or F4/80 staining suggesting that tested AAV serotypes do not induce cell death or inflammation and are safe for corneal gene therapy
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