bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective trial to identify optimal bladder cancer surveillance protocol: reducing costs while maximizing sensitivity
Authors: Kamat Ashish M. , Karam Jose A. , Grossman H. Barton , Kader A. Karim , Munsell Mark , Dinney Colin P. 
Published: March 2011

Study Type – Diagnostic (exploratory cohort)Level of Evidence 2bWhat’s known on the subject? and What does the study add?A plethora of urinary markers are available with the purported benefit of identifying bladder tumours that evade detection with cystoscopy alone. Clinicians often infer that this translates into earlier detection of invasive disease and helps control costs.This prospective trial suggests that in experienced hands, cystoscopy alone is the most cost‐effective strategy to detect recurrence of non‐invasive bladder cancer. Using urinary markers in all patients significantly adds to cost and hence must be individualized.OBJECTIVE• To assess the cost‐effectiveness of using cytological evaluation, NMP22 BladderChek®, and fluorescence in situ hybridization (FISH) UroVysion® in addition to cystoscopy in patients with a history of bladder cancer undergoing surveillance for recurrence.PATIENTS AND METHODS• In all, 200 consecutive patients with a history of bladder cancer not invading the muscle were prospectively enrolled at The University of Texas MD Anderson Cancer Center.• Five surveillance strategies were compared: (i) cystoscopy alone; (ii) cystoscopy and NMP22; (iii) cystoscopy and FISH; (iv) cystoscopy and cytology; and (v) cystoscopy and positive NMP22 confirmed by positive FISH.• The cost per cancer detected was calculated.• For patients with an initial positive test and negative cystoscopy, tumour detected at first follow‐up was assumed to be too small to be visualized at the initial assessment and the biomarker was credited with early detection.RESULTS• Cancer was detected in 13 patients at study entry.• Detection rates for the five surveillance strategies were: (i) 52%, (ii) 56%, (iii) 72%, (iv) 60%, and (v) 56%.• The costs per tumour detected (at the time of initial marker analysis) were (i) $7692; (ii) $12 000; (iii) $26 462; (iv) $11 846; and (v) $10 292.• When early detection of biomarkers was factored in, the CPTD became: (i) $7692; (ii) $11 143; (iii) $19 111; (iv) $10 267; and (v) $9557.• There were 12 new cancers detected at first follow‐up (median time, 4.1 months). None of the tumours detected by biomarkers but not by cystoscopy were invasive.CONCLUSIONS• Cystoscopy alone remains the most cost‐effective strategy to detect recurrence of bladder cancer not invading the muscle.• The addition of urinary markers adds to cost, without improved detection of invasive disease.
DURATION‐2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once‐weekly exenatide
Authors: Wysham C. , Bergenstal R. , Malloy J. , Yan P. , Walsh B. , Malone J. , Taylor K. 
Published: March 2011

Diabet. Med. 28, 705–714 (2011)AbstractAims  In the initial 26‐week, double‐blind, double‐dummy assessment period of the DURATION‐2 trial in patients with Type 2 diabetes on metformin, the once‐weekly glucagon‐like peptide 1 (GLP‐1) receptor agonist exenatide once‐weekly resulted in greater HbA1c improvement and weight reduction compared with maximum approved daily doses of sitagliptin or pioglitazone. This subsequent, 26‐week, open‐label, uncontrolled assessment period evaluated the safety and efficacy of (i) continued exenatide once‐weekly treatment and (ii) switching from sitagliptin or pioglitazone to exenatide once‐weekly.Methods  Randomised oral medications were discontinued and all patients received exenatide once‐weekly. Of the 364 patients [original baseline HbA1c 8.5 ± 1.1% (70 mmol/mol), fasting plasma glucose 9.0 ± 2.5 mmol/l, weight 88 ± 20 kg) who continued into the open‐label period, 319 patients (88%) completed 52 weeks.Results  Evaluable patients who received only exenatide once‐weekly demonstrated significant 52‐week improvements (least square mean ± se) in HbA1c (−1.6 ± 0.1%), fasting plasma glucose (−1.8 ± 0.3 mmol/l) and weight (−1.8 ± 0.5 kg). Evaluable patients who switched from sitagliptin to exenatide once‐weekly demonstrated significant incremental improvements in HbA1c (−0.3 ± 0.1%), fasting plasma glucose (−0.7 ± 0.2 mmol/l) and weight (−1.1 ± 0.3 kg). Patients who switched from pioglitazone to exenatide once‐weekly maintained HbA1c and fasting plasma glucose improvements (week 52: −1.6 ± 0.1%, −1.7 ± 0.3 mmol/l), with significant weight reduction (−3.0 ± 0.3 kg). Exenatide once‐weekly was generally well tolerated and adverse events were predominantly mild or moderate in intensity. Nausea was the most frequent adverse event in this assessment period (intent‐to‐treat: exenatide once‐weekly‐only 5%; sitagliptin → exenatide once‐weekly 11%; pioglitazone → exenatide once‐weekly 10%). No major hypoglycaemia was observed.Conclusions  Patients who switched to once‐weekly exenatide from daily sitagliptin or pioglitazone had improved or sustained glycaemic control, with weight loss.
Mobile phone support is associated with reduced ketoacidosis in young adults
Authors: Farrell K. , Holmes–Walker D. J. 
Published: March 2011

Diabet. Med. 28, 1001–1004 (2011)AbstractAims  To determine if access to mobile phone support for sick‐day management is associated with reduced hospital admissions with diabetic ketoacidosis in young adults aged 15–25 with Type 1 diabetes.Methods  This was an observational study with data collected prospectively from January 2005 to December 2008. A mobile phone support service for sick‐day management began in May 2005. Data from clinic attendees (group 1), including age, sex, diabetes duration, referral age, insulin therapy delivery, clinic attendance and HbA1c, were compared with clinic attendees with diabetic ketosis accessing sick‐day management phone support (group 2), clinic attendees not accessing phone support and admitted with diabetic ketoacidosis (group 3) and non‐clinic attendees admitted with diabetic ketoacidosis (group 4).Results  Age was similar in all groups. Patients in group 3 had significantly shorter duration of diabetes (6.8 ± 3.1 years) than groups 1 or 2 (10.1 and 9.8 years, respectively). Diabetes control was poor in all presentations of diabetic ketoacidosis (groups 2–4, HbA1c > 97 mmol/mol, > 11%) and was significantly higher than clinic attendees without ketosis (HbA1c 70 mmol/mol, 8.6%; P < 0.001). There was similar attendance at the clinic across all three groups, 2.9 compared with 2.4 compared with 2.1 visits/year, respectively. Thirty‐one patients accessed phone support on 83 occasions for sick‐day management (mean 2.7 contacts/episode); two patients progressed to admission with diabetic ketoacidosis. Diabetic ketoacidosis admission rates in the clinic population fell significantly from baseline, 0.10 to 0.05 admissions per patient per year (P < 0.05) in the third year.Conclusion  Mobile phone support is associated with reduced progression of ketosis to diabetic ketoacidosis in young adults despite poor diabetes control.
Retention, early dropout and treatment completion among therapeutic community admissions
Authors: DARKE SHANE , CAMPBELL GABRIELLE , POPPLE GARTH 
Published: March 2011

AbstractIntroduction and Aims. The study aimed to ascertain the association between baseline client characteristics, drug use and psychopathology on length of stay, treatment completion and early separation in drug free therapeutic communities.Design and Methods. Prospective longitudinal follow up of 191 treatment admissions to We Help Ourselves drug free treatment services.Results. The median length of stay was 39 days. A total of 17% of treatment entrants dropped out in the first week, and 34% successfully completed the treatment program. Length of stay was independently associated with a previous history of treatment completion (β = 0.21, P < 0.001), higher Short Form‐12 physical health scores (β = 0.16, P < 0.05) and lifetime prison history (β = −0.15, P < 0.05). Independent predictors of early separation were recent prison release [odds ratio (OR) 2.64, confidence interval (CI) 1.08–6.42] and a lower perception of the likeliness of completing treatment (OR 2.38, CI 1.01–5.46), with independent predictors of treatment completion being male gender (OR 2.56, CI 1.19–5.51) and fewer stressful life events (OR 0.84, CI 0.72–0.97). Drug use and psychopathology were not related to length of stay, early separation or treatment completion.Discussion and Conclusions. Different parameters of treatment stay were predicted by different variables. The fact that neither psychopathology nor primary problem drug was related to treatment indicates that these should not be seen as poor prognostic indicators for treatment success in a drug free treatment setting.[Darke S, Campbell G, Popple G. Retention, early dropout and treatment completion among therapeutic community admissions. Drug Alcohol Rev 2012;31:64–71]
Gold loans in the Australian gold mining industry: Do gold loans allow gold producers to increase leverage?
Authors: Heaney Richard , Wai Nicholas , Walker Julie 
Published: March 2011

AbstractThis paper tests the hypothesis that gold producers exhibit greater leverage where gold loans are used. As the choice of gold producers and the study period essentially avoids debt tax shield effects, the paper focuses on information asymmetry and agency costs explanations for leverage. Theory suggests hedging can reduce the cost of debt but it has little impact if management is not committed to adopting the promised hedging policy. The implicit hedge in gold loans commits management to hedging and so greater leverage is expected for producers adopting gold loans. Results from the analysis are consistent with this hypothesis.
The role of current and non‐current accruals in the relation between stock returns and earnings
Authors: Loftus Janice A. , Sin Samantha 
Published: March 2011

AbstractThis study examines the role of accruals in the relation between stock returns and earnings for intervals of one to four years. We argue that the roles of current and non‐current accruals differ because the former turn over more frequently while the latter include long term timing differences and permanent differences. Accordingly, the roles of both categories of accruals are examined over intervals within and beyond the cycle of current accruals. The results suggest that accruals strengthen the association between stock returns and earnings and that they are more important for shorter intervals. Further, non‐current accruals play a dominant role in the relation between stock returns and earnings while the effect of current accruals is negligible for all intervals examined.
Distortion effects and extreme observations in empirical research: An analysis of the incremental information content of cash flows
Authors: Wilson Cynthia R. 
Published: March 2011

AbstractLinear regression models are used in a number of studies examining the presence or absence of incremental information content in cash flows. The results of these studies are not consistent. This paper provides evidence of the impact that extreme observations can exert on parameter estimates in a regression model. Two techniques commonly used to address the problem of extreme observations are considered. These techniques, winsorising the data and trimming the data, are compared to a regression diagnostic technique, Cook's distance. The comparison of these techniques provides evidence that the choice of technique can determine the significance or otherwise of regression results. This paper concludes that the inconsistency in reported results examining the incremental information content in cash flows may be attributed to the techniques adopted to address the issue of extreme observations.
Cross‐sectional determinants of New Zealand share market returns
Authors: Bryant Paul S. , Eleswarapu Venkat R. 
Published: March 2011

AbstractWe present evidence of the cross‐sectional relation between security returns, beta, firm size and book‐to‐market ratio over the period 1971 to 1993 on the New Zealand sharemarket. Our results suggest that the NZSE‐40 market index is not a mean‐variance efficient market proxy—the betas calculated with respect to it being of little use for explaining expected returns cross‐sectionally. Also, there is a significant positive relation between book‐to‐market ratio and average return.
Establishing specialty jurisdictions in medicine: the case of American obstetrics and gynaecology
Authors: Zetka Jr. James R. 
Published: March 2011

AbstractThe profession of medicine has evolved into an extremely specialised occupation. Yet, recent research has neglected the intra‐occupational processes influencing medical specialisation. This article aims to correct this oversight. It develops an historical account of intra‐occupational factors influencing the decision to establish gynaecologic oncology as American ob/gyn’s surgical subspecialty in 1972. Working within the framework initially developed by Everett C. Hughes and his students, the article examines this development as the outcome of a three‐party relationship among gynaecologic oncologists, American ob/gyns, and gynaecologic pelvic surgeons. Aggressive movement by the gynaecologic pelvic surgeons challenging the established élite’s identity definition for the ob/gyn specialty helped spur official recognition of gynaecologic oncology, a less threatening subspecialty. The article draws theoretical implications from the case regarding the role of a threatening other in influencing the specialisation process.
Frailty in elderly persons with essential tremor: a population‐based study (NEDICES)
Authors: Louis E. D. , Benito‐León J. , Vega S. , Bermejo‐Pareja F. ,   On behalf of the Neurological Disorders in Central Spain (NEDICES) Study Group
Published: March 2011

Background and purpose:  Essential tremor (ET), one of the most prevalent neurological diseases, has been associated with a variety of comorbidities and, in some studies, a modest increase in risk of mortality. The mechanisms underlying this possible increased mortality have yet to be explored, although one possibility is increased frailty. Frailty has not been studied in ET, and our objective was to address this gap in knowledge. We hypothesized that frailty would be greater in ET cases than in controls.Methods:  A 20‐item frailty score assessed comorbid conditions, number of medications, and functional activity. The frailty score was compared in 237 non‐demented elderly ET cases and 3903 non‐demented age‐matched controls from a population‐based study in central Spain.Results:  The frailty score was higher in ET cases than in controls (8.6 ± 5.2 vs. 6.8 ± 4.6, P < 0.001). Stratifying the frailty score into quartiles and tertiles similarly revealed case–control differences (both P < 0.001). The frailty score also increased with age (r = 0.25, P < 0.001), was higher in women than men (P = 0.02), was correlated with subjective rating of health status (r = 0.42, P < 0.001), and was inversely correlated with body weight (r = −0.06, P < 0.001) and hours/day that participants performed moderate or intensive physical activities (r = −0.16, P < 0.001).Conclusion:  Essential tremor cases had increased frailty compared to their counterparts without this disease. Whether this increased frailty is a contributor to the increased risk of mortality that has been observed in some studies is a question that deserves further scrutiny.
Clinical and genetic analysis of spinocerebellar ataxia in Mali
Authors: Traoré M. , Coulibaly T. , Meilleur K. G. , La Pean A. , Sangaré M. , Landouré G. , Mochel F. , Karambé M. , Guinto C. O. , Fischbeck K. H. 
Published: March 2011

Background:  Autosomal dominant cerebellar ataxia, currently denominated spinocerebellar ataxia (SCAs), represents a heterogeneous group of neurodegenerative disorders affecting the cerebellum and its connections. We describe the clinical and molecular findings in 16 patients originating from Malian families, who suffer from progressive cerebellar ataxia syndrome.Methods and results:  Molecular analysis allows genetic profiles of SCA to be distinguished. In seven patients, SCA type 2 (CAG) mutation was expanded from 39 to 43 repeats. SCA type 7 (CAG) mutation was confirmed in six patients. Mutations were expanded from 49 to 59 repeats. In three patients, SCA type3 was diagnosed and CAG mutation was expanded to 73 repeats.Conclusions:  Our data suggest that the most frequent types of SCA are SCA2 and SCA7. However, further studies are needed to confirm these preliminary results.
Association of HLA‐DRB1*15 allele and CSF oligoclonal bands in a Spanish multiple sclerosis cohort
Authors: Romero‐Pinel L. , Martínez‐Yélamos S. , Bau L. , Matas E. , Gubieras L. , María Pujal J. , Morandeira F. , Bas J. , Arbizu T. 
Published: March 2011

Background and objective:  The HLA‐DRB1*15 allele is consistently associated with multiple sclerosis (MS) susceptibility in most studied populations. This study investigated the association between HLA‐DRB1 alleles and the presence of oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid (CSF) in a Spanish population with MS.Methods:  The HLA‐DRB1 typing was performed in 268 patients with sporadic MS and the detection of OCB in CSF. HLA‐DRB1 allelic frequencies were compared between OCB‐positive and OCB‐negative patients, and both groups were also compared with 1088 unrelated healthy controls. Moreover, we correlated the various HLA‐DRB1 genotypes, considering all the combinations of both parental alleles found with the presence or absence of OCB.Results:  We found 206 OCB‐positive and 62 OCB‐negative patients. The HLA‐DRB1*15 allele in OCB‐positive patients had a higher frequency when compared with OCB‐negative patients (39.3% in OCB‐positive vs. 16.1% in OCB‐negative, OR = 1.38 95% CI = 1.18–1.61, P < 0.001). The other alleles did not show differences. When we compared with controls, the HLA‐DRB1*15 allele was associated with the disease only in the OCB‐positive patients group. None of the 55 genotypes found showed any association with the presence or absence of OCB.Conclusions:  HLA‐DRB1*15 allele is associated with OCB‐positive patients with MS when studying a Spanish MS population.
The telomerase activator TA‐65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence
Authors: de Jesus Bruno Bernardes , Schneeberger Kerstin , Vera Elsa , Tejera Agueda , Harley Calvin B. , Blasco Maria A. 
Published: March 2011

SummaryHere, we show that a small‐molecule activator of telomerase (TA‐65) purified from the root of Astragalus membranaceus is capable of increasing average telomere length and decreasing the percentage of critically short telomeres and of DNA damage in haploinsufficient mouse embryonic fibroblasts (MEFs) that harbor critically short telomeres and a single copy of the telomerase RNA Terc gene (G3 Terc+/− MEFs). Importantly, TA‐65 does not cause telomere elongation or rescue DNA damage in similarly treated telomerase‐deficient G3 Terc−/− littermate MEFs. These results indicate that TA‐65 treatment results in telomerase‐dependent elongation of short telomeres and rescue of associated DNA damage, thus demonstrating that TA‐65 mechanism of action is through the telomerase pathway. In addition, we demonstrate that TA‐65 is capable of increasing mouse telomerase reverse transcriptase levels in some mouse tissues and elongating critically short telomeres when supplemented as part of a standard diet in mice. Finally, TA‐65 dietary supplementation in female mice leads to an improvement of certain health‐span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.
The case for peripheral CB1 receptor blockade in the treatment of visceral obesity and its cardiometabolic complications
Authors: Kunos George , Tam Joseph 
Published: March 2011

In this review, we consider the role of endocannabinoids and cannabinoid‐1 (CB1) cannabinoid receptors in metabolic regulation and as mediators of the thrifty phenotype that underlies the metabolic syndrome. We survey the actions of endocannabinoids on food intake and body weight, as well as on the metabolic complications of visceral obesity, including fatty liver, insulin resistance and dyslipidemias. Special emphasis is placed on weighing the relative importance of CB1 receptors located in peripheral tissues versus the central nervous system in mediating the metabolic effects of endocannabinoids. Finally, we review recent observations that indicate that peripherally restricted CB1 receptor antagonists retain efficacy in reducing weight and improving metabolic abnormalities in mouse models of obesity without causing behavioural effects predictive of neuropsychiatric side effects in humans.LINKED ARTICLES This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
Protein kinase A and the exchange protein directly activated by cAMP (Epac) modulate phenotype plasticity in human airway smooth muscle
Authors: Roscioni Sara S , Prins Alwin G , Elzinga Carolina RS , Menzen Mark H , Dekkers Bart GJ , Halayko Andrew J , Meurs Herman , Maarsingh Harm , Schmidt Martina 
Published: March 2011

BACKGROUND AND PURPOSE Platelet‐derived growth factor (PDGF) modulates the airway smooth muscle (ASM) ‘contractile’ phenotype to a more ‘proliferative’ phenotype, resulting in increased proliferation and reduced contractility. Such phenotypic modulation may contribute to airway remodelling in asthma. We have previously shown that the cAMP effector molecules, protein kinase A (PKA) and the exchange protein directly activated by cAMP (Epac) inhibited PDGF‐induced phenotypic modulation in bovine ASM. Here, we investigated these mechanisms in human ASM strips and cells.EXPERIMENTAL APPROACH ASM strips were incubated with PDGF in the absence or presence of the activators of Epac (8‐pCPT‐2′‐O‐Me‐cAMP) or of PKA (6‐Bnz‐cAMP) for 4 days. Strips were mounted for isometric contraction experiments or analysed for the expression of contractile markers. Cell proliferation was measured and proliferative markers were analysed under similar conditions.KEY RESULTS Activation of Epac and PKA prevented PDGF‐induced ASM strip hypocontractility, and restored the expression of smooth muscle actin, myosin and calponin, which had been markedly diminished by PDGF. Epac and PKA activation inhibited the PDGF‐induced ASM cell proliferation and G1/S phase transition and the expression and phosphorylation of cell cycle regulators.CONCLUSIONS AND IMPLICATIONS Epac and PKA maintain a normally contractile ASM phenotype in a mitogenic environment, suggesting that specific activators of Epac and PKA may be beneficial in the treatment of airway remodelling in asthma.