bluuebunny/crossref_metadata_2025_split huggingface dataset:
Environmental geochemistry of the Hycroft Mine: a case study on the limitation of Sobek-style acid-generation predictions
Authors: Prestia Amy , Bowell Robert , Warrender Ruth , Barnes Andrew , Lassiter Deborah 
Published: July 2013

The Hycroft Mine is an open pit gold mine situated along the eastern edge of the Black Rock Desert in NW Nevada, a semi-arid region where annual evaporation significantly exceeds precipitation. The Hycroft deposit is hosted in volcanic breccias and conglomerates of the Tertiary Kamma Mountain volcanic group that have been faulted by north-trending structures that acted as conduits for hydrothermal fluids. An acid-leaching event resulted in the development of vuggy, quartz alunite-altered zones produced by the removal of most minerals, including those capable of buffering acid. Accessory minerals associated with the acid leach zones are rare, except native sulphur which is locally abundant. The complex sulphur mineralogy of the Hycroft deposit, coupled with the deficiency of acid-neutralizing minerals, limits the application of traditional Sobek-style Acid-Base Accounting (ABA) methods that rely upon sulphur speciation data to predict acid-generation potential. A comparison of results from geochemical predictive tests including the modified Sobek ABA method, Net Acid Generation (NAG) test and kinetic humidity cell test (HCT) illustrates the complexity of interpreting ABA data for material containing native sulphur and low solubility sulphate minerals such as alunite.
Comparing ABA data to HCT results shows the predictions of acid generation from the ABA test are not consistent with those from the HCT, which is considered a more definitive test for the prediction of acid and metals mobility. The results of this study indicate the ABA test does not provide a reliable prediction of acid generation for samples containing native sulphur and low solubility sulphate minerals. A reasonably good correlation is, however, observed between the HCT and NAG results, suggesting the NAG test is a more effective tool for predicting the geochemical behavior of the Hycroft deposit, and potentially also other deposits with complex sulphur mineralogy. The presence of native sulphur in the acid leach material presents additional challenges with respect to acid-generation prediction due to the unique properties of this mineral. Although acid generation is predicted from the NAG test for samples containing native sulphur, the actual amount of acid and metal release generated by this mechanism in the HCT is limited in comparison to that associated with natural pyrite oxidation, which is the main contributor to acid rock drainage. The potential for acid generation from this mechanism is further limited by the semi-arid site conditions that are unlikely to produce conditions similar to the humidity cell tests that are designed to accelerate the weathering process and enhance mineral-water reaction rates. This study demonstrates the importance of considering the site-specific mineralogical characteristics of the deposit in the selection of the most appropriate geochemical test methods to use in the prediction of potential acid generation.
Mesenchymal CD44 Expression Contributes to the Acquisition of an Activated Fibroblast Phenotype via TWIST Activation in the Tumor Microenvironment
Authors: Spaeth Erika L. , Labaff Adam M. , Toole Bryan P. , Klopp Ann , Andreeff Michael , Marini Frank C. 
Published: July 2013

Abstract
Tumor–stroma interactions play a crucial role in cancer progression by eliciting factors that promote proliferative, angiogenic, and invasive supports to the tumor microenvironment. Mesenchymal stromal/stem cells (MSC) contribute to stroma in part as cancer-associated fibroblasts (CAF), but a complete understanding of how MSC contribute to the tumor stroma is lacking. In this study, we show how CAF phenotypes rely upon MSC expression of the multifunctional cell surface glycoprotein CD44, a putative stem cell marker. Through bone marrow transplantation experiments in a transgenic mouse model of cancer, we determined that CD44 deficiency leads to a relative reduction in the contribution of bone marrow–derived cells to tumor stroma. CD44 attenuation in MSC limited their expression of CAF markers induced by tumor conditioning, and these MSC migrated poorly and provided weak angiogenic support compared with wild-type MSC. These defects were linked to deficiencies in the ability of CD44-attenuated MSC to transcriptionally upregulate Twist expression. Together, our results establish that CD44 expression contributes to critical functions in the tumor stroma. Cancer Res; 73(17); 5347–59. ©2013 AACR.
Generation of Tumor Antigen-Specific T Cell Lines from Pediatric Patients with Acute Lymphoblastic Leukemia—Implications for Immunotherapy
Authors: Weber Gerrit , Caruana Ignazio , Rouce Rayne H. , Barrett A. John , Gerdemann Ulrike , Leen Ann M. , Rabin Karen R. , Bollard Catherine M. 
Published: July 2013

Abstract
Purpose: Although modern cure rates for childhood acute lymphoblastic leukemia (ALL) exceed 80%, the outlook remains poor in patients with high-risk disease and those who relapse, especially when allogeneic hematopoietic stem cell transplantation is not feasible. Strategies to improve outcome and prevent relapse are therefore required. Immunotherapy with antigen-specific T cells can have antileukemic activity without the toxicities seen with intensive chemotherapy, and therefore represents an attractive strategy to improve the outcome of high-risk patients with ALL. We explored the feasibility of generating tumor antigen-specific T cells ex vivo from the peripheral blood of 50 patients with ALL [26 National Cancer Institute (NCI) high-risk and 24 standard-risk] receiving maintenance therapy.
Experimental Design: Peripheral blood mononuclear cells were stimulated with autologous dendritic cells pulsed with complete peptide libraries of WT1, Survivin, MAGE-A3, and PRAME, antigens frequently expressed on ALL blasts.
Results: T-cell lines were successfully expanded from all patients, despite low lymphocyte counts and irrespective of NCI risk group. Antigen-specificity was observed in more than 50% of patients after the initial stimulation and increased to more than 90% after three stimulations as assessed in IFN-γ-enzyme-linked immunospot (ELISpot) and 51Cr-release assays. Moreover, tumor-specific responses were observed by reduction of autologous leukemia blasts in short- and long-term coculture experiments.
Conclusion: This study supports the use of immunotherapy with adoptively transferred autologous tumor antigen-specific T cells to prevent relapse and improve the prognosis of patients with high-risk ALL. Clin Cancer Res; 19(18); 5079–91. ©2013 AACR.
Chk1/2 Inhibition Overcomes the Cisplatin Resistance of Head and Neck Cancer Cells Secondary to the Loss of Functional p53
Authors: Gadhikar Mayur A. , Sciuto Maria Rita , Alves Marcus Vinicius Ortega , Pickering Curtis R. , Osman Abdullah A. , Neskey David M. , Zhao Mei , Fitzgerald Alison L. , Myers Jeffrey N. , Frederick Mitchell J. 
Published: July 2013

Abstract
Despite the use of multimodality therapy using cisplatin to treat patients with advanced stage squamous cell carcinoma of the head and neck (HNSCC), there is an unacceptably high rate of treatment failure. TP53 is the most commonly mutated gene in HNSCC, and the impact of p53 mutation on response to cisplatin treatment is poorly understood. Here, we show unambiguously that wild-type TP53 (wtp53) is associated with sensitivity of HNSCC cells to cisplatin treatment, whereas mutation or loss of TP53 is associated with cisplatin resistance. We also show that senescence is the major cellular response to cisplatin in wtp53 HNSCC cells and that cisplatin resistance in p53-null or -mutant TP53 cells is due to their lack of senescence. Given the dependence on checkpoint kinase (Chk)1/2 kinases to mediate the DNA damage response in p53-deficient cells, there is potential to exploit this to therapeutic advantage through targeted inhibition of the Chk1/2 kinases. Treatment of p53-deficient HNSCC cells with the Chk inhibitor AZD7762 sensitizes them to cisplatin through induction of mitotic cell death. This is the first report showing the ability of a Chk kinase inhibitor to sensitize TP53-deficient HNSCC to cisplatin in a synthetic lethal manner, which has significance given the frequency of TP53 mutations in this disease and because cisplatin has become part of standard therapy for aggressive HNSCC tumors. These preclinical data provide evidence that a personalized approach to the treatment of HNSCC based on Chk inhibition in p53-mutant tumors may be feasible. Mol Cancer Ther; 12(9); 1860–73. ©2013 AACR.
Comparative Tolerability and Harms of Individual Statins
Authors: Naci Huseyin , Brugts Jasper , Ades Tony 
Published: July 2013

Background—
Our objective was to estimate the comparative harms of individual statins using both placebo-controlled and active-comparator trials.

Methods and Results—
We systematically reviewed randomized trials evaluating different statins in participants with and without cardiovascular disease. We performed random-effects pairwise and network meta-analyses to quantify the relative harms of individual statins. We included 55 two-armed placebo-controlled and 80 two- or multiarmed active-comparator trials including 246 955 individuals. According to pairwise meta-analyses, individual statins were not different than control in terms of myalgia, creatine kinase elevation, cancer, and discontinuations because of adverse events. Statins as a class resulted in significantly higher odds of diabetes mellitus (odds ratio, 1.09; 95% confidence interval, 1.02–1.16) and transaminase elevations (odds ratio, 1.51; 95% confidence interval, 1.24–1.84) compared with control. When individual statins were compared in network meta-analyses, there were numerous statistically detectable differences, favoring simvastatin and pravastatin. According to dose-level comparisons, individual statins resulted in higher odds of discontinuations with higher doses of atorvastatin and rosuvastatin. Similarly, higher doses of atorvasatin, fluvastatin, lovastatin, and simvastatin were associated with higher odds of transaminase elevations. Simvastatin at its highest doses was associated with creatine kinase elevations (odds ratio, 4.14; 95% credible interval, 1.08–16.24). Meta-regression analyses adjusting for study-level age at baseline, low-density lipoprotein cholesterol level, and publication year did not explain heterogeneity. There was no detectable inconsistency in the network.

Conclusions—
As a class, adverse events associated with statin therapy are not common. Statins are not associated with cancer risk but do result in a higher odds of diabetes mellitus. Among individual statins, simvastatin and pravastatin seem safer and more tolerable than other statins.
Transcatheter Aortic Valve Replacement in Nonsurgical Candidates With Severe, Symptomatic Aortic Stenosis
Authors: Simons Cyrena T. , Cipriano Lauren E. , Shah Rashmee U. , Garber Alan M. , Owens Douglas K. , Hlatky Mark A. 
Published: July 2013

Background—
Transcatheter aortic valve replacement (TAVR) seems to improve the survival and quality of life of patients with aortic stenosis ineligible for surgical aortic valve replacement.

Methods and Results—
We used a decision analytic Markov model to estimate lifetime costs and benefits in a hypothetical cohort of patients with severe, symptomatic aortic stenosis who were ineligible for surgical aortic valve replacement. The model compared transfemoral TAVR with medical management and was calibrated to the Placement of Aortic Transcatheter Valves (PARTNER) trial. TAVR increased life expectancy from 2.08 to 2.93 years and quality-adjusted life expectancy from 1.19 to 1.93 years. TAVR also reduced subsequent hospitalizations by 1.40 but increased complications, particularly stroke (from 1% to 11% lifetime risk), and also increased lifetime costs from $83 600 to $1 69 100. The incremental cost-effectiveness of TAVR was $1 16 500 per quality-adjusted life-year gained ($99 900 per life-year gained). Results were robust to reasonable changes in individual variables but were sensitive to the level of annual healthcare costs caused by noncardiac diseases and to the projected life expectancy of medically treated patients.

Conclusions—
TAVR seems to be an effective but somewhat expensive alternative to medical management among patients with symptomatic aortic stenosis ineligible for surgery. TAVR is more cost-effective for patients with a lower burden of noncardiac disease.
Toll-Like Receptor 4 Antagonist Attenuates Intracerebral Hemorrhage–Induced Brain Injury
Authors: Wang Yan-Chun , Wang Peng-Fei , Fang Huang , Chen Jing , Xiong Xiao-Yi , Yang Qing-Wu 
Published: July 2013

Background and Purpose—
Accumulating evidence indicates that inflammatory responses cause secondary injury after intracerebral hemorrhage (ICH). We recently demonstrated the involvement of toll-like receptor 4 (TLR4) signaling in these processes. The purpose of the current study was to investigate the protective effect and mechanism of TAK-242 (Ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1 -carboxylate, Takeda), a TLR4 antagonist, in an ICH mouse model.

Methods—
TAK-242 was intraperitoneally injected 6 hours after ICH once daily for 5 successive days. We assessed neurological deficit scores; changes in brain water content; and levels of inflammatory factors, DNA damage, and neuronal degeneration in perihematomal region 1, 3, and 5 days after ICH. Peripheral inflammatory cell infiltration was determined using flow cytometry; and the expression of TLR4 downstream signaling molecules was assessed by Western blot.

Results—
TAK-242 significantly reduced brain water content, neurological deficit scores, and levels of inflammatory factors. The levels of DNA damage and neuronal degeneration were also significantly decreased, as was peripheral inflammatory cell infiltration. The expression of TLR4 downstream signaling molecules, including myeloid differentiation primary response gene 88, toll/IR-1(TIR)-domain-containing adaptor protein inducing interferon-beta IκBα, nuclear factor-κBp65, and phosphorylated nuclear factor-κBp65, was significantly downregulated.

Conclusions—
The results suggest that TLR4 antagonist reduced inflammatory injury and neurological deficits in a mouse model of ICH. The mechanism may involve decreased expression of signaling molecules downstream of TLR4.
Twenty-Four-Year Trends in the Incidence of Ischemic Stroke in Sweden From 1987 to 2010
Authors: Rosengren Annika , Giang Kok Wai , Lappas Georgios , Jern Christina , Torén Kjell , Björck Lena 
Published: July 2013

Background and Purpose—
The incidence of stroke in Sweden increased between 1989 and 2000 among people aged ≤65 years, but more recent data on those aged >65 years are lacking.

Methods—
Through the Swedish Hospital Discharge and Cause of Death registries, we identified all cases of nonfatal and fatal ischemic stroke (IS) among people aged 18 to 84 years during 1987–2010 in Sweden.

Results—
Of the 391 081 stroke cases identified, 1.6% were 18 to 44 years, 16.7% were 45 to 64 years, and 81.7% were 65 to 84 years. Among people aged 18 to 44 years, there was a continuous increase in the incidence of stroke of 1.3% (95% confidence interval, 0.8%–1.8%) per year for men and 1.6% (1.0%–2.3%) per year for women. Among men and women aged 45 to 64 years, slightly declining rates were observed from the late 1990s, with a mean annual decrease of 0.4% (0.1%–0.7%) among men and 0.6% (0.2%–1.0%) among women. Among men aged 65 to 84 years, a decrease of 3.7% in IS (3.4%–4.0%) per year was observed from the late 1990s. This was more marked in women, where an initial decrease of 2.5% (2.1%–2.9%) per year was followed by an accelerated decrease of 5.1% (4.4%–5.8%) after 2005. Mortality from IS decreased markedly in all age groups.

Conclusions—
The incidence of IS in elderly people in Sweden is now decreasing, whereas the decline in IS incidence in the middle-aged people is much less steep. The increasing incidence of stroke in the young, particularly if carried forward to an older age, is concerning.
Timeliness of Intravenous Thrombolysis via Telestroke in Georgia
Authors: Bruno Askiel , Lanning Katherine M. , Gross Hartmut , Hess David C. , Nichols Fenwick T. , Switzer Jeffrey A. 
Published: July 2013

Background and Purpose—
Through 2-way live video and audio communication, telestroke enhances urgent treatment of patients with acute stroke in emergency departments (EDs) without immediate access to on-site specialists. To assess for opportunities to shorten the door to thrombolysis time, we measured multiple time intervals in a telestroke system.

Methods—
We retrospectively analyzed 115 records of consecutive acute stroke patients treated with intravenous thrombolysis during a 20-month period via a statewide telestroke system in 17 EDs in Georgia. On the basis of times documented in the telestroke system, we calculated the time elapsed between the following events: ED arrival, telestroke patient registration, start of specialist consultation, head computed tomography, thrombolysis recommendation, and thrombolysis initiation.

Results—
The most conspicuous delay was from ED arrival to telestroke patient registration (median, 39 minutes; interquartile range, 21–56). Median time from ED arrival to thrombolysis initiation was 88 minutes, interquartile range 75 to 105. Thrombolysis was initiated within 60 minutes from ED arrival in 13% of patients.

Conclusions—
The greatest opportunity to expedite acute thrombolysis via telestroke is by shortening the time from ED arrival to telestroke patient registration.
Spatial Averaging of HF Radar Data for Wave Measurement Applications
Authors: Wyatt Lucy R. , Jaffrés Jasmine B. D. , Heron Mal L. 
Published: July 2013

Abstract
HF radar data are often collected for time periods that are optimized for current measurement applications where, in many cases, very high temporal resolution is needed. Previous work has demonstrated that this does not provide sufficient averaging for robust wave measurements to be made. It was shown that improvements could be made by averaging the radar data for longer time periods. HF radar provides measurements over space as well as in time, so there is also the possibility to average in space. However, the radar data are correlated in space because of the range and azimuth processing. The implications of this are discussed and estimates of the impact on the reduction in variance in the radar Doppler spectral estimates are obtained. Spatial inhomogeneities and temporal nonstationarity in the ocean wave field itself also need to be taken into account. It is suggested that temporal averaging over periods of up to one hour and spatial averaging over 9–25 nearest neighbors may be suitable, and these will be explored in later work.
A Diabatic Lagrangian Technique for the Analysis of Convective Storms. Part II: Application to a Radar-Observed Storm
Authors: Ziegler Conrad L. 
Published: July 2013

Abstract
A new diabatic Lagrangian analysis (DLA) technique that derives predicted fields of potential temperature, water vapor and cloud water mixing ratios, and virtual buoyancy from three-dimensional, time-dependent wind and reflectivity fields (see Part I) is applied to the radar-observed 9 June 2009 supercell storm during the Second Verification of the Origins of Rotation in Tornadoes Experiment (VORTEX2). The DLA diagnoses fields of rain and graupel content from radar reflectivity and predicts the evolution of analysis variables following radar-inferred air trajectories in the evolving storm with application of the diagnosed precipitation fields to calculate Lagrangian-frame microphysical processes. Simple damping and surface flux terms and initialization of trajectories from heterogeneous, parametric mesoscale analysis fields are also included in the predictive Lagrangian calculations. The DLA output compares favorably with observations of surface in situ temperature and water vapor mixing ratio and accumulated rainfall from a catchment rain gauge in the 9 June 2009 storm.
Negotiating Site-Based Management and Expanded Teacher Decision Making
Authors: Mayer Anysia Peni , Donaldson Morgaen L. , LeChasseur Kimberly , Welton Anjalé D. , Cobb Casey D. 
Published: July 2013

Purpose: This article presents findings from a study of six schools in the Together Initiative (TI), which facilitates increased school autonomy from districts and expands teacher decision-making authority. This study aims to understand how TI’s theory of action changed structures, cultures, and agency as the concepts of site-based management and expanded teacher decision making were interpreted and implemented by district and school leaders and teachers. Research Design: Data were collected over the first 2 years of the initiative using a concurrent mixed-methods design. Field notes from more than 200 hours of observations and transcripts of 231 semistructured interviews with stakeholders were coded using the constant-comparative method. Findings from qualitative data were triangulated with annual teacher survey findings. Findings: Implementation of TI varied across the six schools and depended greatly on school staffs’ existing relationships the district, principal support for decision-making structures, and the extent to which school cultures reflected trust and teachers were able to enact greater agency. Only two schools experienced moderate increases in site-based management and expanded teacher decision making; those that did not were missing at least one of these structural or cultural supports. Conclusions: At a time when charter schools are touted as an effective reform model, this article informs policy and practice on the original charter concept—autonomous, innovative district schools. Our findings suggest that creating contexts where site-based management can flourish is far more complicated than changing structures or establishing supportive school cultures.
Extracorporeal membrane oxygenation in adults: experience from the Middle East
Authors: Sajjad Mohammad , Osman Ahmed , Mohsen Salah , Alanazi Mosleh , Ugurlucan Murat , Canver Charles 
Published: July 2013

Background: The literature reports conflicting results for survival after extracorporeal membrane oxygenator support, and survival differs in pediatric and adult patients. We present our institutional experience of adult extracorporeal membrane oxygenator support. Methods: From January 2007 to December 2009, 19 adult patients required extracorporeal membrane oxygenator support after cardiac surgery or catheter interventions. It was provided on an emergency basis to 11 patients, urgently to 5, and electively to 3. Indications included post-cardiotomy cardiogenic shock, post-cardiotomy acute respiratory failure, emergency cardiac resuscitation, and post-percutaneous coronary intervention cardiogenic shock. The mean duration of support was 4 days (range, 1–11 days). Results: Seven (36.84%) patients could be weaned off extracorporeal membrane oxygenator support; one (14.28%) of them survived to hospital discharge and the other 6 (85.71%) died in hospital. Twelve (63.15%) patients could not be weaned off and died while still on extracorporeal membrane oxygenator support. Overall 30-day hospital mortality was 94.73%, and survival to discharge was 5.26%. Conclusion: Our institutional experience of extracorporeal membrane oxygenator support for cardiac indications in adult patients indicates poor survival. It significantly increased costs by delaying imminent death and prolonging stay in the intensive care unit.