bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Trial of Combretastatin A4 Phosphate (CA4P) in Combination with Bevacizumab in Patients with Advanced Cancer
Authors: Nathan Paul , Zweifel Martin , Padhani Anwar R. , Koh Dow-Mu , Ng Matthew , Collins David J. , Harris Adrian , Carden Craig , Smythe Jon , Fisher Nita , Taylor N. Jane , Stirling J. James , Lu Shiao-Ping , Leach Martin O. , Rustin Gordon J.S. , Judson Ian 
Published: May 2012

Abstract
Purpose: The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to a VDA attenuates the revascularization of the surviving tumor rim and thus significantly increases antitumor activity.
Experimental Design: Patients with advanced solid malignancies received CA4P at 45, 54, or 63 mg/m2 on day 1, day 8, and then every 14 days. Bevacizumab 10 mg/kg was given on day 8 and at subsequent cycles four hours after CA4P. Functional imaging with dynamic contrast enhanced-MRI (DCE-MRI) was conducted at baseline, after CA4P alone, and after cycle 1 CA4P + bevacizumab.
Results: A total of 63 mg/m2 CA4P + 10 mg/kg bevacizumab q14 is the recommended phase II dose. A total of 15 patients were enrolled. Dose-limiting toxicities were grade III asymptomatic atrial fibrillation and grade IV liver hemorrhage in a patient with a history of hemorrhage. Most common toxicities were hypertension, headache, lymphopenia, pruritus, and pyrexia. Asymptomatic electrocardiographic changes were seen in five patients. Nine of 14 patients experienced disease stabilization. A patient with ovarian cancer had a CA125 response lasting for more than a year. DCE-MRI showed statistically significant reductions in tumor perfusion/vascular permeability, which reversed after CA4P alone but which were sustained following bevacizumab. Circulating CD34+ and CD133+ bone marrow progenitors increased following CA4P as did VEGF and granulocyte colony-stimulating factor levels.
Conclusions: CA4P in combination with bevacizumab appears safe and well tolerated in this dosing schedule. CA4P induced profound vascular changes, which were maintained by the presence of bevacizumab. Clin Cancer Res; 18(12); 3428–39. ©2012 AACR.
Comparison of Invasive and Noninvasive Assessment of Aortic Stenosis Severity in the Elderly
Authors: Gertz Zachary M. , Raina Amresh , O'Donnell William , McCauley Brian D. , Shellenberger Charlene , Kolansky Daniel M. , Wilensky Robert L. , Forfia Paul R. , Herrmann Howard C. 
Published: May 2012

Background—
Aortic valve area (AVA) in aortic stenosis (AS) can be assessed noninvasively or invasively, typically with similar results. These techniques have not been validated in elderly patients, where common assumptions make them most prone to error. Accurate assessment of AVA is crucial to determine which patients are appropriate candidates for aortic valve replacement.

Methods and Results—

Fifty elderly patients (mean 86 years, 46% female) referred for cardiac catheterization to evaluate AS also underwent transthoracic echocardiography within 24 hours. To minimize assumptions all patients had 3-dimensional echocardiography (Echo-3D), and at catheterization using directly measured oxygen consumption (Cath-mVo
2
) and thermodilution cardiac output (Cath-TD). Correlation between Cath-mVo
2
and Echo-3D AVA was poor (
r
=0.41). Cath-TD AVA had a moderate correlation with Echo-3D AVA (
r
=0.59). Cath-mVo
2
(AVA=0.69 cm
2
) and Cath-TD (AVA=0.66 cm
2
) underestimated AVA compared with Echo-3D (AVA=0.76 cm
2;
P
=0.08 for comparison with Cath-mVo
2
;
P
=0.001 for Cath-TD). Compared with Echo-3D, the sensitivity and specificity for determining critical disease (AVA <0.8 cm
2
) were 81% and 42% for Cath-mVo
2
, and 97% and 53% for Cath-TD. The only independent predictor of the difference between noninvasive and invasive AVA was stroke volume index (
P
<0.01). Resistance, a less flow-dependent measure, showed a stronger correlation between Echo-3D and Cath-mVo
2
(
r
=0.69), and Echo-3D and Cath-TD (
r
=0.77).

Conclusions—
Standard techniques of AVA assessment for AS show poor correlation in elderly patients, with frequent misclassification of critical AS. Less flow-dependent measures, such as resistance, should be considered to ensure that only appropriate patients are treated with aortic valve replacement.
Numerical Tests of the Weak Pressure Gradient Approximation
Authors: Romps David M. 
Published: May 2012

Abstract
Cloud-resolving simulations of convection over a surface temperature hot spot are used to evaluate the weak pressure gradient (WPG) and weak temperature gradient (WTG) approximations. The premise of the relaxed form of WTG—that vertical velocity is equal to buoyancy times a positive time scale—is found to be violated by thick layers of negative buoyancy in steady-state ascent. The premise of WPG—that horizontal divergence and pressure anomalies are collocated—is validated by these simulations. When implemented in a cloud-resolving model, WPG replicates buoyancy transients exceptionally well, including the adiabatic lifting of air below buoyancy anomalies. WTG captures neither this effect nor the associated triggering of moist convection. For steady states, WTG produces vertical velocity profiles that are too top heavy. On the other hand, WPG generates velocity profiles that closely match fully resolved hot-spot simulations. Taken together, the evidence suggests that WPG is a relatively accurate method for parameterizing supradomain-scale (SDS) dynamics.
Reconstructing the South Pacific Convergence Zone Position during the Presatellite Era: A La Niña Case Study
Authors: Lorrey Andrew , Dalu Giovanni , Renwick James , Diamond Howard , Gaetani Marco 
Published: May 2012

Abstract
Sixty-four southwest Pacific island meteorological stations were used to develop ENSO-related austral warm season (November–April) rainfall climatologies for 1961–90. Historical data for the same station set were then examined for 1955/56, one of the strongest La Niñas of the twentieth century. The pattern for that event was typical of a well-coupled protracted La Niña, with above-normal rainfall (&gt;150%) observed for 17 stations in the case study.
Tropical cyclone tracks were also used to illustrate the proximal effects of historical storms on station rainfall. Several stations that were located along the northern edge of the tropical cyclone swarm, but south of a region of anomalously low rainfall, were selected as possible candidates having been close to the mean South Pacific convergence zone (SPCZ) location. Linear interpolations between those stations highlighted a likely SPCZ position for the 1955/56 event.
The reconstructed SPCZ location indicated a position southwest of normal, consistent with many La Niñas observed during the satellite era. The 1955/56 SPCZ reconstruction compared favorably with NOAA Cooperative Institute for Research in Environmental Sciences (CIRES) twentieth-century reanalysis (20CR) positions of maximum atmospheric water content and omega (time derivative of pressure that illustrates vertical velocity, and a proxy for convection and SPCZ location) at 500 hPa. Comparisons between Global Precipitation Climatology Project (GPCP) warm season rainfall composite plots for several satellite era La Niñas and one well-coupled La Niña event that occurred during 2010/11 to omega at 500 hPa and maximum rainfall amounts suggest that the 1955/56 reconstruction from in situ rainfall measurements captured the SPCZ location. These findings suggest that use of the 20CR could help to identify hemispheric-scale atmospheric circulation features like the SPCZ and improve understanding of ENSO dynamics prior to the satellite era.
Expression Pattern of Apurinic/Apyrimidinic Endonuclease in Sinonasal Squamous Cell Carcinoma
Authors: Lee Jin Woo , Jin Jun , Rha Ki‐Sang , Kim Yong Min 
Published: May 2012

ObjectiveTo evaluate the apurinic/apyrimidinic endonuclease 1 (APE1) expression in sinonasal squamous cell carcinomas (SCC) and to examine the correlation between APE1 expression patterns and various clinicopathological factors associated with sinonasal SCC that include SCC with inverted papilloma (SCCwIP) and SCC alone.Study DesignCase‐control study.SettingChungnam National University Hospital.Subjects and MethodsThe expressions of APE1 were analyzed by means of immunohistochemistry in 30 sinonasal SCC, including 14 SCC patients associated with IP and 16 patients with SCC alone. A total of 19 patients who had been diagnosed with chronic rhinosinusitis with nasal polyposis and who required endoscopic sinus surgery were used as the control group. The degrees of APE1 expression were analyzed with respect to the following clinicopathologic variables: age, sex, T stage, histologic differentiation, distant metastasis, and recurrence.ResultsCytoplasmic staining of APE1 was significantly higher in SCC compared with SCCwIP (68.75% vs 14.29%). Cytoplasmic staining of APE1 was significantly associated with T stage (P =. 044) in SCC and histologic grade (P =. 0025) in sinonasal SCC. Nuclear staining of APE1 was significantly associated with distant metastasis (P =. 022) in SCC.ConclusionThese results suggest that the nuclear and cytoplasmic expression of APE1 may be related to tumor invasiveness and prognosis in sinonasal SCC. The suppression of APE1 expression can potentially be a new target for future sinonasal SCC therapies.
Mitomycin C–Enhanced Revision Endoscopic Dacryocystorhinostomy
Authors: Ragab Sameh M. , Elsherif Hossam S. , Shehata Emad M. , Younes Ahmed , Gamea Ahmed M. 
Published: May 2012

Objectives(1) To conduct an adequately powered randomized controlled trial investigating the safety and efficacy of mitomycin C–enhanced revision endoscopic dacryocystorhinostomy (DCR) and (2) to analyze causes of failure after primary endoscopic DCR.Study DesignA randomized controlled study.SettingGeneral hospital.Subjects and MethodsSeventy‐six revision endoscopic DCRs were randomized into 2 groups: endoscopic DCR with mitomycin (group I), where 0.5 mg/mL mitomycin C was applied for 10 minutes, and endoscopic DCR without mitomycin (group II). Follow‐up settings were done to document the patient’s subjective improvement, to judge ostium patency on irrigation, and to record any complications.ResultsCauses of failure in the original 92 patients included canalicular obstruction (14%), small misplaced bony window (43%), very small nasolacrimal stoma due to development of synechia (23%), and complete closure of nasolacrimal stoma with tough fibrous tissue (63%). There was no significant difference between the 2 groups in subjective and objective success rates and adverse events. Group I demonstrated a significantly longer operative time and a significantly lower number of debridement sessions (mean of 1.2 vs 1.9).ConclusionsRecurrent nasolacrimal duct obstruction after primary endoscopic DCR is mainly due to reclosure of the nasolacrimal stoma with synechia and fashioning of the small misplaced bony window. Mitomycin C does not increase the success rate of revision endoscopic DCR. It is a safe procedure and may be of value only in patients inaccessible to strict follow‐up because it induces a better healing profile in terms of mucosal recovery, wound healing, and less need for debridement sessions.
The effect of supported standing in adults with upper motor neurone disorders: a systematic review
Authors: Newman Meredith , Barker Karen 
Published: May 2012

Objectives: To evaluate whether supported standing can affect lower limb muscle length, spasticity, bone mineral density or the function of adults with upper motor neurone disorders. Data sources: A search was conducted of MEDLINE, EMBASE, AMED, CINAHL and Cochrane library electronic databases; clinical trial registers via www.controlled-trials.com and complemented with citation tracking. Review methods: Two reviewers independently evaluated eligibility and methodological quality. Class I and II studies of assisted standing for adults with stroke, multiple sclerosis, traumatic brain injury or spinal cord injury were eligible. A domain-based risk of bias approach was used to assess quality. Results: Seventeen studies were included: 11 class I and 6 class II studies involving 540 participants, of whom 73% were non-ambulant. Quality was generally low, with only two high quality trials identified. High-quality evidence suggested tilt-table standing has a small effect on preventing loss of ankle dorsiflexion. One high-quality study found a low-dose standing programme did not alter bone loss early after spinal injury. Class II low-quality evidence suggested long-term, higher dose programmes may slow bone loss. Limited evidence for the effectiveness of standing on spasticity and function was inconclusive. Conclusion: Supported standing can prevent small losses of ankle mobility but the clinical importance of these effects is uncertain. Low-dose standing is unlikely to protect bone health.
Investigation on the long-term water absorption behavior and cell morphology of foamed wood–plastic nanocomposites
Authors: Kord Behzad 
Published: May 2012

This research explores the effects of chemical foaming agent and nanoclay on the long-term water absorption and cell morphology of wood–plastic nanocomposites. To meet this objective, the nanoclay, high-density polyethylene, and coupling agent were compounded and then granulated and were mixed with wood flour and blowing agent in a twin-screw extruder. Consequently, foaming process was completed in injection stage. The amount of wood flour was fixed at 50 wt% for all the samples. For nanoclay and chemical blowing agent, different levels of 0, 2 and 4 per hundred resins (phr) and 0, 0.5, 1 and 1.5 phr were considered, respectively. The long-term water absorptions of samples were evaluated by immersing them in water for several weeks, and water diffusion coefficients were also calculated by evaluating the water absorption isotherms. Results indicated that the water absorption, cell size, and average cell density of composites increased with increase in chemical foaming agent loadings. However, by the addition of nanoclay to wood–plastic composite foams, the water absorption and cell size decreased and their cell density increased. Scanning electron microscopy confirmed that the chemical foaming agent and nanoclay contents had significant influence on density reduction in foamed composites. X-Ray diffraction patterns revealed that the nanocomposites formed were intercalated. The mechanism of water absorption of the foamed wood–plastic nanocomposites under study followed the kinetics of a Fickian diffusion process.
Patients’ Views on Failure to Gain Expected Clinical Beneficial Outcomes From Participation in Palliative Medicine Clinical Trials
Authors: Siu Steven W. K. , Leung Pamela P. Y. , Liu Rico K. Y. , Leung T. W. 
Published: May 2012

Reason for the Study: This study aims to understand patients’ views on failing to gain expected beneficial outcomes from palliative medicine clinical trials. This is a qualitative study involving semistructured interviews. Main Findings: Seven patients were interviewed. Despite loss of initial hope in benefiting themselves in terms of better disease or symptom control, patients interviewed still found joining clinical trials meaningful experience in terms of benefiting future patients and being valuable life experience. Experience in interacting with research staff partly formulated final impressions on clinical trial participation experience. Principal Conclusions: Joining well-designed clinical trials unlikely causes harm to patients. Caring attitudes of researchers and maintaining good researcher–patient relationships can help patients in meaning-finding process, especially if they have failed to gain anticipated clinical benefits.
Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan
Authors: Bernardo Maria Ester , Piras Eugenia , Vacca Adriana , Giorgiani Giovanna , Zecca Marco , Bertaina Alice , Pagliara Daria , Contoli Benedetta , Pinto Rita Maria , Caocci Giovanni , Mastronuzzi Angela , La Nasa Giorgio , Locatelli Franco 
Published: May 2012

Abstract
Sixty thalassemia patients (median age, 7 years; range, 1-37) underwent allogeneic hematopoietic stem cell transplantation (HSCT) after a preparation combining thiotepa, treosulfan, and fludarabine. Before HSCT, 27 children were assigned to risk class 1 of the Pesaro classification, 17 to class 2, and 4 to class 3; 12 patients were adults. Twenty patients were transplanted from an HLA-identical sibling and 40 from an unrelated donor. The cumulative incidence of graft failure and transplantation-related mortality was 9% and 7%, respectively. Eight patients experienced grade II-IV acute GVHD, the cumulative incidence being 14%. Among 56 patients at risk, 1 developed limited chronic GVHD. With a median follow-up of 36 months (range, 4-72), the 5-year probability of survival and thalassemia-free survival are 93% and 84%, respectively. Neither the class of risk nor the donor used influenced outcome. This treosulfan-based preparation proved to be safe and effective for thalassemia patients given allogeneic HSCT.
Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657
Authors: Esserman Laura J. , Berry Donald A. , DeMichele Angela , Carey Lisa , Davis Sarah E. , Buxton Meredith , Hudis Cliff , Gray Joe W. , Perou Charles , Yau Christina , Livasy Chad , Krontiras Helen , Montgomery Leslie , Tripathy Debasish , Lehman Constance , Liu Minetta C. , Olopade Olufunmilayo I. , Rugo Hope S. , Carpenter John T. , Dressler Lynn , Chhieng David , Singh Baljit , Mies Carolyn , Rabban Joseph , Chen Yunn-Yi , Giri Dilip , van 't Veer Laura , Hylton Nola 
Published: May 2012

Purpose Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. Patients and Methods Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. Results In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. Conclusion In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.
Intrinsic Network Connectivity Reflects Consistency of Synesthetic Experiences
Authors: Dovern Anna , Fink Gereon R. , Fromme A. Christina B. , Wohlschläger Afra M. , Weiss Peter H. , Riedl Valentin 
Published: May 2012

Studying cognitive processes underlying synesthesia, a condition in which stimulation of one sensory modality automatically leads to abnormal additional sensory perception, allows insights into the neural mechanisms of normal and abnormal cross-modal sensory processing.Consistent with the notion that synesthesia results from hyperconnectivity, functional connectivity analysis (adopting independent component analysis and seed-based correlation analysis) of resting-state functional magnetic resonance imaging data of 12 grapheme–color synesthetes and 12 nonsynesthetic control subjects revealed, in addition to increased intranetwork connectivity, both a global and a specific (medial and lateral visual networks to a right frontoparietal network) increase of intrinsic internetwork connectivity in grapheme–color synesthesia. Moreover, this increased intrinsic network connectivity reflected the strength of synesthetic experiences. These findings constitute the first direct evidence of increased functional network connectivity in synesthesia.In addition to this significant contribution to the understanding of the neural mechanisms of synesthesia, our results have important general implications. In combination with data derived from clinical populations, our data strongly suggest that altered differences in intrinsic network connectivity are directly related to the phenomenology of human experiences.
Progression of acromegalic arthropathy despite long-term biochemical control: a prospective, radiological study
Authors: Claessen K M J A , Ramautar S R , Pereira A M , Smit J W A , Roelfsema F , Romijn J A , Kroon H M , Kloppenburg M , Biermasz N R 
Published: May 2012

ObjectiveArthropathy is an invalidating complication of acromegaly, of which the prognosis and determinants are currently unknown in treated acromegaly. Therefore, the objective of the present study was to investigate the radiographic progression of arthropathy over a mean follow-up period of 2.6 years and determinants of outcome in patients with long-term, well-controlled acromegaly.DesignProspective follow-up study.MethodsIn a prospective cohort study we studied 58 patients (mean age 62, women 41%) with controlled acromegaly for a mean of 17.6 years. Radiographic progression of joint disease was defined by the Osteoarthritis Research Society International classification as a 1-point increase in joint space narrowing (JSN) or osteophyte scores on radiographs of the hands, knees, and hips obtained at the first study visit and after 2.6 years. Potential risk factors for progression were assessed.ResultsProgression of osteophytes and JSN was observed in 72 and 74% of patients respectively. Higher age predisposed for osteophyte progression. Patients with biochemical control by somatostatin (SMS) analogs had more progression of osteophytosis than surgically cured patients (odds ratio=18.9, P=0.025), independent of age, sex, BMI, baseline IGF1 SDS and exon 3 deletion of the GHR. This was also evident for JSN progression, as were higher age and higher baseline IGF1 SDS.ConclusionsAcromegalic patients have progressive JSN and osteophytosis, despite long-term biochemical control. Parameters reflecting GH/IGF1 activity were associated with progressive joint disease. Remarkably, biochemical control by SMS analogs was associated with more progression than surgical cure. Although the present study is not a randomized controlled trial, this may indicate insufficient GH control according to current criteria and the need for more aggressive therapy.