bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory Monocyte Mobilization Decreases Patient Survival in Pancreatic Cancer: A Role for Targeting the CCL2/CCR2 Axis
Authors: Sanford Dominic E. , Belt Brian A. , Panni Roheena Z. , Mayer Allese , Deshpande Anjali D. , Carpenter Danielle , Mitchem Jonathan B. , Plambeck-Suess Stacey M. , Worley Lori A. , Goetz Brian D. , Wang-Gillam Andrea , Eberlein Timothy J. , Denardo David G. , Goedegebuure Simon Peter , Linehan David C. 
Published: May 2013

Abstract
Purpose: To determine the role of the CCL2/CCR2 axis and inflammatory monocytes (CCR2+/CD14+) as immunotherapeutic targets in the treatment of pancreatic cancer.
Experimental Design: Survival analysis was conducted to determine if the prevalence of preoperative blood monocytes correlates with survival in patients with pancreatic cancer following tumor resection. Inflammatory monocyte prevalence in the blood and bone marrow of patients with pancreatic cancer and controls was compared. The immunosuppressive properties of inflammatory monocytes and macrophages in the blood and tumors, respectively, of patients with pancreatic cancer were assessed. CCL2 expression by human pancreatic cancer tumors was compared with normal pancreas. A novel CCR2 inhibitor (PF-04136309) was tested in an orthotopic model of murine pancreatic cancer.
Results: Monocyte prevalence in the peripheral blood correlates inversely with survival, and low monocyte prevalence is an independent predictor of increased survival in patients with pancreatic cancer with resected tumors. Inflammatory monocytes are increased in the blood and decreased in the bone marrow of patients with pancreatic cancer compared with controls. An increased ratio of inflammatory monocytes in the blood versus the bone marrow is a novel predictor of decreased patient survival following tumor resection. Human pancreatic cancer produces CCL2, and immunosuppressive CCR2+ macrophages infiltrate these tumors. Patients with tumors that exhibit high CCL2 expression/low CD8 T-cell infiltrate have significantly decreased survival. In mice, CCR2 blockade depletes inflammatory monocytes and macrophages from the primary tumor and premetastatic liver resulting in enhanced antitumor immunity, decreased tumor growth, and reduced metastasis.
Conclusions: Inflammatory monocyte recruitment is critical to pancreatic cancer progression, and targeting CCR2 may be an effective immunotherapeutic strategy in this disease. Clin Cancer Res; 19(13); 3404–15. ©2013 AACR.
Dalfampridine Improves Sensorimotor Function in Rats With Chronic Deficits After Middle Cerebral Artery Occlusion
Authors: Iaci Jennifer F. , Parry Tom J. , Huang Zhihong , Finklestein Seth P. , Ren JingMei , Barrile Dana K. , Davenport Matthew D. , Wu Rui , Blight Andrew R. , Caggiano Anthony O. 
Published: May 2013

Background and Purpose—
Stroke survivors often have permanent deficits that are only partially addressed by physical therapy. This study evaluated the effects of dalfampridine, a potassium channel blocker, on persistent sensorimotor deficits in rats with treatment initiated 4 or 8 weeks after stroke.

Methods—
Rats underwent permanent middle cerebral artery occlusion. Sensorimotor function was measured using limb-placing and body-swing symmetry tests, which normally show a partial recovery from initial deficits that plateaus ≈4 weeks after permanent middle cerebral artery occlusion. Dalfampridine was administered starting at 4 or 8 weeks after permanent middle cerebral artery occlusion in 2 blinded, vehicle-controlled studies. Plasma samples were collected and brain tissue was processed for histologic assessment.

Results—
Dalfampridine treatment (0.5–2.0 mg/kg) improved forelimb- and hindlimb-placing responses and body-swing symmetry in a reversible and dose-dependent manner. Plasma dalfampridine concentrations correlated with dose. Brain infarct volumes showed no differences between treatment groups.

Conclusions—
Dalfampridine improves sensorimotor function in the rat permanent middle cerebral artery occlusion model. Dalfampridine extended-release tablets (prolonged release fampridine outside the United States) are used to improve walking in patients with multiple sclerosis, and these preclinical data provide a strong rationale for examining the potential of dalfampridine to treat chronic stable deficits in stroke patients.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01605825
Impact of Acute Cocaine Use on Aneurysmal Subarachnoid Hemorrhage
Authors: Chang Tiffany R. , Kowalski Robert G. , Caserta Filissa , Carhuapoma Juan Ricardo , Tamargo Rafael J. , Naval Neeraj S. 
Published: May 2013

Background and Purpose—
Acute cocaine use has been temporally associated with aneurysmal subarachnoid hemorrhage (aSAH). This study analyzes the impact of cocaine use on patient presentation, complications, and outcomes.

Methods—
Data of patients admitted with aSAH between 1991 and 2009 were reviewed to determine impact of acute cocaine use (C). These patients were compared with aSAH patients without recent cocaine exposure (NC) in relation to their presentation, complications such as aneurysmal rerupture and delayed cerebral ischemia, and outcomes including hospital mortality and functional outcome.

Results—

Data of 1134 aSAH patients were reviewed; 142 patients (12.5%) had associated cocaine use. Cocaine users were more likely to be younger (mean age: C, 49±11; NC, 53±14;
P
<0.001). There were no differences in rates of poor-grade Hunt and Hess (4–5); (C, 21%; NC, 26%;
P
>0.05), associated intraventricular hemorrhage (C, 56%; NC, 51%;
P
>0.05), or hydrocephalus on admission Head CT (C, 49%; NC, 52%;
P
>0.05). Aneurysm rerupture incidence was higher among cocaine users (C, 7.7%; NC, 2.7%;
P
<0.05). The association of cocaine use with higher risk of delayed cerebral ischemia (C, 22%; NC, 16%;
P
<0.05) was not significant after correcting for other factors. Cocaine users were less likely to survive hospitalization compared with nonusers (mortality: C, 26%; NC, 17%;
P
<0.05); the adjusted odds of hospital mortality were 2.9 times higher among cocaine users (
P
<0.001). There were no differences in functional outcomes between the 2 groups.

Conclusions—
Acute cocaine use was associated with a higher risk of aneurysm rerupture and hospital mortality after aSAH.
Hindcast of the 1976/77 and 1998/99 Climate Shifts in the Pacific
Authors: Ding Hui , Greatbatch Richard J. , Latif Mojib , Park Wonsun , Gerdes Rüdiger 
Published: May 2013

Abstract
The use of a coupled ocean–atmosphere–sea ice model to hindcast (i.e., historical forecast) recent climate variability is described and illustrated for the cases of the 1976/77 and 1998/99 climate shift events in the Pacific. The initialization is achieved by running the coupled model in partially coupled mode whereby global observed wind stress anomalies are used to drive the ocean/sea ice component of the coupled model while maintaining the thermodynamic coupling between the ocean/sea ice and atmosphere components. Here it is shown that hindcast experiments can successfully capture many features associated with the 1976/77 and 1998/99 climate shifts. For instance, hindcast experiments started from the beginning of 1976 can capture sea surface temperature (SST) warming in the central-eastern equatorial Pacific and the positive phase of the Pacific decadal oscillation (PDO) throughout the 9 years following the 1976/77 climate shift, including the deepening of the Aleutian low pressure system. Hindcast experiments started from the beginning of 1998 can also capture part of the anomalous conditions during the 4 years after the 1998/99 climate. The authors argue that the dynamical adjustment of heat content anomalies that are present in the initial conditions in the tropics is important for the successful hindcast of the two climate shifts.
Frequency Domain Multimodel Analysis of the Response of Atlantic Meridional Overturning Circulation to Surface Forcing
Authors: MacMartin Douglas G. , Tziperman Eli , Zanna Laure 
Published: May 2013

Abstract
The dynamics of the Atlantic meridional overturning circulation (AMOC) vary considerably among different climate models; for example, some models show clear peaks in their power spectra while others do not. To elucidate these model differences, transfer functions are used to estimate the frequency domain relationship between surface forcing fields, including sea surface temperature, salinity, and wind stress, and the resulting AMOC response. These are estimated from the outputs of the Coupled Model Intercomparison Project phase 5 (CMIP5) and phase 3 (CMIP3) control runs for eight different models, with a specific focus on Geophysical Fluid Dynamics Laboratory Climate Model, version 2.1 (GFDL CM2.1), and the Community Climate System Model, version 4 (CCSM4), which exhibit rather different spectral behavior. The transfer functions show very little agreement among models for any of the pairs of variables considered, suggesting the existence of systematic model errors and that considerable uncertainty in the simulation of AMOC in current climate models remains. However, a robust feature of the frequency domain analysis is that models with spectral peaks in their AMOC correspond to those in which AMOC variability is more strongly excited by high-latitude surface perturbations that have periods corresponding to the frequency of the spectral peaks. This explains why different models exhibit such different AMOC variability. These differences would not be evident without using a method that explicitly computes the frequency dependence rather than a priori assuming a particular functional form. Finally, transfer functions are used to evaluate two proposed physical mechanisms for model differences in AMOC variability: differences in Labrador Sea stratification and excitation by westward-propagating subsurface Rossby waves.
Regional, Very Heavy Daily Precipitation in CMIP5 Simulations
Authors: Kawazoe Sho , Gutowski William J. 
Published: May 2013

Abstract
The authors analyze the ability of global climate models (GCMs) from phase 5 of the Coupled Model Intercomparison Project (CMIP5) multimodel ensemble to simulate very heavy daily precipitation and its supporting processes, comparing them with observations. Their analysis focuses on an upper Mississippi region for winter (December–February), when it is assumed that resolved synoptic circulation governs precipitation. CMIP5 GCMs generally reproduce well the precipitation versus intensity spectrum seen in observations to intensities as strong as 20 mm day−1. Most models do not produce the highest precipitation intensities seen in observations. Models show good agreement at the 95th percentile, while the coarsest resolution models generally show lower precipitation at high-intensity thresholds, such as the 99.5th percentile. There is no dominant month for simulated very heavy events to occur, although observed very heavy events occur most frequently in December. Further analysis focuses on precipitation events exceeding the 99.5th percentile that occur simultaneously at several points in the region, yielding so-called “widespread events.” Examination of additional fields during widespread very heavy events shows that the models produce these events under the same physical conditions seen in the observations. The coarsest models generally produce similar behavior, although features have smoother spatial distributions. However, the resolution in itself could not be identified as a major reason that separates one model from another. The capabilities of the CMIP5 GCMs examined here support using them to assess changes in very heavy precipitation under future climate scenarios.
Spatiotemporal Variation in Cross-Shelf Exchange across the Inner Shelf of Monterey Bay, California
Authors: Woodson C. Brock 
Published: May 2013

AbstractCross-shelf exchange resulting from wind- and wave-driven flows across the inner shelf has been the focus of a considerable body of work. This contribution extends recent analyses to the central California coastline using 5-yr of moored current observations. Acoustic Doppler Current Profiler (ADCP) data from stations across the Monterey Bay (two in the northern bay and one in the southern bay), in water depths of ~20 m, showed net offshore transport throughout the year. For the northern bay sites, cross-shelf exchange was dominated by Ekman transport driven by along-shelf diurnal sea breezes during the upwelling season. Intense stratification in the northern bay leads to very shallow observed Ekman layers (~5–8 m), and consequently no overlap between bottom and surface Ekman layers within a few hundred meters of the coast. The total transport is less than predicted by theory consistent with models of shallow-water Ekman transport. The observed transport (~42% of full Ekman transport) is shown to be caused by the influence of a positive vorticity that effectively increases the Coriolis parameter. Wave-driven return flow estimated from an offshore buoy was strongly correlated with observed transport during nonupwelling conditions for the northern, outer bay site, but not for the two inner bay sites (northern and southern). In the southern bay, winds and waves have a significantly reduced effect on the cross-shelf exchange. Internal tidal bores are believed to contribute most of the observed cross-shelf exchange in this region.
Therapeutic drug monitoring of mycophenolate mofetil for the treatment of severely active lupus nephritis
Authors: Kittanamongkolchai W , Rukrung C , Supasiri T , Lertjirachai I , Somparn P , Chariyavilaskul P , Avihingsanon Y 
Published: May 2013

Background Plasma mycophenolic acid (MPA) concentrations may predict therapeutic response in active lupus nephritis (LN). We determined the efficacy and safety of a concentration-controlled MPA regime in the treatment of severely active LN. Methods In this prospective study, 19 biopsy-proven class III/IV LN patients were treated with mycophenolate mofetil (MMF) for 48 weeks. The MMF dosage was based on maximal plasma MPA concentration at 1-hour post dose (MPA-C1). All patients had plasma MPA-C1 levels monitored weekly until achieving the targeted level of >13 mg/L. A low-dose steroid protocol was started at 0.5 mg/kg/day and rapidly tapered to 5 mg/day. Therapeutic response was evaluated at week 24 and week 48. MPA area-under-the curve (MPA-AUC0–12h) was measured at week 12 to verify the optimum dosage. Results No death or end-stage kidney disease occurred in this study. Seventeen patients (89%) responded to therapy at week 24 with four (21%) patients having complete response. There was no renal relapse at week 48 and four more patients had converted from partial response to complete response. Seventy eight percent of patients achieved the recommended MPA-AUC0–12h level. No association between plasma MPA concentrations and adverse reactions or infections was found. Conclusions MPA-C1 may be a practical monitoring of MPA levels in patients with LN. It is convenient to monitor and may facilitate an optimum estimate of MPA exposure.
Clinical impact of early brain atrophy in clinically isolated syndromes
Authors: Pérez-Miralles F , Sastre-Garriga J , Tintoré M , Arrambide G , Nos C , Perkal H , Río J , Edo MC , Horga A , Castilló J , Auger C , Huerga E , Rovira A , Montalban X 
Published: May 2013

Background: The impact of global and tissue-specific brain atrophy on conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS) is not fully gauged. Objectives: We aimed to determine the magnitude and clinical relevance of brain volume dynamics in the first year after a CIS. Methods: We assessed 176 patients with CIS within 3 months of onset, clinically and by conventional magnetic resonance imaging (MRI) scans, at baseline and 1 year after clinical onset. We determined the percentage of brain volume change (PBVC) and the brain parenchymal (BPF), grey matter (GMF) and white matter (WMF) fractions. Results: The mean follow-up time was 53 months (SD = 16.8): 76 patients (43%) experienced a second attack, 32 (18%) fulfilled MRI-only 2005 McDonald criteria and 68 (39%) remained as CIS. Statistically significant decreases in the volume measures tested were observed in patients with a second attack, for BPF and PBVC; in both MS groups for GMF; whereas in all groups, the WMF was unchanged. Patients with a second attack had larger PBVC decreases (− 0.65% versus + 0.059%; p < 0.001). PBVC decreases below − 0.817% independently predicted shorter times to a second attack. Conclusions: Global brain and grey matter volume loss occurred within the first year after a CIS; brain volume loss predicted conversion to MS.
In Situ Aortobiiliac Reconstruction of Infected Aneurysm Using a Single Superficial Femoral Vein
Authors: Grass Fabian , Deglise Sébastien , Corpataux Jean-Marc , Saucy François 
Published: May 2013

Objective: To demonstrate successful in situ aortoiliac reconstruction of an infected infrarenal aneurysm using one single superficial femoral vein (SFV). Methods: In situ reconstruction using the right SFV sutured in end-to-end anastomosis with the aorta and distally with the right common iliac artery and in end-to-side anastomosis with the left common iliac artery. Results: The operating time was less than reported for aortic in situ reconstruction with bilateral SFV harvesting. The duplex scan 3 months postoperatively showed permeability of the bypass without any anastomotic stenosis or pseudoaneurysm. The right common femoral, popliteal, and greater saphenous veins were patent without thrombus, and the patient did not complain about peripheral edema. Conclusions: The use of only one instead of both the SFVs for aortobiiliac in situ reconstruction might be a way to reduce operating time and allow autogenous venous reconstruction even in patients with limited availability of venous material.
Validating indirect fire models with field experiments
Authors: Åkesson Bernt M. , Lappi Esa , Pettersson Ville H. , Malmi Eric , Syrjänen Sampo , Vulli Marko , Stenius Kari 
Published: May 2013

Field experiments were used to evaluate three different indirect fire models: the cookie cutter and the Carleton damage functions and a simplified physical model for fragmenting ammunition. Data from three field tests, in which a total of 66 mortar bombs (120 mm high explosive) were fired in flat terrain, is used for validation. The results imply that no universal parameters, that would fit the results, can be found for the damage function models while the physical model predicted the field test results consistently without parameter fitting.
The utility of an online diagnostic decision support system (Isabel) in general practice: a process evaluation
Authors: Henderson Emily J , Rubin Greg P 
Published: May 2013

Objectives To evaluate the utility of Isabel, an online diagnostic decision support system developed by Isabel Healthcare primarily for secondary medical care, in the general practice setting. Design Focus groups were conducted with clinicians to understand why and how they used the system. A modified online post-use survey asked practitioners about its impact on their decision-making. Normalization process theory (NPT) was used as a theoretical framework to determine whether the system could be incorporated into routine clinical practice. Setting The system was introduced by NHS County Durham and Darlington in the UK in selected general practices as a three-month pilot. Participants General practitioners and nurse practitioners who had access to Isabel as part of the Primary Care Trust's pilot. Main outcome measures General practitioners’ views, experiences and usage of the system. Results Seven general practices agreed to pilot Isabel. Two practices did not subsequently use it. The remaining five practices conducted searches on 16 patients. Post-use surveys ( n = 10) indicated that Isabel had little impact on diagnostic decision-making. Focus group participants stated that, although the diagnoses produced by Isabel in general did not have an impact on their decision-making, they would find the tool useful if it were better tailored to the primary care setting. Our analysis concluded that normalization was not likely to occur in its current form. Conclusions Isabel was of limited utility in this short pilot study and may need further modification for use in general practice.
Junior doctors and healthcare reforms: are they ready? A questionnaire study
Authors: Palazzo Stefano , Chehab Omar 
Published: May 2013

Objectives To assess the awareness, understanding and opinions of National Health Service (NHS) reforms among foundation year junior doctors. Design Participants completed a 16 question online survey, consisting of multiple-choice questions and questions with free text responses. Setting Foundation doctors were all working within one of the four London, Oxford or Severn foundation schools. Participants One hundred and two foundation year junior doctors. Main outcome measures Understanding and awareness of NHS reforms and health politics in general as assessed through six free text and multiple-choice answers to a set of basic factual questions. Opinions of the reforms were assessed through Likert scale (1–5) responses to seven questions. Results Basic understanding of health politics and NHS reforms was poor, even on issues affecting future training. A total of 17.7% could not name the health secretary, 66.7% did not know the budget of the NHS and 71.6% did not know who would be responsible for healthcare commissioning after the reforms. A total of 68.7% of respondents reported being interested in the reforms and 63.7% reported being concerned about their effect on their own career path. Despite this, 63.7% self-reported poor understanding of the NHS reforms and 90.2% felt they would value formal education on the current changes. Conclusions Despite being interested and concerned, junior doctors are surprisingly uninformed about the NHS reforms. Given the findings of this study, more work needs to be done to educate the current cohort of medical students and foundation year doctors and engage them with the changes taking place.