bluuebunny/crossref_metadata_2025 huggingface dataset:
Fifty Percent Reduced-Dose Cerebral CT Perfusion Imaging of Alzheimer’s Disease
Authors: Tang Zhen , Pi Xiaoling , Chen Feng , Shi Linghua , Gong Haiting , Fu Hongmei , Qu Zhengwan
Published: May 2012

To evaluate the value of 50% reduced-dose cerebral computed tomography (CT)perfusion imaging (CTPI) to show the perfusion abnormalities in Alzheimer’s disease (AD), as an attempt to develop a new imaging protocol with lower radiation dose to track the correlation of AD with regional blood flow abnormalities. A total of 52 patients with AD were assigned to the AD group and 28 healthy volunteers served as the control group. All participants were given a 50% reduced-dose cerebral CTPI (current was reduced from 160 to 80 mA) test by a multislice spiral CT scanner. Perfusion parameters of the bilateral frontal cortex, temporal cortex, hippocampus, and basal ganglia were measured, including the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). Both the CBV and CBF values of the measured regions were significantly higher in the healthy control group than in the AD group ( P < .05), while the MTT and TTP values of these cerebral areas were significantly lower in the healthy control group than in the AD group ( P < .05). Four perfusion parameters, namely the MTT of the left frontal cortex, right temporal cortex, right basal ganglia, and right hippocampus, had the greatest sensitivity and a striking correlation with the incidence of AD. The blood flow per unit of time in the regions of interest was significantly lower in the AD group, which provides new evidence for the existence of microcirculation disturbance and ischemia in AD. The 50% reduced-dose cerebral CTPI scan is valuable to show the regional perfusion abnormalities in the patients with AD.
Can Rowland Universal Dementia Assessment Scale (RUDAS) Replace Mini-Mental State Examination (MMSE) for Dementia Screening in a Thai Geriatric Outpatient Setting?
Authors: Limpawattana Panita , Tiamkao Somsak , Sawanyawisuth Kittisak , Thinkhamrop Bandit
Published: May 2012

Mini-mental-State Examination (MMSE) is a widely used tool for dementia screening. However, several limitations are found and the Rowland Universal Dementia Assessment Scale (RUDAS) appears to be an alternative test. The objective in this study was to compare the performance of MMSE-Thai 2002 and RUDAS-Thai for dementia screening, and to determine their performances and identify their optimal cut-off points. The participants were older patients from a Geriatric and Neurology Outpatient Clinic, Srinagarind Hospital, Khon Kaen University. The RUDAS-Thai and the MMSE-Thai 2002 were administered to each participant. Subsequently, a specialist physician assessed each participant for dementia. Results showed the area under receiver operating characteristic curve for both RUDAS-Thai (81.0%; 95%CI, 74.8-87.2) and MMSE-Thai 2002 (81.2%; 95%CI, 74.9-87.4) were equal. A score of 24 or lower provided an optimal cut-off point. Our finding supports that the RUDAS-Thai can be an effective alternative test for dementia screening. For both test scores, a score of 24 or lower is an optimal cut-off point to provide an indication of developing dementia.
Endovascular Therapy for Overcoming Challenges Presented With Blunt Abdominal Aortic Injury
Authors: Gilani Ramyar , Saucedo-Crespo Hector , Scott Bradford G. , Tsai Peter I. , Wall Metthew J. , Mattox Kenneth L.
Published: May 2012

Blunt abdominal aortic injury (BAAI) is a rare and lethal injury requiring surgical management. Injury patterns can be complex and surgical strategy should accommodate specific case circumstances. Endovascular solutions appear appropriate and preferred in certain cases of BAAI, which, however, may not be applicable due to device limitations in regard to patient anatomy and limited operating room capability. However, endovascular therapy can be pursued with limited fluoroscopy capability and consumable availability providing a solution that is expeditious and effective for select cases of BAAI.
“The brain is such a delicate thing”: an exploration of fear and seizures among young people with epilepsy
Authors: Ryan Sara , Räisänen Ulla
Published: May 2012

Epilepsy is a condition where pathology, diverse manifestations and attached social understandings contribute to an emotional experience unlike many other chronic conditions. The emotional dimension to epilepsy has been little considered in existing research.

Objectives: To explore the emotional experience of young people with epilepsy.

Methods: A qualitative study involving in-depth interviews with 37 young people diagnosed with epilepsy.

Results: Fear emerged as the key emotion and this largely related to the experience, or anticipated experience, of seizure activity. Three key features of fear and epilepsy emerged through the analysis; harm, temporality and action. The fear experienced was not only external, relating to immediate injury, but also internal in terms of potential damage to the brain. The embodied nature of epilepsy can, therefore, present a threat to conceptions of the self. Underlying this internal dimension of fear is an understanding of the brain as central to the sense of self.

Conclusions: The experience of epilepsy does not only involve fear of physical harm but also fear of a loss of self. We conclude that there are broader (alternative) readings of the experience of epilepsy that are often overlooked.
Let’s prevent diabetes: study protocol for a cluster randomised controlled trial of an educational intervention in a multi-ethnic UK population with screen detected impaired glucose regulation
Authors: Gray Laura J , Khunti Kamlesh , Williams Sian , Goldby Stephanie , Troughton Jacqui , Yates Thomas , Gray Alastair , Davies Melanie J ,   for the Let’s Prevent Collaborators
Published: May 2012

Background

The prevention of type 2 diabetes is a globally recognised health care priority, but there is a lack of rigorous research investigating optimal methods of translating diabetes prevention programmes, based on the promotion of a healthy lifestyle, into routine primary care. The aim of the study is to establish whether a pragmatic structured education programme targeting lifestyle and behaviour change in conjunction with motivational maintenance via the telephone can reduce the incidence of type 2 diabetes in people with impaired glucose regulation (a composite of impaired glucose tolerance and/or impaired fasting glucose) identified through a validated risk score screening programme in primary care.

Design

Cluster randomised controlled trial undertaken at the level of primary care practices. Follow-up will be conducted at 12, 24 and 36 months. The primary outcome is the incidence of type 2 diabetes. Secondary outcomes include changes in HbA1c, blood glucose levels, cardiovascular risk, the presence of the Metabolic Syndrome and the cost-effectiveness of the intervention.

Methods

The study consists of screening and intervention phases within 44 general practices coordinated from a single academic research centre. Those at high risk of impaired glucose regulation or type 2 diabetes are identified using a risk score and invited for screening using a 75 g-oral glucose tolerance test. Those with screen detected impaired glucose regulation will be invited to take part in the trial. Practices will be randomised to standard care or the intensive arm. Participants from intensive arm practices will receive a structured education programme with motivational maintenance via the telephone and annual refresher sessions. The study will run from 2009–2014.

Discussion

This study will provide new evidence surrounding the long-term effectiveness of a diabetes prevention programme conducted within routine primary care in the United Kingdom.

Trial registration

Clinicaltrials.gov NCT00677937
Relation between electrical properties of aerosol-deposited BaTiO3 thin films and their mechanical hardness measured by nano-indentation
Authors: Kim Hong-Ki , Oh Jong-Min , In Kim Soo , Kim Hyung-Jun , Lee Chang Woo , Nam Song-Min
Published: May 2012

To achieve a high capacitance density for embedded decoupling capacitor applications, the aerosol deposition (AD) process was applied as a thin film deposition process. BaTiO3 films were fabricated on Cu substrates by the AD process at room temperature, and the film thickness was reduced to confirm the limit of the critical minimum thickness for dielectric properties. As a result, the BaTiO3 thin films that were less than 1-μm thick showed unstable electric properties owing to their high leakage currents. Therefore, to overcome this problem, the causes of the high leakage currents were investigated. In this study, it was confirmed that by comparing BaTiO3 thin films on Cu substrates with those on stainless steels (SUS) substrates, macroscopic defects and rough interfaces between films and substrates influence the leakage currents. Moreover, based on the deposition mechanism of the AD process, it was considered that the BaTiO3 thin films on Cu substrates with thicknesses of less than 1 μm are formed with chinks and weak particle-to-particle bonding, giving rise to leakage currents. In order to confirm the relation between the above-mentioned surface morphologies and the dielectric behavior, the hardness of BaTiO3 films on Cu and SUS substrates was investigated by nano-indentation. Consequently, we proposed that the chinks and weak particle-to-particle bonding in the BaTiO3 thin films with thicknesses of less than 0.5 μm on Cu substrates could be the main cause of the high leakage currents.
Role of JNK Isoforms in the Development of Neuropathic Pain following Sciatic Nerve Transection in the Mouse
Authors: Manassero Giusi , Repetto Ivan E , Cobianchi Stefano , Valsecchi Valeria , Bonny Christophe , Rossi Ferdinando , Vercelli Alessandro
Published: May 2012

Background:

Current tools for analgesia are often only partially successful, thus investigations of new targets for pain therapy stimulate great interest. Consequent to peripheral nerve injury, c-Jun N-terminal kinase (JNK) activity in cells of the dorsal root ganglia (DRGs) and spinal cord is involved in triggering neuropathic pain. However, the relative contribution of distinct JNK isoforms is unclear. Using knockout mice for single isoforms, and blockade of JNK activity by a peptide inhibitor, we have used behavioral tests to analyze the contribution of JNK in the development of neuropathic pain after unilateral sciatic nerve transection. In addition, immunohistochemical labelling for the growth associated protein (GAP)-43 and Calcitonin Gene Related Peptide (CGRP) in DRGs was used to relate injury related compensatory growth to altered sensory function.

Results:

Peripheral nerve injury produced pain–related behavior on the ipsilateral hindpaw, accompanied by an increase in the percentage of GAP43-immunoreactive (IR) neurons and a decrease in the percentage of CGRP-IR neurons in the lumbar DRGs. The JNK inhibitor, D-JNKI-1, successfully modulated the effects of the sciatic nerve transection. The onset of neuropathic pain was not prevented by the deletion of a single JNK isoform, leading us to conclude that all JNK isoforms collectively contribute to maintain neuropathy. Autotomy behavior, typically induced by sciatic nerve axotomy, was absent in both the JNK1 and JNK3 knockout mice.

Conclusions:

JNK signaling plays an important role in regulating pain threshold: the inhibition of all of the JNK isoforms prevents the onset of neuropathic pain, while the deletion of a single splice JNK isoform mitigates established sensory abnormalities. JNK inactivation also has an effect on axonal sprouting following peripheral nerve injury.
The Altar Machine in the Church Mother of Gangi (Palermo, Italy). Interpretation of the past uses, scientific investigation and preservation challenge
Authors: Lo Monaco Angela , Marabelli Maurizio , Pelosi Claudia , Salvo Michele
Published: May 2012

Background

The aim of this work was to study the Altar Machine in the Church Mother of Gangi, a little town near Palermo (Italy) regarding the history, the technical manufacture, the constitutive materials and the state of preservation.

The Altar Machine was dated back to the second half of the 18th century; it is constituted by carved and painted wood, a complex system of winch and pulleys allows move various statues and parts of the Machine in accordance with the baroque scenography machineries.

Results

The observation and survey of the mechanisms allowed formulate hypothesis on a more ancient mode of operation of the Altar Machine.

Laboratory analysis revealed the presence of many superimposed layers constituted by several different materials (protein binders, siccative oils, natural terpene resins, shellac, calcium carbonate, gypsum, lead white, brass, zinc white, iron oxides) and different wood species employed for the original and restoration elements of the Machine. This is due to a continuous usage of the object that has got a demo-ethno-anthropological significance.

Microclimate monitoring (relative humidity RH and temperature T) put in evidence that most of the data fall outside the tolerance intervals, i.e. the RH and T limits defined by the international standards. In particular, T values were generally high (out of the tolerance range) but they appeared to be quite constant; on the other hand RH values fell almost always inside the tolerance area but they often exhibited dangerous variations.

Conclusions

The characterization of the constitutive materials provided useful information both to support the dating of the Machine proposed by the inscription and to obtain a base of data for a possible conservation work.

The microclimate monitoring put in evidence that the temperature and relative humidity values are not always suitable to correctly preserve the artefact. The careful in situ investigation confirmed an on-going climate induced damage to the Altar Machine that, associated to the deterioration caused by its usage, may have dramatic consequences on this unique and peculiar work of art.

The results of this work will have potential implications in the near future regarding a probable conservation project on the Machine.
Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children
Authors: Liu XiWang , Chen QiXing , Shi ShanShan , Shi Zhuo , Lin Ru , Tan LinHua , Yu JianGen , Shu Qiang , Fang XiangMing
Published: May 2012

Introduction

Acute lung injury (ALI) after cardiac surgery is associated with a high postoperative morbidity and mortality, but few predictors are known for the occurrence of the complication. This study evaluated whether elevated plasma levels of soluble receptor for advanced glycation end products (sRAGE) and S100A12 reflected impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB).

Methods

Consecutive children younger than 3 years after cardiac surgery were prospectively enrolled and assigned to ALI and non-ALI groups, according to the American-European Consensus Criteria. Plasma concentrations of sRAGE and S100A12 were measured at baseline, before, and immediately after CPB, as well as 1 hour, 12 hours, and 24 hours after operation.

Results

Fifty-eight patients were enrolled and 16 (27.6%) developed postoperative ALI. Plasma sRAGE and S100A12 levels increased immediately after CPB and remained significantly higher in the ALI group even 24 hour after operation (P < 0.01). In addition, a one-way MANOVA revealed that the overall sRAGE and S100A12 levels were higher in the ALI group than in the non-ALI group immediately after CPB (P < 0.001). The multivariate logistic regression analysis showed that the plasma sRAGE level immediately after CPB was an independent predictor for postoperative ALI (OR, 1.088; 95% CI, 1.011 to 1.171; P = 0.025). Increased sRAGE and S100A12 levels immediately after CPB were significantly correlated with a lower PaO2/FiO2 ratio (P < 0.01) and higher radiographic lung-injury score (P < 0.01), as well as longer mechanical ventilation time (sRAGEN: r = 0.405; P = 0.002; S100A12N: r = 0.322; P = 0.014), longer surgical intensive care unit stay (sRAGEN: r = 0.421; P = 0.001; S100A12N: r = 0.365; P = 0.005) and hospital stay (sRAGEN: r = 0.329; P = 0.012; S100A12N: r = 0.471; P = 0.001).

Conclusions

Elevated sRAGE and S100A12 levels correlate with impaired lung function, and sRAGE is a useful early biomarker of ALI in infants and young children undergoing cardiac surgery.
Brentuximab Vedotin (SGN-35) in Patients With Relapsed or Refractory Systemic Anaplastic Large-Cell Lymphoma: Results of a Phase II Study
Authors: Pro Barbara , Advani Ranjana , Brice Pauline , Bartlett Nancy L. , Rosenblatt Joseph D. , Illidge Tim , Matous Jeffrey , Ramchandren Radhakrishnan , Fanale Michelle , Connors Joseph M. , Yang Yin , Sievers Eric L. , Kennedy Dana A. , Shustov Andrei
Published: May 2012

Purpose

Systemic anaplastic large-cell lymphoma (ALCL) is an aggressive subtype of T-cell lymphoma characterized by the uniform expression of CD30. The antibody-drug conjugate brentuximab vedotin delivers the potent antimicrotubule agent monomethylauristatin E to CD30-positive malignant cells. A phase II multicenter trial was conducted to evaluate the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory systemic ALCL.

Patients and Methods

Patients with systemic ALCL and recurrent disease after at least one prior therapy received brentuximab vedotin 1.8 mg/kg intravenously every 3 weeks over 30 minutes as an outpatient infusion. The primary end point of the study was overall objective response rate as assessed by independent central review.

Results

Of 58 patients treated in the study, 50 patients (86%) achieved an objective response, 33 patients (57%) achieved a complete remission (CR), and 17 patients (29%) achieved a partial remission. The median durations of overall response and CR were 12.6 and 13.2 months, respectively. Grade 3 or 4 adverse events in ≥ 10% of patients were neutropenia (21%), thrombocytopenia (14%), and peripheral sensory neuropathy (12%).

Conclusion

Brentuximab vedotin induced objective responses in the majority of patients and CRs in more than half of patients with recurrent systemic ALCL. Targeted therapy with this CD30-directed antibody-drug conjugate may be an effective treatment for relapsed or refractory systemic ALCL and warrants further studies in front-line therapy.
Scarring, Disfigurement, and Quality of Life in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Kinahan Karen E. , Sharp Lisa K. , Seidel Kristy , Leisenring Wendy , Didwania Aarati , Lacouture Mario E. , Stovall Marilyn , Haryani Anand , Robison Leslie L. , Krull Kevin R.
Published: May 2012

Purpose

Childhood cancer survivors are at increased risk for adverse outcomes and chronic medical conditions. Treatment-related scarring, disfigurement, and persistent hair loss, in addition to their long-term impact on psychological distress or health-related quality of life (HRQOL), have received little attention.

Patients and Methods

Self-reported scarring/disfigurement and persistent hair loss were examined in 14,358 survivors and 4,023 siblings from the Childhood Cancer Survivor Study. Multivariable models were used to examine associations with demographic and cancer treatment. The impact of disfigurement and hair loss on HRQOL (ie, Medical Outcomes Short Form–36) and emotional distress (ie, Brief Symptom Inventory–18) was examined.

Results

Survivors reported a significantly higher rate of scarring/disfigurement compared with siblings for head/neck (25.1% v 8.4%), arms/legs (18.2% v 10.2%), and chest/abdomen (38.1% v 9.1%), as well as hair loss (14.0% v 6.3%). In age-, sex-, and race-adjusted models, cranial radiation exposure ≥ 36 Gy increased risk for head/neck disfigurement (relative risk [RR], 2.42; 95% CI, 2.22 to 2.65) and hair loss (RR, 4.24; 95% CI, 3.63 to 4.95). Adjusting for cranial radiation, age, sex, race, education, and marital status, survivor hair loss increased risk of anxiety (RR, 1.60; 95% CI, 1.23 to 2.07), whereas head/neck disfigurement increased risk of depression (RR, 1.19; 95% CI, 1.01 to 1.41). Limitations due to emotional symptoms were associated with head/neck disfigurement (RR, 1.24; 95% CI, 1.10 to 1.41), arm/leg disfigurement (RR, 1.19; 95% CI, 1.05 to 1.35), and hair loss (RR, 1.26; 95% CI, 1.09 to 1.47).

Conclusion

Survivors of childhood cancer are at increased risk for disfigurement and persistent hair loss, which is associated with future emotional distress and reduced quality of life. Future studies are needed to better identify and manage functional outcomes in these patients.
Effects of a Brief Multimedia Psychoeducational Intervention on the Attitudes and Interest of Patients With Cancer Regarding Clinical Trial Participation: A Multicenter Randomized Controlled Trial
Authors: Jacobsen Paul B. , Wells Kristen J. , Meade Cathy D. , Quinn Gwendolyn P. , Lee Ji-Hyun , Fulp William J. , Gray Jhanelle E. , Baz Rachid C. , Springett Gregory M. , Levine Richard M. , Markham Merry-Jennifer , Schreiber Fred J. , Cartwright Thomas H. , Burke James M. , Siegel Robert D. , Malafa Mokenge P. , Sullivan Daniel
Published: May 2012

Purpose

The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials.

Patients and Methods

A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later.

Results

Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials.

Conclusion

A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials.
Cardiopulmonary Function and Age-Related Decline Across the Breast Cancer Survivorship Continuum
Authors: Jones Lee W. , Courneya Kerry S. , Mackey John R. , Muss Hyman B. , Pituskin Edith N. , Scott Jessica M. , Hornsby Whitney E. , Coan April D. , Herndon James E. , Douglas Pamela S. , Haykowsky Mark
Published: May 2012

Purpose

To evaluate cardiopulmonary function (as measured by peak oxygen consumption [VO2peak]) across the breast cancer continuum and its prognostic significance in women with metastatic disease.

Patients and Methods

Patients with breast cancer representing four cross-sectional cohorts—that is, (1) before, (2) during, and (3) after adjuvant therapy for nonmetastatic disease, and (4) during therapy in metastatic disease—were studied. A cardiopulmonary exercise test (CPET) with expired gas analysis was used to assess VO2peak. A Cox proportional hazards model was used to estimate the risk of death according to VO2peak category (< 15.4 v ≥ 15.4 mL · kg−1 · min−1) with adjustment for clinical factors.

Results

A total of 248 women (age, 55 ± 8 years) completed a CPET. Mean VO2peak was 17.8 ± a standard deviation of 4.3 mL · kg−1 · min−1, the equivalent of 27% ± 17% below age-matched healthy sedentary women. For the entire cohort, 32% had a VO2peak less than 15.4 mL · kg−1 · min−1—the VO2peak required for functional independence. VO2peak was significantly different across breast cancer cohorts for relative (mL · kg−1 · min−1) and absolute (L · min−1) VO2peak (P = .017 and P < .001, respectively); VO2peak was lowest in women with metastatic disease. In patients with metastatic disease (n = 52), compared with patients achieving a VO2peak ≤ 1.09 L · min−1, the adjusted hazard ratio for death was 0.32 (95% CI, 0.16 to 0.67, P = .002) for a VO2peak more than 1.09 L · min−1.

Conclusion

Patients with breast cancer have marked impairment in VO2peak across the entire survivorship continuum. VO2peak may be an independent predictor of survival in metastatic disease.
Efficacy and Safety of Regorafenib in Patients With Metastatic and/or Unresectable GI Stromal Tumor After Failure of Imatinib and Sunitinib: A Multicenter Phase II Trial
Authors: George Suzanne , Wang Qian , Heinrich Michael C. , Corless Christopher L. , Zhu Meijun , Butrynski James E. , Morgan Jeffrey A. , Wagner Andrew J. , Choy Edwin , Tap William D. , Yap Jeffrey T. , Van den Abbeele Annick D. , Manola Judith B. , Solomon Sarah M. , Fletcher Jonathan A. , von Mehren Margaret , Demetri George D.
Published: May 2012

Purpose

Metastatic GI stromal tumor (GIST) is a life-threatening disease with no therapy of proven efficacy after failure of imatinib and sunitinib. Regorafenib is a structurally unique inhibitor of multiple cancer-associated kinases, including KIT and platelet-derived growth factor receptor (PDGFR), with broad-spectrum anticancer activity in preclinical and early-phase trials. Because KIT and PDGFR-α remain drivers of GIST after resistance to imatinib and sunitinib, we performed a multicenter single-stage phase II trial of regorafenib in patients with advanced GIST after failure of at least imatinib and sunitinib.

Patients and Methods

Patients received regorafenib orally, 160 mg daily, on days 1 to 21 of a 28-day cycle. Disease assessment was performed every two cycles per RECIST 1.1. Primary end point was clinical benefit rate (CBR), defined as objective responses (ie, complete or partial response [PR] as well as stable disease [SD] ≥ 16 weeks). Serial tumor biopsies were obtained from consenting patients whenever possible.

Results

From February to December 2010, 34 patients were enrolled at four US centers. As of July 28, 2011, 33 patients had received at least two cycles of regorafenib (range, two to 17 cycles). CBR was 79% (95% CI, 61% to 91%). Four patients achieved PR, and 22 exhibited SD ≥ 16 weeks. Median progression-free survival was 10.0 months. The most common grade 3 toxicities were hypertension and hand-foot-skin reaction.

Conclusion

Regorafenib has significant activity in patients with advanced GIST after failure of both imatinib and sunitinib. A phase III trial of regorafenib versus placebo is ongoing to define more fully the safety and efficacy of regorafenib in this setting.
BRAF/NRAS Mutation Frequencies Among Primary Tumors and Metastases in Patients With Melanoma
Authors: Colombino Maria , Capone Mariaelena , Lissia Amelia , Cossu Antonio , Rubino Corrado , De Giorgi Vincenzo , Massi Daniela , Fonsatti Ester , Staibano Stefania , Nappi Oscar , Pagani Elena , Casula Milena , Manca Antonella , Sini MariaCristina , Franco Renato , Botti Gerardo , Caracò Corrado , Mozzillo Nicola , Ascierto Paolo A. , Palmieri Giuseppe
Published: May 2012

Purpose

The prevalence of BRAF, NRAS, and p16CDKN2A mutations during melanoma progression remains inconclusive. We investigated the prevalence and distribution of mutations in these genes in different melanoma tissues.

Patients and Methods

In all, 291 tumor tissues from 132 patients with melanoma were screened. Paired samples of primary melanomas (n = 102) and synchronous or asynchronous metastases from the same patients (n = 165) were included. Tissue samples underwent mutation analysis (automated DNA sequencing). Secondary lesions included lymph nodes (n = 84), and skin (n = 36), visceral (n = 25), and brain (n = 44) sites.

Results

BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15% NRAS); 62% in lymph nodes, 61% subcutaneous, 56% visceral, and 70% in brain sites. Mutations were observed in 63% of metastases (48% BRAF; 15% NRAS), a nonsignificant increase in mutation frequency after progression from primary melanoma. Of the paired samples, lymph nodes (93% consistency) and visceral metastases (96% consistency) presented a highly similar distribution of BRAF/NRAS mutations versus primary melanomas, with a significantly less consistent pattern in brain (80%) and skin metastases (75%). This suggests that independent subclones are generated in some patients. p16CDKN2A mutations were identified in 7% and 14% of primary melanomas and metastases, with a low consistency (31%) between secondary and primary tumor samples.

Conclusion

In the era of targeted therapies, assessment of the spectrum and distribution of alterations in molecular targets among patients with melanoma is needed. Our findings about the prevalence of BRAF/NRAS/p16CDKN2A mutations in paired tumor lesions from patients with melanoma may be useful in the management of this disease.
Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab
Authors: Weber Jeffrey S. , Kähler Katharina C. , Hauschild Axel
Published: May 2012

Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152)—ipilimumab and tremelimumab—have been investigated in metastatic melanoma and other cancers and have shown promising results. Recently, ipilimumab was approved by the US Food and Drug Administration for the treatment of metastatic melanoma. We review the literature on managing the adverse effects and kinetics of tumor regression with ipilimumab and provide guidelines on their management. During treatment with these antibodies, a unique set of adverse effects may occur, called immune-related adverse events (irAEs). These include rashes, which may rarely progress to life-threatening toxic epidermal necrolysis, and colitis, characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab. Early recognition of irAEs and initiation of treatment are critical to reduce the risk of sequelae. Interestingly, irAEs correlated with treatment response in some studies. Unique kinetics of response have been observed with CTLA-4 blockade with at least four patterns: (1) response in baseline lesions by week 12, with no new lesions seen; (2) stable disease, followed by a slow, steady decline in total tumor burden; (3) regression of tumor after initial increase in total tumor burden; and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. We provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy.
Buddhist Walking Meditations and Contemporary Art of Southeast Asia
Authors: Ly Boreth
Published: May 2012

This essay considers the significant role that Engaged Buddhism plays in contemporary art of Southeast Asia. It argues that this modern Buddhist intellectual movement, which came about in the 1960s in Southeast Asia as a response to political crisis in the world, merits visibility in positions. I look closely at the works by two artists, Montien Boonma and Ann Hamilton. I argue that their works are artistic embodiments of Vipassana meditation and social sufferings, both issues that Engaged Buddhism engages with. Furthermore, I point out that Boonma's installations and Hamilton's site-specific works create a path where the viewers are invited to walk in and to participate in the space of compassion and mindful healing. Last, this essay is a poetic meditation on the political role that Buddhist walking meditation plays as a silent political resistance to an increasingly tourist world of Southeast Asia. I have chosen with deliberation a poetic style of writing that subverts the traditional academic style of writing and in effect, provides an alternative way of articulation that challenges the hegemonic mode of representations in the academy.
Is a New Internationalism Possible?
Authors: Hui Wang
Published: May 2012

This short commemorative piece notes the twenty-year relationship of editors Wang Hui and Tani Barlow and Wang's strong commitment to the international world of journal publication. Wang's long career as a journal founder and editor and his utopian hopes for continuing development of internationalist work through journal projects are noted.
The Polycomb group protein Ring1b is essential for pectoral fin development
Authors: van der Velden Yme U. , Wang Liqin , van Lohuizen Maarten , Haramis Anna-Pavlina G.
Published: May 2012

Polycomb group (PcG) proteins are transcriptional repressors that mediate epigenetic gene silencing by chromatin modification. PcG-mediated gene repression is implicated in development, cell differentiation, stem-cell fate maintenance and cancer. However, analysis of the roles of PcG proteins in orchestrating vertebrate developmental programs in vivo has been hampered by the early embryonic lethality of several PcG gene knockouts in mice. Here, we demonstrate that zebrafish Ring1b, the E3 ligase in Polycomb Repressive Complex 1 (PRC1), is essential for pectoral fin development. We show that differentiation of lateral plate mesoderm (LPM) cells into presumptive pectoral fin precursors is initiated normally in ring1b mutants, but fin bud outgrowth is impaired. Fgf signaling, which is essential for migration, proliferation and cell-fate maintenance during fin development, is not sufficiently activated in ring1b mutants. Exogenous application of FGF4, as well as enhanced stimulation of Fgf signaling by overactivated Wnt signaling in apc mutants, partially restores the fin developmental program. These results reveal that, in the absence of functional Ring1b, fin bud cells fail to execute the pectoral fin developmental program. Together, our results demonstrate that PcG-mediated gene regulation is essential for sustained Fgf signaling in vertebrate limb development.
Drosophila primordial germ cell migration requires epithelial remodeling of the endoderm
Authors: Seifert Jessica R. K. , Lehmann Ruth
Published: May 2012

Trans-epithelial migration describes the ability of migrating cells to cross epithelial tissues and occurs during development, infection, inflammation, immune surveillance, wound healing and cancer metastasis. Here we investigate Drosophila primordial germ cells (PGCs), which migrate through the endodermal epithelium. Through live imaging and genetic experimentation we demonstrate that PGCs take advantage of endodermal tissue remodeling to gain access to the gonadal mesoderm and are unable to migrate through intact epithelial tissues. These results are in contrast to the behavior of leukocytes, which actively loosen epithelial junctions to migrate, and raise the possibility that in other contexts in which migrating cells appear to breach tissue barriers, they are actually exploiting existing tissue permeability. Therefore, the use of active invasive programs is not the sole mechanism to infiltrate tissues.
Re-eroticizing the Hoopoe: Tereus in Aristophanes' Birds
Authors: Holmes Daniel
Published: May 2012

In Aristophanes' Birds the character Tereus plays a pivotal role in persuading the bird chorus to hear Peisetairus' plan for founding a powerful bird-polis. One must ask how Peisetairus achieves his initial persuasion of Tereus, who has happily left behind the violent tyranny of his tragic role, to take on the gods and jeopardize his tranquility. Unlike Dobrov and others, who argue that the comic Tereus is a complete inversion of the tragic character from Sophocles' Tereus , I argue that Aristophanes depicts a comic Tereus who shows from the beginning latent tyrannical and, in particular, erotic qualities that Peisetairus exploits and who thus provides the bridge for erotic human beings to establish an imperial, aerial polis among the contentedly self-sufficient birds.
Leo Baekeland’s Transatlantic Struggle for Bakelite: Patenting Inside and Outside of America
Authors: Mercelis Joris
Published: May 2012

This article analyzes Leo Baekeland’s efforts to secure patent protection on “Bakelite,” the synthetic plastic resin that he invented in 1907, and to exploit the resulting intellectual property rights. It connects the transfer of Baekeland’s intellectual property (IP) to a German-based company with Baekeland’s entrepreneurial choices and IP record in the United States. It also shows that Baekeland’s experiences with European patent regimes shaped his criticism of the U.S. model. His attempts to address perceived shortcomings of the U.S. patent regime, however, did not lead to a satisfactory outcome.
Constraint-Based Task Specification and Control for Visual Servoing Application Scenarios
Authors: de Laet Tinne , Smits Ruben , Bruyninckx Herman , de Schutter Joris
Published: May 2012

This paper reformulates image-based visual servoing as a constraint-based robot task, in order to integrate it seamlessly with other task constraints in image space, in Cartesian space, in the joint space of the robot, or in the “image space” of any other sensor (e. g. force, distance). This approach allows us to fuse various kinds of sensor data. The integration takes place via the specification of generic “feature coordinates”, defined in the different task spaces. Independent control loops are defined to control the individual feature coordinate setpoints, in each of these task spaces. The outputs of the control loops are instantaneously combined into joint velocity setpoints for a velocity-controlled robot that executes the task. The paper includes experimental results for different application scenarios.
Untersuchung eines Miniatur-Nullpunktspannsystems für die Mikro-Fertigung
Authors: Neugebauer Michael , Neuschaefer-Rube Ulrich
Published: May 2012

Ein Nullpunktspannsystem für die Mikro-Fertigung wurde mit Hilfe eines Mikro-Koordinatenmessgerätes auf seine Eigenschaften untersucht. Für die Bewertung des Spannsystems wurden geeignete Kennwerte definiert. Die Wechselgenauigkeit des untersuchten Spannsystems betrug 1,6 μm und die Wiederholgenauigkeit lag unter 0,2 μm.
Effect of EMG‐based Feedback on Posture Correction during Computer Operation
Authors: Park Se‐yeon , Yoo Won‐gyu
Published: May 2012

Effect of EMG‐based Feedback on Posture Correction during Computer Operation: Se‐yeon PARK, et al. Department of Physical Therapy, The Graduate School, Inje University, Republic of Korea—

Objective

The aim of this study was to investigate the effects of an EMG‐based feedback device on the human musculoskeletal system by assessing the kinematics of the lumbar and cervical regions during computer operation.

Methods

Using an EMG device, measurements were collected under four conditions: with feedback from the upper trapezius muscle, from the L4‐erector spinae muscles and from both and without feedback (control). During periods of 15 min of computer operation, kinematic data were collected using the Zebris motion analysis system to investigate 14 university employees.

Results

Feedback assessment effectively reduced the kinematic changes in the sagittal plane compared with the control (p<0.05). Feedback from the L4 erector spinae reduced the trunk flexion and forward head angles, which were significantly different compared with those under the feedback from the upper trapezius and the control conditions (p<0.05).

Conclusion

We observed that the use of an EMG‐based feedback device was effective in reducing habitual forward head and flexed‐relaxed postures during computer operation. Additionally, posture correction from the lumbar region could be a way to reduce forward head posture as well as flexed‐relaxed posture.
Prevalence of Cardiovascular Disease Risk Factors Among US Adolescents, 1999−2008
Authors: May Ashleigh L. , Kuklina Elena V. , Yoon Paula W.
Published: May 2012

OBJECTIVE:

Overweight and obesity during adolescence are associated with an increased risk for cardiovascular disease (CVD) risk factors. The objective of this study was to examine the recent trends in the prevalence of selected biological CVD risk factors and the prevalence of these risk factors by overweight/obesity status among US adolescents.

METHODS:

The NHANES is a cross-sectional, stratified, multistage probability sample survey of the US civilian, noninstitutionalized population. The study sample included 3383 participants aged 12 to 19 years from the 1999 through 2008 NHANES.

RESULTS:

Among the US adolescents aged 12 to 19 years, the overall prevalence was 14% for prehypertension/hypertension, 22% for borderline-high/high low-density lipoprotein cholesterol, 6% for low high-density lipoprotein cholesterol (<35 mg/dL), and 15% for prediabetes/diabetes during the survey period from 1999 to 2008. No significant change in the prevalence of prehypertension/hypertension (17% and 13%) and borderline-high/high low-density lipoprotein cholesterol (23% and 19%) was observed from 1999–2000 to 2007–2008, but the prevalence of prediabetes/diabetes increased from 9% to 23%. A consistent dose-response increase in the prevalence of each of these CVD risk factors was observed by weight categories: the estimated 37%, 49%, and 61% of the overweight, obese, and normal-weight adolescents, respectively, had at least 1 of these CVD risk factors during the 1999 through 2008 study period.

CONCLUSIONS:

The results of this national study indicate that US adolescents carry a substantial burden of CVD risk factors, especially those youth who are overweight or obese.
Childhood Cancer Incidence Trends in Association With US Folic Acid Fortification (1986–2008)
Authors: Linabery Amy M. , Johnson Kimberly J. , Ross Julie A.
Published: May 2012

OBJECTIVE:

Epidemiologic evidence indicates that prenatal vitamin supplementation reduces risk for some childhood cancers; however, a systematic evaluation of population-based childhood cancer incidence trends after fortification of enriched grain products with folic acid in the United States in 1996–1998 has not been previously reported. Here we describe temporal trends in childhood cancer incidence in association with US folic acid fortification.

METHODS:

Using Surveillance, Epidemiology, and End Results program data (1986–2008), we calculated incidence rate ratios and 95% confidence intervals to compare pre- and postfortification cancer incidence rates in children aged 0 to 4 years. Incidence trends were also evaluated by using joinpoint and loess regression models.

RESULTS:

From 1986 through 2008, 8829 children aged 0 to 4 years were diagnosed with malignancies, including 3790 and 3299 in utero during the pre- and postfortification periods, respectively. Pre- and postfortification incidence rates were similar for all cancers combined and for most specific cancer types. Rates of Wilms tumor (WT), primitive neuroectodermal tumors (PNETs), and ependymomas were significantly lower postfortification. Joinpoint regression models detected increasing WT incidence from 1986 through 1997 followed by a sizable decline from 1997 through 2008, and increasing PNET incidence from 1986 through 1993 followed by a sharp decrease from 1993 through 2008. Loess curves indicated similar patterns.

CONCLUSIONS:

These results provide support for a decrease in WT and possibly PNET incidence, but not other childhood cancers, after US folic acid fortification.
Características mineralógicas de uma topossequência de solos da região de São Pedro, Estado de São Paulo
Authors: Demattê J.L.I. , Holowaychuck N.
Published: May 2012

Foram estudados oito pedons localizados em uma topossequência de aproximadamente 25 km de extensão, na região de São Pedro, Estado de São Paulo, indo do rio Piracicaba, na Depressão Paleozóica até o rio Jacaré-Pupira, no Planalto Ocidental. A fração argila da maioria dos solos estudados é formada principalmente por caulinita e gibbsita. Pedons localizados nas superfícies mais baixas (Pedons 1 a 5) possuem baixo teor de gibbsita (menos que 6%) enquanto que os solos localizados nas altas superfícies (Pedons 6, 7 e 8) possuem teores de gibbsita variando de 12 a 54%. Pedon 3 apresenta uma composição mineralógica diferente dos demais solos; a quantidade de minerais de grade 2:1 (mica, vermiculita e montmorilonita) é grande, com teores entre 30 e 70%. Nos demais solos o teor de minerais de grande 2:1 é baixo (menos que 80%) representado principalmente pela vermiculita. Para os solos localizados nas superfícies mais baixas existe correlação entre a mineralogia da argila e as idades das superfícies fisiográficas. Esta relação não é aparente para os solos localizados nas superfícies elevadas. A transformação de caulinita para gibbsita é observada.
Adubacão foliar de mudas de café (Coffea arabica, L., var. Mundo Nôvo) com três fontes de nitrogênio - 15N
Authors: Vasquez A. R. , Neptune A. M. L.
Published: May 2012

O presente trabalho foi conduzido com a finalidade de se avaliar o efeito da aplicação foliar no nitrogênio em mudas de café (Coffea arabica L, var. Mundo Nôvo). Para isso, três fontes de fertilizantes nitrogenados - NaNO3, (NH4)2SO4 e (NH2)2CO - enriquecidos com 0,7, 0,6 e 0,4% de átomos de 15N em excesso, respectivamente, foram utilizados, aplicando-as de vários modos: 1) aplicação da dose total de cada fonte de nitrogênio ao solo; 2) aplicação da dose total de cada fonte exclusivamente foliar e 3) aplicação da metade desta dose total ao solo e da outra metade por via foliar, além das correspondentes testemunhas. O desenho experimental foi de blocos ao acaso, com 14 tratamentos e 3 repetições, com parte dos tratamentos em arranjo fatorial. As mudas de café, de 6 meses de idade foram cultivadas em casa de vegetação, durante um período de 7 meses. A seguir, as palantas foram separadas em frações raiz, caule e folha. Sobre estas frações, secas em estufa, pesadas e moídas, procedeu-se às análises químicas do nitrogênio e à determinação da relação isotópica 14N/15N. A produção de matéria seca, a quantidade de nitrogênio absorvido, aquela proveniente do solo e do fertilizante, por cada tratamento, em cada fração e na planta toda. foram utilizados para avaliar o efeito da adubação foliar ds fontes de nitrogênio. Pra a aplicação foliar do nitrogênio, foi construído um sistema espacial de pulverização. De acordo com os resultados obtidos são apresentadas, a continuação, as seguintes inferências. De maneira geral, a aplicação das três fontes de nitrogênio ao solo, seguida pela aplicação combinada ao solo e à folha, deram maior produção de matéria seca, não havendo diferença entre as fontes. Em relação a absorção do nitrogênio total, foi verificada uma maior absorção com a aplicação ao solo das três fontes de nitrogênio. No que diz respeito ao nitrogênio nas plantulas provenientes do fertilizante, a aplicação ao solo foi superior a aplicação foliar, para as três fontes. A porcentagem da eficiência do nitrogênio foi de 39%. Na aplicação foliar, a eficiência do nitrogênio foi 12,8%, 9,7% e 8,6% para nitrato de sódio, a uréia e o sulfato de amônio respectivamente. Na aplicação combinada, metade solo mais metade folha, a eficiência foi de 33,5%, 23,3% e 22,7% para o nitrato de sódio, o sulfato de amônio e a uréia, respectivamente. É difícil, no presente trabalho, explicar a pouca absorção do nitrogênio aplicada por pulverização foliar, destacando-se o nitrato de sódio em relação Ys outras fontes.