bluuebunny/crossref_metadata_2025_split huggingface dataset:
A model for extending antiretroviral care beyond the rural health centre
Authors: Wools‐Kaloustian Kara K , Sidle John E , Selke Henry M , Vedanthan Rajesh , Kemboi Emmanuel K , Boit Lillian J , Jebet Viola T , Carroll Aaron E , Tierney William M , Kimaiyo Sylvester 
Published: September 2009

BackgroundA major obstacle facing many lower‐income countries in establishing and maintaining HIV treatment programmes is the scarcity of trained health care providers. To address this shortage, the World Health Organization has recommend task shifting to HIV‐infected peers.MethodsWe designed a model of HIV care that utilizes HIV‐infected patients, community care coordinators (CCCs), to care for their clinically stable peers with the assistance of preprogrammed personal digital assistants (PDAs). Rather than presenting for the standard of care, monthly clinic visits, in this model, patients were seen every three months in clinics and monthly by their CCCs in the community during the interim two months. This study was conducted in Kosirai Division, western Kenya, where eight of the 24 sub‐locations (defined geographic areas) within the division were randomly assigned to the intervention with the remainder used as controls.Prior to entering the field, CCCs underwent intensive didactic training and mentoring related to the assessment and support of HIV patients, as well as the use of PDAs. PDAs were programmed with specific questions and to issue alerts if responses fell outside of pre‐established parameters. CCCs were regularly evaluated in six performance areas. An impressionistic analysis on the transcripts from the monthly group meetings that formed the basis of the continuous feedback and quality improvement programme was used to assess this model.ResultsAll eight of the assigned CCCs successfully passed their training and mentoring, entered the field and remained active for the two years of the study. On evaluation of the CCCs, 89% of their summary scores were documented as superior during Year 1 and 94% as superior during Year 2. Six themes emerged from the impressionistic analysis in Year 1: confidentiality and “community” disclosure; roles and responsibilities; logistics; clinical care partnership; antiretroviral adherence; and PDA issues. At the end of the trial, of those patients not lost to follow up, 64% (56 of 87) in the intervention and 52% (58 of 103) in the control group were willing to continue in the programme (p = 0.26).ConclusionWe found that an antiretroviral treatment delivery model that shifted patient monitoring and antiretroviral dispensing tasks into the community by HIV‐infected patients was both acceptable and feasible.Trial registrationClinicalTrials.gov ID NCT00371540
Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study
Authors: Schwartz Noa , Rubinstein Tamar , Burkly Linda C , Collins Christopher E , Blanco Irene , Su Lihe , Hojaili Bernard , Mackay Meggan , Aranow Cynthia , Stohl William , Rovin Brad H , Michaelson Jennifer S , Putterman Chaim 
Published: September 2009

Abstract
Introduction
TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-κB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has been recently introduced. Thus, TWEAK levels may serve as an indication of LN presence and activity.

Methods
Multicenter cohorts of systemic lupus erythematosus (SLE) patients and controls were recruited for cross-sectional and longitudinal analysis of urinary TWEAK (uTWEAK) and/or serum TWEAK (sTWEAK) levels as potential biomarkers of LN. The performance of TWEAK as a biomarker for nephritis was compared with routinely used laboratory tests in lupus patients, including anti-double stranded DNA antibodies and levels of C3 and C4.

Results
uTWEAK levels were significantly higher in LN patients than in non-LN SLE patients and other disease control groups (P = 0.039). Furthermore, uTWEAK was better at distinguishing between LN and non-LN SLE patients than anti-DNA antibodies and complement levels, while high uTWEAK levels predicted LN in SLE patients with an odds ratio of 7.36 (95% confidence interval = 2.25 to 24.07; P = 0.001). uTWEAK levels peaked during LN flares, and were significantly higher during the flare than at 4 and 6 months prior to or following the flare event. A linear mixed-effects model showed a significant association between uTWEAK levels in SLE patients and their disease activity over time (P = 0.008). sTWEAK levels, however, were not found to correlate with the presence of LN or the degree of nephritis activity.

Conclusions
High uTWEAK levels are indicative of LN, as opposed to non-LN SLE and other healthy and disease control populations, and reflect renal disease activity in longitudinal follow-up. Thus, our study further supports a role for TWEAK in the pathogenesis of LN, and provides strong evidence for uTWEAK as a candidate clinical biomarker for LN.
Estrogen and progesterone receptors have distinct roles in the establishment of the hyperplastic phenotype in PR-A transgenic mice
Authors: Simian Marina , Bissell Mina J , Barcellos-Hoff Mary Helen , Shyamala Gopalan 
Published: September 2009

Abstract
Introduction
Expression of the A and B forms of progesterone receptor (PR) in an appropriate ratio is critical for mammary development. Mammary glands of PR-A transgenic mice, carrying an additional A form of PR as a transgene, exhibit morphological features associated with the development of mammary tumors. Our objective was to determine the roles of estrogen (E) and progesterone (P) in the genesis of mammary hyperplasias/preneoplasias in PR-A transgenics.

Methods
We subjected PR-A mice to hormonal treatments and analyzed mammary glands for the presence of hyperplasias and used BrdU incorporation to measure proliferation. Quantitative image analysis was carried out to compare levels of latency-associated peptide and transforming growth factor beta 1 (TGFβ1) between PR-A and PR-B transgenics. Basement membrane disruption was examined by immunofluorescence and proteolytic activity by zymography.

Results
The hyperplastic phenotype of PR-A transgenics is inhibited by ovariectomy, and is reversed by treatment with E + P. Studies using the antiestrogen ICI 182,780 or antiprogestins RU486 or ZK 98,299 show that the increase in proliferation requires signaling through E/estrogen receptor alpha but is not sufficient to give rise to hyperplasias, whereas signaling through P/PR has little impact on proliferation but is essential for the manifestation of hyperplasias. Increased proliferation is correlated with decreased TGFβ1 activation in the PR-A transgenics. Analysis of basement membrane integrity showed loss of laminin-5, collagen III and collagen IV in mammary glands of PR-A mice, which is restored by ovariectomy. Examination of matrix metalloproteases (MMPs) showed that total levels of MMP-2 correlate with the steady-state levels of PR, and that areas of laminin-5 loss coincide with those of activation of MMP-2 in PR-A transgenics. Activation of MMP-2 is dependent on treatment with E and P in ovariectomized wild-type mice, but is achieved only by treatment with P in PR-A mice.

Conclusions
These data establish a link between hormonal response, proliferation, modulation of MMP activity and maintenance of basement membrane integrity that depend on a balance in the expression levels of PR-A and PR-B isoforms. Notably, concomitant increased proliferation, due to inhibition of TGFβ1 activation, and loss of basement membrane integrity, via increased MMP-2 activity, appear to be prerequisites for the PR-A hyperplastic phenotype.
Candidemia on presentation to the hospital: development and validation of a risk score
Authors: Shorr Andrew F , Tabak Ying P , Johannes Richard S , Sun Xiaowu , Spalding James , Kollef Marin H 
Published: September 2009

Abstract
Introduction
Candidemia results in substantial morbidity and mortality, especially if initial antifungal therapy is delayed or is inappropriate; however, candidemia is difficult to diagnose because of its nonspecific presentation.

Methods
To develop a risk score for identifying hospitalized patients with candidemia, we performed a retrospective analysis of a large database of 176 acute-care hospitals in the United States. We studied 64,019 patients with bloodstream infection (BSI) on presentation from 2000 through 2005 (derivation cohort) and 24,685 from 2006 to 2007 (validation cohort). We used recursive partitioning (RPART) to identify the best discriminators for Candida as the cause of BSI. We compared three sets of models (equal-weight, unequal-weight, vs full model with additional variables from logistic regression model) for sensitivity analysis.

Results
The RPART identified 6 variables as the best discriminators: age < 65 years, temperature ≤ 98°F or severe altered mental status, cachexia, previous hospitalization within 30 days, admitted from other healthcare facility, and need for mechanical ventilation. The prevalence for patients presented with 0 through 6 risk factors in the derivation cohort was 28.7%, 38.8%, 21.8%, 8.3%, 2.1%, 0.3%, and < 0.1% respectively. The corresponding candidemia rates were 0.4% (69/18,355), 0.8% (196/24,811), 1.6% (229/13,984), 3.2% (168/5,330), 4.2% (58/1,371), 9.6% (15/157), and 27.3% (3/11) respectively (P < 0.0001). Findings were similar in the validation cohort (P < 0.0001). The equal-weight risk score model, which signed 1 point to each risk factor, yielded good discrimination in both cohorts with areas under the receiver operating curve (AUROCs) of 0.70 versus 0.71 (derivation versus validation). AUROC values were similar for the unequal-weight model, which signed different weight to each risk factor based on multivariable logistic regression coefficient, (AUROCs, 0.70-0.72). Both equal-weight and unequal-weight models were well calibrated (all Hosmer-Lemshow P > 0.10, indicating predicted and observed candidemia rates did not differ significant across the 7 risk stratus). The full model with 16 risk factors had slightly higher AUROCs (0.74 versus 0.73 for derivation versus validation); however, 7 variables were no longer significant in the recalibrated model for the validation cohort, indicating that the additional items did not materially enhance the model.

Conclusions
A simple equal-weight risk score differentiated patients' risk for candidemia in a graded fashion upon hospital presentation.
Trastuzumab Plus Anastrozole Versus Anastrozole Alone for the Treatment of Postmenopausal Women With Human Epidermal Growth Factor Receptor 2–Positive, Hormone Receptor–Positive Metastatic Breast Cancer: Results From the Randomized Phase III TAnDEM Study
Authors: Kaufman Bella , Mackey John R. , Clemens Michael R. , Bapsy Poonamalle P. , Vaid Ashok , Wardley Andrew , Tjulandin Sergei , Jahn Michaela , Lehle Michaela , Feyereislova Andrea , Révil Cédric , Jones Alison 
Published: September 2009

PurposeTAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor–copositive metastatic breast cancer (MBC).Patients and MethodsPostmenopausal women with HER2/hormone receptor–copositive MBC were randomly assigned to anastrozole (1 mg/d orally) with or without trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression. The primary end point was progression-free survival (PFS) in the intent-to-treat population.ResultsOverall, 103 patients received trastuzumab plus anastrozole; 104 received anastrozole alone. Patients in the trastuzumab plus anastrozole arm experienced significant improvements in PFS compared with patients receiving anastrozole alone (hazard ratio = 0.63; 95% CI, 0.47 to 0.84; median PFS, 4.8 v 2.4 months; log-rank P = .0016). In patients with centrally confirmed hormone receptor positivity (n = 150), median PFS was 5.6 and 3.8 months in the trastuzumab plus anastrozole and anastrozole alone arms, respectively (log-rank P = .006). Overall survival in the overall and centrally confirmed hormone receptor–positive populations showed no statistically significant treatment difference; however, 70% of patients in the anastrozole alone arm crossed over to receive trastuzumab after progression on anastrozole alone. Incidence of grade 3 and 4 adverse events was 23% and 5%, respectively, in the trastuzumab plus anastrozole arm, and 15% and 1%, respectively, in the anastrozole alone arm; one patient in the combination arm experienced New York Heart Association class II congestive heart failure.ConclusionTrastuzumab plus anastrozole improves outcomes for patients with HER2/hormone receptor–copositive MBC compared with anastrozole alone, although adverse events and serious adverse events were more frequent with the combination.
Multicenter, Phase I, Dose-Escalation Trial of Lenalidomide Plus Bortezomib for Relapsed and Relapsed/Refractory Multiple Myeloma
Authors: Richardson Paul G. , Weller Edie , Jagannath Sundar , Avigan David E. , Alsina Melissa , Schlossman Robert L. , Mazumder Amitabha , Munshi Nikhil C. , Ghobrial Irene M. , Doss Deborah , Warren Diane L. , Lunde Laura E. , McKenney Mary , Delaney Carol , Mitsiades Constantine S. , Hideshima Teru , Dalton William , Knight Robert , Esseltine Dixie-Lee , Anderson Kenneth C. 
Published: September 2009

Purpose Lenalidomide and bortezomib are active in relapsed and relapsed/refractory multiple myeloma (MM). In preclinical studies, lenalidomide sensitized MM cells to bortezomib and dexamethasone. This phase I, dose-escalation study (ie, NCT00153933) evaluated safety and determined the maximum-tolerated dose (MTD) of lenalidomide plus bortezomib in patients with relapsed or with relapsed and refractory MM. Patients and Methods Patients received lenalidomide 5, 10, or 15 mg/d on days 1 through 14 and received bortezomib 1.0 or 1.3 mg/m2 on days 1, 4, 8, and 11 of 21-day cycles. Dexamethasone (20mg or 40 mg on days 1, 2, 4, 5, 8, 9, 11, and 12) was added for progressive disease after two cycles. Primary end points were safety and MTD determination. Results Thirty-eight patients were enrolled across six dose cohorts. The MTD was lenalidomide 15 mg/d plus bortezomib 1.0 mg/m2. Dose-limiting toxicities (n = 1 for each) were grade 3 hyponatremia and herpes zoster reactivation and grade 4 neutropenia. The most common treatment-related, grades 3 to 4 toxicities included reversible neutropenia, thrombocytopenia, anemia, and leukopenia. Among 36 response-evaluable patients, 61% (90% CI, 46% to 75%) achieved minimal response or better. Among 18 patients who had dexamethasone added, 83% (90% CI, 62% to 95%) achieved stable disease or better. Median overall survival was 37 months. Conclusion Lenalidomide plus bortezomib was well tolerated and showed promising activity with durable responses in patients with relapsed and relapsed/refractory MM, including patients previously treated with lenalidomide, bortezomib, and/or thalidomide. The combination of lenalidomide, bortezomib, and dexamethasone is being investigated in a phase II study in this setting and in newly diagnosed MM.
Survival After Second Primary Neoplasms of the Brain or Spinal Cord in Survivors of Childhood Cancer: Results From the British Childhood Cancer Survivor Study
Authors: Taylor Aliki J. , Frobisher Clare , Ellison David W. , Reulen Raoul C. , Winter David L. , Taylor Roger E. , Stiller Charles A. , Lancashire Emma R. , Tudor Edward C.G. , Baggott Christina , May Shaun , Hawkins Mike M. 
Published: September 2009

Purpose Survival after brain or spinal cord neoplasms is poor and varies by diagnostic group, age, grade, treatment and pretreatment factors, and location and size of tumor. We carried out a study to investigate survival and factors affecting survival of all diagnostic types of second primary brain or spinal cord neoplasms. Patients and Methods The British Childhood Cancer Survivor Study (BCCSS) is a long-term population-based follow-up study of 17,980 5-year survivors of childhood cancer. We used relative survival and multivariate Cox regression analysis to determine 5-year relative survival and factors affecting survival in second primary meningiomas and gliomas that developed in survivors included in the BCCSS. Results There were 247 second primary brain or spinal cord neoplasms, including 137 meningiomas and 73 gliomas in a young adult population. Five-year relative survival after meningiomas was similar for males (84.0%; 95% CI, 72.6% to 91.1%) and females (81.7%; 95% CI, 69.9% to 89.3%). For gliomas, 5-year relative survival was 19.5% (95% CI, 8.6% to 33.7%) for males and females. Multivariate analysis showed significant heterogeneity by decade of treatment (P = .04), grade (P = .03), and genetic risk (P = .03) for rate of mortality after a meningioma. For gliomas, survival was significantly affected by grade (P < .001). Conclusion Our results indicate survival is poor after second primary glioma in this young adult population, although survival after second primary meningioma is good. Our study has clinical implications for the surveillance of childhood cancer survivors at risk of developing second primary brain tumors, in particular survivors of childhood acute lymphoblastic leukemia or childhood brain tumors.
To Tell or Not to Tell: The Community Wants to Know About Expensive Anticancer Drugs As a Potential Treatment Option
Authors: Mileshkin Linda , Schofield Penelope E. , Jefford Michael , Agalianos Emilia , Levine Michele , Herschtal Alan , Savulescu Julian , Thomson Jacqui Ann , Zalcberg John R. 
Published: September 2009

Purpose Many new cancer treatments are available only at significant financial cost to the patient. We previously reported that Australian medical oncologists commonly do not discuss unsubsidized, expensive anticancer drugs (EACD) because of concern about causing distress. We argued that this position was not consistent with modern ethical principals but wanted to seek the community viewpoint. Methods A cross-sectional telephone survey of the Australian general public was performed. Respondents' views were sought about three hypothetical scenarios in which they were diagnosed with incurable cancer and an EACD treatment (out-of-pocket cost US$25,000) was available. Results Responses were obtained from 1,255 respondents (response rate, 43%). One hundred thirty-seven (11%) had a prior cancer diagnosis. Ninety-one percent of respondents wanted to be told by their doctor about an EACD that could improve survival by an additional 4 to 6 months, with 51% prepared to pay for it. People were more willing to pay if the drug could improve quality of life (71%) or if there was no effective standard treatment (76%). Sixty-eight percent believed the government should pay. Cost would be a significant financial burden for 31% of those willing to pay. Those more likely to want to be informed were younger, employed, better-educated, or had higher income levels (P < .05). Responses did not vary with the person's personal experience of cancer. Of the 9% who did not wish to be informed, half of these were concerned about the information causing distress. Conclusion The Australian general public wants to be informed about EACD as potential treatment options, even if they are not willing or readily able to pay for them.
Lapatinib Combined With Letrozole Versus Letrozole and Placebo As First-Line Therapy for Postmenopausal Hormone Receptor–Positive Metastatic Breast Cancer
Authors: Johnston Stephen , Pippen John , Pivot Xavier , Lichinitser Mikhail , Sadeghi Saeed , Dieras Veronique , Gomez Henry Leonidas , Romieu Gilles , Manikhas Alexey , Kennedy M. John , Press Michael F. , Maltzman Julie , Florance Allison , O'Rourke Lisa , Oliva Cristina , Stein Steven , Pegram Mark 
Published: September 2009

PurposeCross-talk between human epidermal growth factor receptors and hormone receptor pathways may cause endocrine resistance in breast cancer. This trial evaluated the effect of adding lapatinib, a dual tyrosine kinase inhibitor blocking epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2), to the aromatase inhibitor letrozole as first-line treatment of hormone receptor (HR) –positive metastatic breast cancer (MBC).Patients and MethodsPostmenopausal women with HR-positive MBC were randomly assigned to daily letrozole (2.5 mg orally) plus lapatinib (1,500 mg orally) or letrozole and placebo. The primary end point was progression-free survival (PFS) in the HER2-positive population.ResultsIn HR-positive, HER2-positive patients (n = 219), addition of lapatinib to letrozole significantly reduced the risk of disease progression versus letrozole-placebo (hazard ratio [HR] = 0.71; 95% CI, 0.53 to 0.96; P = .019); median PFS was 8.2 v 3.0 months, respectively. Clinical benefit (responsive or stable disease ≥ 6 months) was significantly greater for lapatinib-letrozole versus letrozole-placebo (48% v 29%, respectively; odds ratio [OR] = 0.4; 95% CI, 0.2 to 0.8; P = .003). Patients with centrally confirmed HR-positive, HER2-negative tumors (n = 952) had no improvement in PFS. A preplanned Cox regression analysis identified prior antiestrogen therapy as a significant factor in the HER2-negative population; a nonsignificant trend toward prolonged PFS for lapatinib-letrozole was seen in patients who experienced relapse less than 6 months since prior tamoxifen discontinuation (HR = 0.78; 95% CI, 0.57 to 1.07; P = .117). Grade 3 or 4 adverse events were more common in the lapatinib-letrozole arm versus letrozole-placebo arm (diarrhea, 10% v 1%; rash, 1% v 0%, respectively), but they were manageable.ConclusionThis trial demonstrated that a combined targeted strategy with letrozole and lapatinib significantly enhances PFS and clinical benefit rates in patients with MBC that coexpresses HR and HER2.
A Comparison of the Performance of Environmentally Friendly Anhydrous Fire Resistant Hydraulic Fluids
Authors: Greaves Martin R. , Knoell Jim C. 
Published: September 2009

Abstract
Many industries benefit from using fire resistant hydraulic fluids including aviation, steel processing, aluminum die-casting, marine, mining, and many more. In recent years, environmental performance has become an increasingly important feature of hydraulic fluids notably in Europe with the introduction of the European Eco-Label and in the United States with the recommendations provided by the 2002 U.S. Farm Bill for procurement of bio-based materials by Federal agencies. Environmental performance favors esters and vegetable oils as the preferred technologies today but polyalkylene glycols (PAGs) offer an alternative option although they are not derived from renewable sources. The performance of several environmentally friendly fire resistant anhydrous hydraulic fluids based on these technologies has been evaluated in laboratory bench tests. All fluids exhibit excellent hydraulic vane pump wear performance. In high temperature oxidation studies, synthetic products based on esters and PAGs, out-perform vegetable oils. Hydrolytic stability results show hydrolysis of synthetic esters and vegetable oils occurs to form acids in contrast to a PAG formulation, which is more stable. Furthermore the unique water solubility and non-sheening aspects of the PAG product indicate it may be a more favorable choice for use in applications where fluid leakage into water-ways is a concern. By understanding the performance of each product technology, direction can be provided in the type of equipment and industries where these fluids can be used and a discussion pertaining to this is presented herein.