bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic and public health impact of 2007–2010 tobacco tax increases in Ukraine
Authors: Ross Hana , Stoklosa Michal , Krasovsky Konstantin 
Published: June 2011

ObjectiveTo evaluate the impact of the dynamic 2007–2010 tobacco tax policy in Ukraine on cigarette prices, cigarette consumption, tobacco tax revenue and the tobacco industry's price strategy.MethodsUsing data on cigarette sales, cigarette prices, income and tobacco control policies, price elasticities of cigarette demand in Ukraine were estimated using two methods. Annual data were used to generate point price elasticity estimates, while monthly data were used in a two-step Engle–Granger procedure.ResultsThe point price elasticity estimate is data sensitive and ranges from −0.11 to −0.62, centring around −0.32. The regression model estimates a long-run price elasticity of −0.28. Cigarette consumption fell by 13% in 2009 and 15% in 2010 while the tax revenue increased by US$700 million and by US$500 million in 2009 and 2010, respectively, compared to the previous year. Tax increases have changed the tobacco industry's price strategy from one of shielding consumers from the impact of smaller tax hikes in 2007–2008, to one of increasing industry net-of-tax prices, after recent, larger tax increases.ConclusionsThe higher real tobacco excise taxes of 2009 and 2010 have significantly reduced tobacco consumption in Ukraine, resulting in encouraging public health and fiscal gains. It will be important for cigarette prices/taxes to keep pace with inflation and income growth for this impact to be sustained.
Infection with Brucella ceti and high levels of polychlorinated biphenyls in bottlenose dolphins (Tursiops truncatus) stranded in south‐west England
Authors: Davison N. J. , Perrett L. L. , Law R. J. , Dawson C. E. , Stubberfield E. J. , Monies R. J. , Deaville R. , Jepson P. D. 
Published: June 2011

Eight bottlenose dolphins (Tursiops truncatus) that stranded in Cornwall, south‐west England, between June 2004 and December 2007 were examined using standardised postmortem examination and bacteriological methods. Evidence of Brucella species infection was found in four of these dolphins on culture. In addition, of the eight dolphins, four were positive and two were weakly positive for antibodies to Brucella species on serological analyses of pericardial and other fluids using a competitive ELISA and two indirect ELISAs. High or very high levels of the sum of 25 individual chlorobiphenyl congeners (∑25CBs) were also determined in blubber samples from two of the dolphins (45.5 and 446.6 mg/kg lipid weight).
Keap1 Mutations and Nrf2 Pathway Activation in Epithelial Ovarian Cancer
Authors: Konstantinopoulos Panagiotis A. , Spentzos Dimitrios , Fountzilas Elena , Francoeur Nancy , Sanisetty Srisowmya , Grammatikos Alexandros P. , Hecht Jonathan L. , Cannistra Stephen A. 
Published: June 2011

Abstract
Resistance to platinum-based chemotherapy develops in the majority of patients with epithelial ovarian cancer (EOC). Platinum compounds form electrophilic intermediates that mediate DNA cross-linking and induce double-strand DNA breaks. Because the cellular response to electrophilic xenobiotics is partly mediated by Keap1–Nrf2 pathway, we evaluated the presence of Kelch-like ECH–associated protein 1 (Keap1) mutations and NF-E2–related factor 2 (Nrf2) pathway activation in EOC and correlated these with platinum resistance and clinical outcome. Nrf2 immunohistochemistry revealed nuclear localization (a surrogate of pathway activation) in over half of EOC patient specimens examined, with more common occurrence in the clear cell EOC subtype. Quantitative real-time PCR revealed that Nrf2 target genes were upregulated in tumors with nuclear positivity for Nrf2. Microarray analysis also showed upregulation of Nrf2 target genes in clear cell EOCs compared with other EOC subtypes. In addition, Keap1 sequence analysis revealed genetic mutations in 29% of clear cell samples and 8% of nonclear cell tumors. RNAi-mediated knockdown of Keap1 was associated with Nrf2 pathway activation and resistance to carboplatin in vitro. Importantly, patients with evidence of Nrf2 pathway activation had fewer complete clinical responses to platinum-based therapy, were enriched for platinum resistance, and had shorter median overall survival compared with those who did not show evidence of Nrf2 pathway activation. Our findings identify Keap1 mutations in EOC and they suggest a previously unrecognized role for the Keap1–Nrf2 pathway in mediating chemotherapeutic responses in this disease. Cancer Res; 71(15); 5081–9. ©2011 AACR.
Role of Smac in Determining the Chemotherapeutic Response of Esophageal Squamous Cell Carcinoma
Authors: Xu Yang , Zhou Lanping , Huang Jing , Liu Fang , Yu Jian , Zhan Qimin , Zhang Lin , Zhao Xiaohang 
Published: June 2011

Abstract
Purpose: Second mitochondria-derived activator of caspase (Smac) regulates chemotherapy-induced apoptosis. Smac mimetics have been tested in clinical trials as chemosensitizers. We determined the role of Smac in modulating the chemosensitivity of esophageal squamous cell carcinoma (ESCC).
Experimental Design: Smac expression was evaluated in tissues from ESCC patients with differential chemotherapeutic responses. The effects of Smac knockdown and Smac mimetics on the chemosensitivity of ESCC cells and the molecular mechanisms by which Smac and Smac mimetics modulate chemosensitivity were determined. The therapeutic responses of ESCC cells with different Smac statuses were compared using xenograft models.
Results: We found that Smac was significantly downregulated in most ESCC samples (36.8%, 25/68, P = 0.001), and Smac expression differed significantly (P &lt; 0.05) between chemosensitive and chemoresistant tumors. The associations of tested factors and their responses were examined using logistic regression analysis. In ESCC cells treated with cisplatin, a common chemotherapeutic drug, Smac and cytochrome c were released from mitochondria, and caspase-3 and caspase-9 were activated. Knockdown of Smac abrogated cisplatin-induced apoptosis, mitochondrial dysfunction, cytochrome c release, and caspase activation. Smac deficiency also reduced the effect of cisplatin on long-term cell viability, and led to cisplatin resistance in xenograft tumors in vivo. LBW242, a small molecule Smac mimetic, enhanced cisplatin-induced apoptosis and caspase activation and restored cisplatin sensitivity in Smac-deficient cells.
Conclusion: Our data suggested that downregulation of Smac may be a chemoresistance mechanism in ESCC. Combinations of Smac mimetics with chemotherapeutic agents may have therapeutic benefits for the treatment of esophageal cancer. Clin Cancer Res; 17(16); 5412–22. ©2011 AACR.
Lapatinib Activity in Premalignant Lesions and HER-2–Positive Cancer of the Breast in a Randomized, Placebo-Controlled Presurgical Trial
Authors: DeCensi Andrea , Puntoni Matteo , Pruneri Giancarlo , Guerrieri-Gonzaga Aliana , Lazzeroni Matteo , Serrano Davide , Macis Debora , Johansson Harriet , Pala Oriana , Luini Alberto , Veronesi Paolo , Galimberti Viviana , Dotti Maria Cristina , Viale Giuseppe , Bonanni Bernardo 
Published: June 2011

Abstract
Dual epidermal growth factor receptor (EGFR) and HER2 targeting with the tyrosine kinase inhibitor lapatinib is approved for treating advanced HER2-positive breast cancer and can prevent estrogen receptor (ER)-negative mammary tumors in HER2 transgenic mouse models. Ki-67 labeling index (LI) has prognostic and predictive value and can be used to screen drugs' therapeutic and preventive potential in a clinical model of short-term presurgical therapy of breast cancer. We conducted a randomized, placebo-controlled trial of lapatinib (1500 mg/d) administered orally for three weeks between biopsy and surgery in 60 women with HER-2–positive breast cancer to assess lapatinib biomarker (including the primary endpoint, Ki-67 LI) and clinical activity in invasive breast cancer, adjacent ductal intraepithelial neoplasia (DIN, which comprises ductal carcinoma in situ and atypical ductal hyperplasia), and distant ductal hyperplasia without atypia (DH). Ki-67 LI increased progressively in association with disease stage, increasing in the placebo arm, for example, by medians of 3% in DH to 20% in DIN to 30% in invasive cancer. Ki-67 LI in cancer tissue decreased by a mean (±SD) of 9.3% (±34.2) in the lapatinib arm and increased by 15.1% (±30.9) in the placebo arm (P = 0.008). Compared with placebo, lapatinib reduced Ki-67 significantly more in ER-negative tumors (by 34.8%; P = 0.01) but not significantly more in ER-positive tumors (by 12.3%; P = 0.2) and reduced Ki-67 more (nonsignificantly) in cytosol PTEN-overexpressing tumors (P = 0.057). The prevalence of DIN in post-treatment surgical specimens of both arms was similar (70%–76%), with a median Ki-67 of 15% (range, 5%–35%) on lapatinib versus 20% (5%–60%) on placebo (P = 0.067). The prevalence of DH also was similar in both arms (&gt;90%), with a median Ki-67 of 1% (1%–7%) on lapatinib versus 3% (1%–5%) on placebo (P = 0.006). Other results of lapatinib versus placebo, respectively, were as follows: Median tumor diameter at surgery of 18 mm (11 mm–57 mm) versus 24 mm (10 mm–37 mm; P = 0.009); partial response of 13.6% versus 3.7%, stable disease of 59.1% versus 40.7%, and progression of 27.3% versus 55.6% (P-trend = 0.035). In conclusion, short-term lapatinib decreased cell proliferation in DIN, DH, and invasive HER-2–positive (especially ER-negative) breast cancer, thus providing the rationale for further clinical development of lapatinib for breast cancer prevention in high-risk patients, including those with HER-2–positive DIN. Cancer Prev Res; 4(8); 1181–9. ©2011 AACR.
Clustering of risk behaviours among African American adults
Authors: Baruth M , Addy CL , Wilcox S , Dowda M 
Published: June 2011

Objectives: Individuals may engage in more than one risk behaviour at any given time. The extent to which risk behaviours cluster among African American adults has been largely unexplored. This study examined the prevalence and clustering of three risk behaviours among African American church members: smoking; low moderate-to-vigorous intensity leisure time physical activity (leisure MVPA); and low fruit and vegetable consumption. Design: Cross-sectional study. Setting: African Methodist Episcopal churches in South Carolina. Method: Participants self-reported leisure MVPA, fruit and vegetable consumption and smoking. The prevalence of single and multiple risk behaviours was computed. To examine whether risk behaviours clustered, a series of hierarchical log-linear models (SAS CATMOD) were fitted to the observed counts. Results: Of the 1123 participants, 7.0% smoked, 56.0% engaged in <150 minutes/week of leisure MVPA and 76.8% consumed <5 servings/day of fruit and vegetables; 11.8% of the sample had no risk behaviours, 39.5% had one, 45.7% had two and 2.9% had all three. The most common risk behaviour cluster was low leisure MVPA and low fruit and vegetable consumption (42.1%). Results from the log-linear models showed dependence among low fruit and vegetable consumption and low leisure MVPA, independent of smoking status. Conclusions: Church members who engaged in low levels of leisure MVPA were more likely to have low fruit and vegetable consumption, regardless of smoking status. These findings suggest that these two behaviours should not be considered in isolation from one another when developing behaviour change interventions; interventions targeting both behaviours may be more effective.
Clinical Practice Guideline: Polysomnography for Sleep‐Disordered Breathing Prior to Tonsillectomy in Children
Authors: Roland Peter S. , Rosenfeld Richard M. , Brooks Lee J. , Friedman Norman R. , Jones Jacqueline , Kim Tae W. , Kuhar Siobhan , Mitchell Ron B. , Seidman Michael D. , Sheldon Stephen H. , Jones Stephanie , Robertson Peter 
Published: June 2011

Objective. This guideline provides otolaryngologists with evidence‐based recommendations for using polysomnography in assessing children, aged 2 to 18 years, with sleep‐disordered breathing and are candidates for tonsillectomy, with or without adenoidectomy. Polysomnography is the electrographic recording of simultaneous physiologic variables during sleep and is currently considered the gold standard for objectively assessing sleep disorders.Purpose. There is no current consensus or guideline on when children 2 to 18 years of age, who are candidates for tonsillectomy, are recommended to have polysomnography. The primary purpose of this guideline is to improve referral patterns for polysomnography among these patients. In creating this guideline, the American Academy of Otolaryngology—Head and Neck Surgery Foundation selected a panel representing the fields of anesthesiology, pulmonology medicine, otolaryngology–head and neck surgery, pediatrics, and sleep medicine.Results. The committee made the following recommendations: (1) before determining the need for tonsillectomy, the clinician should refer children with sleep‐disordered breathing for polysomnography if they exhibit certain complex medical conditions such as obesity, Down syndrome, craniofacial abnormalities, neuromuscular disorders, sickle cell disease, or mucopolysaccharidoses. (2) The clinician should advocate for polysomnography prior to tonsillectomy for sleep‐disordered breathing in children without any of the comorbidities listed in statement 1 for whom the need for surgery is uncertain or when there is discordance between tonsillar size on physical examination and the reported severity of sleep‐disordered breathing. (3) Clinicians should communicate polysomnography results to the anesthesiologist prior to the induction of anesthesia for tonsillectomy in a child with sleep‐disordered breathing. (4) Clinicians should admit children with obstructive sleep apnea documented on polysomnography for inpatient, overnight monitoring after tonsillectomy if they are younger than age 3 or have severe obstructive sleep apnea (apnea‐hypopnea index of 10 or more obstructive events/hour, oxygen saturation nadir less than 80%, or both). (5) In children for whom polysomnography is indicated to assess sleep‐disordered breathing prior to tonsillectomy, clinicians should obtain laboratory‐based polysomnography, when available.
Tympanostomy Tube Placement and Vestibular Function in Children
Authors: Cohen Michael S. , Mandel Ellen M. , Furman Joseph M. , Sparto Patrick J. , Casselbrant Margaretha L. 
Published: June 2011

ObjectiveTo determine the effect of bilateral myringotomy with tube placement (BMT) on balance in children 4 to 7 years old.Study DesignCase‐control study.SettingTertiary‐care academic hospital.Subjects and MethodsChildren with otitis media with effusion (OME) who were scheduled for BMT underwent rotational chair testing (RCT) and computerized dynamic posturography (CDP) preoperatively and at 1, 3, and 6 months postoperatively. Control children without a significant history of middle ear disease were tested at the same intervals. Analysis of covariance was performed to evaluate the effect of BMT on RCT and CDP outcomes with age as a covariate.ResultsSeventy‐two cases and 56 controls were enrolled. Mean (SD) age was 69 (12) months for cases and 72 (15) months for controls. No difference was seen between groups on RCT outcomes or sensory organization test (SOT) scores. Higher sway velocity during CDP was observed in the OME group both preoperatively and 1 month postoperatively. This difference was not statistically significant. There was no difference between groups 3 months postoperatively. At 6 months, the BMT group had a statistically significant decrease in sway velocity compared with the control group.ConclusionNo difference was observed between children with OME and controls in RCT or SOT scores. Gradual improvement in sway velocity was observed after BMT. At the final time point, the groups did significantly differ in speed of sway, although the preoperative baseline difference failed to reach statistical significance. The authors suggest that physicians continue to inquire about balance development in patients with OME.
Shoulder Range of Motion Measures as Risk Factors for Shoulder and Elbow Injuries in High School Softball and Baseball Players
Authors: Shanley Ellen , Rauh Mitchell J. , Michener Lori A. , Ellenbecker Todd S. , Garrison J. Craig , Thigpen Charles A. 
Published: June 2011

Background: Range of motion deficits in shoulder external rotation (ER), internal rotation (IR), total rotation range of motion (ER + IR), and horizontal adduction (HA) have been retrospectively associated with overhand athletes’ arm injuries. Hypothesis: The authors expected the incidence of upper extremity injury in high school softball and baseball players with side-to-side shoulder range of motion deficits to be greater than the incidence of upper extremity injury in players with normal shoulder range of motion. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: High school softball and baseball players (N = 246) participated. Before the start of the season, passive shoulder ER, IR, and HA were assessed at 90° of abduction with the scapula stabilized. Relative risk (RR) was calculated to examine range of motion measure, by categorical criteria, and risk of upper extremity injury. Results: Twenty-seven shoulder and elbow injuries (9 softball, 18 baseball) were observed during the season. The dominant shoulder of all injured players and baseball players displayed a significant decrease in HA ( P = .05) and IR ( P = .04). The dominant shoulder total rotation of injured baseball players displayed a significant decrease (mean difference = 8.0° ± 0.1°; P = .05) as compared with the dominant shoulder of uninjured baseball players. Players who displayed a decrease of ≥25° of IR in the dominant shoulder were at 4 times greater risk of upper extremity injury compared with players with a <25° decrease in IR, especially for baseball players. While we observed a 1.5 to 2 times increased risk of injury for the 10° to 20° loss in rotational range of motion for the overall sample and baseball, the risk estimates were not statistically significant ( P > .05). Conclusion: There are large mean deficits in shoulder IR and HA between injured and noninjured players, but not in ER or total rotation. Passive shoulder IR loss ≥25° as compared bilaterally was predictive of arm injury. Shoulder range of motion deficits differed between sports and appeared more predictive of injury for baseball players.
Anti-Epstein–Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel
Authors: Munger KL , Levin LI , O’Reilly EJ , Falk KI , Ascherio A 
Published: June 2011

Background: Elevated Epstein–Barr virus (EBV) antibody titers are risk factors for multiple sclerosis (MS), but the strength and consistency of this association are not well characterized. Objectives: The objectives of this study were to determine whether this association is confounded by vitamin D or modified by gender or race, and the usefulness of EBV nuclear antigen (EBNA) antibodies as a marker for MS. Methods: We conducted a prospective study among US military personnel. Antibody titers against EBV antigens were measured in serum samples from 222 individuals who developed MS and 444 age, sex, and race/ethnicity matched controls. Conditional logistic regression was used to estimate relative risks. Results: MS risk increased with increasing titers of anti-EBNA complex ( p < 10−9) and anti-EBNA-1 ( p = 5.8 × 10−9) titers. MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers <20 (95% confidence interval [CI] 9.6–136), and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 <20 (95% CI 2.6–23). These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels. Areas under the receiver operating characteristic (ROC) curves were 0.67 for EBNA complex and 0.65 for EBNA-1. Conclusions: Serum titers of pre-onset anti-EBNA antibodies are strong, robust markers of MS risk and could be useful in an MS risk score.
Coupling decomposition and truncation for the analysis of complex fault trees
Authors: Contini S , Matuzas V 
Published: June 2011

The analysis of large and complex fault trees is a very difficult task. The main limiting factor is an insufficient working memory. Several methods are available in literature to reduce the working memory requirement including modularization, the so-called ‘re-writing rules’, and truncation, i.e. the use of logic and/or probabilistic cut-offs to determine only the most important system failure modes. The truncation method is very effective, as it allows significant reductions in the computational effort; however, it implies the estimation of the truncation error, a problem not yet solved satisfactorily. Recently, a new method based on the decomposition of a complex fault tree into a set of mutually exclusive simpler fault trees was proposed. The decomposition is repeatedly applied until the generated trees are sufficiently simple to be exactly analysed with the available working memory. Theoretically, this approach would allow the exact analysis of fault trees of any complexity, but the related computation times are generally too high. The scope of this paper is to show how the combined application of decomposition and truncation constitutes a valuable method to analyse complex fault trees. The upper and lower bounds of the top-event probability, obtained by applying this method, are very close to the exact value and their difference depends on the dimension of the available working memory. Furthermore, the probabilistic quantification, including the importance measures of basic events, can easily be performed by properly combining the results from the independent analysis of all simpler fault trees. The developed methodology has been implemented in a software tool and successfully applied to the analysis of several complex fault trees, some of which are considered in this paper.
Productivity improvement through chatter-free milling in workshops
Authors: Quintana G , Campa F J , Ciurana J , de Lacalle L N Lopez 
Published: June 2011

High-speed machining has improved performance in manufacturing sectors such as the aeronautical, automotive, and mould and die industries. However, one problem of reaching such high speeds is the self-excitation of the spindle-tool system during the machining process. This so-called chatter vibration produces several negative effects: a reduction in surface quality and accuracy, and in tool and spindle life. Nowadays, it is still the most common limitation to increased productivity and quality of metal-removal operations. Although theoretically calculated stability-lobe diagrams can be used to calculate stable cutting conditions, some uncertainties affect the accuracy of this solution. This paper presents a method based on experimental tests where an inclined plane in the workpiece is machined at several spindle speeds. The gradual increase of the axial depth of cut allows the milling to be interrupted when chatter is detected. The final result is that the stability lobes are machined in the workpiece. This method can be used for process optimization and avoiding trial and error tests to determine optimal depths of cut and spindle speeds. The creation of a database with the optimal cutting conditions for a given spindle-tool holder-tool system can help the computer aided manufacturing (CAM) programmer select the cutting conditions that maximize the material removal rate and avoid vibration problems. The method presented is especially suitable for small- and medium-sized workshops where operators are unfamiliar with analytical methods or modelling techniques. It is an interesting way of saving money that does not require complex knowledge, and can easily be applied without additional costs owing to its simplicity.