bluuebunny/crossref_metadata_2025 huggingface dataset:
NF-κB Gene Signature Predicts Prostate Cancer Progression
Authors: Jin Renjie , Yi Yajun , Yull Fiona E. , Blackwell Timothy S. , Clark Peter E. , Koyama Tatsuki , Smith Joseph A. , Matusik Robert J.
Published: April 2014

In many patients with prostate cancer, the cancer will be recurrent and eventually progress to lethal metastatic disease after primary treatment, such as surgery or radiation therapy. Therefore, it would be beneficial to better predict which patients with early-stage prostate cancer would progress or recur after primary definitive treatment. In addition, many studies indicate that activation of NF-κB signaling correlates with prostate cancer progression; however, the precise underlying mechanism is not fully understood. Our studies show that activation of NF-κB signaling via deletion of one allele of its inhibitor, IκBα, did not induce prostatic tumorigenesis in our mouse model. However, activation of NF-κB signaling did increase the rate of tumor progression in the Hi-Myc mouse prostate cancer model when compared with Hi-Myc alone. Using the nonmalignant NF-κB–activated androgen-depleted mouse prostate, a NF-κB–activated recurrence predictor 21 (NARP21) gene signature was generated. The NARP21 signature successfully predicted disease-specific survival and distant metastases-free survival in patients with prostate cancer. This transgenic mouse model–derived gene signature provides a useful and unique molecular profile for human prostate cancer prognosis, which could be used on a prostatic biopsy to predict indolent versus aggressive behavior of the cancer after surgery. Cancer Res; 74(10); 2763–72. ©2014 AACR.
SPINK1 Protein Expression and Prostate Cancer Progression
Authors: Flavin Richard , Pettersson Andreas , Hendrickson Whitney K. , Fiorentino Michelangelo , Finn Stephen , Kunz Lauren , Judson Gregory L. , Lis Rosina , Bailey Dyane , Fiore Christopher , Nuttall Elizabeth , Martin Neil E. , Stack Edward , Penney Kathryn L. , Rider Jennifer R. , Sinnott Jennifer , Sweeney Christopher , Sesso Howard D. , Fall Katja , Giovannucci Edward , Kantoff Philip , Stampfer Meir , Loda Massimo , Mucci Lorelei A.
Published: April 2014

Purpose: SPINK1 overexpression has been described in prostate cancer and is linked with poor prognosis in many cancers. The objective of this study was to characterize the association between SPINK1 overexpression and prostate cancer–specific survival.

Experimental Design: The study included 879 participants in the U.S. Physicians' Health Study and Health Professionals Follow-Up Study, diagnosed with prostate cancer (1983–2004) and treated by radical prostatectomy. Protein tumor expression of SPINK1 was evaluated by immunohistochemistry on tumor tissue microarrays.

Results: Seventy-four of 879 (8%) prostate cancer tumors were SPINK1 positive. Immunohistochemical data were available for PTEN, p-Akt, pS6, stathmin, androgen receptor (AR), and ERG (as a measure of the TMPRSS2:ERG translocation). Compared with SPINK1-negative tumors, SPINK1-positive tumors showed higher PTEN and stathmin expression, and lower expression of AR (P < 0.01). SPINK1 overexpression was seen in 47 of 427 (11%) ERG-negative samples and in 19 of 427 (4%) ERG-positive cases (P = 0.0003). We found no significant associations between SPINK1 status and Gleason grade or tumor stage. There was no association between SPINK1 expression and biochemical recurrence (P = 0.56). Moreover, there was no association between SPINK1 expression and prostate cancer mortality (there were 75 lethal cases of prostate cancer during a mean of 13.5 years follow-up; HR = 0.71; 95% confidence interval, 0.29–1.76).

Conclusions: Our results suggest that SPINK1 protein expression may not be a predictor of recurrence or lethal prostate cancer amongst men treated by radical prostatectomy. SPINK1 and ERG protein expression do not seem to be entirely mutually exclusive, as some previous studies have suggested. Clin Cancer Res; 20(18); 4904–11. ©2014 AACR.
Biomarker Analyses from a Placebo-Controlled Phase II Study Evaluating Erlotinib ± Onartuzumab in Advanced Non–Small Cell Lung Cancer: MET Expression Levels Are Predictive of Patient Benefit
Authors: Koeppen Hartmut , Yu Wei , Zha Jiping , Pandita Ajay , Penuel Elicia , Rangell Linda , Raja Rajiv , Mohan Sankar , Patel Rajesh , Desai Rupal , Fu Ling , Do An , Parab Vaishali , Xia Xiaoling , Januario Tom , Louie Sharianne G. , Filvaroff Ellen , Shames David S. , Wistuba Ignacio , Lipkind Marina , Huang Jenny , Lazarov Mirella , Ramakrishnan Vanitha , Amler Lukas , Phan See-Chun , Patel Premal , Peterson Amy , Yauch Robert L.
Published: April 2014

Purpose: In a recent phase II study of onartuzumab (MetMAb), patients whose non–small cell lung cancer (NSCLC) tissue scored as positive for MET protein by immunohistochemistry (IHC) experienced a significant benefit with onartuzumab plus erlotinib (O+E) versus erlotinib. We describe development and validation of a standardized MET IHC assay and, retrospectively, evaluate multiple biomarkers as predictors of patient benefit.

Experimental Design: Biomarkers related to MET and/or EGF receptor (EGFR) signaling were measured by IHC, FISH, quantitative reverse transcription PCR, mutation detection techniques, and ELISA.

Results: A positive correlation between IHC, Western blotting, and MET mRNA expression was observed in NSCLC cell lines/tissues. An IHC scoring system of MET expression taking proportional and intensity-based thresholds into consideration was applied in an analysis of the phase II study and resulted in the best differentiation of outcomes. Further analyses revealed a nonsignificant overall survival (OS) improvement with O+E in patients with high MET copy number (mean ≥5 copies/cell by FISH); however, benefit was maintained in “MET IHC-positive”/MET FISH-negative patients (HR, 0.37; P = 0.01). MET, EGFR, amphiregulin, epiregulin, or HGF mRNA expression did not predict a significant benefit with onartuzumab; a nonsignificant OS improvement was observed in patients with high tumor MET mRNA levels (HR, 0.59; P = 0.23). Patients with low baseline plasma hepatocyte growth factor (HGF) exhibited an HR for OS of 0.519 (P = 0.09) in favor of onartuzumab treatment.

Conclusions: MET IHC remains the most robust predictor of OS and progression-free survival benefit from O+E relative to all examined exploratory markers. Clin Cancer Res; 20(17); 4488–98. ©2014 AACR.
Prognostic and Predictive Values of the Immunoscore in Patients with Rectal Cancer
Authors: Anitei Maria-Gabriela , Zeitoun Guy , Mlecnik Bernhard , Marliot Florence , Haicheur Nacilla , Todosi Ana-Maria , Kirilovsky Amos , Lagorce Christine , Bindea Gabriela , Ferariu Dan , Danciu Mihai , Bruneval Patrick , Scripcariu Viorel , Chevallier Jean-Marc , Zinzindohoué Franck , Berger Anne , Galon Jérôme , Pagès Franck
Published: April 2014

Purpose: To determine whether the tumor immune infiltrate, as recently evaluated with the Immunoscore methodology, could be a useful prognostic marker in patients with rectal cancers.

Experimental design: The influence of the immune infiltrate on patient's outcome was investigated in patients with or without preoperative chemoradiation therapy (pCRT). The density of total (CD3+) and cytotoxic (CD8+) T lymphocytes was evaluated by immunohistochemistry and quantified by a dedicated image analysis software in surgical specimens of patients with rectal cancer (n = 111) who did not receive pCRT and in tumor biopsies performed before pCRT from additional 55 patients. The results were correlated with tumor recurrence, patient's survival, and response to pCRT.

Results: The densities of CD3+ and CD8+ lymphocytes and the associated Immunoscore (from I0 to I4) were significantly correlated with differences in disease-free and overall survival (HR, 1.81 and 1.72, respectively; all P < 0.005). Cox multivariate analysis supports the advantage of the Immunoscore compared with the tumor–node–metastasis (TNM) staging in predicting recurrence and survival (all P < 0.001). Lymph node ratio added information in a prognostic model (all P < 0.05). In addition, high infiltration of CD3+ and CD8+ lymphocytes in tumor biopsies was associated with downstaging of the tumor after pCRT (CD3+ cells; Fisher exact test P = 0.01).

Conclusions: The Immunoscore could be a useful prognostic marker in patients with rectal cancer treated by primary surgery. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of response to pCRT. Clin Cancer Res; 20(7); 1891–9. ©2014 AACR.
KRAS Codon 12 and 13 Mutations in Relation to Disease-Free Survival in BRAF–Wild-Type Stage III Colon Cancers from an Adjuvant Chemotherapy Trial (N0147 Alliance)
Authors: Yoon Harry H. , Tougeron David , Shi Qian , Alberts Steven R. , Mahoney Michelle R. , Nelson Garth D. , Nair Suresh G. , Thibodeau Stephen N. , Goldberg Richard M. , Sargent Daniel J. , Sinicrope Frank A. ,   for the Alliance for Clinical Trials in Oncology
Published: April 2014

Purpose: We examined the prognostic impact of specific KRAS mutations in patients with stage III colon adenocarcinoma receiving adjuvant FOLFOX alone or combined with cetuximab in a phase III trial (N0147). Analysis was restricted to BRAF–wild-type tumors, because BRAF mutation was associated with poor prognosis, and BRAF and KRAS mutations are mutually exclusive.

Experimental Design: The seven most common KRAS mutations in codon 12 and codon 13 were examined in 2,478 BRAF–wild-type tumors. Because KRAS mutations in codon 12 (n = 779) or 13 (n = 220) were not predictive of adjuvant cetuximab benefit, study arms were pooled for analysis. Disease-free survival (DFS) was evaluated by HRs using Cox models.

Results: KRAS mutations in codon 12 (multivariate HR, 1.52; 95% confidence interval, CI, 1.28–1.80; P < 0.0001) or codon 13 (multivariate HR, 1.36; 95% CI, 1.04–1.77; P = 0.0248) were significantly associated with shorter DFS compared with patients with wild-type KRAS/BRAF tumors, independent of covariates. KRAS codon 12 mutations were independently associated with proficient mismatch repair (P < 0.0001), proximal tumor site (P < 0.0001), low grade, age, and sex, whereas codon 13 mutations were associated with proximal site (P < 0.0001).

Conclusion: KRAS mutations in either codon 12 or 13 are associated with inferior survival in patients with resected stage III colon cancer. These data highlight the importance of accurate molecular characterization and the significant role of KRAS mutations in both codons in the progression of this malignancy in the adjuvant setting. Clin Cancer Res; 20(11); 3033–43. ©2014 AACR.
Inhibition of mTOR Signaling Reduces PELP1-Mediated Tumor Growth and Therapy Resistance
Authors: Gonugunta Vijay K. , Sareddy Gangadhara R. , Krishnan Samaya Rajeshwari , Cortez Valerie , Roy Sudipa Saha , Tekmal Rajeshwar Rao , Vadlamudi Ratna K.
Published: April 2014

Proline, Glutamic acid-, and Leucine-rich Protein 1 (PELP1) is a proto-oncogene that modulates estrogen receptor (ER) signaling. PELP1 expression is upregulated in breast cancer, contributes to therapy resistance, and is a prognostic marker of poor survival. In a subset of breast tumors, PELP1 is predominantly localized in the cytoplasm and PELP1 participates in extranuclear signaling by facilitating ER interactions with Src and phosphoinositide 3-kinase (PI3K). However, the mechanism by which PELP1 extranuclear actions contributes to cancer progression and therapy resistance remains unclear. In this study, we discovered that PELP1 cross-talked with the serine/threonine protein kinase mTOR and modulated mTOR signaling. PELP1 knockdown significantly reduced the activation of mTOR downstream signaling components. Conversely, PELP1 overexpression excessively activated mTOR signaling components. We detected the presence of the mTOR signaling complex proteins in PELP1 immunoprecipitates. mTOR-targeting drugs (rapamycin and AZD8055) significantly reduced proliferation of PELP1-overexpressed breast cancer cells in both in vitro and in vivo xenograft tumor models. MCF7 cells that uniquely retain PELP1 in the cytoplasm showed resistance to hormonal therapy and mTOR inhibitors sensitized PELP1cyto cells to hormonal therapy in xenograft assays. Notably, immunohistochemical studies using xenograft tumors derived from PELP1 overexpression model cells showed increased mTOR signaling and inhibition of mTOR rendered PELP1-driven tumors to be highly sensitive to therapeutic inhibition. Collectively, our data identified the PELP1–mTOR axis as a novel component of PELP1 oncogenic functions and suggest that mTOR inhibitor(s) will be effective chemotherapeutic agents for downregulating PELP1 oncogenic functions. Mol Cancer Ther; 13(6); 1578–88. ©2014 AACR.
Natural Compound Alternol Induces Oxidative Stress–Dependent Apoptotic Cell Death Preferentially in Prostate Cancer Cells
Authors: Tang Yuzhe , Chen Ruibao , Huang Yan , Li Guodong , Huang Yiling , Chen Jiepeng , Duan Lili , Zhu Bao-Ting , Thrasher J. Brantley , Zhang Xu , Li Benyi
Published: April 2014

Prostate cancers at the late stage of castration resistance are not responding well to most of current therapies available in clinic, reflecting a desperate need of novel treatment for this life-threatening disease. In this study, we evaluated the anticancer effect of a recently isolated natural compound, Alternol, in multiple prostate cancer cell lines with the properties of advanced prostate cancers in comparison to prostate-derived nonmalignant cells. As assessed by trypan blue exclusion assay, significant cell death was observed in all prostate cancer cell lines except DU145 but not in nonmalignant (RWPE-1 and BPH1) cells. Further analyses revealed that Alternol-induced cell death was an apoptotic response in a dose- and time-dependent manner, as evidenced by the appearance of apoptosis hallmarks such as caspase-3 processing and PARP cleavage. Interestingly, Alternol-induced cell death was completely abolished by reactive oxygen species scavengers N-acetylcysteine and dihydrolipoic acid. We also demonstrated that the proapoptotic Bax protein was activated after Alternol treatment and was critical for Alternol-induced apoptosis. Animal xenograft experiments in nude mice showed that Alternol treatment largely suppressed tumor growth of PC-3 xenografts but not Bax-null DU-145 xenografts in vivo. These data suggest that Alternol might serve as a novel anticancer agent for patients with late-stage prostate cancer. Mol Cancer Ther; 13(6); 1526–36. ©2014 AACR.
Chronic Kidney Disease in an Electronic Health Record Problem List: Quality of Care, ESRD, and Mortality
Authors: Jolly Stacey E. , Navaneethan Sankar D. , Schold Jesse D. , Arrigain Susana , Sharp John W. , Jain Anil K. , Schreiber Martin J. , Simon James F. , Nally Joseph V.
Published: April 2014

Background: Whether chronic kidney disease (CKD) recognition in an electronic health record (EHR) problem list improves processes of care or clinical outcomes of end-stage renal disease (ESRD) and death is unclear. Methods: We identified patients who had at least 1 year of follow-up (2005-2009) in our EHR-based CKD registry (n = 25,742). CKD recognition was defined by having ICD-9 codes for CKD, diabetic kidney disease, or hypertensive kidney disease in the problem list. We calculated proportions of patients with and without CKD recognition and examined differences by demographics, clinical factors, and development of ESRD or mortality. We evaluated differences in the proportion of patients with CKD-specific laboratory results checked before and after recognition among cases and propensity-matched controls. Results: Only 11% (n = 2,735) had CKD recognition in the problem list and they were younger (68 vs. 71 years), a higher proportion were male (61 vs. 37%) and African-American (21 vs. 10%) compared to those unrecognized. CKD-specific laboratory results for patients with estimated glomerular filtration rate (eGFR) 30-59 including intact parathyroid hormone (23 vs. 6%), vitamin D (22 vs. 18%), phosphorus (29 vs. 7%), and a urine check for proteinuria (55 vs. 36%) were significantly more likely to be done among those with CKD recognition (all p < 0.05). Similar results were found for eGFR <30 except for proteinuria and in our propensity score-matched control analysis. There was no independent association of CKD recognition with ESRD or mortality. Conclusions: CKD recognition in the EHR problem list was low, but translated into more CKD-specific processes of care; however ESRD or mortality were not affected.
Mitotic Stability of Small Supernumerary Marker Chromosomes: A Study Based on 93 Immortalized Cell Lines
Authors: Spittel Hannes , Kubek Florian , Kreskowski Katharina , Ziegler Monika , Klein Elisabeth , Hamid Ahmed B. , Kosyakova Nadezda , Radhakrishnan Gopakumar , Junge Annelore , Kozlowski Peter , Schulze Berndt , Martin Thomas , Huhle Dagmar , Mehnert Karl , Rodríguez Laura , Ergun Mehmet A. , Sarri Catherine , Militaru Mariela , Stipoljev Fedora , Tittelbach Hanne , Vasheghani Faezeh , de Bello Cioffi Marcelo , Hussein Shaymaa S. , Fan Xiaobo , Volleth Marianne , Liehr Thomas
Published: April 2014

Small supernumerary marker chromosomes (sSMC) are known for being present in mosaic form as 47,+mar/46 in >50% of the cases with this kind of extra chromosomes. However, no detailed studies have been done for the mitotic stability of sSMC so far, mainly due to the lack of a corresponding in vitro model system. Recently, we established an sSMC-cell bank (Else Kröner-Fresenius-sSMC-cellbank) with >150 cell lines. Therefore, 93 selected sSMC cases were studied here for the presence of the corresponding marker chromosomes before and after Epstein-Barr virus-induced immortalization. The obtained results showed that dicentric inverted duplicated-shaped sSMC are by far more stable in vitro than monocentric centric minute- or ring-shaped sSMC. Simultaneously, a review of the literature revealed that a comparable shape-dependent mitotic stability can be found in vivo in sSMC carriers. Additionally, a possible impact of the age of the sSMC carrier on mitotic stability was found: sSMC cell lines established from patients between 10-20 years of age were predominantly mitotically unstable. The latter finding was independent of the sSMC shape. The present study shows that in vitro models can lead to new and exciting insights into the biology of this genetically and clinically heterogeneous patient group.
Intermittent Pneumatic Compression Pump for Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Shao Yi , Qi Kang , Zhou Qing-Hua , Zhong Dian-Sheng
Published: April 2014

Background: Breast cancer-related lymphedema (BCRL) is a common complication after the treatment of breast cancer. The objective of this study was to determine whether the use of an intermittent pneumatic pump (IPC) could manage lymphedema effectively. Methods: We searched PubMed, EMBASE, and the Cochrane Library for related trials to compare the percent of volume reduction and subjective symptoms. Results: 7 randomized controlled trials, with 287 patients, were included. Results showed that the use of the IPC could alleviate lymphedema, but no significant difference between routine management of lymphedema with or without pneumatic pump existed. Conclusion: Current trials fail to show the effectiveness of the addition of an IPC to the routine management of BCRL.
Disruption of Mammalian Target of Rapamycin Complex 1 in Macrophages Decreases Chemokine Gene Expression and Atherosclerosis
Authors: Ai Ding , Jiang Hongfeng , Westerterp Marit , Murphy Andrew J. , Wang Mi , Ganda Anjali , Abramowicz Sandra , Welch Carrie , Almazan Felicidad , Zhu Yi , Miller Yury I. , Tall Alan R.
Published: April 2014

Rationale:

The mammalian target of rapamycin complex 1 inhibitor, rapamycin, has been shown to decrease atherosclerosis, even while increasing plasma low-density lipoprotein levels. This suggests an antiatherogenic effect possibly mediated by the modulation of inflammatory responses in atherosclerotic plaques.

Objective:

Our aim was to assess the role of macrophage mammalian target of rapamycin complex 1 in atherogenesis.

Methods and Results:

We transplanted bone marrow from mice in which a key mammalian target of rapamycin complex 1 adaptor, regulatory-associated protein of mTOR, was deleted in macrophages by Cre/loxP recombination (
Mac-Rap

KO

mice) into
Ldlr
−/−
mice and then fed them the Western-type diet. Atherosclerotic lesions from
Mac-Rap

KO

mice showed decreased infiltration of macrophages, lesion size, and chemokine gene expression compared with control mice. Treatment of macrophages with minimally modified low-density lipoprotein resulted in increased levels of chemokine mRNAs and signal transducer and activator of transcription (STAT) 3 phosphorylation; these effects were reduced in
Mac-Rap

KO

macrophages. Although wild-type and
Mac-Rap

KO

macrophages showed similar STAT3 phosphorylation on Tyr705,
Mac-Rap

KO

macrophages showed decreased STAT3Ser727 phosphorylation in response to minimally modified low-density lipoprotein treatment and decreased
Ccl2
promoter binding of STAT3.

Conclusions:

The results demonstrate cross-talk between nutritionally induced mammalian target of rapamycin complex 1 signaling and minimally modified low-density lipoprotein–mediated inflammatory signaling via combinatorial phosphorylation of STAT3 in macrophages, leading to increased STAT3 activity on the chemokine (C-C motif) ligand 2 (monocyte chemoattractant protein 1) promoter with proatherogenic consequences.
Low Serum Ferroxidase I Activity Is Associated With Mortality in Heart Failure and Related to Both Peroxynitrite-Induced Cysteine Oxidation and Tyrosine Nitration of Ceruloplasmin
Authors: Cabassi Aderville , Binno Simone Maurizio , Tedeschi Stefano , Ruzicka Valerie , Dancelli Simona , Rocco Rossana , Vicini Vanni , Coghi Pietro , Regolisti Giuseppe , Montanari Alberto , Fiaccadori Enrico , Govoni Paolo , Piepoli Massimo , de Champlain Jacques
Published: April 2014

Rationale:

Ceruloplasmin antioxidant function is mainly related to its ferroxidase I (FeOxI) activity, which influences iron-dependent oxidative and nitrosative radical species generation. Peroxynitrite, whose production is increased in heart failure (HF), can affect ceruloplasmin antioxidant function through amino acid modification.

Objective:

We investigated the relationship between FeOxI and ceruloplasmin tyrosine and cysteine modification and explored in a cohort of patients with HF the potential clinical relevance of serum FeOxI.

Methods and Results:

In patients with chronic HF (n=96, 76±9 years; New York Heart Association class, 2.9±0.8) and age-matched controls (n=35), serum FeOxI, FeOxII, ceruloplasmin, nitrotyrosine-bound ceruloplasmin, B-type natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were measured, and the patients were followed up for 24 months. Ceruloplasmin, B-type natriuretic peptide, norepinephrine, and high-sensitivity C-reactive protein were increased in HF versus controls. FeOxI was decreased in HF (−20%) and inversely related to nitrotyrosine-bound ceruloplasmin (
r
, −0.305;
P
=0.003). In HF, FeOxI lower tertile had a mortality rate doubled compared with middle-higher tertiles. FeOxI emerged as a mortality predictor (hazard ratio, 2.95; 95% confidence intervals [1.29–6.75];
P
=0.011) after adjustment for age, sex, hypertension, smoking, sodium level, estimated glomerular filtration rate, and high-sensitivity C-reactive protein. In experimental settings, peroxynitrite incubation of serum samples and isolated purified ceruloplasmin reduced FeOxI activity while increasing ceruloplasmin tyrosine nitration and cysteine thiol oxidation. Reduced glutathione prevented peroxynitrite-induced FeOxI drop, tyrosine nitration, and cysteine oxidation; flavonoid(−)-epicatechin, which prevented ceruloplasmin tyrosine nitration but not cysteine oxidation, partially impeded peroxynitrite-induced FeOxI drop.

Conclusions:

Reduced activity of serum FeOxI is associated with ceruloplasmin nitration and reduced survival in patients with HF. Both ceruloplasmin tyrosine nitration and cysteine thiol oxidation may be operant in vivo in peroxynitrite-induced FeOxI activity inhibition.
Early Adult to Midlife Cardiovascular Risk Factors and Cognitive Function
Authors: Yaffe Kristine , Vittinghoff Eric , Pletcher Mark J. , Hoang Tina D. , Launer Lenore J. , Whitmer Rachel A. , Coker Laura H. , Sidney Stephen
Published: April 2014

Background—

Studies have linked midlife and late-life cardiovascular risk factors (CVRFs) to cognitive function, yet little is known about CVRF exposure in early adulthood and subsequent cognitive function. In addition, most studies rely on single assessments of CVRFs, which may not accurately reflect long-term exposure. We sought to determine the association between cumulative exposure to CVRFs from early to middle adulthood and cognitive function at midlife.

Methods and Results—

In a prospective study of 3381 adults (age, 18–30 years at baseline) with 25 years of follow-up, we assessed cognitive function at year 25 (2010–2011) with the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning Test analyzed with standardized
z
scores. The primary predictor was 25-year cumulative exposure estimated by areas under the curve for resting systolic and diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher cumulative systolic and diastolic blood pressures and fasting blood glucose were consistently associated with worse cognition on all 3 tests. These associations were significant primarily for exposures above recommended guidelines; cognitive test
z
scores were between 0.06 and 0.30 points less, on average, for each 1-SD increase in risk factor area under the curve after adjustment for age, race, sex, and education (
P
<0.05 for all). Fewer significant associations were observed for cholesterol.

Conclusions—

Cumulative exposure to CVRFs from early to middle adulthood, especially above recommended guidelines, was associated with worse cognition in midlife. The meaning of this association and whether it warrants more aggressive treatment of CVRFs earlier in life require further investigation.
Specific Respiratory Neuron Types Have Increased Excitability That Drive Presympathetic Neurones in Neurogenic Hypertension
Authors: Moraes Davi J. A. , Machado Benedito H. , Paton Julian F. R.
Published: April 2014

A major aspect of hypertension is excessive sympathetic activity but the reasons for this remain elusive. Sympathetic tone is increased in the spontaneously hypertensive (SH) rat reflecting, in part, enhanced respiratory–sympathetic coupling. We aimed to identify which respiratory cells might have altered properties. Using the working heart–brain stem preparation, we monitored simultaneously sympathetic and respiratory nerve activity in combination with intracellular recordings of physiologically characterized medullary presympathetic or respiratory neurons. In SH rats, respiratory modulation of both inspiratory and postinspiratory phases of sympathetic activity was larger relative to Wistar rats. An additional burst of sympathetic activity in the preinspiratory phase was also present in SH rats. After synaptic isolation of rostral medullary presympathetic neurons, there was no difference in their excitability compared with neurons in Wistar rats. Rather, both pre-Bötzinger preinspiratory and Bötzinger postinspiratory neurons had increased neuronal excitability in SH rats relative to Wistar rats; this was attributed to higher input resistance/reduced leak current in preinspiratory neurons and reduced calcium activated potassium conductance in postinspiratory neurons. Thus, the respiratory network of the SH rat is reconfigured to a pattern dominated by heightened excitability of preinspiratory and postinspiratory neurons. These neurons both provide augmented excitatory synaptic drive to rostral medullary presympathetic neurons contributing to excessive sympathetic nerve activity associated with hypertension in the in situ SH rat. Our data indicate selective modulation of potassium conductances in 2 subsets of respiratory neurons contributing to neurogenic hypertension.
Strategy for Standardization of Preeclampsia Research Study Design
Authors: Myatt Leslie , Redman Christopher W. , Staff Anne Cathrine , Hansson Stefan , Wilson Melissa L. , Laivuori Hannele , Poston Lucilla , Roberts James M.
Published: April 2014

Preeclampsia remains a major problem worldwide for mothers and babies. Despite intensive study, we have not been able to improve the management or early recognition of preeclampsia. At least part of this is because of failure to standardize the approach to studying this complex syndrome. It is possible that within the syndrome there may be different phenotypes with pathogenic pathways that differ between the subtypes. The capacity to recognize and to exploit different subtypes is of obvious importance for prediction, prevention, and treatment. We present a strategy for research to study preeclampsia, which will allow discrimination of such possible subtypes and also allow comparison and perhaps combinations of findings in different studies by standardized data and biosample collection. To make studies relevant to current clinical practice, the definition of preeclampsia can be that currently used and accepted. However, more importantly, sufficient data should be collected to allow other diagnostic criteria to be used and applied retrospectively. To that end, we present what we consider to be the minimum requirements for a data set in a study of preeclampsia that will facilitate comparisons. We also present a comprehensive or optimal data set for in-depth investigation of pathophysiology. As we approach the definition of phenotypes of preeclampsia by clinical and biochemical criteria, adherence to standardized protocols will hasten our understanding of the causes of preeclampsia and development of targeted treatment strategies
The Modern Privilege of Life
Authors: Ziarek Krzysztof
Published: April 2014

Abstract

This essay reconsiders the notion of “world” by looking critically at the idiom of life dominating current critical debates. Showing how and why life should be displaced from the privileged position it has assumed in modernity, it examines Arendt’s and Heidegger’s comments on the world. In The Human Condition, Arendt provides an interesting philosophical and cultural account of the rise of life to prominence in the modern age, pointing out its detrimental effects on the understanding of the world and human action. Heidegger, on the other hand, executes, through his idiomatic approach to mortality, perhaps the most radical displacement of life in an attempt to rethink and bring to eminence being and the event of the world. At stake is a different experience of the world and a change in the understanding of the human, situating the human (and) life always already in response to the nonrepeatable event of being.
Introduction: French Language(s) in Contact Worldwide
Authors: Gadet Françoise , Ludwig Ralph
Published: April 2014

The awareness of language that culminated in France with the French Revolution has remained dominant till the present day: a nation une et indivisible corresponds to a concept of the national language as a homogenous entity, self-sufficient and free from outside and dialectal influences. This conception is contradicted by two historical facts, however. Firstly, various waves of language contact were constitutive of the emergence and development of the French language from the very beginning. Secondly, a new structure of varieties developed through the colonial expansion of France outside Europe, in which many forms of language contact are of significant importance. The best way to capture this diversity adequately is to adhere to a broadly ecological approach (linguistic ecology) that takes into account various parameters, such as history, social context, competence, and universals. This is demonstrated with samples of transcribed speech from Togo, Guadeloupe and Nova Scotia. The linguistic ecology approach is the guiding principle of all the articles in this volume.
Hybrid Languages in Canada Involving French
Authors: Papen Robert A.
Published: April 2014

Valdman et al. (2005) claims there exist two mixed languages involving French in North America: Michif – a blend of French and Cree – and Chiac – a blend of French and English. The purpose of this article is to compare the sociolinguistic history as well as the linguistic structures of these two linguistic entities in order to show that even though there are a number of interesting similarities between the two, their histories, and more importantly their structures, show that Michif and Chiac are not to be considered as belonging to the same linguistic class. Michif is a true Bilingual Mixed Language (Thomason, 1997) while Chiac has not yet attained the status of an independent language and should more rightly be considered as a “fossilized mixed code” (Winford, 2003).
Phylogeny and taxonomy of Ceriporiopsis (Polyporales) with descriptions of two new species from southern China
Authors: Cui Bao-Kai , Zhao Chang-Lin
Published: April 2014

Phylogenies of Ceriporiopsis and related genera were studied using DNA sequences from the ITS+28S nuclear ribosomal RNA gene regions. Two species, Ceriporiopsis alboaurantia and C. semisupina, are described as new to science. Ceriporiopsis alboaurantia is characterized by annual growth habit, resupinate basidiocarps with white pore surface when fresh, turning to apricot-orange to dark orange upon drying, monomitic hyphal system with clamped generative hyphae encrusted with pale yellow crystals, ellipsoid and thin-walled basidiospores (4–5 ´ 3–3.3 µm), and plenty of pale-yellow to pale-orange oily substances in subiculum and trama. Ceriporiopsis semisupina is distinguished by annual, effused-reflexed basidiocarps with greyish brown to reddish brown pore surface, monomitic hyphal system with clamped generative hyphae bearing crystalline incrustation, long-clavate basidia, ellipsoid and thin-walled basidiospores (4–4.5 ´ 3–3.3 µm). Like previous study, the phylogenetic analysis presented here also showed that Ceriporiopsis is not monophyletic and the sampled species were grouped in four clades, including phlebia clade, residual polyporoid clade, tyromyces clade and gelatoporia clade.
Revision of the genus Apophua Morley, 1913, from Japan
(Hymenoptera, Ichneumonidae, Banchinae)
Authors: WATANABE KYOHEI , MAETO KAORU
Published: April 2014

Japanese species of the genus Apophua Morley, 1913, are revised. Eleven species are found from Japan and two of them, A. elegans sp. nov. and A. yamato sp. nov., are newly described. Distribution data and an updated key to Japanese species are provided.
Four new species of the grass feeding leafhopper genus Nicolaus Lindberg (Hemiptera: Cicadellidae: Deltocephalinae) from the Indian subcontinent
Authors: VIRAKTAMATH C. A. , WEBB M. D.
Published: April 2014

The leafhopper genus Nicolaus Lindberg is recorded from India and Pakistan for the first time. Four new species, N. abuensis sp. nov., N. bidentatus sp. nov., N. cornutus sp. nov. and N. serratus sp. nov. are described and illustrated. N. bihamatus Xing & Li, earlier known from China is recorded from India and Pakistan. A key to the species of Nicolaus from the study area is provided.
The ancient Balkan lakes harbor a new endemic species of Diaphanosoma Fischer, 1850 (Crustacea: Branchiopoda: Cladocera)
Authors: KOROVCHINSKY NIKOLAI M. , PETKOVSKI TRAJAN K.
Published: April 2014

Diaphanosoma macedonicum sp. nov. is described from material collected from the ancient Lakes Dojran and Prespa, located in the central part of the Balkan Peninsula. It can be regarded as a member of the “D. mongolianum” species group. It is characterized by specific, but not readily visible features, such as the absence of a thorn near the posterior valve margins, as well as setules between setae of the ventral valve inflection, and the presence of more chitinized integument. The discovery of this new species previously identified as "Diaphanosoma brachyurum (Liévin)" highlights the necessity of more detailed investigations of the zooplankton of Balkan lakes potentially populated by greater numbers of endemic cladoceran species. A short overview of the ancient lakes in the Central Balkans is provided.
Two ‘new’ renicolid trematodes (Trematoda: Digenea: Renicolidae) from the California horn snail, Cerithidea californica (Haldeman, 1840) (Gastropoda: Potamididae)
Authors: HECHINGER RYAN F. , MIURA OSAMU
Published: April 2014

This manuscript describes the daughter parthenitae (sporocysts) and cercariae of two species of renicolid xiphidiocercaria that infect the California horn snail, Cerithidea californica, which serves as first intermediate host for a diverse and ecologically important guild of digenean trematode parasitic castrators. The two species described here have previously been considered to be a single morphospecies in ecological and evolutionary research. We provide provisional species names to respect that digenean alpha taxonomy is currently focused on sexual (adult) stages, while simultaneously respecting the spirit and utility of formal nomenclature in providing unambiguously unique, species-level names that also clarify to the extent possible species’ taxonomic affiliations. The first species, Renicola sp. “polychaetophila” is most readily distinguishable from previously described renicolid xiphidiocercariae by a combination of (1) having a penetration gland duct arrangement of 2[(1+3+1)+1], (2) having one pair of penetration glands positioned anteriorly to the main gland cluster, (3) lacking tegmental spines, and (4) infecting Cerithidea californica. The second species, Renicola sp. “martini”, is most readily distinguishable from other renicolid xiphidiocercariae that also have tegmental spines by a combination of (1) having a simple, bullet-shaped oral stylet sclerotized for 50–80% of its length, (2) having a cystogenous-gland field with an anterior-most extent about half way between the oral and ventral suckers, and (3) in infecting Cerithidea californica. Phylogenetic analyses using DNA (COI and ITS1) sequence data support that these two trematodes represent distinct species of Renicola. We also (1) provide an emended diagnosis for renicolid cercariae, (2) highlight a few morphological characters that may be useful for future taxonomic work involving renicolid xiphidiocercariae, and (3) suggest that future descriptive work involving trematode parthenitae include more information pertaining to the group of parthenitae as a whole.
A new species of Anarta Ochsenheimer, 1816 from Mongolian and Russian Altai (Lepidoptera, Noctuidae)
Authors: VOLYNKIN ANTON V. , IVANOVA MARIA S.
Published: April 2014

Anarta Ochsenheimer, 1816 is a hadenine genus restricted to Palaearctic and Nearctic Regions. The genus includes about 80 described species and subdivided into seven subgenera (Hacker 1998; Fibiger et al. 2011): Trichoclea Grote, 1883 (= Hadula Staudinger, 1889), Cardiestra Boursin, 1963, Ptochicestra Hacker, 1998, Aglossestra Hampson, 1905, Calocestra Beck, 1991, Pulchrohadula Hacker, 1998 and Anarta Ochsenheimer, 1816 (= Discestra Hampson, 1905). The group has been revised by Hacker (1998). Anarta, Trichoclea, Hadula and Discestra were been synonymized by Fibiger & Hacker (2005).
Leaf Area Index Variation for Crop, Pasture, and Tree in Response to Climatic Variation in the Goulburn–Broken Catchment, Australia
Authors: Tesemma Zelalem K. , Wei Yongping , Western Andrew W. , Peel Murray C.
Published: April 2014

Previous studies have reported relationships between mean annual climatic variables and mean annual leaf area index (LAI), but the seasonal and spatial variability of this relationship for different vegetation cover types in different climate zones have rarely been explored in Australia. The authors developed simple models using remotely sensed LAI data from the Moderate Resolution Imaging Spectroradiometer (MODIS) and gridded climatic data from the Australian Water Availability Project. They were able to relate seasonal and annual LAI of three different land cover types (tree, pasture, and crop) with climatic variables for the period 2000–09 in the Goulburn–Broken catchment, Australia. Strong relationships were obtained between annual LAI of crop, pasture, and tree with annual precipitation (R2 = 0.70, 0.65, and 0.82, respectively). Monthly LAI of each land cover type also showed a strong relationship (R2 = 0.92, 0.95, and 0.95) with the difference between precipitation P and reference crop evapotranspiration (PET; P − PET) for crop, pasture, and tree. Independent model calibration and validation showed good agreement with remotely sensed MODIS LAI. The results from the application of the developed model on the future impact of climate change suggest that under all climate scenarios crop, pasture, and tree showed consistent decreases in mean annual LAI. For the future climate change scenarios considered, crop showed a decline of 7%–38%, pasture showed a decline of 5%–24%, and tree showed a decline of 2%–11% from the historical mean annual. These results can be used to assess the impacts of future climatic and land cover changes on water resources by coupling them with hydrological models.
A Global Surface Ocean fCO2 Climatology Based on a Feed-Forward Neural Network
Authors: Zeng J. , Nojiri Y. , Landschützer P. , Telszewski M. , Nakaoka S.
Published: April 2014

A feed-forward neural network is used to create a monthly climatology of the sea surface fugacity of CO2 (fCO2) on a 1° × 1° spatial resolution. Using 127 880 data points from 1990 to 2011 in the track-gridded database of the Surface Ocean CO2 Atlas version 2.0 (Bakker et al.), the model yields a global mean fCO2 increase rate of 1.50 μatm yr−1. The rate was used to normalize multiple years’ fCO2 observations to the reference year of 2000. A total of 73 265 data points from the normalized data were used to model the global fCO2 climatology. The model simulates monthly fCO2 distributions that agree well with observations and yields an anthropogenic CO2 update of −1.9 to −2.3 PgC yr−1. The range reflects the uncertainty related to using different wind products for the flux calculation. This estimate is in good agreement with the recently derived best estimate by Wanninkhof et al. The model product benefits from a finer spatial resolution compared to the product of Lamont–Doherty Earth Observatory (Takahashi et al.), which is currently the most frequently used product. It therefore has the potential to improve estimates of the global ocean CO2 uptake. The method’s benefits include but are not limited to the following: (i) a fixed structure is not required to model fCO2 as a nonlinear function of biogeochemical variables, (ii) only one neural network configuration is sufficient to model global fCO2 in all seasons, and (iii) the model can be extended to produce global fCO2 maps at a higher resolution in time and space as long as the required data for input variables are available.
Social Process of Adaptation to Environmental Changes: How Eastern African Societies Intervene between Crops and Climate
Authors: Mwongera Caroline , Boyard-Micheau Joseph , Baron Christian , Leclerc Christian
Published: April 2014

Studies on climate change can only be conducted on a long time scale, and observing how societies adapt their sowing practices to climate variability is challenging and costly. As an alternative, a space and time substitution design was used, changes in space corresponding to that induced in time by environmental change. On the eastern slope of Mount Kenya, the Tharaka community, originating from the lowlands (750 m), moved up to the midlands (950 m) with their lowland-adapted resources, whereas the Mwimbi, originating from wetter upland (1100 m), moved down to the midlands with their highland-adapted genetic resources. A weather station was installed at 950 and 1100 m, and a logistic model was used to analyze the probability of sowing failure as a function of the length of dry spells after sowing. A total of 1691 plots in 40 surveyed farms were surveyed to compare the Mwimbi and Tharaka during 2 yr and four growing seasons, controlling crops and altitude. Although seed-sowing practices were similar in both communities, the relative risk of sowing failure was 3.3 times more for the Mwimbi than for the Tharaka during the Short Rains, and 1.5 times more during the Long Rains. This difference can be explained by within-community seed exchanges, as Tharaka seeds, originally from the lowlands, are adapted to drier conditions, whereas Mwimbi seeds are adapted to wetter conditions. The findings suggest an impact of historical and social factors on the mitigation of sowing failure risk. Thus, they must be considered as an integral part of the adaptation process to climate variability and change.
Casualties of Social Combat
Authors: Faris Robert , Felmlee Diane
Published: April 2014

We point to group processes of status conflict and norm enforcement as fundamental elements in the development of school-based victimization. Socially vulnerable youth are frequently harassed for violating norms, but the logic of status competition implies they are not the only victims: to the extent that aggression is instrumental for social climbing, increases in status should increase risk—at least until the pinnacle of the hierarchy is reached. Victimization causes serious harm, and, we argue, at the margin these consequences will be magnified by status. We test these ideas using longitudinal network data on friendship and victimization from 19 schools. For most students, status increases the risk of victimization. However, youth at the uppermost extremes of the school hierarchy—students in the top 5 percent of centrality and those with cross-gender friendships where such friendships are rare—sit just above the fray, unlikely to fall victim to their peers. As expected, females and physically or socially vulnerable youth are victimized at particularly high rates. Victims experience psychological distress and social marginalization, and these adverse effects are magnified by status. For most students, gains in status increase the likelihood of victimization and the severity of its consequences.
Is the Motherhood Penalty Larger for Low-Wage Women? A Comment on Quantile Regression
Authors: Killewald Alexandra , Bearak Jonathan
Published: April 2014

In this comment, we offer a nontechnical discussion of conventional (conditional) multivariate quantile regression, with an emphasis on the appropriate interpretation of results. We discuss its distinction from unconditional quantile regression, an analytic method that can be used to estimate varying associations between predictors and outcome at different points of the outcome distribution. We argue that the research question posed by Budig and Hodges (2010)—whether the motherhood penalty is larger for low-wage women—cannot be answered with the authors’ conditional quantile regression models. Using more appropriate unconditional quantile regression models, we find, in contrast to Budig and Hodges’s claims, that the motherhood penalty is not largest for low-wage women.