bluuebunny/crossref_metadata_2025 huggingface dataset:
Reputation and science: examining the effectiveness of DBT in the treatment of borderline personality disorder
Authors: Bendit Nicholas
Published: November 2013

Objective:

This paper examines the evidence base for dialectical behaviour therapy (DBT) in the treatment of patients with borderline personality disorder (BPD).

Conclusion:

DBT has built an impressive reputation within psychology and psychiatry as an effective treatment for deliberate self harm and chronic suicidal behaviours in patients with BPD. However, when each of the randomised controlled trials that comprise this evidence base is examined carefully, the actual results are less convincing about DBT’s positive reputation.
Dialysis-related transcriptomic profiling: The pivotal role of heparanase
Authors: Zaza Gianluigi , Masola Valentina , Granata Simona , Pontrelli Paola , Sallustio Fabio , Gesualdo Loreto , Gambaro Giovanni , Grandaliano Giuseppe , Lupo Antonio
Published: November 2013

Peritoneal (PD) and hemodialysis (HD) represent the leading renal replacement therapies in advanced chronic kidney disease (CKD). Although absolutely necessary to ensure patient survival, these treatments are responsible for considerable biological alterations primarily due to the un-physiological contact of blood and tissues with bioincompatible devices or plastificants. Although extensively described, this complex dialysis-related deregulated bio-molecular machinery is still not completely known. Therefore, to select a set of genes deregulated in patients on dialysis treatment and to assess the possible differences between dialysis modalities, we measured the expression level of 132 genes involved in proteoglycans (PGs) biosynthesis/metabolism by microarray in peripheral blood mononuclear cells (PBMCs), biological elements involved in the inflammatory/immune response, from 5 healthy subjects (HS), 9 CKD, 10 PD, and 17 HD patients. We focused on PGs biosynthesis/metabolism pathways because of their involvement in the onset and development of several CKD-related clinical complications. Statistical analysis/bioinformatics identified 70 genes discriminating HD/PD patients from HS/CKD subjects ( P < 0.009, FDR < 5%). Twenty-five genes were up-regulated (e.g. HPSE, VCAN, and VEGFA) and 45 down-regulated (e.g. IDS and HEXA) in PD/HD compared to HS/CKD. Gene expression and plasma activity of Heparanase (HPSE), one of the top selected up-regulated genes in PD/HD, validated microarray results. In addition, for the second part of the study, HPSE plasmatic activities were first assessed in an independent testing-group (7 HS, 10 CKD, 17 PD, and 11 HD), and then correlated with high-sensitive C reactive protein (HS-CRP) measurements. HPSE activity was higher in PD and HD versus CKD/HS and it correlated with HS-CRP levels ( R2 = 0.37, P = 0.007). Lipopolysaccharide (LPS)-stimulated PBMCs showed a significant up-regulation of HPSE mRNA level ( P = 0.04). Our results revealed that dialysis treatments induce change in the transcriptomic pattern of biosynthetic proteoglycans in PBMCs with an up-regulation of HPSE. Our selected genes could be useful in the future as potential biomarkers and new therapeutic targets.
Matters of the Heart
Authors: Matthews Karen A.
Published: November 2013

Cardiovascular diseases (CVD) are the major cause of death in men and women in the United States. Type A behavior research was a starting point for psychological science’s understanding of the development of CVD. Health psychology science has broadened its scope to consider other psychological constructs as potential risk factors, multilevel models and a life span approach, and new mechanistic pathways that could apply to a number of disease outcomes other than CVD.
Myeloperoxidase influences the complement regulatory function of modified C-reactive protein
Authors: Xu Peng-cheng , Li Zhi-ying , Yang Xiao-wei , Zhao Ming-hui , Chen Min
Published: November 2013

In patients with active anti-neutrophil cytoplasmic Ab (ANCA)-associated vasculitis (AAV), there are high levels of circulating C-reactive protein (CRP), which can inhibit the alternative complement pathway by binding factor H and triggering the classical complement pathway by binding C1q. However, the alternative, not the classical, complement pathway has been proven to play an important role in AAV. We found that both purified myeloperoxidase (MPO) and MPO released from ANCA-stimulated neutrophils could bind modified CRP (mCRP), but not pentameric CRP. Furthermore, MPO could block the binding between mCRP and factor H, as well as the binding between mCRP and C1q. Binding with mCRP did not influence the enzymatic activity of MPO. Binding with mCRP also did not influence the binding between MPO and its physical inhibitor, ceruloplasmin, as well as the binding between MPO and MPO–ANCA. The results indicated that MPO might be a complement regulator and inhibit the negative regulatory effect of CRP on the alternative complement pathway.
Gastrointestinal motility revisited: The wireless motility capsule
Authors: Farmer Adam D , Scott S Mark , Hobson Anthony R
Published: November 2013

Introduction

The wireless motility capsule (WMC) is a novel ambulatory technology that concurrently measures intraluminal pH, temperature, and pressure as it traverses the gastrointestinal tract.

Objectives

We aim to provide a concise summary of the WMC, detailing the procedure for its administration and the parameters it records. We also review the evidence that has validated the WMC against other methods currently regarded as ‘gold standard’.

Conclusions

The WMC offers a number of advantages over and above current techniques, especially with respect to patient tolerability, safety, and standardization. The WMC represents a considerable enhancement of the researchers’ and clinicians’ investigatory armamentarium. If this technology becomes widely adopted, coupled with international consensus upon the interpretation of physiological data derived therein, it may herald a new and exciting era in gastrointestinal physiology.
Metabolite and transcriptome analysis during fasting suggest a role for the p53-Ddit4 axis in major metabolic tissues
Authors: Schupp Michael , Chen Fang , Briggs Erika R , Rao Shilpa , Pelzmann Helmut J , Pessentheiner Ariane R , Bogner-Strauss Juliane G , Lazar Mitchell A , Baldwin Don , Prokesch Andreas
Published: November 2013

Background

Fasting induces specific molecular and metabolic adaptions in most organisms. In biomedical research fasting is used in metabolic studies to synchronize nutritional states of study subjects. Because there is a lack of standardization for this procedure, we need a deeper understanding of the dynamics and the molecular mechanisms in fasting.

Results

We investigated the dynamic changes of liver gene expression and serum parameters of mice at several time points during a 48 hour fasting experiment and then focused on the global gene expression changes in epididymal white adipose tissue (WAT) as well as on pathways common to WAT, liver, and skeletal muscle. This approach produced several intriguing insights: (i) rather than a sequential activation of biochemical pathways in fasted liver, as current knowledge dictates, our data indicates a concerted parallel response; (ii) this first characterization of the transcriptome signature of WAT of fasted mice reveals a remarkable activation of components of the transcription apparatus; (iii) most importantly, our bioinformatic analyses indicate p53 as central node in the regulation of fasting in major metabolic tissues; and (iv) forced expression of Ddit4, a fasting-regulated p53 target gene, is sufficient to augment lipolysis in cultured adipocytes.

Conclusions

In summary, this combination of focused and global profiling approaches provides a comprehensive molecular characterization of the processes operating during fasting in mice and suggests a role for p53, and its downstream target Ddit4, as novel components in the transcriptional response to food deprivation.
Parkin depletion delays motor decline dose-dependently without overtly affecting neuropathology in α-synuclein transgenic mice
Authors: Fournier Margot , Roux Amandine , Garrigue Jérôme , Muriel Marie-Paule , Blanche Paul , Lashuel Hilal A , Anderson John P , Barbour Robin , Huang Jiping , du Montcel Sophie Tezenas , Brice Alexis , Corti Olga
Published: November 2013

Background

Mutations of the gene encoding the major component of Lewy bodies (LB), α-synuclein (α-syn), cause autosomal dominant forms of Parkinson’s disease (PD), whereas loss-of-function mutations of the gene encoding the multifunctional E3 ubiquitin-protein ligase Parkin account for autosomal recessive forms of the disease. Parkin overproduction protects against α-syn-dependent neurodegeneration in various in vitro and in vivo models, but it remains unclear whether this process is affected by Parkin deficiency. We addressed this issue, by carrying out more detailed analyses of transgenic mice overproducing the A30P variant of human α-syn (hA30Pα-syn) and with two, one or no parkin knockout alleles.

Results

Longitudinal behavioral follow-up of these mice indicated that Parkin depletion delayed disease-predictive sensorimotor impairment due to α-syn accumulation, in a dose-dependent fashion. At the end stage of the disease, neuronal deposits containing fibrillar α-syn species phosphorylated at S129 (PS129α-syn) were the predominant neuropathological feature in hA30Pα-syn mice, regardless of their parkin expression. Some of these deposits colocalized with the LB markers ubiquitin and α-syn truncated at D135 (α-synD135), indicating that PS129α-syn is subjected to secondary posttranslational modification (PTM); these features were not significantly affected by parkin dysfunction.

Conclusions

These findings suggest that Parkin deficiency acts as a protective modifier in α-syn-dependent neurodegeneration, without overtly affecting the composition and characteristics of α-syn deposits in end-stage disease.
Influenza and hepatitis B vaccination coverage among healthcare workers in Croatian hospitals: a series of cross-sectional surveys, 2006–2011
Authors: Civljak Rok , Papic Neven , Stamenic Valerija , Kalenic Smilja , Kuzman Ilija , Car Josip
Published: November 2013

Background

Healthcare workers (HCWs) are at an increased risk of exposure to and transmission of infectious diseases. Vaccination lowers morbidity and mortality of HCWs and their patients. To assess vaccination coverage for influenza and hepatitis B virus (HBV) among HCWs in Croatian hospitals, we conducted yearly nationwide surveys.

Methods

From 2006 to 2011, all 66 Croatian public hospitals, representing 43–60% of all the HCWs in Croatia, were included. Statistical analysis was performed using the Kruskal–Wallis analysis of variance, Dunn’s multiple comparison analysis and the chi-square test, as appropriate.

Results

The median seasonal influenza vaccination coverage rates in pre-pandemic (2006–2008) seasons were 36%, 25% and 29%, respectively. By occupation, influenza vaccination rates among physicians were 33 ± 21%, 33 ± 22% among graduate nurses, 30±34% among other HCWs, 26 ± 21% among housekeeping and the lowest, 23 ± 17%, among practical nurses (p < 0.01). In 2009–2010 season, seasonal influenza vaccination coverage was 30%, while overall vaccination coverage against pandemic influenza was fewer than 5%. Median vaccination coverage in the post-pandemic seasons of 2010–2011 and 2011–2012 decreased to 15% and 14%, respectively (reduction of 24% and 35%, respectively, p < 0.0001). Meanwhile, the median mandatory HBV vaccination coverage was 98%, albeit with considerable differences according to work setting (range 19–100%) and occupation (range 4–100%).

Conclusions

We found substantial year-on-year variations in seasonal influenza vaccination rates, with reduction in post pandemic influenza seasons. HBV vaccination is satisfactory compared to seasonal influenza vaccination coverage, although substantial variations by occupation and work setting were observed. These findings highlight the need for national strategies that optimize vaccination coverage among HCWs in Croatian hospitals. Further studies are needed to establish the potential role of mandatory vaccination for seasonal influenza.
Genetic mapping of high caries experience on human chromosome 13
Authors: Küchler Erika C , Deeley Kathleen , Ho Bao , Linkowski Samantha , Meyer Chelsea , Noel Jacqueline , Kouzbari M Zahir , Bezamat Mariana , Granjeiro José M , Antunes Leonardo S , Antunes Livia Azeredo , de Abreu Fernanda Volpe , Costa Marcelo C , Tannure Patricia N , Seymen Figen , Koruyucu Mine , Patir Asli , Mereb Juan C , Poletta Fernando A , Castilla Eduardo E , Orioli Ieda M , Marazita Mary L , Vieira Alexandre R
Published: November 2013

Background

Our previous genome-wide linkage scan mapped five loci for caries experience. The purpose of this study was to fine map one of these loci, the locus 13q31.1, in order to identify genetic contributors to caries.

Methods

Seventy-two pedigrees from the Philippines were studied. Caries experience was recorded and DNA was extracted from blood samples obtained from all subjects. Sixty-one single nucleotide polymorphisms (SNPs) in 13q31.1 were genotyped. Association between caries experience and alleles was tested. We also studied 1,481 DNA samples obtained from saliva of subjects from the USA, 918 children from Brazil, and 275 children from Turkey, in order to follow up the results found in the Filipino families. We used the AliBaba2.1 software to determine if the nucleotide changes of the associated SNPs changed the prediction of the presence of transcription-binding site sequences and we also analyzed the gene expression of the genes selected based on binding predictions. Mutation analysis was also performed in 33 Filipino individuals of a segment of 13q31.1 that is highly conserved in mammals.

Results

Statistically significant association with high caries experience was found for 11 markers in 13q31.1 in the Filipino families. Haplotype analysis also confirmed these results. In the populations used for follow-up purposes, associations were found between high caries experience and a subset of these markers. Regarding the prediction of the transcription-binding site, the base change of the SNP rs17074565 was found to change the predicted-binding of genes that could be involved in the pathogenesis of caries. When the sequence has the allele C of rs17074565, the potential transcription factors binding the sequence are GR and GATA1. When the subject carries the G allele of rs17074565, the potential transcription factor predicted to bind to the sequence is GATA3. The expression of GR in whole saliva was higher in individuals with low caries experience when compared to individuals with high caries experience (p = 0.046). No mutations were found in the highly conserved sequence.

Conclusions

Genetic factors contributing to caries experience may exist in 13q31.1. The rs17074565 is located in an intergenic region and is predicted to disrupt the binding sites of two different transcription factors that might be involved with caries experience. GR expression in saliva may be a biomarker for caries risk and should be further explored.
Towards an optimized inhibition of liver stage development assay (ILSDA) for Plasmodium falciparum
Authors: Zou Xiaoyan , House Brent L , Zyzak Michael D , Richie Thomas L , Gerbasi Vincent R
Published: November 2013

Background

Experimental vaccines targetingPlasmodium falciparumhave had some success in recent years. These vaccines use attenuated parasites, recombinant sporozoite proteins, or DNA and virus combinations to induce cell-mediated immune responses and/or antibodies targeting sporozoite surface proteins. To capitalize on the success of these vaccines and understand the mechanisms by which these vaccines function, it is important to develop assays that measure correlates of protection in volunteers. The inhibition of liver stage development assay (ILSDA) tests antibodies for the ability to block sporozoite development in hepatocytes. As such the ILSDA is an excellent candidate assay to identify correlates of humoral protection, particularly against the liver stage of malaria infection. In addition, the ILSDA can be used as a tool to evaluate novel sporozoite antigens for future vaccine development. Historically the ILSDA has suffered from low sporozoite infection rates, absence of standardized reagents, and the subjectivity associated with the traditional primary outcome measures, which depend on microscopy of stained hepatocyte cultures. This study worked to significantly improve sporozoite infection rates in hepatocytes, modify key steps in the assay protocol to reduce experimental variability, and demonstrate the utility of the ILSDA in testing antibodies targeting the circumsporozoite protein.

Methods

Cryopreserved primary human hepatocytes,Plasmodium falciparumsporozoites, and circumsporozoite antibodies were used to optimize the ILSDA.

Results

Inoculation of cryopreserved primary human hepatocytes withPlasmodium falciparumsporozoites improved liver stage development in the ILSDA compared to HCO4 cells. In the ILSDA, circumsporozoite antibodies suppressed liver stage development in cryopreserved primary human hepatocytes in a concentration-dependent manner. Antibody-mediated suppression of parasite development in the ILSDA at a 96-hour endpoint was more robust than the 24-hour endpoint.

Conclusions

ILSDA performance is improved by the use of cryopreserved primary human hepatocytes, expediting interactions between sporozoites and hepatocytes, and extending the assay endpoint.
Chronic cough and obstructive sleep apnoea in a sleep laboratory-based pulmonary practice
Authors: Wang Tsai-Yu , Lo Yu-Lun , Liu Wen-Te , Lin Shu-Min , Lin Ting-Yu , Kuo Chih-Hsi , Chung Fu-Tsai , Chou Pai-Chien , Chang Po-Jui , Ni Yung-Lun , Ho Shu-Chuan , Lin Horng-Chyuan , Wang Chun-Hua , Yu Chih-Teng , Kuo Han-Pin
Published: November 2013

Background

Obstructive sleep apnoea (OSA) has recently been identified as a possible aetiology for chronic cough. The aim of this study was to compare the incidence of chronic cough between patients with and without OSA and the impact of continuous positive airway pressure (CPAP) treatment in resolving chronic cough.

Methods

Patients referred to the sleep laboratory from January 2012 to June 2012 were retrospectively enrolled. Clinical data, treatment course and resolution of chronic cough were analysed. Specifically, gastro-oesophageal reflux (GERD), upper airway cough syndrome, asthma, apnoea-hypopnoea index and the impact of CPAP treatment on chronic cough were assessed.

Results

A total of 131 patients were reviewed. The incidence of chronic cough in the OSA group was significantly higher than the non-OSA group (39/99 (39.4%) vs. 4/32 (12.5%), p = 0.005). Both GERD and apnoea-hypopnoea index were significantly associated with chronic cough in univariate analysis. After multivariate logistic regression, GERD was the only independent factor for chronic cough. Moreover, the resolution of chronic cough was more significant in the OSA patients with CPAP treatment compared with those not receiving CPAP treatment (12/18 (66.7%) vs. 2/21 (9.5%), p = 0.010).

Conclusion

The incidence of chronic cough was significantly higher in the OSA patients. In addition, CPAP treatment significantly improved chronic cough. Therefore, OSA may be a contributory factor to chronic cough.
Vitamin D related genes in lung development and asthma pathogenesis
Authors: Kho Alvin T , Sharma Sunita , Qiu Weiliang , Gaedigk Roger , Klanderman Barbara , Niu Simin , Anderson Chris , Leeder James S , Weiss Scott T , Tantisira Kelan G
Published: November 2013

Background

Poor maternal vitamin D intake is a risk factor for subsequent childhood asthma, suggesting thatin uterochanges related to vitamin D responsive genes might play a crucial role in later disease susceptibility. We hypothesized that vitamin D pathway genes are developmentally active in the fetal lung and that these developmental genes would be associated with asthma susceptibility and regulation in asthma.

Methods

Vitamin D pathway genes were derived from PubMed and Gene Ontology surveys. Principal component analysis was used to identify characteristic lung development genes.

Results

Vitamin D regulated genes were markedly over-represented in normal human (odds ratio OR 2.15, 95% confidence interval CI: 1.69-2.74) and mouse (OR 2.68, 95% CI: 2.12-3.39) developing lung transcriptomes. 38 vitamin D pathway genes were in both developing lung transcriptomes with >63% of genes more highly expressed in the later than earlier stages of development. In immortalized B-cells derived from 95 asthmatics and their unaffected siblings, 12 of the 38 (31.6%) vitamin D pathway lung development genes were significantly differentially expressed (OR 3.00, 95% CI: 1.43-6.21), whereas 11 (29%) genes were significantly differentially expressed in 43 control versus vitamin D treated immortalized B-cells from Childhood Asthma Management Program subjects (OR 2.62, 95% CI: 1.22-5.50). 4 genes,LAMP3,PIP5K1B,SCARB2andTXNIPwere identified in both groups; each displays significant biologic plausibility for a role in asthma.

Conclusions

Our findings demonstrate a significant association between early lung development and asthma–related phenotypes for vitamin D pathway genes, supporting a genomic mechanistic basis for the epidemiologic observations relating maternal vitamin D intake and childhood asthma susceptibility.
Seismic ray tracing in anisotropic media: A modified Newton algorithm for solving highly nonlinear systems
Authors: Wang Yanghua
Published: November 2013

Seismic ray tracing with a path-bending method leads to a nonlinear system that has much stronger nonlinearity in anisotropic media than the counterpart in isotropic media. Any path perturbation causes changes to directional velocities, which depend not only upon the spatial position but also upon the local propagation direction in anisotropic media. To combat the high nonlinearity of the problem, the Newton-type iterative algorithm is modified by enforcing Fermat’s minimum-time principle as a constraint for the solution update, instead of conventional error minimization in the nonlinear system. As the algebraic problem is incorporated with the physical principle, it is able to stabilize the solution for such a highly nonlinear problem as ray tracing in realistically complicated anisotropic media. With this modified algorithm, two ray-tracing schemes are presented. The first scheme involves newly derived raypath equations, which are approximate for anisotropic media but the minimum-time constraint will ensure that the solution steadily converges to the true solution. The second scheme is based on the minimal variation principle. It is more efficient than the first one as it solves a tridiagonal system and does not need to compute the Jacobian and its inverse in each iteration. Even in this second scheme, Fermat’s minimum-time constraint is employed for the solution update, so as to guarantee a robust convergence of the iterative solution in anisotropic media.
Time-series analysis of diffusion interferometry data and its application to Bayesian inversion of synthetic borehole pressure data
Authors: Shamsalsadati Sharmin , Weiss Chester J.
Published: November 2013

Interferometry methods in exploration geophysics are premised on a powerful theoretical foundation in which the ambient noise observed at discrete locations can be manipulated through either crosscorrelation or convolution to yield the response of a virtual “active source” experiment (i.e., the empirical Green’s function, abbreviated as EGF) without the actual deployment of physical sources. Sources of the ambient background may be either naturally occurring or engineered. Regardless, the theory for diffusive systems requires them to be volumetrically distributed over an infinite domain. The central question is then, “What region for the ambient sources matters most for good EGF estimation?” Here, we build on previous work in frequency domain EGF estimation by extending the analysis to the time domain where the broadband response is driven by the continuum of diffusive length scales therein. Analysis of the double half-space diffusion model (simulating a lithologic contact) demonstrates that sources between the two receiver locations have the most impact on EGF accuracy, and that when either of the receivers is close to the lithologic contact, the sources must also extend more deeply, into the high-diffusivity side to maintain accuracy. We further examine the suitability for inversion of EGF signals built with the limited and finite ambient source distributions expected in actual exploration scenarios. One-dimensional Bayesian inversion of singlewell and crosswell configurations of a three-layered system simulating a reservoir layer between two impermeable layers revealed that transient EGF signals were reliably invertible when sources were constrained to the middle reservoir layer. In production monitoring settings, natural sources originating from pumping and subsequent flow-related physics (pressure diffusion, electrochemical and seismoelectric effects, etc.), this result suggests that EGF signals may be a useful measure of reservoir properties.
Damping Scaling Factors for Vertical Elastic Response Spectra for Shallow Crustal Earthquakes in Active Tectonic Regions
Authors: Rezaeian Sanaz , Bozorgnia Yousef , Idriss I. M. , Abrahamson Norman A. , Campbell Kenneth W. , Silva Walter J.
Published: November 2013

This paper develops a new model for a damping scaling factor (DSF) that can be used to adjust elastic response spectral ordinates for the vertical component of earthquake ground motion at a 5% viscous damping ratio to ordinates at damping ratios between 0.5% and 30%. Using the extensive NGA-West2 database of recorded ground motions from worldwide shallow crustal earthquakes in active tectonic regions, a functional form for the median DSF is proposed that depends on the damping ratio, spectral period, earthquake magnitude, and distance. Standard deviation is a function of the damping ratio and spectral period. The proposed model is compared to the DSF for the “average” horizontal component. In general, the peak in DSF is shifted toward shorter periods and is farther from unity for the vertical component. Also, the standard deviation of DSF for vertical motion is slightly higher than that observed for the “average” horizontal component.
Randomized, Open-Label, Phase III Study Comparing Irinotecan With Paclitaxel in Patients With Advanced Gastric Cancer Without Severe Peritoneal Metastasis After Failure of Prior Combination Chemotherapy Using Fluoropyrimidine Plus Platinum: WJOG 4007 Trial
Authors: Hironaka Shuichi , Ueda Shinya , Yasui Hirofumi , Nishina Tomohiro , Tsuda Masahiro , Tsumura Takehiko , Sugimoto Naotoshi , Shimodaira Hideki , Tokunaga Shinya , Moriwaki Toshikazu , Esaki Taito , Nagase Michitaka , Fujitani Kazumasa , Yamaguchi Kensei , Ura Takashi , Hamamoto Yasuo , Morita Satoshi , Okamoto Isamu , Boku Narikazu , Hyodo Ichinosuke
Published: November 2013

Purpose

This phase III study compared treatment with weekly paclitaxel and biweekly irinotecan in patients with advanced gastric cancer refractory to treatment with fluoropyrimidine plus platinum.

Patients and Methods

Patients were randomly assigned to receive either paclitaxel (80 mg/m2 on days 1, 8, and 15, every 4 weeks) or irinotecan (150 mg/m2 on days 1 and 15, every 4 weeks). Primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), response rate, adverse events, and proportion of patients who received third-line chemotherapy.

Results

Of 223 patients, 219 were eligible for analysis. Median OS was 9.5 months in 108 patients allocated to the paclitaxel group and 8.4 months in 111 patients allocated to the irinotecan group (hazard ratio [HR], 1.13; 95% CI, 0.86 to 1.49; P = .38). Median PFS was 3.6 months in the paclitaxel group and 2.3 months in the irinotecan group (HR, 1.14; 95% CI, 0.88 to 1.49; P = .33). Response rate was 20.9% in the paclitaxel group and 13.6% in the irinotecan group (P = .24). Common grade 3 to 4 adverse events were neutropenia (paclitaxel group, 28.7%; irinotecan group, 39.1%), anemia (21.3%; 30.0%), and anorexia (7.4%; 17.3%). Treatment-related deaths occurred in two patients (1.8%) in the irinotecan group. Third-line chemotherapy was administered in 97 patients (89.8%) after paclitaxel treatment and in 80 patients (72.1%) after irinotecan treatment (P = .001).

Conclusion

No statistically significant difference was observed between paclitaxel and irinotecan for OS. Both are reasonable second-line treatment options for advanced gastric cancer.
Use of Statins and the Risk of Death in Patients With Prostate Cancer
Authors: Yu Oriana , Eberg Maria , Benayoun Serge , Aprikian Armen , Batist Gerald , Suissa Samy , Azoulay Laurent
Published: November 2013

Purpose

To determine whether the use of statins after prostate cancer diagnosis is associated with a decreased risk of cancer-related mortality and all-cause mortality and to assess whether this association is modified by prediagnostic use of statins.

Patients and Methods

A cohort of 11,772 men newly diagnosed with nonmetastatic prostate cancer between April 1, 1998, and December 31, 2009, followed until October 1, 2012, was identified using a large population-based electronic database from the United Kingdom. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% CIs of mortality outcomes associated with postdiagnostic use of statins, lagged by 1 year to account for latency considerations and to minimize reverse causality, and considering effect modification by prediagnostic use of statins.

Results

During a mean follow-up time of 4.4 years (standard deviation, 2.9 years), 3,499 deaths occurred, including 1,791 from prostate cancer. Postdiagnostic use of statins was associated with a decreased risk of prostate cancer mortality (HR, 0.76; 95% CI, 0.66 to 0.88) and all-cause mortality (HR, 0.86; 95% CI, 0.78 to 0.95). These decreased risks of prostate cancer mortality and all-cause mortality were more pronounced in patients who also used statins before diagnosis (HR, 0.55; 95% CI, 0.41 to 0.74; and HR, 0.66; 95% CI, 0.53 to 0.81, respectively), with weaker effects in patients who initiated the treatment only after diagnosis (HR, 0.82; 95% CI, 0.71 to 0.96; and HR, 0.91; 95% CI, 0.82 to 1.01, respectively).

Conclusion

Overall, the use of statins after diagnosis was associated with a decreased risk in prostate cancer mortality. However, this effect was stronger in patients who also used statins before diagnosis.
Relapsed Hodgkin Lymphoma in Older Patients: A Comprehensive Analysis From the German Hodgkin Study Group
Authors: Böll Boris , Goergen Helen , Arndt Nils , Meissner Julia , Krause Stefan W. , Schnell Roland , von Tresckow Bastian , Eichenauer Dennis A. , Sasse Stephanie , Fuchs Michael , Behringer Karolin , Klimm Beate C. , Naumann Ralph , Diehl Volker , Engert Andreas , Borchmann Peter
Published: November 2013

Purpose

Progression or relapse of Hodgkin lymphoma (HL) is common among older patients. However, prognosis and effects of second-line treatment are thus far unknown.

Patients and Methods

We investigated second-line treatment and survival in older patients with progressive or relapsed HL. Patients treated within German Hodgkin Study Group first-line studies between 1993 and 2007 were screened for refractory disease or relapse (RR-HL). Patients with RR-HL age ≥ 60 years at first-line treatment were included in this analysis.

Results

We identified 105 patients (median age, 66 years); 28%, 31%, and 41% had progressive disease, early relapse, or late relapse, respectively. Second-line treatment strategies included intensified salvage regimens (22%), conventional polychemotherapy and/or salvage-radiotherapy with curative intent (42%), and palliative approaches (31%). Median overall survival (OS) for the entire cohort was 12 months; OS at 3 years was 31% (95% CI, 22% to 40%). A prognostic score with risk factors (RFs) of early relapse, clinical stage III/IV, and anemia identified patients with favorable and unfavorable prognosis (≤ one RF: 3-year OS, 59%; 95% CI, 44% to 74%; ≥ two RFs: 3-year OS, 9%; 95% CI, 1% to 18%). In low-risk patients, the impact of therapy on survival was significant in favor of the conventional polychemotherapy/salvage radiotherapy approach. In high-risk patients, OS was low overall and did not differ significantly among treatment strategies.

Conclusion

OS in older patients with RR-HL can be predicted using a simple prognostic score. Poor outcome in high-risk patients cannot be overcome by any of the applied treatment strategies. Our results might help to guide treatment decisions and evaluate new compounds in these patients.
Personal History of Prostate Cancer and Increased Risk of Incident Melanoma in the United States
Authors: Li Wen-Qing , Qureshi Abrar A. , Ma Jing , Goldstein Alisa M. , Giovannucci Edward L. , Stampfer Meir J. , Han Jiali
Published: November 2013

Purpose

Steroid hormones, particularly androgens, play a major role in prostatic carcinogenesis. Personal history of severe acne, a surrogate for higher androgen activity, has been associated with an increased risk of prostate cancer (PCa), and one recent study indicated that severe teenage acne was a novel risk factor for melanoma. These findings suggest a possible relationship between PCa and risk of melanoma. We prospectively evaluated this association among US men.

Methods

A total of 42,372 participants in the Health Professionals' Follow-Up Study (HPFS; 1986 to 2010) were included. Biennially self-reported PCa diagnosis was confirmed using pathology reports. Diagnosis of melanoma and nonmelanoma skin cancer (NMSC) was self-reported biennially, and diagnosis of melanoma was pathologically confirmed. We sought to confirm the association in 18,603 participants from the Physicians' Health Study (PHS; 1982 to 1998).

Results

We identified 539 melanomas in the HPFS. Personal history of PCa was associated with an increased risk of melanoma (multivariate-adjusted hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54). Although we also detected a marginally increased risk of NMSC associated with PCa (HR, 1.08; 95% CI, 0.995 to 1.16), the difference in the magnitude of the association between melanoma and NMSC was significant (P for heterogeneity = .002). We did not find an altered risk of melanoma associated with personal history of other cancers. The association between PCa and risk of incident melanoma was confirmed in the PHS (HR, 2.17; 95% CI, 1.12 to 4.21).

Conclusion

Personal history of PCa is associated with an increased risk of melanoma, which may not be entirely a result of greater medical scrutiny.
Combination of Exercise Training and Diet Restriction Normalizes Limited Exercise Capacity and Impaired Skeletal Muscle Function in Diet-Induced Diabetic Mice
Authors: Suga Tadashi , Kinugawa Shintaro , Takada Shingo , Kadoguchi Tomoyasu , Fukushima Arata , Homma Tsuneaki , Masaki Yoshihiro , Furihata Takaaki , Takahashi Masashige , Sobirin Mochamad A. , Ono Taisuke , Hirabayashi Kagami , Yokota Takashi , Tanaka Shinya , Okita Koichi , Tsutsui Hiroyuki
Published: November 2013

Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.
Impaired Glucocorticoid Production and Response to Stress in Arntl-Deficient Male Mice
Authors: Leliavski Alexei , Shostak Anton , Husse Jana , Oster Henrik
Published: November 2013

The basic helix-loop-helix transcription factor Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL, also known as BMAL1 or MOP3) is a core component of the circadian timing system in mammals, which orchestrates 24-hour rhythms of physiology and behavior. Genetic ablation of Arntl in mice leads to behavioral and physiological arrhythmicity, including loss of circadian baseline regulation of glucocorticoids (GCs). GCs are important downstream regulators of circadian tissue clocks and have essential functions in the physiological adaptation to stress. The role of the clock machinery in the regulation of stress-induced GC release, however, is not well understood. Here we show that already under unstressed conditions Arntl-deficient mice suffer from hypocortisolism with impaired adrenal responsiveness to ACTH and down-regulated transcription of genes involved in cholesterol transport in adrenocortical cells. Under stress they show diminished GC and behavioral responses and develop behavioral resistance to acute and subchronic stressors, as shown using forced swim, tail suspension, and sucrose preference tests. These data suggest that the clock gene Arntl regulates circadian and acute secretion of GCs by the adrenal gland. Arntl disruption, probably via its effect on adrenal clock function, modulates stress axis activity and, thus, may promote resistance to both acute and repeated stress.
Succinate-to-Fumarate Ratio as a New Metabolic Marker to Detect the Presence of SDHB/D-related Paraganglioma: Initial Experimental and Ex Vivo Findings
Authors: Lendvai Nikoletta , Pawlosky Robert , Bullova Petra , Eisenhofer Graeme , Patocs Attila , Veech Richard L. , Pacak Karel
Published: November 2013

Pheochromocytomas (PHEOs) and paragangliomas (PGLs; extra-adrenal tumors) are rare neuroendocrine chromaffin cell tumors with a hereditary background in about 30%–35%. Those caused by succinate dehydrogenase subunit B (SDHB) germline mutations are associated with a high metastatic potential and ultimately higher patient mortality. Succinate dehydrogenase converts succinate to fumarate, uniquely linking the Krebs cycle and oxidative phosphorylation. SDH mutations result in the accumulation of succinate associated with various metabolic disturbances and the shift to aerobic glycolysis in tumor tissue. In the present study, we measured succinate and fumarate levels in mouse pheochromocytoma (MPC) and mouse tumor tissue (MTT) cells and in 10 apparently sporadic, 10 SDHB-, 5 SDHD-, and 2 neurofibromatosis 1–related PHEOs/PGLs and plasma samples using mass spectrometry. We found that the succinate-to-fumarate ratio was significantly higher in the SDHB- and SDHD-related PGLs than in apparently sporadic and neurofibromatosis 1–related PHEOs/PGLs (P = .0376). To further support our data, we silenced SDHB expression in MPC and MTT cells and evaluated the succinate and fumarate levels. Compared with control samples, SDHB-silenced MTT cells also showed an increase in the succinate-to-fumarate ratio (MTT cells: 2.45 vs 7.53), similar to the findings in SDHB-related PGLs. The present findings for the first time demonstrate a significantly increased succinate-to-fumarate ratio in SDHB/D-related PGLs and thus suggest this ratio may be used as a new metabolic marker for the detection of SDHB/D-related PHEOs/PGLs.
The World of David Foster Wallace
Authors: Konstantinou Lee
Published: November 2013

This essay investigates the common charge that contemporary US fiction and the literature of 9/11 have failed to meaningfully engage with the world. While it is true that American fiction has become increasingly insular and that the New York City-based publishing industry systematically fails to translate non-English works into English, I argue that critiques of the whole literary field, based on the close reading of individual texts, overlook the systemic and institutional grounds of American unworldliness. David Foster Wallace’s 2004 novella, “The Suffering Channel,” offers critics of American literary parochialism a text that is difficult to assimilate neatly into current interpretive practices. “The Suffering Channel” depicts a cast of characters who work for Style magazine in the months immediately preceding the 9/11 terrorist attacks. Focused on these characters’ attempts to write a human-interest story about a man who is able to defecate perfectly formed sculptures made of shit, “The Suffering Channel” satirizes the insularity and narcissism that plagues Americans, even those who, like the interns who work at Style, imagine themselves to be cosmopolitans. Wallace also insists on the necessity of exploring that insular perspective in its own terms. Wallace’s novella invites its reader to simultaneously identify and disidentify with an unworldly American perspective and, in doing so, to create a negative map of the world. This is both a political and literary project for Wallace. At the same time that he critiques the postmodern parochialism of the US culture industries, he uses his proleptic style to force his readers into experiencing dread when encountering American consumer culture. Ultimately, Wallace takes himself to be an example of the sort of limited perspective he seeks to critique, suggesting that the solution to American unworldliness requires not individual changes in consciousness or literary habit but a wholesale transformation of US educational and cultural institutions.
Imagination Sterilized: The Workings of the Global Spectacle
Authors: Hung Ruth Y. Y.
Published: November 2013

The theme of this essay is the immediacy of visuality, the dominant form of experience by which the species thinks itself of and in the world, as continuous with the world. Since the early years of the twenty-first century, a series of global spectacles has emerged and broken away from notions of ideology. This emergence testifies to the transformed role of the state in a globalized capital formation and the occurrence of two paradigm shifts: from the narrative to the visual, and from the image’s dominance of aesthetic representation to its dominance by global capital. The global spectacle, together with the new social media, has contributed to the creation of “visual allure” as a place to build common sense and the ethics of hedonism. It does so not only by its ability to create a more extensive level of commodity fetishism but also by virtue of its ability to map on the species an encompassing system of apparatuses in which every cultural diversity, every individual desire, and every version and vision of life become essentially a realization of one of the possibilities contained within the imagineering of the system. The global spectacles celebrate the intersections of the postindustrial financial economy and the human’s present ways of being atop a series of social and aesthetic categories that are at once privatized, social, and cultural. These categories are timeless pleasure, impulsive subjectivity, and recuperative possibilities. This essay elaborates on these categories and their complementary relations with the global spectacle.
Left-right asymmetry: lessons from Cancún
Authors: Burdine Rebecca D. , Caspary Tamara
Published: November 2013

The satellite symposium on ‘Making and breaking the left-right axis: implications of laterality in development and disease’ was held in June 2013 in conjunction with the 17th International Society for Developmental Biology meeting in Cancún, Mexico. As we summarize here, leaders in the field gathered at the symposium to discuss recent advances in understanding how left-right asymmetry is generated and utilized across the animal kingdom.
Paracrine rescued lobulogenesis in chimeric outgrowths comprised of progesterone receptor null mammary epithelium and redirected wild-type testicular cells
Authors: Bruno R.D. , Boulanger C.A. , Rosenfield S.M. , Anderson L.H. , Lydon J.P. , Smith G.H.
Published: November 2013

We have previously shown that non-mammary and tumorigenic cells can respond to the signals of the mammary niche and alter their cell fate to that of mammary epithelial progenitor cells. Here we tested the hypothesis that paracrine signals from progesterone receptor (PR) expressing mammary epithelial cells are dispensable for redirection of testicular cells, and that re-directed wild-type testicular-derived mammary cells can rescue lobulogenesis of PR-null mammary epithelium via paracrine signaling during pregnancy. We injected PR-null epithelial cells mixed with testicular cells from wild-type adult male mice into cleared fat-pads of recipient mice. The testicular cells were redirected in vivo to mammary epithelial cell fate during regeneration of the mammary epithelium, and persisted in second-generation outgrowths. In the process, the re-directed testicular cells rescued the developmentally deficient PR null cells, signaling them via the paracrine factor RANKL to produce alveolar secretory structures during pregnancy. This is the first demonstration that paracrine signaling required for alveolar development is not required for cellular reprogramming in the mammary gland, and that reprogrammed testicular cells can provide paracrine signals to the surrounding mammary epithelium.
CAREER GUIDANCE IN CONTINUOUS EDUCATION SYSTEM
Authors: Демченко  , Demchenko A. , Солодков  , Solodkov S. , Пальянов  , Palyanov M.
Published: November 2013

In this paper the questions of network interaction of comprehensive schools and social partners in the career guidance organization related to continuous education system are considered as well as creation of educational and branch clusters; the most eff ective directions related to career guidance program in municipal education system are defi ned.
Limitations of Fundamental Human Rights and Freedoms in International Law and Novations in the Russian Criminal Legislation
Authors: Ромашев Юрий , Romashyev YUriy
Published: November 2013

The author analyses new amendments related to state secrets protection: amendments to Article 275 ‘High Treason’, Article 276 ‘Espionage’, Article 283 ‘Disclosure of a State Secret’, and adopted Article 283.1 ‘Illegal Receipt of Information Constituting a State Secret’ of the Criminal Code of the Russian Federation in respect to their conformity with acceptable restrictions of fundamental human rights and freedoms. Special attention is paid to theoretical and action-oriented aspects of restrictions of fundamental human rights and freedoms. The author investigates relevant provisions of international documents, practice of the European Court of Human Rights, doctrines of leading experts in this sphere. The author notes that the criteria for restricting fundamental human rights and freedoms should be established entirely under the law and be indispensable and applicable in a democratic society, be aimed at the protection of national security and public order. The author draws the conclusion on the urgent character and timeliness of introducing the abovementioned novations into the Russian criminal legislation, and their conformity with generally recognized principles and rules of international law.