bluuebunny/crossref_metadata_2025_split huggingface dataset:
MHC Class I–Presented Tumor Antigens Identified in Ovarian Cancer by Immunoproteomic Analysis Are Targets for T-Cell Responses against Breast and Ovarian Cancer
Authors: Morse Michael A. , Secord Angeles A. , Blackwell Kimberly , Hobeika Amy C. , Sinnathamby Gomathinayagam , Osada Takuya , Hafner Julie , Philip Mohan , Clay Timothy M. , Lyerly H. Kim , Philip Ramila 
Published: February 2011

AbstractPurpose: The purpose of this study is to test whether peptide epitopes chosen from among those naturally processed and overpresented within MHC molecules by malignant, but not normal cells, when formulated into cancer vaccines, could activate antitumor T-cell responses in humans.Experimental Design: Mixtures of human leukocyte antigen A2 (HLA-A2)-binding ovarian cancer-associated peptides were used to activate naive T cells to generate antigen-specific T cells that could recognize ovarian and breast cancers in vitro. Combinations of these peptides (0.3 mg of each peptide or 1 mg of each peptide) were formulated into vaccines in conjunction with Montanide ISA-51 and granulocyte monocyte colony stimulating factor which were used to vaccinate patients with ovarian and breast cancer without evidence of clinical disease in parallel pilot clinical trials.Results: T cells specific for individual peptides could be generated in vitro by using mixtures of peptides, and these T cells recognized ovarian and breast cancers but not nonmalignant cells. Patient vaccinations were well tolerated with the exception of local erythema and induration at the injection site. Nine of the 14 vaccinated patients responded immunologically to their vaccine by inducing peptide-specific T-cell responses that were capable of recognizing HLA-matched breast and ovarian cancer cells.Conclusion: Mixtures of specific peptides identified as naturally presented on cancer cells and capable of activating tumor-specific T cells in vitro also initiate or augment immune responses toward solid tumors in cancer patients. Clin Cancer Res; 17(10); 3408–19. ©2011 AACR.
Impaired platelet function and peripartum bleeding in women with Gaucher disease
Authors: Simchen Michal , Oz Rotem , Shenkman Boris , Zimran Ari , Elstein Deborah , Kenet Gili 
Published: February 2011

SummaryThe risk of bleeding during delivery may be increased in women with Gaucher disease. We aimed to evaluate potential predictors for peripartum haemorrhage (PPH) during childbirth in these patients, while focusing upon coagulation tests and platelet function assays. Women with type 1 Gaucher disease who gave birth at Sheba Medical Center between 1999–2009 comprised the study cohort. Data collected included disease history, enzyme treatment, platelet counts, delivery and pregnancy outcome. PPH was defined as excessive bleeding during or immediately following delivery. Coagulation studies and platelet function tests, including aggregometry and cone and platelet (CPA) analyses, were performed on all women. We compared women with PPH (bleeders) and non-bleeders. Furthermore, women with abnormal CPA platelet function tests were compared with those with normal CPA platelet function with regards to the risk for PPH in at least one pregnancy. Forty-five pregnancies of 20 women were studied. Six women received enzyme replacement therapy during pregnancy. Mean platelet count prior to delivery was 83,000/μl ± 35,000/μl. Fourteen out of 45 (31%) deliveries were complicated by PPH. Neither thrombocytopenia nor enzyme therapy predicted PPH. Twelve out of 13 women with PPH (92.3%) versus 2/7 non-bleeders (28.6%) had impaired platelet aggregation (less than the 3rd percentile of normal average aggregate size values), when tested by CPA, (odds ratio [OR] 17.8, 95% confidence interval [CI] 2.5; 126.2; p=0.007). Notably, 78.6% of women with impaired CPA aggregation developed PPH during at least one delivery, as opposed to 16.7% of those with normal CPA platelet function tests (OR 11.6, 95% CI 1.7–77.7, p=0.018). In conclusion, women with type 1 Gaucher disease who have abnormal platelet function tests may have an increased risk of PPH.
Long-term secondary prophylaxis in children, adolescents and young adults with von Willebrand disease
Authors: Halimeh Susan , Krümpel Anne , Rott Hannelore , Bogdanova Nadja , Budde Ulrich , Manner Daniela , Faeser Britta , Mesters Rolf , Nowak-Göttl Ulrike 
Published: February 2011

SummaryIn patients with von Willebrand disease (VWD) replacement therapy with factor VIII/von Willebrand (VWF) concentrates is increasingly applied as prophylactic regimen. Since 2000, 82 consecutively enrolled patients with clinically relevant bleeding episodes (spontaneous, peri- or postoperative) were diagnosed with VWD [type 1: 42/82; type 2: 24/82; type 3: 13/82; acquired: 3/82]. In all patients, decision for initiating prophylaxis was based on a bleeding score > 2 prior to diagnosis, concomitant with recurrent bleeds associated with anaemia in patients with on-demand VWD therapy. We report results on secondary prophylactic VWF replacement therapy applied in 32 patients [children n=13; adolescents n=7; adults n=12] with VWD [type 1: 4; type 2: 15; type 3: 13], 15 of which were females, and nine of these at the reproductive period. Eight patients were treated with Humate P→ or Wilate→ (n=24). Median [min-max] dose [vWF:RCo] was 40 [20–47] IU/kg, 23 patients were given substitution therapy twice weekly, seven patients three times a week, and two children four times per week. Within a 12-month-period haemoglobin concentrations returned to normal values. Median duration of prophylaxis was three years. Recurrent bleeding episodes stopped in 31 of 32 patients, whereas inhibitors developed in one. Following a 12-month observation period the monthly bleeding frequency and the bleeding score was significantly reduced [3 vs. 0.07; 3 vs. 0: p< 0.001], compared to the preprophylaxis/pre-diagnostic values. The use of secondary prophylactic VWF replacement therapy is an effective tolerated treatment modality, highly beneficial for patients with VWD, who present with recurrent bleeding events during on-demand therapy.
The value of 64-detector row computed tomography for the exclusion of pulmonary embolism
Authors: Conti Giorgio de , Minotto Isabella , Filippi Lucia , Mongiat Marta , Faveri Daniele de , Maurizi Francesca , Valle Fabio Dalla , Piovella Chiara , Pagnan Antonio , Prandoni Paolo , Pesavento Raffaele ,   for the TACEP study
Published: February 2011

SummaryRecently, a diagnostic strategy using a clinical decision rule, D-dimer testing and spiral computed tomography (CT) was found to be effective in the evaluation of patients with clinically suspected pulmonary embolism (PE). However, the rate of venous thromboembolic complications in the three-month follow-up of patients with negative CT was still substantial and included fatal events. It was the objective to evaluate the safety of withholding anticoagulants after a normal 64-detector row CT (64-DCT) scan from a cohort of patients with suspected PE. A total of 545 consecutive patients with clinically suspected first episode of PE and either likely pre-test probability of PE (using the simplified Wells score) or unlikely pre-test probability in combination with a positive D-dimer underwent a 64-DCT. 64-DCT scanning was inconclusive in nine patients (1.6%), confirmed the presence of PE in 169 (31%), and ruled out the diagnosis in the remaining 367. During the three-month follow-up of the 367 patients one developed symptomatic distal deep-vein thrombosis (0.27%; 95%CI, 0.0 to 1.51%) and none developed PE (0 %; 95%CI, 0 to 1.0%). We conclude that 64-DCT scanning has the potential to safely exclude the presence of PE virtually in all patients presenting with clinical suspicion of this clinical disorder.
Upstream Clopidogrel Use and the Efficacy and Safety of Early Eptifibatide Treatment in Patients With Acute Coronary Syndrome
Authors: Wang Tracy Y. , White Jennifer A. , Tricoci Pierluigi , Giugliano Robert P. , Zeymer Uwe , Harrington Robert A. , Montalescot Gilles , James Stefan K. , Van de Werf Frans , Armstrong Paul W. , Braunwald Eugene , Califf Robert M. , Newby L. Kristin 
Published: February 2011

Background—
In the Early Glycoprotein IIb/IIIa Inhibition in Patients with Non–ST-Segment Elevation Acute Coronary Syndrome (EARLY ACS) trial, routine preangiography eptifibatide use was not superior to delayed provisional use but led to more bleeding. This analysis examines efficacy and safety of early eptifibatide in the setting of concurrent upstream clopidogrel use.

Methods and Results—

In EARLY-ACS, clopidogrel use and timing were determined by treating physicians, but randomization to early eptifibatide versus placebo was stratified by the intent to use upstream clopidogrel. Among 9166 non-ST-elevation acute coronary syndrome patients who underwent coronary angiography, intent to use upstream clopidogrel was declared in 6895 (75%), and 7068 (77%) received upstream clopidogrel. After multivariable adjustment, intended upstream clopidogrel use did not differentially influence the effect of early eptifibatide on the primary end point of 96-hour death/myocardial infarction/recurrent ischemia requiring urgent revascularization/thrombotic bailout (interaction
P
=0.988). Early eptifibatide use reduced 30-day death/myocardial infarction among patients with intended upstream clopidogrel (adjusted odds ratio 0.85; 95% confidence interval 0.73 to 0.99) but not among those without intended upstream clopidogrel use (adjusted odds ratio 1.02; 95% confidence interval 0.80 to 1.30). However, the clopidogrel by randomized treatment interaction term was not significant (
P
=0.23). Thrombolysis in Myocardial Infarction major bleeding risk was increased with early eptifibatide in the setting of upstream clopidogrel use. Results were similar using actual clopidogrel treatment strata.

Conclusions—
Routine early eptifibatide use, compared with delayed provisional use, may be associated with lower 30-day ischemic risk in non-ST-elevation acute coronary syndrome patients also treated with clopidogrel before angiography. The benefit–risk ratio of intensive platelet inhibition with combined early use of antiplatelet agents needs further evaluation in prospective randomized trials.

Clinical Trial Registration—

http://www.clinicaltrials.gov
. Unique identifier NCT00089895.
Remote Ischemic Preconditioning Protects the Brain Against Injury After Hypothermic Circulatory Arrest
Authors: Jensen Hanna A. , Loukogeorgakis Stavros , Yannopoulos Fredrik , Rimpiläinen Eija , Petzold Axel , Tuominen Hannu , Lepola Pasi , MacAllister Raymond J. , Deanfield John E. , Mäkelä Tuomas , Alestalo Kirsi , Kiviluoma Kai , Anttila Vesa , Tsang Victor , Juvonen Tatu 
Published: February 2011

Background—
Ischemic preconditioning (IPC) is a mechanism protecting tissues from injury during ischemia and reperfusion. Remote IPC (RIPC) can be elicited by applying brief periods of ischemia to tissues with ischemic tolerance, thus protecting vital organs more susceptible to ischemic damage. Using a porcine model, we determined whether RIPC of the limb is protective against brain injury caused by hypothermic circulatory arrest (HCA).

Methods and Results—
Twelve piglets were randomized to control and RIPC groups. RIPC was induced in advance of cardiopulmonary bypass by 4 cycles of 5 minutes of ischemia of the hind limb. All animals underwent cardiopulmonary bypass followed by 60 minutes of HCA at 18°C. Brain metabolism and electroencephalographic activity were monitored for 8 hours after HCA. Assessment of neurological status was performed for a week postoperatively. Finally, brain tissue was harvested for histopathological analysis.

Study groups were balanced for baseline and intraoperative parameters. Brain lactate concentration was significantly lower (
P
<0.0001, ANOVA) and recovery of electroencephalographic activity faster (
P
<0.05, ANOVA) in the RIPC group. RIPC had a beneficial effect on neurological function during the 7-day follow-up (behavioral score;
P
<0.0001 versus control, ANOVA). Histopathological analysis demonstrated a significant reduction in cerebral injury in RIPC animals (injury score; mean [interquartile range]: control 5.8 [3.8 to 7.5] versus RIPC 1.5 [0.5 to 2.5],
P
<0.001,
t
test).

Conclusions—
These data demonstrate that RIPC protects the brain against HCA-induced injury, resulting in accelerated recovery of neurological function. RIPC might be neuroprotective in patients undergoing surgery with HCA and improve long-term outcomes. Clinical trials to test this hypothesis are warranted.
Teleconnection Pathways of ENSO and the IOD and the Mechanisms for Impacts on Australian Rainfall
Authors: Cai Wenju , van Rensch Peter , Cowan Tim , Hendon Harry H. 
Published: February 2011

Abstract
Impacts of El Niño–Southern Oscillation (ENSO) and the Indian Ocean dipole (IOD) on Australian rainfall are diagnosed from the perspective of tropical and extratropical teleconnections triggered by tropical sea surface temperature (SST) variations. The tropical teleconnection is understood as the equatorially trapped, deep baroclinic response to the diabatic (convective) heating anomalies induced by the tropical SST anomalies. These diabatic heating anomalies also excite equivalent barotropic Rossby wave trains that propagate into the extratropics. The main direct tropical teleconnection during ENSO is the Southern Oscillation (SO), whose impact on Australian rainfall is argued to be mainly confined to near-tropical portions of eastern Australia. Rainfall is suppressed during El Niño because near-tropical eastern Australia directly experiences subsidence and higher surface pressure associated with the western pole of the SO. Impacts on extratropical Australian rainfall during El Niño are argued to stem primarily from the Rossby wave trains forced by convective variations in the Indian Ocean, for which the IOD is a primary source of variability. These equivalent-barotropic Rossby wave trains emanating from the Indian Ocean induce changes to the midlatitude westerlies across southern Australia, thereby affecting rainfall through changes in mean-state baroclinicity, west–east steering, and possibly orographic effects. Although the IOD does not mature until austral spring, its impact on Australian rainfall during winter is also ascribed to this mechanism. Because ENSO is largely unrelated to the IOD during austral winter, there is limited impact of ENSO on rainfall across southern latitudes of Australia in winter. A strong impact of ENSO on southern Australia rainfall in spring is ascribed to the strong covariation of ENSO and the IOD in this season. Implications of this pathway from the tropical Indian Ocean for impacts of both the IOD and ENSO on southern Australian climate are discussed with regard to the ability to make seasonal climate predictions and with regard to the role of trends in tropical SST for driving trends in Australian climate.
A Cloud-Resolving 4DVAR Assimilation Experiment for a Local Heavy Rainfall Event in the Tokyo Metropolitan Area
Authors: Kawabata Takuya , Kuroda Tohru , Seko Hiromu , Saito Kazuo 
Published: February 2011

Abstract
A cloud-resolving nonhydrostatic four-dimensional variational data assimilation system (NHM-4DVAR) was modified to directly assimilate radar reflectivity and applied to a data assimilation experiment using actual observations of a heavy rainfall event. Modifications included development of an adjoint model of the warm rain process, extension of control variables, and development of an observation operator for radar reflectivity.
The responses of the modified NHM-4DVAR were confirmed by single-observation assimilation experiments for an isolated deep convection, using pseudo-observations of rainwater at the initial and end times of the data assimilation window. The results showed that the intensity of convection could be adjusted by assimilating appropriate observations of rainwater near the convection and that undesirable convection could be suppressed by assimilating small or no reflectivity.
An assimilation experiment using actual observations of a local heavy rainfall in the Tokyo, Japan, metropolitan area was conducted with a horizontal resolution of 2 km. Precipitable water vapor derived from global positioning system data was assimilated at 5-min intervals within 30-min assimilation windows, and surface and wind profiler data were assimilated at 10-min intervals. Doppler radial wind and radar-reflectivity data below the elevation angle of 5.4° were assimilated at 1-min intervals.
The 4DVAR assimilation reproduced a line-shaped rainband with a shape and intensity consistent with the observation. Assimilation of radar-reflectivity data intensified the rainband and suppressed false convection. The simulated rainband lasted for 1 h in the extended forecast and then gradually decayed. Sustaining the low-level convergence produced by northerly winds in the western part of the rainband was key to prolonging the predictability of the convective system.
Rotating Hydraulics and Upstream Basin Circulation*
Authors: Helfrich Karl R. , Pratt Lawrence J. 
Published: February 2011

Abstract
The flow in a source-fed f-plane basin drained through a strait is explored using a single-layer (reduced gravity) shallow-water numerical model that resolves the hydraulic flow within the strait. The steady upstream basin circulation is found to be sensitive to the nature of the mass source (uniform downwelling, localized downwelling, or boundary inflow). In contrast, the hydraulically controlled flow in the strait is nearly independent of the basin circulation and agrees very well with the Gill-theory solution obtained using the strait geometry and the numerically determined average potential vorticity in the strait entrance region. This Gill solution, however, gives a unique value of the upstream boundary layer flux splitting that does not agree with any of the full numerical solutions. The coupled basin–strait system is shown to select an average overflow potential vorticity corresponding to the Gill solution with maximum fluid depth on the strait boundaries. This state also corresponds to one of maximal upstream basin potential energy. This result is robust to changes in the basin geometry, strait characteristics, the dissipation parameter (linear drag), and the net mass flux. The nonunique relation between basin conditions and overflow transport is significant with regard to deep overflow transport monitoring. It is shown that the potential vorticity selection leads to overflow, or “weir,” transport relations that are well approximated by the zero potential vorticity theory. However, accurate estimates of the transport can only be obtained if conditions within the strait entrance region, and not the basin, are used.
Wind-Driven Recirculations and Exchange in the Labrador and Irminger Seas*
Authors: Spall Michael A. , Pickart Robert S. 
Published: February 2011

Abstract
It is demonstrated that recently observed cyclonic recirculation gyres in the Irminger and Labrador Seas may be forced by the strong cyclonic wind stress curl that develops each winter seaward of the east coast of Greenland. Idealized analytical and numerical models forced with such variable winds over a sloping bottom reproduce the essential aspects of the observed gyres (strength, location, and horizontal and vertical length scales). The communication between the forcing region in the Irminger Sea and the recirculation to the west is achieved by baroclinic topographic Rossby wave propagation along potential vorticity contours. The circulation is characterized as a time-dependent, stratified, topographic beta plume. For weak stratification, as found in the subpolar North Atlantic, the recirculation strength exhibits only weak seasonal variability, consistent with the observations, even though the forcing is active only during the winter. Baroclinic Rossby waves that develop when the wind forcing ceases in springtime interact with the bottom to provide a source of cyclonic vorticity that maintains the circulation until the wind strengthens again in the following winter.
Why Anticyclones Can Split
Authors: Drijfhout S. S. 
Published: February 2011

Abstract
The question of whether anticyclones can split and break up is readdressed using a numerical, multilayer, primitive equation model. Applying the conservation of integrated angular momentum (IAM) to barotropic and baroclinic vortices, it has been argued that anticyclones can never split, no matter what their structure is. When an anticyclone splits, the IAM has to increase as the newly formed eddies are pushed away from their original center. Conservation of IAM prohibits such an increase. Several numerical simulations, however, have shown anticyclonic splitting. In a multilayer model, a vertical transport of IAM is possible. For counterrotating eddies (an anticyclone on top of a cyclone) it is easy to see that a vertical exchange of IAM allows the eddy to break up. For a compensated or weakly corotating eddy, breakup is only possible when, in addition to a vertical transport of IAM, in the deep layer(s) IAM is exchanged between the core of the vortex and the surrounding fluid. In the presence of a tilting interface, the pressure gradient associated with the sea surface height (SSH) anomaly, in particular its non-equivalent-barotropic part, drives the required exchanges. The non-equivalent-barotropic SSH anomaly is associated with the vertical phase lag of the most unstable eigenmode (m = 2), which develops when this mode gains energy by baroclinic energy conversion. The previous conclusion that anticyclones cannot split on their own should be revised to the following: anticyclones cannot split by barotropic processes alone—baroclinic instability is a necessary ingredient for splitting to occur.