bluuebunny/crossref_metadata_2025_split huggingface dataset:
In the End What Matters Most? A Review of Clinical Endpoints in Advanced Breast Cancer
Authors: Verma Sunil , McLeod Deanna , Batist Gerald , Robidoux André , Martins Ilídio R. S. , Mackey John R. 
Published: January 2011

Abstract
Many agents are being studied for the treatment of metastatic breast cancer (MBC), yet few studies have demonstrated longer overall survival (OS), the primary measure of clinical benefit in MBC. This paper examines the key endpoints in clinical trials and U.S. Food and Drug Administration (FDA) approvals of drugs for MBC.
PubMed was searched (1980 to October 2009) for reports of phase III trials investigating chemotherapy and/or targeted therapy agents in MBC. FDA approval histories (1996–2009) for cytotoxic and biological agents indicated for MBC were reviewed.
Of the 73 phase III MBC trials reviewed, a strikingly small proportion of trials demonstrated a gain in OS duration (12%, n = 9). OS gains were less frequently noted in first-line trials (8%) than in trials of second-line plus other lines of therapy (22%). Few trials were designed with the capacity to detect OS effects. Among 37 phase III trials conducted in the last 15 years, only three systemic therapies were approved for first-line use and nine were approved for use as second-line or other lines of therapy. Of these, only four were supported by results showing longer survival times.
There is substantial discordance among the design and conduct of clinical trials, FDA drug approval, and the current view of OS as the ultimate measure of clinical benefit. There is an urgent need to reassess standards for clinical benefit in MBC and to establish guidelines for study design and conduct and drug approval. In the end, what matters most is ensuring rapid access to safe and effective oncology treatments.
Contagious Cancer
Authors: Welsh James S. 
Published: January 2011

Abstract
Although cancer can on occasion be caused by infectious agents such as specific bacteria, parasites, and viruses, it is not generally considered a transmissible disease. In rare circumstances, however, direct communication from one host to another has been documented. The Tasmanian devil is now threatened with extinction in the wild because of a fatal transmissible cancer, devil facial tumor disease (DFTD). Another example is canine transmissible venereal tumor (CTVT or Sticker's sarcoma) in dogs. There is a vast difference in prognosis between these two conditions. DFTD is often fatal within 6 months, whereas most cases of CTVT are eventually rejected by the host dog, who then is conferred lifelong immunity. In man, only scattered case reports exist about such communicable cancers, most often in the setting of organ or hematopoietic stem cell transplants and cancers arising during pregnancy that are transmitted to the fetus. In about one third of cases, transplant recipients develop cancers from donor organs from individuals who were found to harbor malignancies after the transplantation. The fact that two thirds of the time cancer does not develop, along with the fact that cancer very rarely is transmitted from person to person, supports the notion that natural immunity prevents such cancers from taking hold in man. These observations might hold invaluable clues to the immunobiology and possible immunotherapy of cancer.
Supply system factors associated with microbiological drinking water safety in regional New South Wales, Australia, 2001–2007
Authors: Cretikos Michelle , Byleveld Paul , Durrheim David N. , Porigneaux Philippe , Merritt Tony , Leask Sandy 
Published: January 2011

Aim: To determine factors associated with microbiological safety of public drinking water systems in regional New South Wales (NSW), Australia.
Method: We analysed 107,000 end-user drinking water samples for an association between detection of Escherichia coli and drinking water system features, sample year and season using NSW Health Drinking Water Monitoring Program data, 2001–2007. We used negative binomial generalized estimating equations with adjustment for autocorrelation and clustering.
Results: We detected E. coli in over 2% of samples from 40% (129/323) of systems. E. coli detection was significantly more common in earlier years and during summer (p&lt;0.001). On multivariate analysis E. coli detection was significantly associated with smaller systems; watercourse sources; no disinfection or disinfection with ultraviolet only; and higher post-treatment mean turbidity (all p≤0.01). Detection was most strongly associated with lack of disinfection (incidence rate ratio 12.6, p&lt;0.001) and smaller supply systems (1% reduction in E. coli detection for each 1,000 person increase in supply population, p=0.004). Ultraviolet disinfection alone was the least effective disinfection method (p&lt;0.001).
Conclusion: Even in developed countries, drinking water systems without disinfection or serving small populations appear vulnerable to the effects of faecal contamination, which presents a risk of waterborne disease outbreaks.
A Comparison of Multifactor Dimensionality Reduction and L1-Penalized Regression to Identify Gene-Gene Interactions in Genetic Association Studies
Authors: Winham Stacey , Wang Chong , Motsinger-Reif Alison A 
Published: January 2011

Recently, the amount of high-dimensional data has exploded, creating new analytical challenges for human genetics. Furthermore, much evidence suggests that common complex diseases may be due to complex etiologies such as gene-gene interactions, which are difficult to identify in high-dimensional data using traditional statistical approaches. Data-mining approaches are gaining popularity for variable selection in association studies, and one of the most commonly used methods to evaluate potential gene-gene interactions is Multifactor Dimensionality Reduction (MDR). Additionally, a number of penalized regression techniques, such as Lasso, are gaining popularity within the statistical community and are now being applied to association studies, including extensions for interactions. In this study, we compare the performance of MDR, the traditional lasso with L1 penalty (TL1), and the group lasso for categorical data with group-wise L1 penalty (GL1) to detect gene-gene interactions through a broad range of simulations.We find that each method has both advantages and disadvantages, and relative performance is context dependent. TL1 frequently over-fits, identifying false positive as well as true positive loci. MDR has higher power for epistatic models that exhibit independent main effects; for both Lasso methods, main effects tend to dominate. For purely epistatic models, GL1 has the best performance for lower minor allele frequencies, but MDR performs best for higher frequencies. These results provide guidance of when each approach might be best suited for detecting and characterizing interactions with different mechanisms.
Can Rising Inequality Explain Aggregate Trends in Marriage? Evidence from U.S. States, 1977-2005
Authors: Coughlin Tristan P. , Drewianka Scott D 
Published: January 2011

Abstract
We investigate the hypothesis that rising wage inequality caused declines in the U.S. aggregate marriage hazard since 1970. Despite confirming previous findings that inequality accounts for much of the decline among young adults before 1990, we find that the aggregate marriage hazard became much less sensitive to inequality thereafter. Our explanation for the weakened relationship relies on the theoretical prediction, which we verify empirically, that inequality influences marital decisions of young singles much more than those of older singles. The aggregate marriage hazard thus became less responsive to inequality over this period because the unmarried population became older.
Oligopoly on a Salop Circle with Centre
Authors: Madden Paul , Pezzino Mario 
Published: January 2011

Abstract
We study an oligopolistic market in which consumers located around the perimeter of a Salop circle buy either from firms around this perimeter (providing horizontally differentiated goods) or from a firm located at the centre of the circle (providing a homogeneous good). An entry-pricing game is studied. The market equilibria and social optima indicate various possible market failures, including cases in which the market is served only by perimeter firms whilst central provision would be socially optimal (in this sense, more extreme than the standard Salop excessive product differentiation). Moreover, for some parameters, the standard Salop result might be reversed.
The Urine Albumin-to-Creatinine Ratio
Authors: Erman Arie , Rahamimov Ruth , Mashraki Tiki , Levy-Drummer Rachel S. , Winkler Janos , David Iskra , Hirsh Yehudit , Gafter Uzi , Chagnac Avry 
Published: January 2011

Summary

Background and objectives
Microalbuminuria predicts graft loss and death in the renal transplant population. Measurement of the urinary albumin-to-creatinine ratio (UACR) is recommended for its detection. There is uncertainty regarding the optimal UACR cutoff values. Few studies have examined the accuracy of UACR in the general population and none have been conducted in renal transplant recipients. The aim of this study is to determine the performance of UACR in the renal transplant population.

Design, setting, participants & measurements
Renal transplant recipients with a daily urinary albumin excretion rate of up to 300 mg accurately carried out a 24-hour urine collection and provided a morning urine sample for the measurement of albuminuria and UACR. The performance measures of UACR for the detection of microalbuminuria (30 to 300 mg/d) were calculated using different cutoffs.

Results
Median albuminuria was 23 mg/d, and median UACR was 17 mg/g. The area under the receiver-operating characteristic curve was 0.94 in men and 0.98 in women. The optimal cutoff was 21 mg/g in men and 24 mg/g in women. In men, the 30-, 17-, and 21-mg/g cutoffs provided a sensitivity of 0.79, 0.89, and 0.87. In women, the 30-, 25-, and 24-mg/g cutoffs provided a sensitivity of 0.90, 0.97, and 1.0.

Conclusions
These data show that in the renal transplant population, lower gender-specific cutoffs should be used for the detection of microalbuminuria than the recommended 30-mg/g cutoff. These data support the need for a reappraisal of the 30-mg/g cutoff for the detection of microalbuminuria.
Heart Failure in Long-Term Peritoneal Dialysis Patients
Authors: Wang Angela Yee-Moon , Wang Mei , Lam Christopher Wai-Kei , Chan Iris Hiu-Shuen , Lui Siu-Fai , Sanderson John E. 
Published: January 2011

Summary

Background and objectives
Heart failure occurs frequently in end-stage renal disease patients. However, there are no prospective, longitudinal follow-up data on its prevalence, severity, and risk factors in long-term peritoneal dialysis (PD) patients.

Design, setting, participants, & measurements
A prospective observational study was conducted in 220 long-term PD patients followed up for 4 years or until death. Echocardiography was obtained at baseline. Primary study end points were heart failure and mortality.

Results
Eighty-six patients had a previous history of heart failure at study entry. The cumulative 4-year survival probability was 37.4% and 64.7% for patients with and without previous heart failure, respectively (P < 0.0001). During follow-up, 87 patients (40.9%) developed heart failure, of which 53 were recurrence and 34 were new-onset heart failure. Diabetes, background atherosclerotic vascular disease, systolic hypertension, left ventricular (LV) mass index, systolic dysfunction, and hypoalbuminemia were significant risk factors predicting heart failure in the entire cohort. Diabetes and LV mass and volume index were significant predictors of new-onset heart failure. Systolic hypertension, LV volume index, and hypoalbuminemia were significant predictors of recurrent heart failure.

Conclusions
Heart failure is a highly prevalent complication in long-term PD patients and predicts adverse clinical outcomes. More attention should be focused on improving BP and volume control and identifying treatment strategies that effectively lower atherosclerotic burden and reverse LV hypertrophy, remodeling, and systolic dysfunction in PD patients.
Correlation of preoperative depression and somatic perception scales with postoperative disability and quality of life after lumbar discectomy
Authors: Chaichana Kaisorn L. , Mukherjee Debraj , Adogwa Owoicho , Cheng Joseph S. , McGirt Matthew J. 
Published: January 2011

Object
Lumbar discectomy is the most common surgical procedure performed in the US for patients experiencing back and leg pain from herniated lumbar discs. However, not all patients will benefit from lumbar discectomy. Patients with certain psychological predispositions may be especially vulnerable to poor clinical outcomes.
The goal of this study was therefore to determine the role that preoperative depression and somatic anxiety have on long-term back and leg pain, disability, and quality of life (QOL) for patients undergoing single-level lumbar discectomy.

Methods
In 67 adults undergoing discectomy for a single-level herniated lumbar disc, the authors determined quantitative measurements of leg and back pain (visual analog scale [VAS]), quality of life (36-Item Short Form Health Survey [SF-36]), and disease-specific disability (Oswestry Disability Index) preoperatively and at 6 weeks, 3, 6, and 12 months after surgery. The degree of preoperative depression and somatization was assessed using the Zung Self-Rating Depression Scale and a modified somatic perception questionnaire (MSPQ). Multivariate regression analyses were performed to assess associations between Zung Scale and MSPQ scores with achievement of a minimum clinical important difference (MCID) in each outcome measure by 12 months postoperatively.

Results
All patients completed 12 months of follow-up. Overall, a significant improvement in VAS leg pain, VAS back pain, Oswestry Disability Index, and SF-36 Physical Component Summary scores was observed by 6 weeks after surgery. Improvements in all outcomes were maintained throughout the 12-month follow-up period. Increasing preoperative depression (measured using the Zung Scale) was associated with a decreased likelihood of achieving an MCID in disability (p = 0.006) and QOL (p = 0.04) but was not associated with VAS leg pain (p = 0.96) or back pain (p = 0.85) by 12 months. Increasing preoperative somatic anxiety (measured using the MSPQ) was associated with decreased likelihood of achieving an MCID in disability (p = 0.002) and QOL (p = 0.03) but was not associated with leg pain (p = 0.64) or back pain (p = 0.77) by 12 months.

Conclusions
The Zung Scale and MSPQ are valuable tools for stratifying risk in patients who may not experience clinically relevant improvement in disability and QOL after discectomy. Efforts to address these confounding and underlying contributors of depression and heightened somatic anxiety may improve overall outcomes after lumbar discectomy.
Biomechanical advantage of the index-level pedicle screw in unstable thoracolumbar junction fractures
Authors: Baaj Ali A. , Reyes Phillip M. , Yaqoobi Ali S. , Uribe Juan S. , Vale Fernando L. , Theodore Nicholas , Sonntag Volker K. H. , Crawford Neil R. 
Published: January 2011

Object
Unstable fractures at the thoracolumbar junction often require extended, posterior, segmental pedicular fixation. Some surgeons have reported good clinical outcomes with short-segment constructs if additional pedicle screws are inserted at the fractured level. The goal of this study was to quantify the biomechanical advantage of the index-level screw in a fracture model.

Methods
Six human cadaveric T10–L4 specimens were tested. A 3-column injury at L-1 was simulated, and 4 posterior constructs were tested as follows: one-above-one-below (short construct) with/without index-level screws, and two-above-two-below (long construct) with/without index-level screws. Pure moments were applied quasistatically while 3D motion was measured optoelectronically. The range of motion (ROM) and lax zone across T12–L2 were measured during flexion, extension, left and right lateral bending, and left and right axial rotation.

Results
All constructs significantly reduced the ROM and lax zone in the fractured specimens. With or without index-level screws, the long-segment constructs provided better immobilization than the short-segment constructs during all loading modes. Adding an index-level screw to the short-segment construct significantly improved stability during flexion and lateral bending; there was no significant improvement in stability when an index-level screw was added to the long-segment construct. Overall, bilateral index-level screws decreased the ROM of the 1-level construct by 25% but decreased the ROM of the 2-level construct by only 3%.

Conclusions
In a fracture model, adding index-level pedicle screws to short-segment constructs improves stability, although stability remains less than that provided by long-segment constructs with or without index-level pedicle screws. Therefore, highly unstable fractures likely require extended, long-segment constructs for optimum stability.
Trajectory of the main sensory and motor branches of the lumbar plexus outside the psoas muscle related to the lateral retroperitoneal transpsoas approach
Authors: Dakwar Elias , Vale Fernando L. , Uribe Juan S. 
Published: January 2011

Object
The minimally invasive lateral retroperitoneal transpsoas approach is increasingly used to treat various spinal disorders. Accessing the retroperitoneal space and traversing the abdominal wall poses a risk of injury to the major nervous structures and adds significant morbidity to the procedure. Most of the current literature focuses on the anatomy of the lumbar plexus within the substance of the psoas muscle. However, there is sparse knowledge regarding the trajectory of the lumbar plexus nerves that travel along the retroperitoneum and abdominal wall muscles in relation to the lateral approach to the spine. The objective of this study is to define the anatomical trajectories of the major motor and sensory branches of the lumbar plexus that are located outside the psoas muscle.

Methods
Six adult fresh frozen cadaveric specimens were dissected and studied (12 sides). The relationship between the retroperitoneum, abdominal wall muscles, and the lumbar plexus nerves was analyzed in reference to the minimally invasive lateral retroperitoneal approach. Special attention was given to the lumbar plexus nerves that run outside of psoas muscle in the retroperitoneal cavity and within the abdominal muscle wall.

Results
The skin and muscles of the abdominal wall and the retroperitoneal cavity were dissected and analyzed with respect to the major motor and sensory branches of the lumbar plexus. The authors identified 4 nerves at risk during the lateral approach to the spine: subcostal, iliohypogastric, ilioinguinal, and lateral femoral cutaneous nerves. The anatomical trajectory of each of these nerves is described starting from the spinal column until their termination or exit from the pelvic cavity.

Conclusions
There is risk of direct injury to the main motor/sensory nerves that supply the anterior abdominal muscles during the early stages of the lateral retroperitoneal transpsoas approach while obtaining access to the retroperitoneum. There is also a risk of injury to the ilioinguinal, iliohypogastric, and lateral femoral cutaneous nerves in the retroperitoneal space where they travel obliquely during the blunt retroperitoneal dissection. Moreover, there is a latent possibility of lesioning these nerves with the retractor blades against the anterior iliac crest.
Clinicopathological factors related to regrowth of vestibular schwannoma after incomplete resection
Authors: Fukuda Masafumi , Oishi Makoto , Hiraishi Tetsuya , Natsumeda Manabu , Fujii Yukihiko 
Published: January 2011

Object
The authors retrospectively analyzed various clinicopathological factors to determine which are related to regrowth during a long-term follow-up period in patients who underwent incomplete vestibular schwannoma (VS) resection.

Methods
This study involved 74 patients (25 men and 49 women) in whom a VS was treated surgically via the lateral suboccipital approach, and who had postoperative follow-up periods exceeding 5 years. The mean follow-up was 104.1 months (range 60–241 months), and the mean patient age at surgery was 48.1 years (range 19–75 years). The tumors ranged in size from 0 mm (localized within the internal auditory canal) to 56 mm (28.3 ± 12.2 mm [mean ± SD]).

Results
Gross-total resection (GTR) was performed in 41 (55%) of the 74 patients; subtotal resection ([STR]; 90–99%) in 25 (34%); and partial resection ([PR]; < 90%) in 8 (11%). Regrowth rates in the GTR, STR, and PR groups were 2.4% (1 of 41 cases), 52% (13 of 25), and 62.5% (5 of 8), respectively, and the times to regrowth ranged from 6 to 76 months (median 31.9 months). The regrowth-free survival curves differed significantly between the complete (GTR) and incomplete (STR and PR) resection groups. Eighteen (54.5%) of the 33 patients who underwent incomplete resection showed evidence of regrowth during follow-up. Univariate and multivariate analyses of various factors revealed that both the thickness of the residual tumor, based on MR imaging after surgery, and the MIB-1 index were positively related to residual tumor regrowth. The receiver operating characteristic curves, plotted for both the thickness of the residual tumor and the MIB-1 index, identified the optimal cutoff points for these values as 7.4 mm (sensitivity 83.3%, specificity 86.7%) and 1.6 (sensitivity 83.3%, specificity 66.7%), respectively.

Conclusions
Greater residual tumor thickness, based on MR imaging after the initial surgery, and a higher MIB-1 index are both important factors related to postoperative tumor regrowth in patients who have undergone incomplete VS resection. These patients require frequent neuroimaging investigation during follow-up to assure early detection of tumor regrowth.
A novel transnasal transsphenoidal speculum: a design for both microscopic and endoscopic transsphenoidal pituitary surgery
Authors: Chole Richard A. , Lim Chris , Dunham Brian , Chicoine Michael R. , Dacey Ralph G. 
Published: January 2011

Over the last several years minimally invasive surgical approaches to the sella turcica and parasellar regions have undergone significant change. The transsphenoidal approach to this region has evolved from a sublabial transnasal, to transnasal, to pure endonasal approaches with the increasing popularity of endoscopic over microscopic techniques. Endoscopic and microscopic techniques individually or in combination have their own unique advantages, and the preference of one over the other awaits further technological refinements and surgical experience.
In parallel with this evolution in techniques for transsphenoidal surgery, the authors designed an adaptable versatile speculum for the endonasal/transnasal transsphenoidal approach to the sella turcica and parasellar regions that can be used equally effectively with a microscope or an endoscope. The development of this instrument and its unique features are described, and its initial clinical use is summarized.
This transnasal transsphenoidal speculum has interchangeable blades, unique blade angulations, and independent blade opening mechanisms and allows safe, optimal exposure in all patients regardless of the size and anatomical aberrations of individual nasal and endonasal regions. An attached endoscope carrier further allows it to be used interchangeably with microscopic or endoscopic techniques without having to remove the speculum; likewise, a single surgeon can use both hands without need of an assistant. A forehead headrest component adds further stabilization. This device has been used successfully in 90 transsphenoidal procedures.