bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model
Authors: Veidal Sanne Skovgård , Nielsen Mette Juul , Leeming Diana Julie , Karsdal Morten Asser 
Published: December 2012

Abstract

Background
Accumulation of extracellular matrix (ECM) and increased matrix metalloproteinase (MMP) activity are hallmarks of liver fibrosis. The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl4 treated animals with an ELISA detecting a fragment of type III collagen generated in vitro by MMP-9 (C3M), known to be associated with liver fibrosis and to investigate cAMP modulation of MMP activity and liver tissue turnover in this model.

Findings

In vivo: Rats were treated for 8 weeks with CCl4/Intralipid. Liver slices were cultured for 48 hours. Levels of C3M were determined in the supernatants of slices cultured without treatment, treated with GM6001 (positive control) or treated with IBMX (phosphodiesterase inhibitor). Enzymatic activity of MMP-2 and MMP-9 were studied by gelatin zymography. Ex vivo: The levels of serum C3M increased 77% in the CCl4-treated rats at week 8 (p < 0.01); Levels of C3M increased significantly by 100% in fibrotic liver slices compared to controls after 48 hrs (p < 0.01). By adding GM6001 or IBMX to the media, C3M was restored to control levels. Gelatin zymography demonstrated CCl4-treated animals had highly increased MMP-9, but not MMP-2 activity, compared to slices derived from control animals.

Conclusions
We have combined an ex vivo model of liver fibrosis with measurement of a biochemical marker of collagen degradation in the condition medium. This technology may be used to evaluate the molecular process leading to structural fibrotic changes, as collagen species are the predominant structural part of fibrosis. These data suggest that modulation of cAMP may play a role in regulation of collagen degradation associated with liver fibrosis.
Do immigrants squeeze natives out of bad schedules? Evidence from Italy
Authors: Giuntella Osea 
Published: December 2012

Abstract

Abstract
This paper documents the effect of immigrant concentration on natives’ work schedules. I show that immigrants are more likely to work at non‐standard hours (i.e. evenings, nights and Sundays) and that a higher proportion of immigrants in the local labor market is associated with a lower probability of employed natives working non‐standard shifts. Results are strongest in sectors and occupations that are more accessible to immigrants. In particular, I find that a 1 standard deviation increase in the foreign population residing in a province is associated to a 4% reduction in the natives’ likelihood of working non standard hours.

JEL codes
J15, J81, J61
Phase III Trial of Carboplatin and Paclitaxel With or Without Sorafenib in Metastatic Melanoma
Authors: Flaherty Keith T. , Lee Sandra J. , Zhao Fengmin , Schuchter Lynn M. , Flaherty Lawrence , Kefford Richard , Atkins Michael B. , Leming Philip , Kirkwood John M. 
Published: December 2012

Purpose The primary objective of this study was to determine whether carboplatin, paclitaxel, and sorafenib (CPS) improve overall survival (OS) compared with carboplatin and paclitaxel (CP) in chemotherapy-naive patients with metastatic melanoma. Patients and Methods In this double-blind, randomized, placebo-controlled phase III study, all patients received carboplatin at area under the [concentration-time] curve 6 and paclitaxel 225 mg/m2 intravenously once every 21 days with random assignment to sorafenib 400 mg orally twice per day on days 2 through 19 every 21 days or placebo. The primary end point was OS, and secondary end points included progression-free survival, objective tumor response, and toxicity. Results In all, 823 patients were enrolled over 34 months. At final analysis, the median OS was 11.3 months (95% CI, 9.8 to 12.2 months) for CP and 11.1 months (95% CI, 10.3 to 12.3 months) for CPS; the difference in the OS distribution was not statistically significant by the stratified log-rank test, stratified on American Joint Committee on Cancer (AJCC) stage, Eastern Cooperative Oncology Group (ECOG) performance status, and prior therapy (P = .878). Median progression-free survival was 4.9 months for CPS and 4.2 months for CP (P = .092, stratified log-rank test). Response rate was 20% for CPS and 18% for CP (P = .427). More patients on the CPS arm had grade 3 or higher toxicities (84% v 78%; P = .027), with increased rash, hand-foot syndrome, and thrombocytopenia accounting for most of the difference. Conclusion Sorafenib does not improve OS when given in combination with CP for chemotherapy-naive patients with metastatic melanoma. This study establishes benchmark end points for the CP regimen in first-line therapy of metastatic melanoma.
Longitudinal Screening Algorithm That Incorporates Change Over Time in CA125 Levels Identifies Ovarian Cancer Earlier Than a Single-Threshold Rule
Authors: Drescher Charles W. , Shah Chirag , Thorpe Jason , O'Briant Kathy , Anderson Garnet L. , Berg Christine D. , Urban Nicole , McIntosh Martin W. 
Published: December 2012

Purpose Longitudinal algorithms incorporate change over time in biomarker levels to individualize screening decision rules. Compared with a single-threshold (ST) rule, smaller deviations from baseline biomarker levels are required to signal disease. We demonstrated improvement in ovarian cancer early detection by using a longitudinal algorithm to monitor annual CA125 levels. Patients and Methods We retrospectively evaluated serial preclinical serum CA125 values measured annually in 44 incident ovarian cancer cases identified from participants in the PLCO (Prostate Lung Colorectal and Ovarian) Cancer Screening Trial to determine how frequently and to what extent the parametric empirical Bayes (PEB) longitudinal screening algorithm identifies ovarian cancer earlier than an ST rule. Results The PEB algorithm detected ovarian cancer earlier than an ST rule in a substantial proportion of cases. At 99% specificity, which corresponded to the ST-rule CA125 cutoff ≥ 35 U/mL that was used in the PLCO trial, 20% of cases were identified earlier by using the PEB algorithm. Among these cases, the PEB signaled abnormal CA125 values, on average, 10 months earlier and at a CA125 concentration 42% lower (20 U/mL) than the ST-rule cutoff. The proportion of cases detected earlier by the PEB algorithm and the earliness of detection increased as the specificity of the screening rule was reduced. Conclusion The PEB longitudinal algorithm identifies ovarian cancer earlier and at lower biomarker concentrations than an ST screening algorithm adjusted to the same specificity. Longitudinal biomarker assessment by using the PEB algorithm may have application for screening other solid tumors in which biomarkers are available.
Circulating Tumor Cells As Prognostic Markers in Neuroendocrine Tumors
Authors: Khan Mohid S. , Kirkwood Amy , Tsigani Theodora , Garcia-Hernandez Jorge , Hartley John A. , Caplin Martyn E. , Meyer Tim 
Published: December 2012

Purpose To determine the prognostic significance of circulating tumor cells (CTCs) in patients with neuroendocrine cancer. Patients and Methods In this single-center prospective study, 176 patients with measurable metastatic neuroendocrine tumors (NETs) were recruited. CTCs were measured using a semiautomated technique based on immunomagnetic separation of epithelial cell adhesion molecule–expressing cells. Results Overall, 49% patients had ≥ one CTC, 42% had ≥ two CTCs, and 30% had ≥ five CTCs in 7.5 mL blood. Presence of CTCs was associated with increased burden, increased tumor grade, and elevated serum chromogranin A (CgA). Using a 90-patient training set and 85-patient validation set, we defined a cutoff of < one or ≥ one as the optimal prognostic threshold with respect to progression-free survival (PFS). Applying this threshold, the presence of ≥ one CTC was associated with worse PFS and overall survival (OS; hazard ratios [HRs], 6.6 and 8.0, respectively; both P < .001). In multivariate analysis, CTCs remained significant when other prognostic markers, grade, tumor burden, and CgA were included. Within grades, presence of CTCs was able to define a poor prognostic subgroup. For grade 1, HRs were 5.0 for PFS (P = .017) and 7.2 for OS (P = .023); for grade 2, HRs were 3.5 for PFS (P = .018) and 5.2 for OS (P = .036). Conclusion CTCs are a promising prognostic marker for patients with NETs and should be assessed in the context of clinical trials with defined tumor subtypes and therapy.
Why Is Spiritual Care Infrequent at the End of Life? Spiritual Care Perceptions Among Patients, Nurses, and Physicians and the Role of Training
Authors: Balboni Michael J. , Sullivan Adam , Amobi Adaugo , Phelps Andrea C. , Gorman Daniel P. , Zollfrank Angelika , Peteet John R. , Prigerson Holly G. , VanderWeele Tyler J. , Balboni Tracy A. 
Published: December 2012

Purpose To determine factors contributing to the infrequent provision of spiritual care (SC) by nurses and physicians caring for patients at the end of life (EOL). Patients and Methods This is a survey-based, multisite study conducted from March 2006 through January 2009. All eligible patients with advanced cancer receiving palliative radiation therapy and oncology physician and nurses at four Boston academic centers were approached for study participation; 75 patients (response rate = 73%) and 339 nurses and physicians (response rate = 63%) participated. The survey assessed practical and operational dimensions of SC, including eight SC examples. Outcomes assessed five factors hypothesized to contribute to SC infrequency. Results Most patients with advanced cancer had never received any form of spiritual care from their oncology nurses or physicians (87% and 94%, respectively; P for difference = .043). Majorities of patients indicated that SC is an important component of cancer care from nurses and physicians (86% and 87%, respectively; P = .1). Most nurses and physicians thought that SC should at least occasionally be provided (87% and 80%, respectively; P = .16). Majorities of patients, nurses, and physicians endorsed the appropriateness of eight examples of SC (averages, 78%, 93%, and 87%, respectively; P = .01). In adjusted analyses, the strongest predictor of SC provision by nurses and physicians was reception of SC training (odds ratio [OR] = 11.20, 95% CI, 1.24 to 101; and OR = 7.22, 95% CI, 1.91 to 27.30, respectively). Most nurses and physicians had not received SC training (88% and 86%, respectively; P = .83). Conclusion Patients, nurses, and physicians view SC as an important, appropriate, and beneficial component of EOL care. SC infrequency may be primarily due to lack of training, suggesting that SC training is critical to meeting national EOL care guidelines.
Meta-analysis of LCPUFA Supplementation of Infant Formula and Visual Acuity
Authors: Qawasmi Ahmad , Landeros-Weisenberger Angeli , Bloch Michael H. 
Published: December 2012

BACKGROUND AND OBJECTIVE:
Long-chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to affect visual acuity development in infants. Randomized controlled trials (RCTs) have been conducted to assess whether supplementation of LCPUFAs of infant formulas affects infant visual acuity. This meta-analysis was conducted to evaluate whether LCPUFA supplementation of infant formulas improves infants’ visual acuity.

METHODS:
PubMed and PsycInfo were searched for RCTs assessing the efficacy of LCPUFA supplementation of infant formulas on infant visual acuity. RCTs assessing the effects of LCPUFA supplementation on visual acuity (by using either visual evoked potential or behavioral methods) in the first year of life were included in this meta-analysis. Our primary outcome was the mean difference in visual resolution acuity (measured in logarithm of minimum angle of resolution [logMAR]) between supplemented and unsupplemented infants. We also conducted secondary subgroup analyses and meta-regression examining the effects of LCPUFA dose and timing, preterm versus term birth status, and trial methodologic quality.

RESULTS:
Nineteen studies involving 1949 infants were included. We demonstrated a significant benefit of LCPUFA supplementation on infants’ visual acuity at 2, 4, and 12 months of age when visual acuity was assessed by using visual evoked potential and at 2 months of age by using behavioral methods. There was significant heterogeneity between trials but no evidence of publication bias. Secondary analysis failed to show any moderating effects on the association between LCPUFA supplementation and visual acuity.

CONCLUSIONS:
Current evidence suggests that LCPUFA supplementation of infant formulas improves infants’ visual acuity up to 12 months of age.
Physical Disability After Injury-Related Inpatient Rehabilitation in Children
Authors: Zonfrillo Mark R. , Durbin Dennis R. , Winston Flaura K. , Zhao Huaqing , Stineman Margaret G. 
Published: December 2012

OBJECTIVE:
To determine the residual physical disability after inpatient rehabilitation for children 7 to 18 years old with traumatic injuries.

METHODS:
This was a retrospective cohort study of patients aged 7 to 18 years who underwent inpatient rehabilitation for traumatic injuries from 2002 to 2011. Patients were identified from the Uniform Data System for Medical Rehabilitation. Injuries were captured by using standardized Medicare Inpatient Rehabilitation Facility Patient Assessment Instrument codes. Functional outcome was measured with the Functional Independence Measure (FIM) instrument. A validated, categorical grading system of the FIM motor items was used, consisting of clinically relevant levels of physical achievement from grade 1 (need for total assistance) to grade 7 (completely independent for self-care and mobility).

RESULTS:
A total of 13 798 injured children underwent inpatient rehabilitation across 523 facilities during the 10-year period. After a mean 3-week length of stay, functional limitations were reduced, but children still tended to have residual physical disabilities (median admission grade: 1; median discharge grade: 4). Children with spinal cord injuries, either alone or in combination with other injuries, had lower functional grade at discharge, longer lengths of stay, and more comorbidities at discharge than those with traumatic brain injuries, burns, and multiple injuries (P &lt; .0001 for all comparisons).

CONCLUSIONS:
Children had very severe physical disability on admission to inpatient rehabilitation for traumatic injuries, and those with spinal cord injuries had persistent disability at discharge. These traumatic events during critical stages of development may result in a substantial care burden over the child’s lifespan.
Adult-Onset Autoimmune Diabetes in Europe Is Prevalent With a Broad Clinical Phenotype
Authors: Hawa Mohammed I. , Kolb Hubert , Schloot Nanette , Beyan Huriya , Paschou Stavroula A. , Buzzetti Raffaella , Mauricio Didac , De Leiva Alberto , Yderstraede Knud , Beck-Neilsen Henning , Tuomilehto Jaakko , Sarti Cinzia , Thivolet Charles , Hadden David , Hunter Steven , Schernthaner Guntram , Scherbaum Werner A. , Williams Rhys , Brophy Sinead , Pozzilli Paolo , Leslie Richard David ,   on behalf of the Action LADA consortium
Published: December 2012

OBJECTIVESpecific autoantibodies characterize type 1 diabetes in childhood but are also found in adult-onset diabetes, even when initially non–insulin requiring, e.g., with latent autoimmune diabetes (LADA). We aimed to characterize adult-onset autoimmune diabetes.RESEARCH DESIGN AND METHODSWe consecutively studied 6,156 European diabetic patients attending clinics within 5 years of diagnosis (age range, 30–70 years) examined cross-sectionally clinically and for GAD antibodies (GADA) and antibodies to insulinoma-associated antigen-2 (IA-2A) and zinc-transporter 8 (ZnT8A).RESULTSOf 6,156 patients, 541 (8.8%) had GADA and only 57 (0.9%) IA-2A or ZnT8A alone. More autoantibody-positive than autoantibody-negative patients were younger, leaner, on insulin (49.5 vs. 13.2%), and female (P &lt; 0.0001 for each), though LADA patients (9.7% of total) did not show categorically distinct clinical features from autoantibody-negative type 2 diabetes. Similarly, more GADA patients with high (&gt;200 World Health Organization IU) (n = 403) compared with low (n = 138) titer were female, lean, and insulin treated (54.6 vs. 39.7%) (P &lt; 0.02 for each). Autoantibody-positive patients usually had GADA (541 of 598; 90.5%) and had LADA more often than type 1 autoimmune diabetes (odds ratio 3.3).CONCLUSIONSAdult-onset autoimmune diabetes emerges as a prevalent form of autoimmune diabetes. Our results indicate that adult-onset autoimmune diabetes in Europe encompasses type 1 diabetes and LADA in the same broad clinical and autoantibody-positive spectrum. At diagnosis, patients with adult-onset autoimmune diabetes are usually non–insulin requiring and clinically indistinguishable from patients with type 2 diabetes, though they tend to be younger and leaner. Only with screening for autoantibodies, especially GADA, can they be identified with certainty.
Hypoglycemia, With or Without Insulin Therapy, Is Associated With Increased Mortality Among Hospitalized Patients
Authors: Garg Rajesh , Hurwitz Shelley , Turchin Alexander , Trivedi Apoorva 
Published: December 2012

OBJECTIVE
Hypoglycemia is associated with increased mortality in hospitalized patients. We investigated the relationship between spontaneous hypoglycemia versus insulin-associated hypoglycemia and mortality in hospitalized patients.

RESEARCH DESIGN AND METHODS
Data for this retrospective cohort study were obtained from electronic databases of patients admitted between 1 April 2008 and 30 November 2010. Patients with one or more blood glucose values ≤50 mg/dL on point-of-care glucose testing were considered hypoglycemic. Patients treated with insulin were assumed to have insulin-associated hypoglycemia. Age-, sex-, and race-matched patients with all blood glucose values &gt;70 mg/dL were selected as controls. The Charlson comorbidity index (CCI) was used to control for severity of illness.

RESULTS
There were four groups: 1) noninsulin-treated hypoglycemia (NTH) (n = 135), 2) insulin-treated hypoglycemia (ITH) (n = 961), 3) noninsulin-treated control (NTC) (n = 1,058), and 4) insulin-treated control (ITC) (n = 736). Mortality was higher in the ITH group compared with the ITC group (20.3 vs. 4.5%, P &lt; 0.0001), with a relatively higher CCI (1.8 vs. 1.5%, P &lt; 0.0001), but much higher in the NTH group compared with the NTC group (34.5 vs. 1.1%, P &lt; 0.0001), with much higher CCI (2.4 vs. 1.1%, P &lt; 0.0001). Mortality was higher in the NTH group compared with the ITH group (P &lt; 0.0001) but lower in the NTC group compared with the ITC group (P &lt; 0.0001). After controlling for age, sex, CCI, and admission to the intensive care unit, insulin treatment was associated with a lower mortality among the hypoglycemic patients; hazard ratio of death in the ITH group relative to the NTH group was 0.34 (95% CI 0.25–0.47, P &lt; 0.0001).

CONCLUSIONS
Insulin-associated and spontaneous hypoglycemia are associated with increased mortality among hospitalized patients.
Statins and Risk of Diabetes
Authors: Danaei Goodarz , García Rodríguez Luis A. , Fernandez Cantero Oscar , Hernán Miguel A. 
Published: December 2012

OBJECTIVE
Two meta-analyses of randomized trials of statins found increased risk of type 2 diabetes. One possible explanation is bias due to differential survival when patients who are at higher risk of diabetes survive longer under statin treatment.

RESEARCH DESIGN AND METHODS
We used electronic medical records from 500 general practices in the U.K. and included data from 285,864 men and women aged 50–84 years from January 2000 to December 2010. We emulated the design and analysis of a hypothetical randomized trial of statins, estimated the observational analog of the intention-to-treat effect, and adjusted for differential survival bias using inverse-probability weighting.

RESULTS
During 1.2 million person-years of follow-up, there were 13,455 cases of type 2 diabetes and 8,932 deaths. Statin initiation was associated with increased risk of type 2 diabetes. The hazard ratio (95% CI) of diabetes was 1.45 (1.39–1.50) before adjusting for potential confounders and 1.14 (1.10–1.19) after adjustment. Adjusting for differential survival did not change the estimates. Initiating atorvastatin and simvastatin was associated with increased risk of type 2 diabetes.

CONCLUSIONS
In this sample of the general population, statin therapy was associated with 14% increased risk of type 2 diabetes. Differential survival did not explain this increased risk.
Outcome of Transfibular Ankle Arthrodesis with Ilizarov Apparatus
Authors: Onodera Tomohiro , Majima Tokifumi , Kasahara Yasuhiko , Takahashi Daisuke , Yamazaki Shuji , Ando Ryo , Minami Akio 
Published: December 2012

Background: Both transfibular ankle arthrodesis with fibular onlay grafting and ankle arthrodesis using the Ilizarov apparatus have resulted in acceptable fusion rates. This study analyzed outcomes in the authors' practice for all patients who underwent transfibular ankle arthrodesis with fibular onlay grafting using the Ilizarov apparatus. Materials and Methods: A retrospective review was conducted of all patients who experienced severe ankle pain associated with osteoarthritis, rheumatoid arthritis, talar osteonecrosis, or septic arthritis and underwent transfibular ankle arthrodesis with an Ilizarov apparatus between 1995 and 2010. Postoperative clinical outcomes were evaluated for 42 consecutive patients (43 feet) who received primary or revision ankle arthrodesis using the Ilizarov technique at two centers. Mean duration of follow-up was 4.1 (range, 1.5 to 13) years. Outcomes were assessed using the ankle–hindfoot scale of the American Orthopaedic Foot and Ankle Society. Results: All ankles fused successfully. Mean clinical outcome improved significantly from 36.2 (range, 8 to 64) preoperatively to 77.4 (range, 0 to 86; p < .05) postoperatively. Conclusion: Transfibular ankle arthrodesis using the Ilizarov external fixation system and fibular onlay strut grafting can achieve a very high rate of bony union and lead to general improvements in clinical outcome. Forefoot stabilization with a forefoot ring achieved rigid stabilization resulting in a shorter duration of external fixation. Level of Evidence: IV, Retrospective Case Series
Ni excès d'honneur ni indignité pour le plan d'affaires
Authors: Toutain Olivier , Fayolle Alain 
Published: December 2012

Résumé Le plan d’affaires – ou Business Plan – connaît un grand succès. Il est un des seuls outils capable de relier les mondes académiques, professionnels et politiques impliqués dans le soutien au développement de l’entrepreneuriat. Mais il suscite des critiques et des controverses qui sont à la mesure de ce succès. Plutôt que de « brûler » le plan d’affaires, il convient de le remettre à sa place. Il n’est en effet qu’un moyen et non une fin.
Construire et développer une opportunité entrepreneuriale par la démarche SynOpp
Authors: Chirita Mircea-Gabriel , Masson Marie-Ange , Ananou Claude 
Published: December 2012

Résumé Les milieux universitaires et du conseil s’interrogent de plus en plus sur l’utilité du business plan 1 pour prédire les chances de réussite d’un projet entrepreneurial. À une époque caractérisée par les changements rapides et imprévisibles, il est légitime de s’interroger sur la pertinence du paradigme de la planification. Dans une perspective entrepreneuriale, nous remettons en question la pertinence du business plan comme moyen à la disposition d’un porteur de projet pour présenter l’opportunité qu’il a créée et les moyens pour la mettre en œuvre. Après avoir analysé cet outil, nous allons présenter les fondements d’une autre démarche. Ayant fait ses preuves au Canada depuis plusieurs années, elle rompt avec la réflexion axée sur l’écriture d’un business plan : elle prône l’accompagnement de l’entrepreneur dans l’action.