bluuebunny/crossref_metadata_2025_split huggingface dataset:
How do people with knee osteoarthritis use osteoarthritis pain medications and does this change over time? Data from the Osteoarthritis Initiative
Authors: Kingsbury Sarah R , Hensor Elizabeth MA , Walsh Ceara AE , Hochberg Marc C , Conaghan Philip G 
Published: September 2013

Abstract
Introduction
The aim of this analysis was to describe comprehensively the cross-sectional and longitudinal patterns of analgesic and nutraceutical medication use for knee osteoarthritis (OA) in a contemporary US cohort and to investigate associated demographic and clinical factors.

Methods
Baseline, 12, 24 and 36 month data were obtained retrospectively from the National Institutes of Health Osteoarthritis Initiative. Participants had symptomatic radiographic knee OA. Multiple binary logistic regression models identified characteristics independently associated with the use of analgesics or nutraceuticals.

Results
We included 987 subjects (55.9% female, mean age 61.5 years, 71.0% white). At baseline, 68.2% reported frequent use of a conventional analgesic or nutraceutical for joint pain (for more than half of the previous month). Non-prescription non-steroidal anti-inflammatory drugs (NSAIDs) were the most frequently reported medications (26.8%), even in those more than 75-years old. Multiple conventional analgesics were used by 11.9%. Frequent analgesic use was more likely in women (odds ratio (OR) 1.8 (95% confidence interval (CI) 1.3 to 2.3)) and people with more pain (moderate 1.7 (1.2 to 2.4); severe 3.1 (2.1 to 4.7)); nutraceutical use was less likely in non-whites (0.4 (0.3 to 0.6)), those more than 74-years old (0.6 (0.3 to 0.9)) and those with comorbidities (0.6 (0.5 to 0.9)) and more likely in people with Kellgren-Lawrence (KL) grade 4 (2.2 (1.5 to 3.3)). Overall there was no change in the proportion of participants frequently using prescription or over the counter (OTC) analgesics at 36 months, although most people had changed medication type; of those using a traditional analgesic at baseline approximately one third were still using the same type at 36 months (ranging from 26.2% of baseline prescription NSAID users to 40.6% of baseline acetaminophen users). All participants reporting baseline analgesic use also reported 36 month analgesic use. Female participants (OR 95% CI 1.2 to 3.2, P = 0.009), those with high body mass index (1.2 to 4.8, P = 0.010) and those with moderate (1.6 to 2.6, P = 0.090) or severe (1.8 to 12.0, P = 0.002) baseline pain were more likely to use pain medication during the 36 month follow-up period; participants more than 75-years old were less likely (0.2 to 1.0, P = 0.053).

Conclusions
Most people with knee OA used pharmacological therapies frequently, and use appeared to be according to American College of Rheumatology recommendations. Change in medication type used was common. Persistent non-prescription NSAID use in older people is an area of concern.
Association between mammographic density and basal-like and luminal A breast cancer subtypes
Authors: Razzaghi Hilda , Troester Melissa A , Gierach Gretchen L , Olshan Andrew F , Yankaskas Bonnie C , Millikan Robert C 
Published: September 2013

Abstract
Introduction
Mammographic density is a strong risk factor for breast cancer overall, but few studies have examined the association between mammographic density and specific subtypes of breast cancer, especially aggressive basal-like breast cancers. Because basal-like breast cancers are less frequently screen-detected, it is important to understand how mammographic density relates to risk of basal-like breast cancer.

Methods
We estimated associations between mammographic density and breast cancer risk according to breast cancer subtype. Cases and controls were participants in the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). A total of 491 cases had mammograms within five years prior to and one year after diagnosis and 528 controls had screening or diagnostic mammograms close to the dates of selection into CBCS. Mammographic density was reported to the CMR using Breast Imaging Reporting and Data System categories. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 1 and 2 (HER1 and HER2), and cytokeratin 5/6 (CK5/6) were assessed by immunohistochemistry and dichotomized as positive or negative, with ER+ and/or PR+, and HER2- tumors classified as luminal A and ER-, PR-, HER2-, HER1+ and/or CK5/6+ tumors classified as basal-like breast cancer. Triple negative tumors were defined as negative for ER, PR and HER2. Of the 491 cases 175 were missing information on subtypes; the remaining cases included 181 luminal A, 17 luminal B, 48 basal-like, 29 ER-/PR-/HER2+, and 41 unclassified subtypes. Odds ratios comparing each subtype to all controls and case-case odds ratios comparing mammographic density distributions in basal-like to luminal A breast cancers were estimated using logistic regression.

Results
Mammographic density was associated with increased risk of both luminal A and basal-like breast cancers, although estimates were imprecise. The magnitude of the odds ratio associated with mammographic density was not substantially different between basal-like and luminal A cancers in case–control analyses and case-case analyses (case-case OR = 1.08 (95% confidence interval: 0.30, 3.84)).

Conclusions
These results suggest that risk estimates associated with mammographic density are not distinct for separate breast cancer subtypes (basal-like/triple negative vs. luminal A breast cancers). Studies with a larger number of basal-like breast cancers are needed to confirm our findings.
Changes in dental plaque following hospitalisation in a critical care unit: an observational study
Authors: Sachdev Mishal , Ready Derren , Brealey David , Ryu Jung Hyun , Bercades Georgia , Nagle Janette , Borja-Boluda Susana , Agudo Elisa , Petrie Aviva , Suvan Jean , Donos Nikos , Singer Mervyn , Needleman Ian 
Published: September 2013

Abstract
Introduction
Previous research has suggested that deterioration in oral health can occur following hospitalisation. The impact of such deterioration could increase the risk of oral disease, reduce quality of life and increase the potential for healthcare-associated infections (HCAI) such as healthcare-associated pneumonia (HAP). However, the strength of the evidence is limited by, amongst other factors, the few observational studies published that assess oral health longitudinally. In view of the microbiological component of oral diseases and HCAIs, the objective of this study was to investigate the microbiological changes in dental plaque following hospitalisation in a Critical Care Unit (CCU): (1) total number of cultivable bacteria and (2) presence and changes in specific HAP pathogens.

Methods
We conducted a prospective, longitudinal observational study in the CCU of University College Hospital, London. Study participants were recruited within 24 hours of admission. Dental plaque samples were collected from up to six sites per patient. The primary outcome was microbiological change from baseline to seven days with additional analysis for participants still present at day 14.

Results
50 patients were recruited with 36 available for review at one week, with early discharge accounting for much of the loss to follow-up. The median total viable count of the plaque microbiota at baseline was 4.40 × 105 cfu/ml and increased at week one to 3.44 × 106 cfu/ml. The total viable microbe counts increased by a median of 2.26 × 106 cfu/ml from baseline to week one (95% CI: 3.19 × 106, 1.24 × 107) and this was statistically significant (P < 0.01). Specific HAP bacteria were detected in 26% of participants sampled, although accounted for a relatively low proportion of the total viable bacteria.

Conclusion
Total bacterial count of dental plaque increases during hospitalisation in CCU. This finding, together with the colonisation of dental plaque by HAP bacteria strengthens the evidence for a deterioration in oral health in CCU and a risk factor for negative health and quality of life outcomes.
Contraindicated Use of Bevacizumab and Toxicity in Elderly Patients With Cancer
Authors: Hershman Dawn L. , Wright Jason D. , Lim Emerson , Buono Donna L. , Tsai Wei Yann , Neugut Alfred I. 
Published: September 2013

Purpose Drugs are approved on the basis of randomized trials conducted in selected populations. However, once approved, these treatments are usually expanded to patients ineligible for the trial. Patients and Methods We used the SEER-Medicare database to identify subjects older than 65 years with metastatic breast, lung, and colon cancer, diagnosed between 2004 and 2007 and undergoing follow-up to 2009, who received bevacizumab. We defined a contraindication as having at least two billing claims before bevacizumab for thrombosis, cardiac disease, stroke, hemorrhage, hemoptysis, or GI perforation. We defined toxicity as first development of one of these conditions after therapy. Results Among 16,085 metastatic patients identified, 3,039 (18.9%) received bevacizumab. Receipt of bevacizumab was associated with white race, later year of diagnosis, tumor type, and decreased comorbid conditions. Of patients who received bevacizumab, 1,082 (35.5%) had a contraindication. In multivariate analysis, receipt of bevacizumab with a contraindication was associated with black race (odds ratio [OR] = 2.6; 95% CI, 1.4 to 4.9), increased age, comorbidity, later year of diagnosis, and lower socioeconomic status. Patients with lung (OR = 1.7; 95% CI, 1.1 to 2.4) and colon cancer (OR = 1.4; 95% CI, 1.1 to 1.9) were more likely to have a contraindication. In the group with no contraindication, 30% had a complication after bevacizumab; black patients were more likely to have a complication than were white patients (OR = 1.9; 95% CI, 1.21 to 2.93). Conclusion Our study demonstrates widespread use of bevacizumab among patients who had contraindications. Black patients were less likely to receive the drug, but those who did were more likely to have a contraindication. Efforts to understand toxicity and efficacy in populations excluded from clinical trials are needed.
Effect of Antiviral Treatment With Nucleotide/Nucleoside Analogs on Postoperative Prognosis of Hepatitis B Virus–Related Hepatocellular Carcinoma: A Two-Stage Longitudinal Clinical Study
Authors: Yin Jianhua , Li Nan , Han Yifang , Xue Jie , Deng Yang , Shi Jie , Guo Weixing , Zhang Hongwei , Wang Hongyang , Cheng Shuqun , Cao Guangwen 
Published: September 2013

Purpose Postoperative prognosis of hepatitis B virus (HBV) –related hepatocellular carcinoma (HCC) is poor. The effect of nucleotide/nucleoside analog (NA) treatment on the prognosis has not been fully clarified. Patients and Methods We carried out a two-stage longitudinal study that included a randomized clinical trial (RCT) to evaluate the effect of NA treatment on postoperative prognosis of HBV-HCC. Seven hundred eighty patients (163 in the RCT) were enrolled onto this study following radical hepatectomy. Lamivudine, adefovir dipivoxil, or entecavir were postoperatively administered to antiviral groups. Surgical specimens were examined immunohistochemically for carboxylic acid–terminal truncated HBV X protein (Ct-HBx). Results In the nonrandomized cohort, high viral load (≥ 104 copies/mL) significantly predicted unfavorable overall survival and recurrence-free survival (RFS), whereas antiviral treatment significantly improved both types of survival. In the RCT, antiviral treatment significantly decreased HCC recurrence and HCC-related death, with hazard ratios (HRs) of 0.48 (95% CI, 0.32 to 0.70) and 0.26 (95% CI, 0.14 to 0.50), respectively, in multivariate Cox analyses. Patients who received antiviral treatment had significantly decreased early recurrence (HR, 0.41; 95% CI, 0.27 to 0.62) and improved liver function 6 months after surgery compared with the controls (P < .001). Those with recovered liver function had a higher 2-year RFS rate than those without (P = .003). Ct-HBx expression in adjacent hepatic tissues significantly predicted an unfavorable RFS in the antiviral group (P < .001). Conclusion Although it might not affect the HCC-promoting potential of Ct-HBx, NA treatment is effective in normalizing liver function, decreasing HBV-HCC recurrence, and improving postoperative survival. This effect should be validated in a multicenter phase III RCT.
Phase I Study of ARN-509, a Novel Antiandrogen, in the Treatment of Castration-Resistant Prostate Cancer
Authors: Rathkopf Dana E. , Morris Michael J. , Fox Josef J. , Danila Daniel C. , Slovin Susan F. , Hager Jeffrey H. , Rix Peter J. , Chow Maneval Edna , Chen Isan , Gönen Mithat , Fleisher Martin , Larson Steven M. , Sawyers Charles L. , Scher Howard I. 
Published: September 2013

Purpose ARN-509 is a novel androgen receptor (AR) antagonist for the treatment of castration-resistant prostate cancer (CRPC). ARN-509 inhibits AR nuclear translocation and AR binding to androgen response elements and, unlike bicalutamide, does not exhibit agonist properties in the context of AR overexpression. This first-in-human phase I study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of ARN-509 in men with metastatic CRPC. Patients and Methods Thirty patients with progressive CRPC received continuous daily oral ARN-509 at doses between 30 and 480 mg, preceded by administration of a single dose followed by a 1-week observation period with pharmacokinetic sampling. Positron emission tomography/computed tomography imaging was conducted to monitor [18F]fluoro-α-dihydrotestosterone (FDHT) binding to AR in tumors before and during treatment. Primary objective was to determine pharmacokinetics, safety, and recommended phase II dose. Results Pharmacokinetics were linear and dose proportional. Prostate-specific antigen declines at 12 weeks (≥ 50% reduction from baseline) were observed in 46.7% of patients. Reduction in FDHT uptake was observed at all doses, with a plateau in response at ≥ 120-mg dose, consistent with saturation of AR binding. The most frequently reported adverse event was grade 1/2 fatigue (47%). One dose-limiting toxicity event (grade 3 abdominal pain) occurred at the 300-mg dose. Dose escalation to 480 mg did not identify a maximum-tolerated dose. Conclusion ARN-509 was safe and well tolerated, displayed dose-proportional pharmacokinetics, and demonstrated pharmacodynamic and antitumor activity across all dose levels tested. A maximum efficacious dose of 240 mg daily was selected for phase II exploration based on integration of preclinical and clinical data.
Traditional and Novel Bone Remodeling Markers in Premenopausal and Postmenopausal Women
Authors: Botella Sonsoles , Restituto Patricia , Monreal Ignacio , Colina Inmaculada , Calleja Amparo , Varo Nerea 
Published: September 2013

Context:
Bone turnover markers (BTMs) may identify changes in bone remodeling within a relatively short time interval before changes in bone mineral density can be detected. New markers such as osteoprotegerin, receptor activator of nuclear factor-κB ligand, and sclerostin have emerged, but there is little information about their potential use in clinical practice.

Objectives:
The aim of this study was to analyze the ability of several BTMs to predict bone loss in pre- and postmenopausal women and to monitor the efficacy of treatment in osteoporotic women.

Design, Patients, and Setting:
We performed an observational prospective study in pre- and postmenopausal ambulatory women (n = 72 and n = 152, respectively).

Intervention:
Postmenopausal women with osteoporosis (n = 18) were treated with risedronate and calcium. Women filled out a questionnaire and underwent bone mineral density measurement using dual-energy x-ray absorptiometry at the time of enrollment and after 1 year of follow-up. BTMs were measured at baseline, at 6 months, and after 1 year.

Results:
Increased levels of N-terminal propeptide of type 1 procollagen (P1NP) and β-type I collagen telopeptides (CTXs) were associated with low bone mineral density in the premenopausal (P = .02 and P = .04, respectively) and postmenopausal (P = .03 and P = .02) groups. The best analytical performance to diagnose osteoporosis was for β-CTX, osteocalcin, and P1NP, with areas under the curve of 0.70 (P = .005), 0.64 (P = .048), and 0.71 (P = .003). A significant decrease was found in P1NP, osteocalcin, tartrate-resistant acid phosphatase-5b, β-CTX, and bone alkaline phosphatase after 1 year of treatment (all P &lt; .05).

Conclusions:
Our data suggest that measurement of β-CTX and P1NP shows adequate analytical performance and could potentially be included in algorithms for the screening of osteoporosis. Furthermore, these two markers, along with osteocalcin and tartrate-resistant acid phosphatase-5b, are useful to monitor the response to risedronate.
A three-dimensional musculoskeletal model of the chimpanzee (Pan troglodytes) pelvis and hind limb
Authors: O'Neill Matthew C. , Lee Leng-Feng , Larson Susan G. , Demes Brigitte , Stern Jack T. , Umberger Brian R. 
Published: September 2013

SUMMARY
Musculoskeletal models have become important tools for studying a range of muscle-driven movements. However, most work has been in modern humans, with few applications in other species. Chimpanzees are facultative bipeds and our closest living relatives, and have provided numerous important insights into our own evolution. A chimpanzee musculoskeletal model would allow integration across a wide range of laboratory-based experimental data, providing new insights into the determinants of their locomotor performance capabilities, as well as the origins and evolution of human bipedalism. Here, we described a detailed three-dimensional (3D) musculoskeletal model of the chimpanzee pelvis and hind limb. The model includes geometric representations of bones and joints, as well as 35 muscle–tendon units that were represented using 44 Hill-type muscle models. Muscle architecture data, such as muscle masses, fascicle lengths and pennation angles, were drawn from literature sources. The model permits calculation of 3D muscle moment arms, muscle–tendon lengths and isometric muscle forces over a wide range of joint positions. Muscle–tendon moment arms predicted by the model were generally in good agreement with tendon-excursion estimates from cadaveric specimens. Sensitivity analyses provided information on the parameters that model predictions are most and least sensitive to, which offers important context for interpreting future results obtained with the model. Comparisons with a similar human musculoskeletal model indicate that chimpanzees are better suited for force production over a larger range of joint positions than humans. This study represents an important step in understanding the integrated function of the neuromusculoskeletal systems in chimpanzee locomotion.
Synthesis of New Type Core–Shell Li[Li0.21(Ni0.20Co0.16Mn0.58)0.8(Ni0.2Mn0.2)0.2]O2 Spherical Particles as a Positive Electrode for Lithium Secondary Batteries by Coprecipitation
Authors: Jeon Hyo Jin , Kang Seo Ha , Son Jong Tae 
Published: September 2013

Abstract
Microscale core–shell-structured Li[Li0.21(Ni0.20Co0.16Mn0.58)0.8(Ni0.2Mn0.2)0.2]O2 powders were prepared by a coprecipitation method. To protect the Li[Li0.2(Ni0.14Co0.14Mn0.52)]O2 core material from structural instability at high voltage, a Li[Li0.2(Ni0.4Mn0.4)]O2 shell, which provides structural and thermal stability, was used to encapsulate the core. Spherical morphologies with monodispersed powders were observed in the cross-sectional images obtained by scanning electron microscopy (SEM). To the best of our knowledge, this is the first report of the synthesis of a Mn-rich core–shell.
Governance and CEO Turnover: Do Something or Do the Right Thing?
Authors: Fisman Raymond J. , Khurana Rakesh , Rhodes-Kropf Matthew , Yim Soojin 
Published: September 2013

We study how corporate governance affects firm value through the decision of whether to fire or retain the chief executive officer (CEO). We present a model in which weak governance—which prevents shareholders from controlling the board—protects inferior CEOs from dismissal, while at the same time insulates the board from pressures by biased or uninformed shareholders. Whether stronger governance improves retain/replace decisions depends on which of these effects dominates. We use our theoretical framework to assess the effect of governance on the quality of firing and hiring decisions using data on the CEO dismissals of large U.S. corporations during 1994–2007. Our findings are most consistent with a beneficent effect of weak governance on CEO dismissal decisions, suggesting that insulation from shareholder pressure may allow for better long-term decision making. This paper was accepted by Brad Barber, finance.
A Regression Model for the Copula-Graphic Estimator
Authors: Lo Simon M.S. , Wilke Ralf A. 
Published: September 2013

Abstract
We suggest a pragmatic extension of the non-parametric copula-graphic estimator to a depending competing risks model with covariates. Our model is an attractive empirical approach for practitioners in many disciplines as it does not require knowledge of the marginal distributions. Although non-observable and only set-identifiable in most applications, classical duration models typically impose ad-hoc assumptions on their functional forms. Instead of directly estimating these distributions, we suggest a plug-in regression framework which utilises an estimator for the observable cumulative incidence curves which specification can be visually inspected. We perform simulations and estimate an unemployment duration model to demonstrate the advantages of our model compared to classical duration models such as the Cox proportional hazard model.
When Investment Arbitration Curbs Domestic Regulatory Space: Consistent Solutions through Amicus Curiae Submissions by Regional Organisations
Authors: Cross Ciaran , Schliemann-Radbruch Christian 
Published: September 2013

AbstractTo date, African states have been called before 62 tribunals of the International Centre for the Settlement of Investment Disputes (ICSID); 26 cases are pending. Recently, foreign investors have invoked Bilateral Investment Treaty provisions to challenge legislation aimed at addressing historical inequalities in the distribution of natural resources in Southern Africa (