“A new natural diketopiperazine (1) was obtained from the

“A new natural diketopiperazine (1) was obtained from the culture broth of Microbispora aerata strain imbas-11A, isolated from penguin excrements collected on the Antarctic Livingston Island. Compound 1 was purified consecutively by solvent extraction, silica gel column chromatography and preparative HPLC. The structure of the compound was elucidated by 1D and 2D NMR experiments and mass spectrometric investigations. The absolute configuration of compound 1 was determined by amino acid analysis and NOESY correlations.

A low antiproliferative and cytotoxic effect of trans-cyclo-(D-tryptophanyl-L-tyrosyl) (1) was determined with L-929 mouse fibroblast cells, K-562 human leukemia cells and HeLa human cervix carcinoma. Trans-cyclo-(D-tryptophanyl-L-tyrosyl)

(1) did not show antimicrobial activity at a concentration of 50 mu g per disc against Bacillus subtilis, Staphylococcus aureus, Streptomyces Selleck QNZ viridochromogenes, Escherichia coli, Candida albicans and Mucor miehei.”
“Background: Fondaparinux has been shown to reduce the risk of major bleeding and 30-day mortality compared with enoxaparin, in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). However, its cost effectiveness is not well known.

Objective: To evaluate the effectiveness and economic attractiveness of fondaparinux relative to enoxaparin in patients with NSTE-ACS treated with triple antiplatelet therapy and early (non-urgent) LY2603618 invasive strategy.

Methods: The decision model compares two alternative this website strategies: subcutaneous (SC) enoxaparin (1 mg/kg 12 hourly) versus SC fondaparinux (2.5 mg/day) in NSTE-ACS patients pre-treated with triple antiplatelet therapy and early revascularization. Cost-effectiveness and cost-utility analyses were performed from a healthcare perspective,

based on a Markov model with a time horizon of the patient lifespan. Univariate sensitivity analysis and probabilistic (Monte Carlo) microsimulation analysis were performed.

Results: In the base-case analysis (65 years, Thrombolysis In Myocardial Infarction [TIMI] score 4), the use of fondaparinux was associated with a significant reduction in major bleeding, a slight reduction in adverse cardiac events, and minor improvements in survival and QALYs, together with a small reduction in costs. The dominance of fondaparinux over enoxaparin remained unchanged in the univariate sensitivity analyses. According to Monte Carlo simulation, fondaparinux was cost saving in 99.9% of cases.

Conclusion: Compared with enoxaparin, the use of fondaparinux in patients with NSTE-ACS managed with an early invasive strategy appears to be cost effective, even in patients with a low risk of bleeding.”
“NUT midline carcinoma (NMC) is a rare and aggressive malignant epithelial tumor defined by rearrangement of the NUT gene on chromosome 15.

Having one’s expectations fulfilled, especially in relation to pa

Having one’s expectations fulfilled, especially in relation to pain, was important for a good outcome. The results emphasise the benefit of assessing patient-orientated

Selleckchem Copanlisib outcome in routine practice and the factors that might influence it, such that realistic expectations can be established for patients prior to surgery. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.”
“Purpose of review

This review will highlight recent advances in our understanding of the pathogenesis of Kawasaki disease, highlighting the molecular players involved in regulation of T-cell activation and their affect on disease incidence and outcome in both humans and mouse.

Recent findings

Kawasaki disease is the most common cause of multisystem vasculitis in childhood. The vessels most commonly damaged are the coronary arteries, making Kawasaki disease the number one cause of acquired heart disease in children from the developed world. The contribution of genetics to disease predisposition is clearly implicated, but the mechanisms involved in regulating predisposition to disease susceptibility and outcome are not clearly understood. Two independent approaches have recently identified regulation of T-cell activation as the critical factor in determining

susceptibility and severity of Kawasaki disease. Firstly, genetic analysis of affected Japanese children identified ITPKC, XAV 939 1,4,5-triphosphate 3-kinase C, a kinase involved in regulation of T-cell activation, to be significantly associated with susceptibility SYN-117 to and increased severity of Kawasaki disease. A second independent approach using an animal model of Kawasaki disease has also identified regulation

of T-cell activation, specifically costimulation, the second signal regulating optimal T-cell activation as the critical regulator of susceptibility to and severity of disease.


Understanding the molecular players responsible for dysregulation of the immune response in Kawasaki disease will foster development of improved diagnostic/predictive tools and more rational use of therapeutic agents to improve outcome in affected children.”
“Objective: The aim of this study was to develop and validate a user friendly performance based knee outcome score for use in active patients undergoing TKA surgery.

Design: We prospectively studied a cohort of 50 subjects without any knee symptoms, and 50 patients who underwent TKA for osteoarthritis (OA). The patients were assessed pre- and postoperatively. SF-36 and WOMAC were concurrently administered for comparison. Patients completed seven physical tasks of the finalised outcome instrument which were objectively assessed and scored.

Results: The mean functional score was 31.7 in the normal subjects. The mean functional score improved postoperatively from 10.0 to 17.7 (P < 0.001) in the TKA group.

Currently, the application of MSCs in SOT is being evaluated in p

Currently, the application of MSCs in SOT is being evaluated in phase I/II clinical trials.

Whereas the mechanisms of action used by MSC immunomodulation have been somewhat elucidated in vitro, the data from preclinical transplant models have been unclear. Furthermore, the optimal timing, dose, and route of administration remain to be elucidated. Importantly, MSCs have the SBC-115076 manufacturer ability to sense their environment, which may influence their function. In this article, we discuss the impact of the local microenvironment on MSCs and the mechanisms of MSC immunomodulation in the setting of SOT.”
“The mechanisms of malaria anemia remain incompletely understood although much effort has been put on studies in both human and murine systems. Hematopoiesis Napabucasin inhibitor is regulated by the proliferation, differentiation and maturation of erythropoietic progenitor cells into erythrocytes and is tightly controlled by a complex communication network of cytokines as signal mediators. The present study used the

murine P. yoelii 17XNL malaria model to investigate the profile of cytokines and leukocytes throughout the entire infection. Moreover, malaria induced anemia was studied in comparison with anemia induced by hemorrhage and hemolysis. During the P. yoelii infection, the levels of erythropoietic-related cytokines, such as G-CSF, GMCSF, IL-7, and IL-17, were pronouncedly reduced, while those of regulatory cytokines, such as IL-10 and TNF-alpha, were constantly increased. This cytokine profile corresponded well with the cellular composition during the infection, AZD1152 nmr such as drastically decreased levels of CD4(+) and CD8(+) T cells. The profiles of erythropoiesis or hematopoiesis related cytokines during malarial anemia showed striking differences from those during anemia induced by hemorrhage or hemolysis. This study demonstrates that a markedly dysregulated cytokine network occurred in

this murine malaria model, which may open a new window of insight into the mechanisms of malaria related anemia.”
“Non-invasive vascular studies can provide crucial information on the presence, location, and severity of critical limb ischaemia (CLI), as well as the initial assessment or treatment planning.

Ankle-brachial index with Doppler ultrasound, despite limitations in diabetic and end-stage renal failure patients, is the first-line evaluation of CLI. In this group of patients, toe-brachial index measurement may better establish the diagnosis. Other non-invasive measurements, such as segmental limb pressure, continuous-wave Doppler analysis and pulse volume recording, are of limited accuracy. Transcutaneous oxygen pressure (TcPO2) measurement may be of value when rest pain and ulcerations of the foot are present. Duplex ultrasound is the most important non-invasive tool in CLI patients combining haemodynamic evaluation with imaging modality.

Selective ablation of infiltrating monocyte-derived M Phi followi

Selective ablation of infiltrating monocyte-derived M Phi following SCI while sparing the resident microglia, using either antibody-mediated depletion or conditional ablation by diphtheria toxin, impaired recovery. Reconstitution of the peripheral blood with monocytes resistant to ablation restored the lost motor functions. Importantly, the infiltrating monocyte-derived M Phi displayed a local anti-inflammatory beneficial role, which was critically dependent upon their expression of interleukin 10.

Conclusions: The results of this study attribute a novel anti-inflammatory role to a unique subset LDK378 ic50 of infiltrating monocyte-derived M Phi in SCI recovery, which cannot be provided

by the activated resident microglia. According to our results, limited recovery following SCI can be attributed in part to the inadequate, untimely, spontaneous recruitment of monocytes. This process is amenable to boosting either by active vaccination with a myelin-derived altered peptide ligand, which indicates involvement of adaptive immunity in monocyte recruitment, or by augmenting the naive monocyte pool in the peripheral blood. Thus, click here our study sheds new light on the long-held debate regarding the contribution of M Phi to recovery from CNS injuries, and has potentially far-reaching therapeutic implications.”
“Compared with linear diblock or triblock poly(ethylene glycol)-block-poly(L-lactic acid) copolymer

(PEG-b-PLLA), star-shaped PEG-b-PLLA (sPEG-b-PLLA) copolymers exhibit smaller hydrodynamic radius and lower viscosity and are expected to display peculiar morphologies, thermal properties, and degradation profiles. Compared with the synthesis routine of PEG-b-PLLA form lactide and PEG, the traditional synthesis routine from LA and PEG were suffered by the low reaction efficiency, low purity, lower molecular weight, and wide molecular CP-673451 purchase weight distribution. In this article, multiarm sPEG-b-PLLA copolymer was prepared

from multiarm sPEG and L-lactic acid (LLA using an improved method of melt polycondensation, in which two types of sPEG, that is, sPEG1 (four arm, Mn = 4300) and sPEG2 (three arm, Mn = 3200) were chosen as the core. It was found the molecular weight of sPEG-b-PLLA could be strongly affected by the purity of LLA and sPEGs, and the purification technology of vacuum dewater and vacuum distillation could help to remove most of the impurities in commercial available LLA. The polymers, including sPEG and sPEG-b-PLLA with varied core (sPEG1 and sPEG2) and LLA/sPEG feeding ratios, were characterized and confirmed by 1H-NMR and 13C-NMR spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography, which showed that the terminal hydroxyl group in each arm of sPEGs had reacted with LLA to form sPEG-b-PLLA copolymers with fairly narrow molecular weight distribution. (c) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011″
“Study Design. Retrospective chart review.

A comparison of the relative environmental performances of MSW tr

A comparison of the relative environmental performances of MSW treatment scenario types within each study did not provide a clear confirmation or repudiation of the waste hierarchy.

This paper concludes that many recently published LCAs do not

ensure that the methodological assumptions are made clear to the reader. Lack of transparency makes the results difficult to interpret, and hampers meaningful comparisons between the LCA results. A convergence in the adoption of particular assumptions that are more representative of MSW management systems would facilitate the comparison of the results. (C) 2009 Belnacasan nmr Elsevier Ltd. All rights reserved.”
“Objective: Examine rates of recurrent, spontaneous preterm birth (PTB) in women treated prophylactically with 17 alpha-hydroxyprogesterone caproate (17P) when the penultimate PTB was due to preterm labor (PTL) or preterm premature rupture of the membranes (pPROM). Methods: Retrospective, descriptive, database study of 1183 singleton gestations that initiated prophylactic selleckchem 17P at <21 weeks with a penultimate PTB. Primary outcomes examined were rates of recurrent PTB at <37 and <32 weeks’ gestation in the PTL (n = 939) and pPROM (n = 244) cohorts. Results:

Recurrent PTB <37 weeks occurred in 38% versus 28.3% of the PTL and pPROM cohorts, respectively (p < 0.005). Rates of recurrent PTB <32 weeks were similar. Logistic regression revealed three risk factors increased the odds of recurrent PTB: >1 previous PTB (OR 1.8 [95% CI: 1.33-2.44]); penultimate birth at 28-33.9 weeks’ gestation (OR 1.61 [95% CI: 1.22-2.13]); and, PTL as the indication for delivery in the penultimate PTB (OR 1.66 AZD6244 clinical trial [95% CI: 1.16-2.37]). Conclusion: Several historical factors increase the risk for recurrent PTB

in women receiving 17P. Contrary to earlier studies of PTL and pPROM recurrence, women receiving prophylactic 17P with a penultimate PTB due to pPROM are at lower risk of recurrent PTB than those with a history of PTL.”
“This review aims to characterize direct-reading methods for analysis of volatile organic compounds (VOCs) and nanoparticles (NPs) in workplace air, in terms of general operating principles, analytical parameters, advantages and limitations. Furthermore, we summarize recent studies using direct-reading methods to assess exposure to VOCs and NPs in workplace air, and comment on future applications and potential research interests within this field. (C) 2013 Elsevier Ltd. All rights reserved.”
“In recent years there has been an increased concern regarding the potential use of chemical and biological weapons for mass urban terror. In particular, there are concerns that ricin could be employed as such an agent.

The temperature dependence of the band edge is studied using abso

The temperature dependence of the band edge is studied using absorption spectroscopy and found to be described by electron-phonon interactions. The temperature dependence of the PL emission intensities and lifetimes are

described by a model incorporating the effects of thermal activation and hopping, both of which compete with the radiative process. These factors are smaller than the observed Stokes shift between absorption and emission, and attributed to intra-well electron transfer that varies according to 2D and 3D character. High excitation intensity reveals two PL bands in the sample with intermediate Vorasidenib 2D/3D well morphology. The intensity dependence is described based on screening and bandgap renormalization. (C) 2011 American Institute of Physics. [doi:10.1063/1.3645044]“
“Two Thiazovivin series of nanoclay reinforced, thermoresponsive hydrogels were prepared, one based on poly(N-isopropylacrylamide) (PNIPA) and the other on semi-interpenetrating networks containing PNIPA and poly(N-vinyl pyrrolidone) (PVP), designated as SIPNs. The gels were crosslinked with 1, 3, and 5 wt % inorganic clay (hectorite) and SIPN gels additionally contained

1 wt % of PVP. The hydrogels were tested in the as-prepared state, i.e., at 10 wt % PNIPA concentration in water and at equilibrium (maximum) swelling. Increasing the concentration of nanoclays increases crosslink density, modulus, tensile strength, elongation (except in equilibrium swollen gels), hysteresis and with decreases in the degree of swelling, broadening of the phase transition region, and a decrease in elastic recovery at high deformations. The presence of linear PVP in the networks increases porosity and the pore size, increases swelling, deswelling rates, and hysteresis, but decreases

slightly lower critical solution temperature (LCST), tensile strength, elongation, and elastic recovery. The strongest hydrogels were ones with 10 wt % PNIPA and 5 wt % of nanoclays, displaying tensile strengths of 85 kPa and elongation Gilteritinib of 955%. All properties of hydrogels at the equilibrium swollen state are lower than in the as-prepared state, due to the lower concentration of chains per unit volume, but the trends are preserved. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012″
“To show the efficacy of anti-tumor necrosis factor therapy (etanercept) for treating endometriosis in an experimental model.

A randomized, placebo-controlled, blinded study using rat endometriosis model.

Experimental research center of Ankara Education and Research Hospital.

Twenty-two Wistar female rats.

After peritoneal implantation of endometrial tissue, rats were randomized to two equal intervention groups: control and etanercept-treated groups. After measuring implant volume, blood and peritoneal fluid samples were obtained. Vehicle treatments of 2 mL saline to rats in control and 0.4 mg/kg etanercept SC once weekly were administered in treatment group.

The cell clone with SOX2 overexpression had an approximately 1 3-

The cell clone with SOX2 overexpression had an approximately 1.3-fold higher growth rate compared to parental cells. SOX2 overexpression did not increase the population of cells undergoing apoptosis. Taken together, we developed two SOX2-overexpressing

cell clones, with constitutive SOX2 expression after three weeks of retinoic acid treatment. SOX2 overexpression resulted in altered expression of pluripotency-related genes, increased proliferation, and altered expression of neural markers after three weeks of retinoic acid treatment.”
“P>Here we present the genomic sequence of the African cultivated rice, Oryza glaberrima, and compare these data with the genome sequence of Asian cultivated rice, Oryza sativa. We obtained gene-enriched sequences of O. glaberrima that correspond to about 25% of the ARS-1620 in vivo gene regions of the O. sativa (japonica) genome by methylation filtration and subtractive hybridization of repetitive sequences. While patterns of amino

acid changes did not differ between the two species in terms of the TGF-beta inhibition biochemical properties, genes of O. glaberrima generally showed a larger synonymous-nonsynonymous substitution ratio, suggesting that O. glaberrima has undergone a genome-wide relaxation of purifying selection. We further investigated nucleotide substitutions around splice sites and found that eight genes of O. sativa experienced changes at splice sites after the divergence from O. glaberrima. These changes produced novel introns that partially truncated functional domains, suggesting that these newly emerged introns affect gene function. We also identified 2451 simple sequence repeats (SSRs) from the genomes of O. glaberrima and O. sativa. Although tri-nucleotide repeats were most common among the SSRs and were overrepresented

in the protein-coding sequences, we found that selection against indels of tri-nucleotide repeats was relatively weak in both African and Asian rice. Our genome-wide sequencing of O. glaberrima and in-depth analyses provide rice researchers not only with useful genomic resources for future breeding but also with new insights see more into the genomic evolution of the African and Asian rice species.”
“In the study described here, the antiepileptic effect of dehydroepiandrosterone (DHEA) treatment on iron-induced focal epileptiform activity in the rat brain was investigated. DHEA is a neuroactive corticosteroid hormone synthesized both in the adrenal cortex and in the brain. Its antioxidant properties are well known. As oxidative stress seems to play a major role in epileptogenesis in the iron-induced model of posttraumatic epilepsy, it was of interest to examine whether DHEA would exert antiepileptic activity. DHEA at a dose of 30 mg/kg/day administered intraperitoneally for 7, 14, and 21 days to iron-induced epileptic rats prevented epileptiform electrophysiological activity.

Conclusions: A 6-item questionnaire is a sensitive and easy-to-us

Conclusions: A 6-item questionnaire is a sensitive and easy-to-use screening tool for pediatric USA in a pediatric sleep clinic setting. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“Using the recombinant flocculating Angel yeast F6, long-term repeated batch fermentation for ethanol production

was performed and a high volumetric productivity resulted from half cells not washed and the optimum opportunity of residual glucose 20 g l(-1) of last medium. The obtained highest productivity was 2.07 g l(-1) h(-1), which was improved by 75.4% compared with that of 1.18 Selleck BGJ398 g l(-1) h(-1) in the first batch fermentation. The ethanol concentration reached 8.4% corresponding to the yield of 0.46 g g(-1). These results will contribute greatly to the industrial production of fuel ethanol using the commercial method with the flocculating yeast.”
“Objective-To gather data on cats living in US households, document their neuter status, and identify demographic characteristics associated with neuter status.


CP-690550 random-digit-dial telephone survey.

Sample Population-1,205 adults in the continental United States contacted between April 24, 2007, and May 14, 2007.

Procedures-Information was gathered by means of computer-assisted telephone interviews. Multivariate logit analysis was used to identify demographic characteristics significantly associated with neuter status.

Results-383 of 1,205 (31.8%) respondents reported having at least 1 cat at the time of the survey, yielding an estimated population of 82.4 million cats living in 36.8 million US households. Overall, 680 of 850 (80.0%) cats were reportedly neutered. Of the 371 neutered female cats, 303 (81.7%) had reportedly been neutered Selleckchem LCL161 before having any litters.

Proportion of cats that were neutered differed significantly across annual family income groups, with 96.2% (231/240) of cats in households with annual family incomes >= $75,000 being neutered, 90.7% (231/254) of cats in households with annual family incomes between $35,000 and $74,999 being neutered, and only 51.4% (123/239) of cats in households with annual family incomes < $35,000 being neutered.

Conclusions and Clinical Relevance-Findings suggested that a high percentage (80.0%) of cats living in households in the United States were neutered and that annual family income was the strongest predictor of whether cats in the household were neutered. The present study did not attempt to address stray and feral cats, which represent a substantial but unknown percentage of the total US cat population. (J Am Vet Med Assoc 2009;234:1023-1030)”
“Objective: To investigate the ototoxic effect of boric acid solution prepared with different degree of alcohol.

Methods: This study was performed on 28 young albino guinea pigs.

Interview data were synthesised and used to revise the screening

Interview data were synthesised and used to revise the screening interventions compared within an existing economic model.

Results: The qualitative data indicated broad based support for a glaucoma screening trial S63845 Apoptosis inhibitor to take place in primary care, using ophthalmic trained technical assistants supported by optometry input. The precise location should be tailored to local circumstances.

There was variability in opinion around the choice of screening test and target population. Integrating the interview findings with cost-effectiveness criteria reduced 189 potential components to a two test intervention including either optic nerve photography or screening mode perimetry (a measure of visual field sensitivity)

with or without tonometry (a measure of intraocular pressure). It would be more cost-effective, and thus acceptable in a policy Napabucasin purchase context, to target screening for open angle glaucoma to those at highest risk but for both practicality and equity arguments the optimal strategy was screening a general population cohort beginning at age forty.

Conclusions: Interventions for screening for open angle glaucoma that would be feasible from a service delivery perspective were identified. Integration within an economic modelling framework explicitly highlighted the trade-off between cost-effectiveness, feasibility and equity. This study exemplifies the MRC recommendation to integrate qualitative and quantitative methods in developing complex interventions. The next step in the development pathway should encompass the views of service users.”
“Purpose of review

The diagnosis of growth hormone deficiency (GHD) in childhood is challenging, in large part because of the lack of a true gold standard and the relatively poor performance of available

diagnostic testing. This review phosphatase inhibitor discusses the recent literature on this topic.

Recent findings

Auxology and clinical judgment remain the foundation for the diagnosis of GHD. Provocative growth hormone testing is poorly reproducible, dependent on factors such as body composition and pubertal status, and further limited by significant variability among commercially available growth hormone assays. Measurement of insulin-like growth factor I and insulin-like growth factor-binding protein 3 is not diagnostically useful in isolation but is helpful in combination with other diagnostic measures. Neuroimaging is also useful to inform diagnosis, as pituitary abnormalities suggest a higher likelihood of GHD persisting into adulthood. Although genetic testing is not routinely performed in the diagnosis of GHD at the present time, multiple recent reports raise the possibility that it may play a more important role in diagnosing GHD in the future.

Encouragingly, darapladib, an orally Lp-PLA(2) specific

Encouragingly, darapladib, an orally Lp-PLA(2) specific Selleckchem MAPK Inhibitor Library inhibitor,

has been tested in basic research and preclinical trials and the outcomes are quite striking. Additionally, there are two phase III ongoing clinical trials in evaluating the efficacy and safety of darapladib on cardiovascular outcomes. With regard to the potential values of Lp-PLA(2) in risk stratification, therapeutic regimen establishment and prognosis evaluation in patients with moderate or high risk, our present review is going to summarize the relevant data about the bio-chemical characteristics of Lp-PLA(2), the actions of Lp-PLA2 on atherosclerosis and the results of Lp-PLA(2) in scientific research and clinical studies.”
“Study Design. Survey to all orthopedic and neurosurgeons, a random sample of family physicians (FPs) and patients in Ontario, Canada.

Objective. To identify the dominant clinical factors influencing patient and physician Mdivi-1 inhibitor preferences for lumbar spinal surgery.

Summary of Background Data. Surgery on the degenerative lumbar spine offers significant benefit for patients with moderate-severe symptoms failing nonoperative treatment. Referring FPs have little appreciation of factors that identify the ideal surgical candidate. Differences in preferences may lead to wide variation in referrals and impedes the shared decision-making process.

Methods. We used

conjoint analysis, a rigorous method for eliciting preferences, to determine the importance that respondents place on decisions for lumbar spinal surgery. We identified 6 clinical factors (walking tolerance, pain VX 809 duration, severity, neurologic symptoms, typical onset, and dominant location of pain) and presented hypothetical vignettes

to participants who rated their preference for surgery. Data were analyzed using random-effects ordered probit regression models and the importance of each clinical factor relative to the others was determined.

Results. We obtained responses from 131 surgeons, 202 FPs, and 164 patients. We found that FPs had the highest overall preferences for surgery and surgeons had the lowest. Surgeons placed the highest importance on the location of pain. FPs considered neurologic symptoms, walking tolerance, and severity to be of similar importance. Pain severity, walking tolerance, and duration of pain were the most important factors for patients in deciding for surgery. Orthopedic (over neurosurgical) surgeons had a lower preference for surgery (P < 0.05). Older patients (P < 0.03) and previous surgical consultation (P < 0.03) had greater patient preferences for surgery.

Conclusion. Different preferences for surgery exist between surgeons, FPs, and patients. FPs may reduce over- and under-referrals by appreciating surgeons’ importance on location of pain (leg vs. back).