bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dabigatran is Less Effective Than Warfarin at Attenuating Mechanical Heart Valve‐Induced Thrombin Generation
Authors: Jaffer Iqbal H. , Stafford Alan R. , Fredenburgh James C. , Whitlock Richard P. , Chan Noel C. , Weitz Jeffrey I. 
Published: August 2015

Background

Patients with mechanical heart valves (
MHV
) require warfarin to prevent thromboembolism. Although dabigatran was as effective as warfarin for stroke prevention in atrial fibrillation when compared with warfarin in patients with
MHV
, the study was stopped early because of more strokes and bleeding with dabigatran. To determine why dabigatran was less effective than warfarin, we compared their effects on thrombin generation induced by
MHV
.

Methods and Results

Thrombin generation in the absence or presence of valve leaflets or sewing ring segments (
SRS
) was quantified. Studies were done in control plasma, plasma depleted of factors (F)
XII
,
XI,
or
VII
, plasma containing varying concentrations of dabigatran, or plasma from patients on dabigatran or warfarin with varying dabigatran concentrations or international normalized ratio (
INR
) values. Mean endogenous thrombin potential (
ETP
) increased 1.2‐, 1.5‐, and 1.8‐fold in the presence of leaflets, Teflon
SRS
, and Dacron
SRS
, respectively. Whereas
ETP
in
FVII
‐depleted and control plasma was similar,
ETP
was reduced to background levels in
FXII
‐depleted plasma and abrogated in
FXI
‐depleted plasma. Dabigatran had little effect on
ETP
at concentrations below 400 ng/
mL
, whereas in plasma from warfarin‐treated patients,
ETP
was suppressed with
INR
values over 1.5.

Conclusions

MHV
induce thrombin generation via the intrinsic pathway and generate sufficient thrombin to overwhelm clinically relevant dabigatran concentrations. In contrast, warfarin is more effective than dabigatran at suppressing
MHV
‐induced thrombin generation. These data explain why dabigatran failed in
MHV
patients and suggest that strategies targeting
FXII
or
FXI
may suppress the root cause of thrombosis in such patients.
<p><strong><em>Caudalejeunea yangambiensis</em> (Vanden Berghen) E.W.Jones (Lejeuneaceae) with mature perianths from Ghana</strong></p>
Authors: Wigginton M. J. 
Published: August 2015

Mature perianths of Caudalejeunea yangambiensis (Vanden Berghen) E.W.Jones (Lejeuneaceae) are described for the first time, and the species reported new to Ghana.
Water under a Changing and Uncertain Climate: Lessons from Climate Model Ensembles*
Authors: Boehlert Brent , Solomon Susan , Strzepek Kenneth M. 
Published: August 2015

Abstract
Climate change and rapidly rising global water demand are expected to place unprecedented pressures on already strained water resource systems. Successfully planning for these future changes requires a sound scientific understanding of the timing, location, and magnitude of climate change impacts on water needs and availability—not only average trends but also interannual variability and quantified uncertainties. In recent years, two types of large-ensemble runs of climate projections have become available: those from groups of more than 20 different climate models and those from repeated runs of several individual models. These provide the basis for novel probabilistic evaluation of both projected climate change and the resulting effects on water resources. Using a broad range of available ensembles, this research explores the spatial and temporal patterns of high confidence as well as uncertainty in projected river runoff, irrigation water requirements, basin storage yield, and cost estimates of adapting regional water systems to maintain historical supply. Projections of river runoff show robust between-ensemble agreement in regional drying (e.g., southern Africa and southern Europe) and wetting trends (e.g., northeastern United States). By integrating runoff over space and time, the economic effects of adapting supply systems to 2050 water availability show still broader trend agreement across ensembles. That agreement, obtained across such a wide range of multiple-member climate model ensembles in some locations, suggests a high degree of confidence in direction of change in water availability and provides clearer signals for longer-term investment decisions in water infrastructure.
The Relative Influence of Tropical Sea Surface Temperatures and Radiative Forcing on the Amundsen Sea Low
Authors: Fogt Ryan L. , Wovrosh Alex J. 
Published: August 2015

Abstract
Recent studies suggest that warming trends across West Antarctica and the Antarctic Peninsula and sea ice loss in the adjacent Amundsen and Bellingshausen Seas are linked to changes in the regional atmospheric circulation, represented by the Amundsen Sea low (ASL). Importantly, changes in the ASL have similarly been tied to forcing from the tropics. Here, several model simulations from the Community Atmosphere Model, version 4, are investigated in order to understand the relative roles of tropical sea surface temperature variability and radiative forcing on the variations in trends in the ASL. In comparing across the simulations, it is observed that the addition of time-varying extratropical SSTs and sea ice conditions in general have a much smaller impact on the ASL than tropical SSTs or radiative forcing. Tropical forcing alone explains much of the climatological variability and extreme intensities of the ASL (both strong and weak relative central pressures). The role of radiative forcing is best observed in the ASL trends, with this simulation leading to a marked deepening of the ASL and pressures across the Southern Hemisphere that is consistent with atmospheric reanalysis in austral summer. In austral winter, the simulation with radiative forcing produces stronger trends than observed in reanalysis data, perhaps reflecting the need to couple to an ocean–ice model in order to more realistically simulate the ASL changes. Together, the results suggest that models need to include both the effects from tropical SST variations and radiative forcing when understanding historic and future variations in the ASL.
A Vector Autoregressive ENSO Prediction Model
Authors: Chapman David , Cane Mark A. , Henderson Naomi , Lee Dong Eun , Chen Chen 
Published: August 2015

Abstract
The authors investigate a sea surface temperature anomaly (SSTA)-only vector autoregressive (VAR) model for prediction of El Niño–Southern Oscillation (ENSO). VAR generalizes the linear inverse method (LIM) framework to incorporate an extended state vector including many months of recent prior SSTA in addition to the present state. An SSTA-only VAR model implicitly captures subsurface forcing observable in the LIM residual as red noise. Optimal skill is achieved using a state vector of order 14–17 months in an exhaustive 120-yr cross-validated hindcast assessment. It is found that VAR outperforms LIM, increasing forecast skill by 3 months, in a 30-yr retrospective forecast experiment.
Perioperative Management of Antithrombotic Therapy in Common Otolaryngologic Surgical Procedures
Authors: Hsueh Wayne D. , Hwang Peter H. , Abuzeid Waleed M. 
Published: August 2015

ObjectiveThe perioperative management of patients undergoing otolaryngologic procedures is increasingly complicated by the use of newer antithrombotic agents. Furthermore, with advances in anesthesia and surgical technique, otolaryngologists are presented with the challenge of operating on patients with advanced comorbid diseases. The objective of this review is to provide evidence‐based recommendations on perioperative antithrombotic management for common otolaryngologic procedures.Data SourcesPubMed/MEDLINE.Review MethodsSelected literature on patient‐specific thromboembolic risk, rate of bleeding complications in otolaryngologic procedures, and the interruption of antithrombotic therapy is reviewed and interpreted by expert opinion.ConclusionsBy stratifying patients into either low thromboembolic risk (≤5%) or high thromboembolic risk (>5%) and interpreting this in the context of procedural bleed risk and potential clinical consequences in the event of a bleed, otolaryngologists can make evidence‐based decisions to determine the appropriate perioperative management of antithrombotic therapy.Implications for PracticeWhen the perioperative management of antithrombotic therapy is being decided, 3 critical factors must be considered systematically: the patient’s inherent thromboembolic risk, the risk and potential consequences of bleeding related to the procedure, and the timing of interruption of thromboembolic therapy.
New insights into the immediate outcome of collagenase injections for Dupuytren’s contracture
Authors: Warwick D. J. , Graham D. , Worsley P. 
Published: August 2015

Collagenase clostridium histolyticum is now established as an effective and safe option to treat patients with a single joint affected with Dupuytren’s contracture. We have extended its use to natatory and combined cords. In a prospective consecutive series of 298 cords in 237 patients, the mean total extension loss improved in cords crossing the metacarpophalangeal joint from 46° to 1°, in cords crossing the proximal interphalangeal joint from 56° to 7°, in natatory cords from 130° to 25° and in combined cords from 102° to 16°. The immediate correction of combined cords and natatory cords was less reliable than that obtained in cords crossing the metacarpophalangeal joint or proximal interphalangeal joint. Less severe pre-intervention contractures tended to correct better. We found a high complication rate, which may cause alarm. A total of 21% developed skin splits, with the risk of skin splits generally increasing with more severe pre-injection deformity. Blood blisters were only encountered after manipulation of the more severe contractures. A total of 23 patients (8%) had a spontaneous rupture and 57 patients (19%) had a partial spontaneous rupture. Only 4.9% needed a second injection. We noticed a learning curve, with seven of the first 20 cords (35%) needing a second injection to achieve a satisfactory correction and then only seven (2.5%) in the rest. Level of evidence: IV
No evidence of transmission of chronic lymphocytic leukemia through blood transfusion
Authors: Hjalgrim Henrik , Rostgaard Klaus , Vasan Senthil K. , Ullum Henrik , Erikstrup Christian , Pedersen Ole B. V. , Nielsen Kaspar R. , Titlestad Kjell-Einar , Melbye Mads , Nyrén Olof , Edgren Gustaf 
Published: August 2015

Key Points
Transfusion recipients’ risk of CLL is not affected by postdonation CLL in donor. Recipient CLL does not cluster to individual donors, arguing against MBL transmission.
The effects of human Wharton’s jelly cell transplantation on the intervertebral disc in a canine disc degeneration model
Authors: Zhang Yan , Tao Hui , Gu Tao , Zhou Mingyue , Jia Zhiwei , Jiang Gangqiang , Chen Chun , Han Zhihua , Xu Cheng , Wang Deli , He Qing , Ruan Dike 
Published: August 2015

Abstract
Introduction
Cell-based therapy was a promising treatment method for disc degenerative diseases. Wharton’s jelly cell (WJC) has been explored to cure various human diseases, while it still remains unknown about this MSC for disc repair. In our prior work, WJCs could differentiate into nucleus pulposus (NP)-like cells by co-culturing with NP cells in vitro. Thence, the aim of this study was further to investigate the survival and function of WJCs in vivo after transplantation into degenerated canine discs.

Method
WJCs were isolated from human umbilical cords and labeled with EGFP. The degeneration of L4-5, L5-6, and L6-7 discs of beagles was induced by aspirating the NP tissues. Four weeks after the operation, the injured discs were left to be no treatment at L4-5 (DS group), injected with 0.9 % saline at L5-6 (FS group), and transplanted with EGFP-labeled WJCs at L6-7 (TS group). In all animals, the intact disc L3-4 served as a control (CS group). The animals were followed up for 24 weeks after initial operation. Spine imaging was evaluated at 4, 8, 12, and 24 weeks, respectively. Histologic, biomechanics and gene expression analyses were performed at 24 weeks. Immunohistochemistry for aggrecan, types II collagen, SOX-9 was employed to investigate the matrix formation in the NP.

Results
The TS group showed a significantly smaller reduction in the disc height and T2-weighted signal intensity, and a better spinal segmental stability than DS and FS groups. Histologic assay demonstrated that WJCs were specifically detected in TS group at 24 weeks and the discs of TS group maintained a relatively well preserved structure as compared to the discs of DS and FS groups. Furthermore, real-time PCR and immunohistochemistry demonstrated that expressions of disc matrix genes, aggrecan, type II collagen, and SOX-9, were up-regulated in TS group compared to DS and FS groups.

Conclusion
WJCs could not only survive in the degenerate IVDs, but also promote the disc matrix formation of aggrecan and type II collagen in the degenerate IVDs. It may have value in cell-based therapy for degenerative disc disease.
Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance)
Authors: Leonard John P. , Jung Sin-Ho , Johnson Jeffrey , Pitcher Brandelyn N. , Bartlett Nancy L. , Blum Kristie A. , Czuczman Myron , Giguere Jeffrey K. , Cheson Bruce D. 
Published: August 2015

PurposeLenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies.Patients and MethodsThe Cancer and Leukemia Group B (Alliance) 50401 trial is a randomized phase II trial studying rituximab (375 mg/m2weekly for 4 weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest, in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in cycles 2 to 12), or LR. The rituximab-alone arm was discontinued as a result of poor accrual. Eligibility included recurrent FL and prior rituximab with time to progression of ≥ 6 months from last dose. Aspirin or heparin was recommended for patients at high thrombosis risk.ResultsNinety-one patients (lenalidomide, n = 45; LR, n = 46) received treatment; median age was 63 years (range, 34 to 89 years), and 58% were intermediate or high risk according to the Follicular Lymphoma International Prognostic Index. In the lenalidomide and LR arms, grade 3 to 4 adverse events occurred in 58% and 53% of patients, with 9% and 11% of patients experiencing grade 4 toxicity, respectively; grade 3 to 4 adverse events included neutropenia (16% v 20%, respectively), fatigue (9% v 13%, respectively), and thrombosis (16% [n = 7] v 4% [n = 2], respectively; P = .157). Thirty-six percent of lenalidomide patients and 63% of LR patients completed 12 cycles. Lenalidomide alone was associated with more treatment failures, with 22% of patients discontinuing treatment as a result of adverse events. Dose-intensity exceeded 80% in both arms. Overall response rate was 53% (20% complete response) and 76% (39% complete response) for lenalidomide alone and LR, respectively (P = .029). At the median follow-up of 2.5 years, median time to progression was 1.1 year for lenalidomide alone and 2 years for LR (P = .0023).ConclusionLR is more active than lenalidomide alone in recurrent FL with similar toxicity, warranting further study in B-cell non-Hodgkin lymphoma as a platform for addition of novel agents.
Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study
Authors: Granfeldt Østgård Lene Sofie , Medeiros Bruno C. , Sengeløv Henrik , Nørgaard Mette , Andersen Mette Klarskov , Dufva Inge Høgh , Friis Lone Smidstrup , Kjeldsen Eigil , Marcher Claus Werenberg , Preiss Birgitte , Severinsen Marianne , Nørgaard Jan Maxwell 
Published: August 2015

Purpose Secondary and therapy-related acute myeloid leukemia (sAML and tAML, respectively) remain therapeutic challenges. Still, it is unclear whether their inferior outcome compared with de novo acute myeloid leukemia (AML) varies as a result of previous hematologic disease or can be explained by differences in karyotype and/or age. Patients and Methods In a Danish national population-based study of 3,055 unselected patients with AML diagnosed from 2000 to 2013, we compared the frequencies and characteristics of tAML, myelodysplastic syndrome (MDS) -sAML, and non-MDS-sAML (chronic myelomonocytic leukemia and myeloproliferative neoplasia) versus de novo AML. Limited to intensive therapy patients, we compared chance of complete remission by logistic regression analysis and used a pseudo-value approach to compare relative risk (RR) of death at 90 days, 1 year, and 3 years, overall and stratified by age and karyotype. Results were given crude and adjusted with 95% CIs. Results Overall, frequencies of sAML and tAML were 19.8% and 6.6%, respectively. sAML, but not tAML, was associated with low likelihood of receiving intensive treatment. Among intensive therapy patients (n = 1,567), antecedent myeloid disorder or prior cytotoxic exposure was associated with decreased complete remission rates and inferior survival (3-year adjusted RR for MDS-sAML, non-MDS-sAML, and tAML: RR, 1.14; 95% CI, 1.02 to 1.32; RR, 1.27; 95% CI, 1.16 to 1.34; and RR, 1.16; 95% CI, 1.03 to 1.32, respectively) compared with de novo AML. Among patients ≥ 60 years old and patients with adverse karyotype, previous MDS or tAML did not impact overall outcomes, whereas non-MDS-sAML was associated with inferior survival across age and cytogenetic risk groups (adverse risk cytogenetics: 1-year adjusted RR, 1.47; 95% CI, 1.23 to 1.76; patients ≥ 60 years old: 1-year adjusted RR, 1.31; 95% CI, 1.06 to 1.61). Conclusion Our results support that de novo AML, sAML, and tAML are biologically and prognostically distinct subtypes of AML. Patients with non-MDS-sAML have dismal outcomes, independent of age and cytogenetics. Previous myeloid disorder, age, and cytogenetics are crucial determinants of outcomes and should be integrated in treatment recommendations for these patients.
Cost-Effectiveness Analysis of Regorafenib for Metastatic Colorectal Cancer
Authors: Goldstein Daniel A. , Ahmad Bilal B. , Chen Qiushi , Ayer Turgay , Howard David H. , Lipscomb Joseph , El-Rayes Bassel F. , Flowers Christopher R. 
Published: August 2015

Purpose Regorafenib is a standard-care option for treatment-refractory metastatic colorectal cancer that increases median overall survival by 6 weeks compared with placebo. Given this small incremental clinical benefit, we evaluated the cost-effectiveness of regorafenib in the third-line setting for patients with metastatic colorectal cancer from the US payer perspective. Methods We developed a Markov model to compare the cost and effectiveness of regorafenib with those of placebo in the third-line treatment of metastatic colorectal cancer. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Drug costs were based on Medicare reimbursement rates in 2014. Model robustness was addressed in univariable and probabilistic sensitivity analyses. Results Regorafenib provided an additional 0.04 QALYs (0.13 life-years) at a cost of $40,000, resulting in an incremental cost-effectiveness ratio of $900,000 per QALY. The incremental cost-effectiveness ratio for regorafenib was > $550,000 per QALY in all of our univariable and probabilistic sensitivity analyses. Conclusion Regorafenib provides minimal incremental benefit at high incremental cost per QALY in the third-line management of metastatic colorectal cancer. The cost-effectiveness of regorafenib could be improved by the use of value-based pricing.
A Case for Conservative Management: Characterizing the Natural History of Radiographically Diagnosed Rathke Cleft Cysts
Authors: Culver Silas A. , Grober Yuval , Ornan David A. , Patrie James T. , Oldfield Edward H. , Jane John A. , Thorner Michael O. 
Published: August 2015

Context:
Rathke cleft cysts (RCCs) are benign embryonic remnants of the Rathke's pouch found in 13% to 33% of the general population. When symptomatic, they manifest themselves by compressing adjacent structures, causing pressure effects such as headache, visual disturbance, or pituitary hormone deficits. Most RCCs are asymptomatic, and their management remains controversial. Surgical resection has generally been indicated to treat symptomatic RCCs but carries the risk of complications.

Objective:
Our objective was to better characterize the outcomes for patients with presumed RCCs undergoing conservative management.

Design:
This was a retrospective cohort study.

Setting:
The setting was a pituitary program at a university medical center.

Participants:
The participants were 75 patients with radiographically diagnosed RCCs.

Methods:
All brain magnetic resonance imaging (MRI) scans performed at the University of Virginia from 2006 through 2013 were searched for the words “Rathke cleft cyst,” and pituitary clinic notes from 2007 to 2012 were reviewed for patients identified as probably having an RCC. Images for all patients were reviewed by the interpreting neuroradiologist, and those patients with at least 2 MRI scans were included. The dimensions of each cyst were assessed by the same neuroradiologist, and the volume of each cyst was analyzed as a function of the time from the first image obtained.

Results:
A total of 75 patients (4–76 years old) met our inclusion criteria. The length of follow-up was 1 to 126 months (median 24 months). In 43 patients (57%) no detectable change in the size of their cysts was seen, in 21 patients (28%) cysts increased in size, and in 11 patients (15%) cysts decreased in size. The predicted mean cyst growth rate was not significantly different from 0.

Conclusion:
The increasingly prevalent use of brain imaging modalities such as MRI has resulted in an increase in the incidental discovery of pituitary lesions. Our study demonstrates that the majority of radiologically diagnosed RCCs remain unchanged or decrease in size over time. These results suggest that, in the absence of pressure symptoms, it is reasonable to manage patients with RCCs conservatively.
Lasso, o dilema da estratégia de crescimento
Authors: Mendes Gabriel Aguiar , Leitão Fernanda Gomes , Façanha Karine Forte , Forte Sérgio Henrique Arruda Cavalcante 
Published: August 2015

Uma empresa do ramo de vestuário intimo se confronta com o seguinte questionamento: implantar um canal de vendas virtual como estratégia de crescimento, ou crescer no mercado tradicional?O propósito do caso é mostrar aos alunos o quanto é importante para um varejista, na atualidade, ter estratégias bem definidas de crescimento, bem como a importância dos canais de venda nessa estratégia.DOI: 10.12660/gvcasosv5n1c3http://dx.doi.org/10.12660/gvcasosv5n1c3
Gozzipi: empresa familiar frente ao mundo globalizado
Authors: Frey Eduardo Henrique , Braz Paulo Henrique da Cruz , Cruz Marcia Rohr , Olea Pelayo Munhoz , Frey Marlete Vargas , Camargo Maria Emilia 
Published: August 2015

Vender ou resistir: que estratégia pode adotar uma tradicional empresa familiar diante do assédio de uma multinacional? O caso discute a estratégia de duas empresas que competem no mesmo mercado, uma familiar e outra multinacional. O conteúdo explora a visão estratégica de cada uma delas e mostra a história da empresa familiar e o dilema de manter-se ou ceder ao assédio da empresa multinacional na disputa pelo mercado. DOI: 10.12660/gvcasosv5n1c5http://dx.doi.org/10.12660/gvcasosv5n1c5