bluuebunny/crossref_metadata_2025 huggingface dataset:
Addition of Taxane to Induction Therapy in Head and Neck Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Perl Gali , Ben-Aharon Irit , Popovtzer Aron , Stemmer Salomon M. , Vidal Liat
Published: July 2014

Background: Head and neck cancer, mostly squamous cell carcinoma, ranks sixth among the most common cancers. Despite progress in treatment in recent years, survival remains poor. Since induction chemotherapy has been associated with survival benefit, it is a reasonable treatment option. The standard protocol up to recently has been cisplatin and 5-flourouracil. The addition of taxanes to the standard induction protocol has shown superiority in terms of the overall response rate. Nevertheless, not all trials demonstrated survival benefit. We aimed to evaluate the effect of taxane added to the standard protocol of induction therapy. Methods: We performed a systematic review and meta-analysis of randomized controlled trials that compared the addition of taxane to the standard induction protocol of cisplatin and 5-flourouracil for patients with head and neck malignancy. We searched The Cochrane library, PubMed, LILACS, conference proceedings, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios (HRs) for time-to-event were determined and pooled. Results: A total of 4 trials comprising 1,441 patients were included in this meta-analysis. All patients were available for the meta-analysis of overall survival. Patients treated with the addition of taxane had statistically significant overall survival [HR = 0.82, 95% confidence interval (CI) 0.71-0.94] and progression-free survival (HR = 0.82, 95% CI 0.72-0.93). No effect was observed in larynx preservation rate (relative risk = 0.88, 95% CI 0.64-1.19). The rate of hematological adverse events was higher in the taxane group than in the control group. Conclusions: These results suggest that induction therapy with the addition of taxane is superior to induction therapy with cisplatin and 5-flourouracil in terms of overall survival and progression-free survival. The higher rate of neutropenia and neutropenic fever should be taken into consideration when making treatment decisions.
Presence of an Umbilical Artery Notch in Monochorionic/Monoamniotic Twins
Authors: Aurioles-Garibay Alma , Hernandez-Andrade Edgar , Romero Roberto , Garcia Maynor , Qureshi Faisal , Jacques Suzanne M. , Ahn Hyunyoung , Yeo Lami , Chaiworapongsa Tinnakorn , Hassan Sonia S.
Published: July 2014

Objective: To examine the association between an umbilical artery notch and fetal deterioration in monochorionic/monoamniotic (MC/MA) twins. Methods: Six MC/MA twin pregnancies were admitted at 24-28 weeks of gestation for close fetal surveillance until elective delivery at 32 weeks or earlier in the presence of signs of fetal deterioration. Ultrasound (US) examinations were performed twice weekly. The presence of cord entanglement, umbilical artery notch, abnormal Doppler parameters, a non-reassuring fetal heart rate pattern, or an abnormal fetal biophysical profile were evaluated. Results: Umbilical cord entanglement was observed on US in all pregnancies. The presence of an umbilical artery notch was noted in four out of six pregnancies and in two of them an umbilical artery notch was seen in both twins. The umbilical artery pulsatility index was normal in all fetuses. Doppler parameters of the middle cerebral artery and ductus venosus, fetal biophysical profile and fetal heart rate monitoring remained normal until delivery in all pregnancies. All neonates experienced morbidity related to prematurity; however, all were discharged home in good condition. Conclusion: The presence of an umbilical artery notch and cord entanglement, without other signs of fetal deterioration, are not indicative of an adverse perinatal outcome.
First-Line Combination Chemotherapy with Cisplatin, Etoposide and Ifosfamide for the Treatment of Disseminated Germ Cell Cancer: Re-Evaluation in the Granulocyte Colony-Stimulating Factor Era
Authors: Tanaka Hajime , Yuasa Takeshi , Fujii Yasuhisa , Sakura Mizuaki , Urakami Shinji , Yamamoto Shinya , Masuda Hitoshi , Fukui Iwao , Yonese Junji
Published: July 2014

Background: This study re-evaluated the efficacy and tolerability of cisplatin, etoposide, and ifosfamide (VIP) combination chemotherapy as an alternative first-line regimen for patients with disseminated germ cell cancer (GCC) in this granulocyte colony-stimulating factor (G-CSF) era. Methods: The medical records of 91 consecutive patients with previously untreated disseminated GCC who received first-line VIP between 1995 and 2011 were retrospectively reviewed. Results: The 5-year overall survival rates for patients with good (n = 49), intermediate (n = 22) and poor (n = 20) prognoses according to the International Germ Cell Cancer Collaborative Group classification were 100, 79 and 83%, respectively. G-CSF was given to all patients, and no treatment-related deaths due to myelosuppression occurred. Conclusion: The present study is the first to examine the therapeutic outcomes and safety profile of first-line VIP after routine G-CSF use. VIP might be an alternative first-line regimen for patients with disseminated GCC in this G-CSF era.
Esse est percipi: A Neurophilosophical Model of Psychosis
Authors: Perogamvros Lampros
Published: July 2014

Philosophers, psychiatrists and neuroscientists have all expressed interest in and formulated hypotheses on the nature of hallucinations, but no sufficient integration of these models exists to this date. The objective of this article is to present a neurophilosophical model of psychosis linking the neurobiology with the phenomenology of hallucinations and delusions. It is proposed that psychotic hallucinations could be regarded as ‘intrusions' of subjective idealism, a condition where reality is mind dependent, into realism, a condition where reality is mind independent. Furthermore, delusions would be an attempt by the person to make sense of these intrusions. This approach is supported by phenomenological evidence of increased self-relatedness in hallucinations and delusions, and by current neurobiological evidence on the role of the reward system, default mode network and corollary discharge circuit in positive symptomatology. This model has clinical, research and therapeutic implications, and also demonstrates how scientific results can be informed and enhanced by philosophical theories and vice versa.
Factors Influencing Linezolid-Nonsusceptible Coagulase-Negative Staphylococci Dissemination Among Patients in the Intensive Care Unit: A Retrospective Cohort Study
Authors: Papadimitriou-Olivgeris Matthaios , Giormezis Nikolaos , Fligou Fotini , Liakopoulos Apostolos , Marangos Markos , Anastassiou Evangelos D. , Petinaki Efthimia , Filos Kriton S. , Spiliopoulou Iris
Published: July 2014

Background: The aim of the present study was to identify risk factors for linezolid-nonsusceptible coagulase-negative staphylococci (CNS) dissemination in the intensive care unit. Methods: Among the 246 patients included, 33 revealed a linezolid-nonsusceptible CNS-positive culture specimen, 68 were positive for linezolid-susceptible CNS and 145 served as controls. Isolates were characterized by phenotypic and genotypic methods to species level, susceptibility to antistaphylococcal agents and clones. Results: Among the 33 linezolid-nonsusceptible CNS patients, 29 revealed Staphylococcus epidermidis and 4 Staphylococcus capitis. All S. epidermidis strains belonged to the ST22 clone (by multilocus sequence typing), 26 carried both C2534T and T2504A and 3 strains were C2543T mutations. S. capitis strains were stratified as a common pulsed-field gel electrophoresis type and carried the G2576T mutation. Risk factors for linezolid-nonsusceptible CNS isolation were linezolid administration and mean number of linezolid-nonsusceptible CNS-positive patients in nearby beds per day. Conclusions: These results reinforce the aspect of rational antibiotic usage, but also highlight the need for strict infection control measures to prevent the dissemination of linezolid-nonsusceptible CNS.
Reduced Plasma Corticotropin-Releasing Hormone Levels during Late Gestation in Patients with Intrahepatic Cholestasis of Pregnancy
Authors: Huang Guiqiong , Liu Zhengfei , He Maomao , Wang Xiaodong
Published: July 2014

Objective: Intrahepatic cholestasis of pregnancy (ICP) may lead to sudden onset of stillbirth, which most likely is related to uteroplacental insufficiency and dysregulation of the fetal blood supply. The relaxing effect of corticotropin-releasing hormone (CRH) on blood vessels was measured to examine the role of CRH in the pathogenesis of ICP. Methods: Eighty normal pregnant women and 80 ICP patients were divided into four groups of 20 cases, respectively, each based on gestational age from week 34 to 37. Radioimmunoassay was used to measure CRH in plasma samples collected from all of the subjects. Results: Plasma CRH increased markedly from week 34 to 37 in both ICP and healthy patients, but the increase was lower in the ICP group. Plasma CRH was 322 ± 61 pg/ml in mild ICP cases at 37 weeks' compared to 1,066 ± 173 pg/ml in controls (p < 0.05), but only 218 ± 128 pg/ml in severe ICP (p < 0.05). Plasma CRH was significantly lower at all other measured time points in patients with severe ICP. In ICP patients, there was a negative correlation between plasma CRH and total bile acid (TBA). Conclusion: A limited increasing CRH level and negative correlation of CRH with TBA were unveiled in ICP patients.
TNF-α G308A Gene Polymorphism Has an Impact on Renal Function, Microvascular Permeability, Organ Involvement and Severity of Preeclampsia
Authors: Zubor Pavol , Dokus Karol , Zigo Imrich , Skerenova Maria , Pullmann Rudolf , Danko Jan
Published: July 2014

Background/Aims: Preeclampsia (PE) is a life-threatening complication of pregnancy that is associated with a high rate of maternal and perinatal morbidity and/or mortality worldwide. If untreated, it can progress to eclampsia, which can result in the death of the mother, the fetus or both. The etiology of PE is still uncertain; however, recently the role of the immune system has gained in importance. The role of tumor necrosis factor-α (TNF-α), a cytokine involved in inflammation processes, has been widely investigated in obstetric disorders. The aims of the present study were to investigate the effect of TNF-α gene G308A (rs1800629) polymorphism on disease risk, renal function, microvascular permeability, endothelial cell dysfunction and organ involvement in women with PE. Methods: Initially, 102 3rd-trimester pregnant women (preeclamptic cases and healthy controls) with singleton pregnancy were invited for participation, of which 76 were genotyped for TNF-α G308A polymorphism and evaluated for plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), fibronectin and TNF-α, which were tested for correlations with the profile of PE. The odds ratio (OR) and 95% confidence intervals obtained from unconditional logistic regression were used to test the association between the TNF-α polymorphism and PE risk. For continuous variables, we applied Student's t test and, for categorical variables, the Pearson χ2 or Fisher's exact test. The two-way ANOVA test with Bonferroni correction was used in multivariate analyses. Results: The A allele was more frequent in cases than controls (22.4 vs. 13.2%), which increased disease risk (OR = 2.73). Maternal serum levels of TNF-α, sVCAM-1 and fibronectin were significantly increased in cases (855.8 ± 385.1 pg/ml, 1,243 ± 671 ng/ml, 0.308 ± 0.231 g/l, respectively) compared to controls (301.1 ± 156.1 pg/ml, 651 ± 250 ng/ml, 0.218 ± 0.101 g/l, respectively; p < 0.0001, p < 0.0001 and p = 0.031, respectively), and these levels showed an increasing trend with the mutant allele genotype. Moderate and severe proteinuria was higher in rs1800629 allele A subjects compared to G/G carriers (53.8 vs. 14.3% (p < 0.05) and 13.0 vs. 4.7% (p < 0.01), respectively). The adverse effect of rs1800629 allele A on renal function was confirmed by increased plasma creatine levels, urinary protein excretion and lower tubular resorption rate in preeclamptic patients. Moreover, rs1800629 allele A preeclamptic carriers showed higher serum levels of fibronectin and sVCAM-1 compared to G/G homozygotes. Conclusion: This study reveals a possible association between clinical and laboratory manifestations of PE and the TNF-α gene G308A (rs1800629) polymorphism.
Mozart, Music and Medicine
Authors: Pauwels Ernest K.J. , Volterrani Duccio , Mariani Giuliano , Kostkiewics Magdalena
Published: July 2014

According to the first publication in 1993 by Rauscher et al. [Nature 1993;365:611], the Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448. A further evaluation of this effect has raised the question whether there is a link between music-generated emotions and a higher level of cognitive abilities by mere listening. Positron emission tomography and functional magnetic resonance imaging have revealed that listening to pleasurable music activates cortical and subcortical cerebral areas where emotions are processed. These neurobiological effects of music suggest that auditory stimulation evokes emotions linked to heightened arousal and result in temporarily enhanced performance in many cognitive domains. Music therapy applies this arousal in a clinical setting as it may offer benefits to patients by diverting their attention from unpleasant experiences and future interventions. It has been applied in the context of various important clinical conditions such as cardiovascular disorders, cancer pain, epilepsy, depression and dementia. Furthermore, music may modulate the immune response, among other things, evidenced by increasing the activity of natural killer cells, lymphocytes and interferon-γ, which is an interesting feature as many diseases are related to a misbalanced immune system. Many of these clinical studies, however, suffer from methodological inadequacies. Nevertheless, at present, there is moderate but not altogether convincing evidence that listening to known and liked music helps to decrease the burden of a disease and enhances the immune system by modifying stress.
Usability of Mobile Technology to Screen for Drug-Drug Interactions in Kidney Transplant Patients
Authors: De Silva Lalitha , Diamantidis Clarissa J. , Prakash Divya , Zuckerman Marni , Weir Matthew R.
Published: July 2014

Background and Objectives: Kidney transplant recipients are at increased risk for adverse safety events related to reduced renal function and polypharmacy. Health information technology tools have a precautionary role in improving safety in patients with kidney transplants who are at risk of drug-drug interactions. Materials and Methods: Usability testing of a drug-drug interaction inquiry system on a convenience sample of kidney transplant patients and their family members was conducted between January and April 2013 by a single interviewer. Each participant was provided with 35 tasks to complete on a cell phone with a manual keypad. The tasks were classified according to how it was completed: easily completed, noncritical error, or critical error (where a participant was unable to complete the given task without intervention by the interviewer). The final task was timed using a stop watch. Results: Out of a total of 16 volunteers, 15 completed the testing. The median time to complete the final task was 4 min (range: 2-9). In a cumulative total of 525 tasks, 33 critical errors were noted. Twelve participants had one or more critical errors. The most frequent critical errors were related to typing and spelling mistakes. Twelve out 15 participants were able to complete the final task without any critical errors. Conclusions: Understanding transplant patients' preference in technology use and adapting applications to a variety of technological portals will ensure the most effective use of targeted interventions in patient safety, particularly when applied to preventing drug-drug interactions.
On the Possibility of Lipid-Induced Regulation of Conformation and Immunogenicity of Influenza A Virus H1/N1 Hemagglutinin as Antigen of TI-Complexes
Authors: Vorobieva Natalia , Sanina Nina , Vorontsov Vladimir , Kostetsky Eduard , Mazeika Andrey , Tsybulsky Alexander , Kim Natalia , Shnyrov Valery
Published: July 2014

The tubular immunostimulating complex (TI-complex) consisting of cucumarioside A2-2, cholesterol and monogalactosyldiacylglycerol (MGDG) from marine macrophytes is the perspective antigen delivery system for subunit vaccines. MGDG is a lipid matrix for the protein antigen incorporated in the TI-complex. The aim of the present work was to study the influence of MGDGs from different macrophytes on conformation and immunogenicity of the secreted recombinant uncleaved hemagglutinin monomer (HA0S) of influenza A virus H1/N1. Differential scanning calorimetry, fluorescence spectroscopy and circular dichroism showed a dependence of the conformational changes of HA0S on the microviscosity of MGDG. The most viscous MGDG from Zostera marina induced the strongest rearrangements in protein conformation. Immunization of mice with HA0S within TI-complexes comprising different MGDGs resulted in an approximately 2-fold increase of the levels of anti-HA0S antibodies and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared with those induced by HA0S alone. TI-complexes based on MGDG from Z. marina stimulated the maximal production of GM-CSF. However, humoral immune response (anti-HA0S antibodies), unlike cell-mediated immune response (GM-CSF), did not depend on the physicochemical properties of MGDGs. It is assumed that this is due to the different localization and conformational lipid sensitivity of the HA0S regions, which are responsible for these types of immune responses.
Incidence and Relevance of Proteinuria in Bevacizumab-Treated Patients: Pooled Analysis from Randomized Controlled Trials
Authors: Lafayette Richard A. , McCall Bruce , Li Nicole , Chu Laura , Werner Patricia , Das Asha , Glassock Richard
Published: July 2014

Background: This analysis evaluated the incidence of and risk factors for bevacizumab-related proteinuria and assessed for any associated clinical sequelae, including renal function changes. Methods: Patient-level adverse event and laboratory data from a pooled safety database were used to characterize alterations in urine protein excretion following interventional therapy ± bevacizumab in 17 randomized trials across multiple tumor types. Severity of renal function change was assessed using changes in serum creatinine concentration from baseline values. Potential predictors of proteinuria and the association between proteinuria and other adverse events were also investigated. Results: Among 14,548 patients, the incidence of any-grade proteinuria was 8.2% (733/8,917) and 4.6% (257/5,631) in the bevacizumab and control groups, respectively; rates of grade ≥3 proteinuria were 1.4 and 0.2%. Post-baseline proteinuria grade and bevacizumab were associated with increased rates of renal dysfunction. Patients developing proteinuria had an increased rate of any-grade infection but not thromboembolic events. History of diabetes was the only examined risk factor that appeared to have a significant association with proteinuria development. Conclusions: This analysis confirmed a significant increase in the development of proteinuria during bevacizumab treatment. We also observed an increased rate of renal dysfunction associated with bevacizumab treatment and among subjects with proteinuria, although the dysfunction was generally mild. The development of proteinuria was also associated with a modest increase in risk of infection.
Serum Neutrophil Gelatinase-Associated Lipocalin Levels and Aortic Stiffness in Noncritical Coronary Artery Disease
Authors: Soylu Korhan , Nar Gökay , Aksan Gökhan , Gedikli Ömer , İnci Sinan , Yuksel Serkan , Nar Rukiye , İdil Soylu Ayşegül , Gulel Okan , Şahin Mahmut
Published: July 2014

Aim: The aim of this study was to establish the degree of aortic stiffness and levels of neutrophil gelatinase-associated lipocalin (NGAL) in patients with stable ischemic heart disease. Materials and Methods: Patients who were found to have stable, noncritical lesions on coronary angiography were included in the study [noncritical coronary artery disease (CAD)]. The control group consisted of those patients who had similar risk profiles and metabolic parameters without atherosclerosis on angiography. Results: A total of 101 patients were included in the study of which 56 had noncritical CAD. Whereas the aortic strain (9.11 ± 3.4 vs. 14.01 ± 4.1%, p < 0.001) and aortic distensibility (3.98 ± 1.9 10-6 cm2/dyn vs. 6.33 ± 2.3 10-6 cm2/dyn, p < 0.001) were lower in the noncritical CAD group, the aortic stiffness index was higher (6.34 ± 3.9 vs. 3.37 ± 2.4, p < 0.001) as compared to controls. Serum NGAL levels were higher in the noncritical CAD group (79.29 ± 38.8 vs. 48.05 ± 21.4 ng/ml, p < 0.001). NGAL levels were negatively correlated with aortic strain (p < 0.01, r = 0.57) and distensibility (p < 0.001, r = 0.62), but positively correlated with the aortic stiffness index (p < 0.001, r = 0.72). Conclusion: We show that in patients with noncritical CAD, the degree of aortic stiffness and NGAL levels are higher. These markers can be used as tools for further risk stratification of patients with noncritical CAD.
Attenuated Psychosis Syndrome: Need for Debate on a New Disorder
Authors: Carpenter William T.
Published: July 2014

This ‘pro' statement of the controversial issue, defending the need for a new disorder classification of attenuated psychosis syndrome (APS), provides data supporting the clinical validity of this category and responds to the most frequently asserted criticisms. It provides arguments why APS is not pathologizing non-ill behaviors and is not stigmatizing for those affected but rather they merit clinical attention for what is already manifest. It also argues against the view that establishing the diagnostic category of APS results in an unreasoned excessive use of antipsychotic medications but rather encourages prevention and early intervention programs. Finally, bodies of research are presented which could contribute to further validating APS and provide the preconditions for moving this category from Section 3 to Section 2 of DSM-5.1.
Gastrointestinal Bleeding in Acute Ischemic Stroke: Recent Trends from the Fukuoka Stroke Registry
Authors: Ogata Toshiyasu , Kamouchi Masahiro , Matsuo Ryu , Hata Jun , Kuroda Junya , Ago Tetsuro , Sugimori Hiroshi , Inoue Tooru , Kitazono Takanari ,   on behalf of the Fukuoka Stroke Registry
Published: July 2014

Background: Gastrointestinal (GI) hemorrhage is a potentially serious complication of acute stroke, but its incidence appears to be decreasing. The aim of this study was to elucidate the etiology of GI bleeding and its impact on clinical outcomes in patients with acute ischemic stroke in recent years. Methods: Using the database of the Fukuoka Stroke Registry, 6,529 patients with acute ischemic stroke registered between June 2007 and December 2012 were included in this study. We recorded clinical data including any previous history of peptic ulcer, prestroke drug history including the use of antiplatelets, anticoagulants, steroids and nonsteroidal anti-inflammatory drugs (NSAIDs), and poststroke treatment with suppressing gastric acidity. GI bleeding was defined as any episode of hematemesis or melena on admission or during hospitalization. The cause and origin of bleeding were diagnosed endoscopically. Logistic regression analysis was used to identify risk factors for GI bleeding and its influence on deteriorating neurologic function, death, and poor outcome. Results: GI bleeding occurred in 89 patients (1.4%) under the condition that 66% of the total patients received acid-suppressing agents after admission. Multivariate analysis revealed that GI bleeding was associated with the absence of dyslipidemia (p = 0.03), a previous history of peptic ulcer (p < 0.001), and the severity of baseline neurologic deficit (p = 0.002) but not with antiplatelet drugs, anticoagulants, and NSAIDs. The source was the upper GI tract in 51% of the cases; causes included peptic ulceration (28%) and malignancies (12%), and other or unidentified causes accounted for 60%. GI bleeding mostly occurred within 1 week after stroke onset. Hemoglobin concentration fell by a median value of 2.5 g/dl in patients with GI bleeding. Among them, 28 patients underwent blood transfusion (31.5%). After adjustment for confounding factors, GI bleeding was independently associated with neurologic deterioration (OR 3.9, 95% CI 2.3-6.6, p < 0.001), in-hospital death (OR 6.1, 95% CI 3.1-12.1, p < 0.001), and poor outcome at 3 months (OR 6.8, 95% CI 3.7-12.7, p < 0.001). These associations were significant irrespective of whether patients underwent red blood cell transfusion. Conclusions: GI bleeding infrequently occurred in patients with acute ischemic stroke, which was mostly due to etiologies other than peptic ulcer. GI bleeding was associated with poor clinical outcomes including neurologic deterioration, in-hospital mortality, and poor functional outcome.
Histone H3 Dynamics in Plant Cell Cycle and Development
Authors: Otero Sofía , Desvoyes Bénédicte , Gutierrez Crisanto
Published: July 2014

Chromatin is a macromolecular complex where DNA associates with histone proteins and a variety of non-histone proteins. Among the 4 histone types present in nucleosomes, histone H3 is encoded by a large number of genes in most eukaryotic species and is the histone that contains the largest variety of potential post-translational modifications in the N-terminal amino acid residues. In addition to centromeric histone H3, 2 major types of histone H3 exist, namely the canonical H3.1 and the variant H3.3. In this article, we review the most recent observations on the distinctive features of plant H3 proteins in terms of their expression and dynamics during the cell cycle and at various developmental stages. We also include a discussion on the histone H3 chaperones that actively participate in H3 deposition, in particular CAF-1, HIRA and ASF1, and on the putative plant homologs of human ATRX and DEK chaperones. Accumulating evidence confirms that the balanced deposition of H3.1 and H3.3 is of primary relevance for cell differentiation during plant organogenesis.
Unique Clinicopathology of Proximal Gastric Carcinoma: A Critical Review
Authors: Huang Qin
Published: July 2014

Background: Gastric cancer is a heterogeneous disease with respect to its molecular and histopathological features. Proximal gastric carcinoma (PGC) and distal gastric carcinoma (DGC) are two distinct clinical entities, suggesting the existence of different pathogenic mechanisms. PGC arises in a narrow region of the proximal stomach below the gastroesophageal junction. It accounts for around half of gastric cancers in men, with an increasing incidence worldwide and a predominance in elderly males. Summary: At present, the pathogenic mechanisms involved in the onset of PGC remain unknown. This mini-review presents the most recent findings on the pathology and natural history of this widespread and frequently fatal cancer. Key Message: PGC has unique clinicopathological characteristics distinct from esophageal adenocarcinoma and DGC. Practical Implications: Patients with a high risk for PGC, such as elderly obese men, should undergo upper endoscopy for early detection and appropriate endoscopic therapy in the early stages of disease. Once it has progressed, the cancer is more easily spread, although the current staging systems are not perfectly adapted to the disease. PGC should be staged and treated as a gastric cancer. A separate staging system and genomic studies on this cancer are urgently needed for optimal patient management and appropriate disease prevention.
Durable Response to Crizotinib in a MET-Amplified, KRAS-Mutated Carcinoma of Unknown Primary
Authors: Palma Norma A. , Ali Siraj M. , O'Connor Jamie , Dutta Deepa , Wang Kai , Soman Salil , Palmer Gary A. , Morosini Deborah , Ross Jeffrey S. , Lipson Doron , Stephens Phil J. , Patel Mayur , Miller Vincent A. , Koutrelakos Nicholas
Published: July 2014

Background: Carcinoma of unknown primary (CUP) accounts for 3-5% of all adult solid tumors. An extensive search for the anatomic site of origin is often undertaken in an attempt to tailor systemic treatment, but the latter often has limited efficacy - especially in the setting of an initial treatment failure. Molecularly targeted therapy is an emerging approach that may offer greater efficacy and less toxicity but is most likely to be effective when pairing a tumor harboring a sensitizing genomic alteration with an agent directed at the altered gene product. We report a patient with a CUP harboring a MET amplification with a complete metabolic response to crizotinib despite also harboring a KRAS mutation. Methods: Genomic profiling was performed using a clinical next-generation-sequencing-based assay, FoundationOne®, in a CAP-accredited laboratory certified by Clinical Laboratory Improvement Amendments (Foundation Medicine, Cambridge, Mass., USA). Results: The CUP harbored both MET amplification (16 copies) and a KRAS G12V mutation. The patient was treated with crizotinib, a MET inhibitor, and has experienced a complete normalization of tumor metabolic activity for more than 19 months. Conclusions: Genomic profiling of CUP may reveal clinically meaningful genomic alterations that can guide targeted therapy decision-making. The use of this approach should be studied prospectively as a strategy for the effective treatment of CUP patients and for avoiding resource-intensive workups to identify the tumor site of origin.
Sex Differences in Long-Term Mortality After Myocardial Infarction
Authors: Bucholz Emily M. , Butala Neel M. , Rathore Saif S. , Dreyer Rachel P. , Lansky Alexandra J. , Krumholz Harlan M.
Published: July 2014

Background—

Studies of sex differences in long-term mortality after acute myocardial infarction have reported mixed results. A systematic review is needed to characterize what is known about sex differences in long-term outcomes and to define gaps in knowledge.

Methods and Results—

We searched the Medline database from 1966 to December 2012 to identify all studies that provided sex-based comparisons of mortality after acute myocardial infarction. Only studies with at least 5 years of follow-up were reviewed. Of the 1877 identified abstracts, 52 studies met the inclusion criteria, of which 39 were included in this review. Most studies included fewer than one-third women. There was significant heterogeneity across studies in patient populations, methodology, and risk adjustment, which produced substantial variability in risk estimates. In general, most studies reported higher unadjusted mortality for women compared with men at both 5 and 10 years after acute myocardial infarction; however, many of the differences in mortality became attenuated after adjustment for age. Multivariable models varied between studies; however, most reported a further reduction in sex differences after adjustment for covariates other than age. Few studies examined sex-by-age interactions; however, several studies reported interactions between sex and treatment whereby women have similar mortality risk as men after revascularization.

Conclusions—

Sex differences in long-term mortality after acute myocardial infarction are largely explained by differences in age, comorbidities, and treatment use between women and men. Future research should aim to clarify how these differences in risk factors and presentation contribute to the sex gap in mortality.
Wolff-Parkinson-White Syndrome in the Era of Catheter Ablation
Authors: Pappone Carlo , Vicedomini Gabriele , Manguso Francesco , Saviano Massimo , Baldi Mario , Pappone Alessia , Ciaccio Cristiano , Giannelli Luigi , Ionescu Bogdan , Petretta Andrea , Vitale Raffaele , Cuko Amarild , Calovic Zarko , Fundaliotis Angelica , Moscatiello Mario , Tavazzi Luigi , Santinelli Vincenzo
Published: July 2014

Background—

The management of Wolff-Parkinson-White is based on the distinction between asymptomatic and symptomatic presentations, but evidence is limited in the asymptomatic population.

Methods and Results—

The Wolff-Parkinson-White registry was an 8-year prospective study of either symptomatic or asymptomatic Wolff-Parkinson-White patients referred to our Arrhythmology Department for evaluation or ablation. Inclusion criteria were a baseline electrophysiological testing with or without radiofrequency catheter ablation (RFA). Primary end points were the percentage of patients who experienced ventricular fibrillation (VF) or potentially malignant arrhythmias and risk factors. Among 2169 enrolled patients, 1001 (550 asymptomatic) did not undergo RFA (no-RFA group) and 1168 (206 asymptomatic) underwent ablation (RFA group). There were no differences in clinical and electrophysiological characteristics between the 2 groups except for symptoms. In the no-RFA group, VF occurred in 1.5% of patients, virtually exclusively (13 of 15) in children (median age, 11 years), and was associated with a short accessory pathway antegrade refractory period (
P
<0.001) and atrioventricular reentrant tachycardia initiating atrial fibrillation (
P
<0.001) but not symptoms. In the RFA group, ablation was successful in 98.5%, and after RFA, no patients developed malignant arrhythmias or VF over the 8-year follow-up. Untreated patients were more likely to experience malignant arrhythmias and VF (log-rank
P
<0.001). Time-dependent receiver-operating characteristic curves for predicting VF identified an optimal anterograde effective refractory period of the accessory pathway cutoff of 240 milliseconds.

Conclusions—

The prognosis of the Wolff-Parkinson-White syndrome essentially depends on intrinsic electrophysiological properties of AP rather than on symptoms. RFA performed during the same procedure after electrophysiological testing is of benefit in improving the long-term outcomes.
Atrial Fibrillation and Cognitive Decline–The Role of Subclinical Cerebral Infarcts
Authors: Chen Lin Y. , Lopez Faye L. , Gottesman Rebecca F. , Huxley Rachel R. , Agarwal Sunil K. , Loehr Laura , Mosley Thomas , Alonso Alvaro
Published: July 2014

Background and Purpose—

The mechanism underlying the association of atrial fibrillation (AF) with cognitive decline in stroke-free individuals is unclear. We examined the association of incident AF with cognitive decline in stroke-free individuals, stratified by subclinical cerebral infarcts (SCIs) on brain MRI scans.

Methods—

We analyzed data from 935 stroke-free participants (mean age±SD, 61.5±4.3 years; 62% women; and 51% black) from 1993 to 1995 through 2004 to 2006 in the Atherosclerosis Risk in Communities Study, a biracial community-based prospective cohort study. Cognitive testing (including the digit symbol substitution and the word fluency tests) was performed in 1993 to 1995, 1996 to 1998, and 2004 to 2006 and brain MRI scans in 1993 to 1995 and 2004 to 2006.

Results—

During follow-up, there were 48 incident AF events. Incident AF was associated with greater annual average rate of decline in digit symbol substitution (−0.77; 95% confidence interval, −1.55 to 0.01;
P
=0.054) and word fluency (−0.80; 95% confidence interval, −1.60 to −0.01;
P
=0.048). Among participants without SCIs on brain MRI scans, incident AF was not associated with cognitive decline. In contrast, incident AF was associated with greater annual average rate of decline in word fluency (−2.65; 95% confidence interval, −4.26 to −1.03;
P
=0.002) among participants with prevalent SCIs in 1993 to 1995. Among participants who developed SCIs during follow-up, incident AF was associated with a greater annual average rate of decline in digit symbol substitution (−1.51; 95% confidence interval, −3.02 to −0.01;
P
=0.049).

Conclusions—

The association of incident AF with cognitive decline in stroke-free individuals can be explained by the presence or development of SCIs, raising the possibility of anticoagulation as a strategy to prevent cognitive decline in AF.
Altered Astrocyte–Neuronal Interactions After Hypoxia-Ischemia in the Neonatal Brain in Female and Male Rats
Authors: Morken Tora Sund , Brekke Eva , Håberg Asta , Widerøe Marius , Brubakk Ann-Mari , Sonnewald Ursula
Published: July 2014

Background and Purpose—

Increased susceptibility to excitotoxicity of the neonatal brain after hypoxia-ischemia (HI) may be caused by limited capacity of astrocytes for glutamate uptake, and mitochondrial failure probably plays a key role in the delayed injury cascade. Male infants have poorer outcome than females after HI, possibly linked to differential intermediary metabolism.

Methods—

[1-
13
C]glucose and [1,2-
13
C]acetate were injected at zero, 6, and 48 hours after unilateral HI in 7-day-old rats. Intermediary metabolism was analyzed with magnetic resonance spectroscopy.

Results—

Mitochondrial metabolism was generally reduced in the ipsilateral hemisphere for ≤6 hours after HI, whereas contralaterally, it was reduced in neurons but not in astrocytes. Transfer of glutamate from neurons to astrocytes was increased in the contralateral, but not in the ipsilateral hemisphere at 0 hour, and reduced bilaterally at 6 hours after HI. The transfer of glutamine from astrocytes to glutamatergic neurons was unaltered in both hemispheres, whereas the transfer of glutamine to GABAergic neurons was increased ipsilaterally at 0 hour. Anaplerosis (astrocytes) was decreased, whereas partial pyruvate recycling (astrocytes) was increased directly after HI. Male pups had lower astrocytic mitochondrial metabolism than females immediately after HI, whereas that of females was reduced longer and encompassed both neurons and astrocytes.

Conclusions—

The prolonged depression in mitochondrial metabolism indicates that mitochondria are vulnerable targets in the delayed injury after neonatal HI. The degree of astrocytic malfunction may be a valid indicator of outcome after hypoxic/HI brain injury and may be linked to the differential outcome in males and females.
Flow Diversion Versus Conventional Treatment for Carotid Cavernous Aneurysms
Authors: Zanaty Mario , Chalouhi Nohra , Starke Robert M. , Barros Guilherme , Saigh Mark Philip , Schwartz Eric Winthrop , Ajiboye Norman , Tjoumakaris Stavropoula I. , Hasan David , Rosenwasser Robert H. , Jabbour Pascal
Published: July 2014

Background and Purpose—

Several endovascular treatment options are available for cavernous carotid aneurysms. We compared pipeline embolization device (PED) versus conventional endovascular treatment in terms of evolution of mass effect, complications, recurrence, and retreatment rate.

Methods—

One hundred fifty-seven patients harboring 167 cavernous carotid aneurysms were treated using PED placement, coiling, stent-assisted coiling, and carotid vessel destruction. Procedural complications, angiographic results, and clinical outcomes were analyzed and compared.

Results—

There were no difference in age, sex, and mean aneurysm size between those treated with PED and those treated with conventional endovascular procedures. The patients treated with PED had a significantly lower proportion of small-size aneurysms (<10 mm) and a shorter follow-up duration. Multivariate analysis revealed treatment other than PED (PED: odds ratio [OR], 0.03;
P
=0.002) and size >15 mm (OR, 4.27;
P
=0.003) to be predictors of no improvement in symptoms. The rate of complete occlusion was 81.36% (48 of 59) for PED, 42.25% (39 of 71) for stent-assisted coiling, 27.27% (6 of 22) for coiling, and 73.33% (11 of 15) for carotid vessel destruction. Retreatment was needed in patients with aneurysm size >15 mm (OR, 2.67;
P
=0.037) and those who were not treated with PED (PED: OR, 0.16;
P
=0.006). The rate of major complications was 6.6% (11 of 167). Patients who were treated with PED or stent-assisted coiling had 3.84 lower odds to develop complications (OR, 0.26;
P
<0.05).

Conclusions—

The use of PED should be encouraged, especially in symptomatic patients. We found PED to be associated with less need for future treatment, higher improvement in symptoms rate, and lower rate of complications.
Agriculture and Growth in Oceania
Authors: Gani Azmat , Yasin Jehad
Published: July 2014

This article examines the contribution of agriculture to the economic growth of countries in the Oceania region. The empirical analysis is based on a Cobb-Douglas production function. The estimation methodology follows a combined time-series and cross-sectional form using annual data for the period 1994 to 2006. The major finding of this article is that agricultural growth contributes to overall economic growth of countries in Oceania. In terms of the potential contributors to agricultural expansion, a positive and statistically significant influence of growth in output on the growth of the agricultural sector is confirmed; while a positive effect of government spending on the agricultural sector is also confirmed. The empirical evidence presented in this article leads to the suggestion that agriculture in Oceania ought to be given priority in terms of its long-term development through investment in physical and institutional infrastructure, market access, financial support, skill development and investment incentives.
Economy/Environment Interaction and Global Trade of Materials: An Empirical Examination for 95 Countries between 1980 and 2009
Authors: Hao Feng
Published: July 2014

Political economy theory posits decreasing economic intensity—i.e. the use of fewer materials per unit of economic growth—does not lead to a decrease in material extraction. Modernization theory suggests decreasing economic intensity may lead to a decline in the use of materials. Unequal ecological exchange theory suggests that the dominate position of developed countries in the global trade of materials allows them to protect their own environments by extracting materials elsewhere. By examining data from 95 countries between 1980 and 2009, this paper provides an empirical evaluation to theoretical statements discussed above. Findings show that economic intensity has declined markedly for decades while the total material extraction continues to increase worldwide. More developed countries enjoy an import surplus, while most materials extracted from developing countries are exported abroad. Positive associations (mediated by global trade of materials) exist between material extraction from developing countries and material consumption in developed countries.
The Impact of Donor-funded Community Empowerment Projects on Poverty Alleviation in Zimbabwe
Authors: Tanga Pius T. , Mundau Mulwaini
Published: July 2014

The aim of this paper is to assess the impact of donor-funded community empowerment projects on poverty alleviation in Zimbabwe. The primary data were collected from a questionnaire survey from 52 project members who were from two local ngos that were selected randomly. A semi-structured interview guide designed for two officials of the selected ngos implementing the projects was also used. The findings show that there is heavy dependence on outside funding, no adherence to the principles of the empowerment approach and a failure to positively impact the lives of the project members. This therefore calls for ngos to adopt better empowerment practices: community involvement in decision making, project ownership, and clear lines of communication with the ngos. However the findings also show the strength of linking project members with relevant institutions and training in order to ensure sustainability of community projects that may foster community empowerment towards poverty eradication.
Vortex Preconditioning due to Planetary and Gravity Waves prior to Sudden Stratospheric Warmings
Authors: Albers John R. , Birner Thomas
Published: July 2014

Reanalysis data are used to evaluate the evolution of polar vortex geometry, planetary wave drag, and gravity wave drag prior to split versus displacement sudden stratospheric warmings (SSWs). A composite analysis that extends upward to the lower mesosphere reveals that split SSWs are characterized by a transition from a wide, funnel-shaped vortex that is anomalously strong to a vortex that is constrained about the pole and has little vertical tilt. In contrast, displacement SSWs are characterized by a wide, funnel-shaped vortex that is anomalously weak throughout the prewarming period. Moreover, during split SSWs, gravity wave drag is enhanced in the polar night jet, while planetary wave drag is enhanced within the extratropical surf zone. During displacement SSWs, gravity wave drag is anomalously weak throughout the extratropical stratosphere.

Using the composite analysis as a guide, a case study of the 2009 SSW is conducted in order to evaluate the roles of planetary and gravity waves for preconditioning the polar vortex in terms of two SSW-triggering scenarios: anomalous planetary wave forcing from the troposphere and resonance due to either internal or external Rossby waves. The results support the view that split SSWs are caused by resonance rather than anomalously large wave forcing. Given these findings, it is suggested that vortex preconditioning, which is traditionally defined in terms of vortex geometries that increase poleward wave focusing, may be better described by wave events (planetary and/or gravity) that “tune” the geometry of the vortex toward its resonant excitation points.
Configuration of a Southern Ocean Storm Track
Authors: Bischoff Tobias , Thompson Andrew F.
Published: July 2014

Diagnostics of ocean variability that reflect and influence local transport properties of heat and chemical species vary by an order of magnitude along the Southern Ocean’s Antarctic Circumpolar Current (ACC). Topographic “hotspots” are important regions of localized transport anomalies. This study uses a primitive equation channel model to investigate the structure of eddy kinetic energy (EKE), one measure of variability, in an oceanic regime. A storm-track approach emphasizes the importance of stationary eddies, which result from flow interactions with topography, on setting EKE distributions. The influence of these interactions extends far downstream of the topography and impacts EKE patterns through localized convergence and divergence of heat. Unlike for zonal averages, local contributions to the stationary fluxes from terms that integrate to zero in a zonal average are important. The simulations show a strong sensitivity of the zonal structure as well as the distribution and amplitude of stationary eddy fluxes to the surface wind forcing. By focusing on local, time-averaged stationary eddy fluxes, insight into the dynamical structure of the ACC can be gained that is concealed in the averaging procedure associated with traditional zonal or along-stream analyses.