bluuebunny/crossref_metadata_2025 huggingface dataset:
Essential Oil ofPinus koraiensisExerts Antiobesic and Hypolipidemic Activity via Inhibition of Peroxisome Proliferator-Activated Receptors Gamma Signaling
Authors: Ko Hyun-Suk , Lee Hyo-Jeong , Lee Hyo-Jung , Sohn Eun Jung , Yun Miyong , Lee Min-Ho , Kim Sung-Hoon
Published: August 2013

Our group previously reported that essential oil ofPinus koraiensis(EOPK) exerts antihyperlipidemic effects via upregulation of low-density lipoprotein receptor and inhibition of acyl-coenzyme A. In the present study, we investigated the antiobesity and hypolipidemic mechanism of EOPK usingin vitro3T3-L1 cells andin vivoHFD-fed rats. EOPK markedly suppressed fat accumulation and intracellular triglyceride associated with downregulation of adipogenic transcription factor expression, including PPARγand CEBPαin the differentiated 3T3-L1 adipocytes. Additionally, EOPK attenuated the expression levels of FABP and GPDH as target genes of PPARγduring adipocyte differentiation. Furthermore, PPARγinhibitor GW9662 enhanced the decreased expression of FABP and PPARγand fat accumulation induced by EOPK. To confirm thein vitroactivity of EOPK, animal study was performed by administering normal diet, HFD, and/or EOPK at the dose of 100 or 200 mg/kg for 6 weeks. Consistently, EOPK significantly suppressed body weight gain, serum triglyceride, total cholesterol, LDL cholesterol, and AI value and increased HDL cholesterol in a dose-dependent manner. Immunohistochemistry revealed that EOPK treatment abrogated the expression of PPARγin the liver tissue sections of EOPK-treated rats. Taken together, our findings suggest that EOPK has the antiobesic and hypolipidemic potential via inhibition of PPARγ-related signaling.
Identification of Multiple Mechanisms of Resistance to Vemurafenib in a Patient with BRAFV600E-Mutated Cutaneous Melanoma Successfully Rechallenged after Progression
Authors: Romano Emanuela , Pradervand Sylvain , Paillusson Alexandra , Weber Johann , Harshman Keith , Muehlethaler Katja , Speiser Daniel , Peters Solange , Rimoldi Donata , Michielin Olivier
Published: August 2013

Purpose: To investigate the mechanism(s) of resistance to the RAF-inhibitor vemurafenib, we conducted a comprehensive analysis of the genetic alterations occurring in metastatic lesions from a patient with a BRAFV600E-mutant cutaneous melanoma who, after a first response, underwent subsequent rechallenge with this drug.

Experimental Design: We obtained blood and tissue samples from a patient diagnosed with a BRAFV600E-mutant cutaneous melanoma that was treated with vemurafenib and achieved a near-complete response. At progression, he received additional lines of chemo/immunotherapy and was successfully rechallenged with vemurafenib. Exome and RNA sequencing were conducted on a pretreatment tumor and two subcutaneous resistant metastases, one that was present at baseline and previously responded to vemurafenib (PV1) and one that occurred de novo after reintroduction of the drug (PV2). A culture established from PV1 was also analyzed.

Results: We identified two NRAS-activating somatic mutations, Q61R and Q61K, affecting two main subpopulations in the metastasis PV1 and a BRAF alternative splicing, involving exons 4–10, in the metastasis PV2. These alterations, known to confer resistance to RAF inhibitors, were tumor-specific, mutually exclusive, and were not detected in pretreatment tumor samples. In addition, the oncogenic PIK3CAH1047R mutation was detected in a subpopulation of PV1, but this mutation did not seem to play a major role in vemurafenib resistance in this metastasis.

Conclusions: This work describes the coexistence within the same patient of different molecular mechanisms of resistance to vemurafenib affecting different metastatic sites. These findings have direct implications for the clinical management of BRAF-mutant melanoma. Clin Cancer Res; 19(20); 5749–57. ©2013 AACR.
Differential Response to Neoadjuvant Chemotherapy Among 7 Triple-Negative Breast Cancer Molecular Subtypes
Authors: Masuda Hiroko , Baggerly Keith A. , Wang Ying , Zhang Ya , Gonzalez-Angulo Ana Maria , Meric-Bernstam Funda , Valero Vicente , Lehmann Brian D. , Pietenpol Jennifer A. , Hortobagyi Gabriel N. , Symmans W. Fraser , Ueno Naoto T.
Published: August 2013

Purpose: The clinical relevancy of the 7-subtype classification of triple-negative breast cancer (TNBC) reported by Lehmann and colleagues is unknown. We investigated the clinical relevancy of TNBC heterogeneity by determining pathologic complete response (pCR) rates after neoadjuvant chemotherapy, based on TNBC subtypes.

Experimental Design: We revalidated the Lehmann and colleagues experiments using Affymetrix CEL files from public datasets. We applied these methods to 146 patients with TNBC with gene expression microarrays obtained from June 2000 to March 2010 at our institution. Of those, 130 had received standard neoadjuvant chemotherapy and had evaluable pathologic response data. We classified the TNBC samples by subtype and then correlated subtype and pCR status using Fisher exact test and a logistic regression model. We also assessed survival and compared the subtypes with PAM50 intrinsic subtypes and residual cancer burden (RCB) index.

Results: TNBC subtype and pCR status were significantly associated (P = 0.04379). The basal-like 1 (BL1) subtype had the highest pCR rate (52%); basal-like 2 (BL2) and luminal androgen receptor had the lowest (0% and 10%, respectively). TNBC subtype was an independent predictor of pCR status (P = 0.022) by a likelihood ratio test. The subtypes better predicted pCR status than did the PAM50 intrinsic subtypes (basal-like vs. non basal-like).

Conclusions: Classifying TNBC by 7 subtypes predicts high versus low pCR rate. We confirm the clinical relevancy of the 7 subtypes of TNBC. We need to prospectively validate whether the pCR rate differences translate into long-term outcome differences. The 7-subtype classification may spur innovative personalized medicine strategies for patients with TNBC. Clin Cancer Res; 19(19); 5533–40. ©2013 AACR.
Prognostic Factors in Patients with Advanced Cancer: A Comparison of Clinicopathological Factors and the Development of an Inflammation-Based Prognostic System
Authors: Laird Barry J. , Kaasa Stein , McMillan Donald C. , Fallon Marie T. , Hjermstad Marianne J. , Fayers Peter , Klepstad Pal
Published: August 2013

Purpose: In advanced cancer, oncological treatment is influenced by performance status (PS); however, this has limitations. Biomarkers of systemic inflammation may have prognostic value in advanced cancer. The study compares key factors in prognosis (performance status, patient-reported outcomes; PRO) with an inflammation-based score (Glasgow Prognostic Score, mGPS). A new method of prognosis in advanced cancer (combining performance status and mGPS) is tested and then validated.

Experimental Design: Two international biobanks of patients with advanced cancer were analyzed. Key prognostic factors [performance status, PROs (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30), and mGPS (using C-reactive protein and albumin concentrations)] were examined. The relationship between these and survival was examined using Kaplan–Meier and Cox regression methods, in a test sample before independent validation.

Results: Data were available on 1,825 patients (test) and 631 patients (validation). Median survival ranged from 3.2 months (test) to 7.03 months (validation). On multivariate analysis, performance status (HR 1.62–2.77) and mGPS (HR 1.51–2.27) were independently associated with, and were the strongest predictors of survival (P < 0.01). Survival at 3 months varied from 82% (mGPS 0) to 39% (mGPS 2) and from 75% (performance status 0–1) to 14% (performance status 4). When used together, survival ranged from 88% (mGPS 0, PS 0–1) to 10% (mGPS 2, performance status 4), P < 0.001.

Conclusion: A systemic inflammation-based score, mGPS, and performance status predict survival in advanced cancer. The mGPS is similar to performance status in terms of prognostic power. Used together, performance status and mGPS act synergistically improving prognostic accuracy. This new method may be of considerable value in the management of patients with advanced cancer. Clin Cancer Res; 19(19); 5456–64. ©2013 AACR.
EGFR Inhibition Promotes an Aggressive Invasion Pattern Mediated by Mesenchymal-like Tumor Cells within Squamous Cell Carcinomas
Authors: Basu Devraj , Bewley Arnaud F. , Sperry Steven M. , Montone Kathleen T. , Gimotty Phyllis A. , Rasanen Kati , Facompre Nicole D. , Weinstein Gregory S. , Nakagawa Hiroshi , Diehl J. Alan , Rustgi Anil K. , Herlyn Meenhard
Published: August 2013

Squamous cell carcinomas (SCC) with an infiltrative invasion pattern carry a higher risk of treatment failure. Such infiltrative invasion may be mediated by a mesenchymal-like subpopulation of malignant cells that we have previously shown to arise from epithelial–mesenchymal transition (EMT) and resist epidermal growth factor receptor (EGFR) targeting. Here, we show that SCCs with infiltrative, high-risk invasion patterns contain abundant mesenchymal-like cells, which are rare in tumors with low-risk patterns. This cellular heterogeneity was modeled accurately in three-dimensional culture using collagen-embedded SCC spheroids, which revealed distinct invasive fronts created by collective migration of E-cadherin–positive cells versus infiltrative migration of individual mesenchymal-like cells. Because EGFR expression by mesenchymal-like cells was diminished in the spheroid model and in human SCCs, we hypothesized that SCCs shift toward infiltrative invasion mediated by this subpopulation during anti-EGFR therapy. Anti-EGFR treatment of spheroids using erlotinib or cetuximab enhanced infiltrative invasion by targeting collective migration by E-cadherin–positive cells while sparing mesenchymal-like cells; by contrast, spheroid invasion in absence of mesenchymal-like cells was abrogated by erlotinib. Similarly, cetuximab treatment of xenografts containing mesenchymal-like cells created an infiltrative invasive front composed of this subpopulation, whereas no such shift was observed upon treating xenografts lacking these cells. These results implicate mesenchymal-like SCC cells as key mediators of the infiltrative invasion seen in tumors with locally aggressive behavior. They further show that EGFR inhibition can promote an infiltrative invasion front composed of mesenchymal-like cells preferentially in tumors where they are abundant before therapy. Mol Cancer Ther; 12(10); 2176–86. ©2013 AACR.
Histone Deacetylase Regulation of ATM-Mediated DNA Damage Signaling
Authors: Thurn K. Ted , Thomas Scott , Raha Paromita , Qureshi Ian , Munster Pamela N.
Published: August 2013

Ataxia–telangiectasia mutated (ATM) is a major regulator of the DNA damage response. ATM promotes the activation of BRCA1, CHK2, and p53 leading to the induction of response genes such as CDKN1A (p21), GADD45A, and RRM2B that promote cell-cycle arrest and DNA repair. The upregulation of these response genes may contribute to resistance of cancer cells to genotoxic therapies. Here, we show that histone deacetylases (HDAC) play a major role in mitigating the response of the ATM pathway to DNA damage. HDAC inhibition decreased ATM activation and expression, and attenuated the activation of p53 in vitro and in vivo. Select depletion of HDAC1 and HDAC2 was sufficient to modulate ATM activation, reduce GADD45A and RRM2B induction, and increase sensitivity to DNA strand breaks. The regulation of ATM by HDAC enzymes therefore suggests a vital role for HDAC1 and HDAC2 in the DNA damage response, and the potential use of the ATM pathway as a pharmacodynamic marker for combination therapies involving HDAC inhibitors. Mol Cancer Ther; 12(10); 2078–87. ©2013 AACR.
Novel Inhibitors of Cyclin-Dependent Kinases Combat Hepatocellular Carcinoma without Inducing Chemoresistance
Authors: Haider Christine , Grubinger Markus , Řezníčková Eva , Weiss Thomas S. , Rotheneder Hans , Miklos Walter , Berger Walter , Jorda Radek , Zatloukal Marek , Gucký Tomáš , Strnad Miroslav , Kryštof Vladimír , Mikulits Wolfgang
Published: August 2013

Treatment options for hepatocellular carcinoma using chemotherapeutics at intermediate and advanced stages of disease are limited as patients most rapidly escape from therapy and succumb to disease progression. Mechanisms of the hepatic xenobiotic metabolism are mostly involved in providing chemoresistance to therapeutic compounds. Given the fact that the aberrant activation of cyclin-dependent kinases (CDK) is frequently observed in hepatocellular carcinomas, we focused on the efficacy of the novel compounds BA-12 and BP-14 that antagonize CDK1/2/5/7 and CDK9. Inhibition of those CDKs in human hepatocellular carcinoma cell lines reduced the clonogenicity by arresting cells in S–G2 and G2–M phase of the cell cycle and inducing apoptosis. In contrast, primary human hepatocytes failed to show cytotoxicity and apoptosis. No loss of chemosensitivity was observed in hepatocellular carcinoma cells after long-term exposure to inhibitors. In vivo, treatment of xenografted human hepatocellular carcinomas with BA-12 or BP-14 effectively repressed tumor formation. Moreover, BA-12 or BP-14 significantly diminished diethylnitrosamine (DEN)-induced hepatoma development in mice. These data show that BA-12 or BP-14 exhibit strong antitumorigenic effects in the absence of chemoresistance, resulting in a superior efficacy compared with currently used chemotherapeutics in hepatocellular carcinomas. Mol Cancer Ther; 12(10); 1947–57. ©2013 AACR.
Downregulation of HOPX Controls Metastatic Behavior in Sarcoma Cells and Identifies Genes Associated with Metastasis
Authors: Kovářová Denisa , Plachý Jiří , Kosla Jan , Trejbalová Kateřina , Čermák Vladimír , Hejnar Jiří
Published: August 2013

Comparing the gene expression profiles of metastatic and nonmetastatic cells has the power to reveal candidate metastasis-associated genes, whose involvement in metastasis can be experimentally tested. In this study, differentially expressed genes were explored in the v-src-transformed metastatic cell line PR9692 and its nonmetastatic subclone PR9692-E9. First, the contribution of homeodomain only protein X (HOPX) in metastasis formation and development was assessed. HOPX-specific knockdown decreased HOPX expression in the nonmetastatic subclone and displayed reduced cell motility in vitro. Critically, HOPX knockdown decreased the in vivo metastatic capacity in a syngeneic animal model system. Genomic analyses identified a cadre of genes affected by HOPX knockdown that intersected significantly with genes previously found to be differentially expressed in metastatic versus nonmetastatic cells. Furthermore, 232 genes were found in both screens with at least a two-fold change in gene expression, and a number of high-confidence targets were validated for differential expression. Importantly, significant changes were demonstrated in the protein expression level of three metastatic-associated genes (NCAM, FOXG1, and ITGA4), and knockdown of one of the identified HOPX-regulated metastatic genes, ITGA4, showed marked inhibition of cell motility and metastasis formation. These data demonstrate that HOPX is a metastasis-associated gene and that its knockdown decreases the metastatic activity of v-src-transformed cells through altered gene expression patterns.

Implications: This study provides new mechanistic insight into a HOPX-regulated metastatic dissemination signature. Mol Cancer Res; 11(10); 1235–47. ©2013 AACR.
Does Diffusion Tensor Tractography of the Corticospinal Tract Correctly Reflect Motor Function?
Authors: Min Zhi-gang , Rana Netra , Niu Chen , Ji Huan-mei , Zhang Ming
Published: August 2013

Objective: To investigate the consistency of diffusion tensor tractography of the corticospinal tract on motor function. Clinical Presentations and Intervention: Three patients with brain tumor were admitted to our hospital with impaired motor function. Diffusion tensor imaging (DTI) and tractography were performed in these patients to assess their affected corticospinal tract. The corticospinal tract showed interruption with moderately impaired motor function in 2 patients. The third case had significantly weakened muscle strength on the left upper limb but an intact right corticospinal tract. Conclusion: These cases showed that the corticospinal tracts obtained by DTI with tractography were inconsistent with motor function. Hence, DTI should be interpreted with caution.
Indications for Pediatric External Ventricular Drain Placement and Risk Factors for Conversion to a Ventriculoperitoneal Shunt
Authors: Walker Corey T. , Stone Jonathan J. , Jacobson Max , Phillips Valerie , Silberstein Howard J.
Published: August 2013

Background/Aims: The external ventricular drain (EVD) is commonly used for the treatment of hydrocephalus and intracranial pressure (ICP) monitoring. In this study, we retrospectively reviewed indications for EVD placement over the last 20 years in pediatric patients at our institution. Additionally, we evaluated the rate that an EVD needed to be converted to a ventriculoperitoneal shunt (VPS) and ascertained how hydrocephalus etiology impacted long-term drainage requirements. Methods: Patients that received an EVD between 1990 and 2010 at our institution were identified using billing codes. Demographics, etiology of hydrocephalus, length of stay (LOS) and EVD duration were recorded. Only patients receiving their first EVD were included; those with any prior ventricular catheter (including prior shunts) were excluded from this study. Results: A total of 180 patients underwent first-time placement of an EVD over the 20-year period. Of these, 78.9% were placed on the right side and 81.7% were performed through a frontal burr hole site. The average age of all patients at their initial procedure was 9.3 years (median 9.8; range 0-18), hospital LOS was 22.5 days (median 16; range 1-174) and EVD duration was 7.8 days (median 7; range 1-37). Trauma (43.3%) and neoplasms (32.2%) were the most common indications. Approximately, one quarter of the patients were unable to become EVD independent and, therefore, required a VPS. Only patients receiving an EVD for traumatic brain injury were significantly less likely to be converted to a shunt than other causes of hydrocephalus (relative risk, RR = 0.18, 95% confidence interval, CI = 0.07-0.46). Conversely, patients with neoplasms (RR = 3.56, 95% CI = 1.74-7.31), obstructive hydrocephalus (RR = 5.48, 95% CI = 1.37-22.0) and intraventricular hemorrhage (RR = 9.86, 95% CI = 1.05-92.3) were more likely to need a shunt. Conclusion: Traumatic brain injuries and neoplasms represent the most common indications for EVD placement in the pediatric population. While patients with neoplasm were much more likely to need conversion to a VPS for long-term cerebrospinal fluid diversion, the majority of EVDs in patients with head injuries were successfully weaned.
A Simplified and Structured Teaching Tool for the Evaluation and Management of Pulseless Electrical Activity
Authors: Littmann Laszlo , Bustin Devin J. , Haley Michael W.
Published: August 2013

Cardiac arrest victims who present with pulseless electrical activity (PEA) usually have a grave prognosis. Several conditions, however, have cause-specific treatments which, if applied immediately, can lead to quick and sustained recovery. Current teaching focuses on recollection of numerous conditions that start with the letters H or T as potential causes of PEA. This teaching method is too complex, difficult to recall during resuscitation, and does not provide guidance to the most effective initial interventions. This review proposes a structured algorithm that is based on the differentiation of the PEA rhythm into narrow- or wide-complex subcategories, which simplifies the working differential and initial treatment approach. This, in conjunction with bedside ultrasound, can quickly point towards the most likely cause of PEA and thus guide resuscitation.
Population Pharmacokinetics of Enoxaparin During the Antenatal Period
Authors: Patel Jignesh P. , Green Bruce , Patel Raj K. , Marsh Michael S. , Davies J. Graham , Arya Roopen
Published: August 2013

Background—

The optimal dosing strategy of low-molecular-weight heparins for the treatment of antenatal venous thromboembolism is not known. The physiological changes associated with pregnancy alter the pharmacokinetic profile of low-molecular-weight heparins, which has led to controversy and subsequent variation in practice, when pregnant women with venous thromboembolism are treated with low-molecular-weight heparins. Our objective was to develop a robust pharmacokinetic model of enoxaparin during the antenatal period to address this problem.

Method and Results—

Women prescribed antenatal enoxaparin were eligible to enroll in the study. Recruited women were reviewed monthly and had up to 3 anti-Xa activities (trough and 1 and 3 hours after dose) drawn at each clinic attendance. Compartmental pharmacokinetic modeling was conducted using nonlinear mixed-effects modeling. One hundred twenty-three patients contributed 795 anti-Xa activities for pharmacokinetic modeling purposes. Both enoxaparin clearance and volume of distribution were increased during pregnancy. Simulations of once- versus twice-daily enoxaparin administration demonstrated that both dosing regimens would reach target 3-hour plasma concentrations throughout the duration of the pregnancy. When trough anti-Xa activity was simulated, both once- and twice-daily regimens exhibited an increase in trough anti-Xa activity with the progression of pregnancy. This is explained by the significant increase in volume of distribution observed during pregnancy.

Conclusions—

The half-life of enoxaparin is prolonged with the progression of pregnancy, and our work provides compelling evidence for prescribing once-daily enoxaparin for the treatment of antenatal venous thromboembolism. National and international guideline recommendations should be reconsidered.
Simple Integer Risk Score to Determine Prognosis of Patients With Hypertension and Chronic Stable Coronary Artery Disease
Authors: Bavry Anthony A. , Kumbhani Dharam J. , Gong Yan , Handberg Eileen M. , Cooper‐DeHoff Rhonda M. , Pepine Carl J.
Published: August 2013

Background

It is difficult to accurately determine prognosis of patients with hypertension and chronic stable coronary artery disease (
CAD
). Our aim was to construct a risk score for predicting important adverse events in this population.

Methods and Results

Patients with hypertension and chronic stable
CAD
enrolled in the
IN
ternational
VE
rapamil‐
SR
/Trandolapril
ST
udy (
INVEST
) comprised the study cohort. Candidate predictor variables were obtained from patients with at least 1 postbaseline visit. Patients were divided into development (n=18 484) and validation cohorts (n=2054). Cox regression model identified predictors of the primary outcome: all‐cause mortality, myocardial infarction, or stroke at a mean follow‐up of 2.3 years. The hazard ratio of each variable was rounded to the nearest integer to construct score weights. A score 0 to 4 defined low‐risk, 5 to 6 intermediate‐risk and ≥7 high‐risk. The following variables were retained in the final model: age, residence, body mass index, on‐treatment heart rate and BP, prior myocardial infarction, heart failure, stroke/transient ischemic attack, smoking, diabetes, peripheral arterial disease, and chronic kidney disease. The primary outcome occurred in 2.9% of the low‐risk group, 6.5% of the intermediate‐risk group, and 18.0% of the high‐risk group (
P
for trend <0.0001). The model was good at discriminating those who had an event versus those who did not (C‐statistic=0.75). The model performed well in a validation cohort (C‐statistic=0.77).

Conclusion

Readily available clinical variables can rapidly stratify patients with hypertension and chronic stable
CAD
into useful risk categories.
Circulating Levels of miR‐133a Predict the Regression Potential of Left Ventricular Hypertrophy After Valve Replacement Surgery in Patients With Aortic Stenosis
Authors: García Raquel , Villar Ana V. , Cobo Manuel , Llano Miguel , Martín‐Durán Rafael , Hurlé María A. , Francisco Nistal J.
Published: August 2013

Background

Myocardial micro
RNA
‐133a (miR‐133a) is directly related to reverse remodeling after pressure overload release in aortic stenosis patients. Herein, we assessed the significance of plasma miR‐133a as an accessible biomarker with prognostic value in predicting the reversibility potential of
LV
hypertrophy after aortic valve replacement (
AVR
) in these patients.

Methods and Results

The expressions of mi
R
‐133a and its targets were measured in
LV
biopsies from 74 aortic stenosis patients. Circulating miR‐133a was measured in peripheral and coronary sinus blood.
LV
mass reduction was determined echocardiographically. Myocardial and plasma levels of miR‐133a correlated directly (
r
=0.46,
P
<0.001) supporting the myocardium as a relevant source of plasma miR‐133a. Accordingly, a significant gradient of miR‐133a was found between coronary and systemic venous blood. The preoperative plasma level of mi
R
‐133a was higher in the patients who normalized
LV
mass 1 year after
AVR
than in those exhibiting residual hypertrophy. Logistic regression analysis identified plasma miR‐133a as a positive predictor of the hypertrophy reversibility after surgery. The discrimination of the model yielded an area under the receiver operator characteristic curve of 0.89 (
P
<0.001). Multiple linear regression analysis revealed plasma miR‐133a and its myocardial target Wolf‐Hirschhorn syndrome candidate 2/Negative elongation factor A as opposite predictors of the
LV
mass loss (g) after
AVR
.

Conclusions

Preoperative plasma levels of miR‐133a reflect their myocardial expression and predict the regression potential of
LV
hypertrophy after
AVR
. The value of this bedside information for the surgical timing, particularly in asymptomatic aortic stenosis patients, deserves confirmation in further clinical studies.
Abel Buell, of Connecticut, Prints America's First Map of the United States, 1784
Authors: Cohen Paul E.
Published: August 2013

After the Revolutionary War concluded, the United States found itself holding clear title to much of North America. The first American to delineate this vast territory was engraver and counterfeiter Abel Buell, whose “Map of the United States” is a legendary rarity. This article provides an account of the map and gives a history of the seven surviving copies.
The Revolutionary War Battle America Forgot: Chelsea Creek, 27–28 May 1775
Authors: Brown Craig J. , Mastone Victor T. , Maio Christopher V.
Published: August 2013

Overshadowed by the iconic battles at Lexington/Concord and Bunker Hill, the Battle of Chelsea Creek (27-28 May 1775) is notable for being the provincials’ first coordinated offensive gesture. Moving to interdict livestock and supplies from the besieged British garrison in Boston, they entered into a running engagement with British marines, eventually capturing and destroying the British schooner HMS Diana.
Church Growth in Britain: A Response to Steve Bruce*
Authors: Goodhew David
Published: August 2013

This article examines the extent of church growth in Britain in recent decades, in response to the articulation of the secularisation thesis with regard to Christian congregations in recent British history. It shows that alongside the widely recognised phenomenon of church decline, there has been significant church growth—notably in London, amongst black, Asian, and minority ethnic communities and amongst new churches. This runs counter to many discussions of religion in recent British history, which assume overwhelming and ongoing church decline and which assume any church growth is peripheral. The article recognises evidence of significant church decline—but critiques the view that this should be the sole or the dominant narrative. The findings of the article throw up a range of questions that offer significant new avenues for further research.
Review of the Leafhopper Genus Macrosteles Fieber (Hemiptera: Cicadellidae: Deltocephalinae) from China
Authors: ZHANG YALIN , LU LIN , YONG KWON JUNG
Published: August 2013

The leafhopper genus Macrosteles Fieber in China comprises 25 species including ten new species: Macrosteles brochus Zhang & Lu, M. brunneus Zhang & Lu, M. choui Zhang & Lu, M. ehensis Zhang & Lu, M. gracilis Zhang & Lu, M. falcatus Zhang & Lu, M. haperatus Zhang & Lu, M. nabiae Kwon, M. parastriifrons Zhang & Lu and M. spinosus Kwon. Five species are newly recorded from China, including M. abludens Anufriev, M. albicostalis Vilbaste, M. alpinus (Zetterstedt), M. lividus (Edwards) and M. sordidipennis (Stål). One taxon previously treated as a subspecies of M. fascifrons (Stål) is elevated to species rank: M. lindbergi Dlabola, n. stat. The following six new synonyms are proposed: M. bimaculatus Dai, Li & Chen, 2008 = M. lividus (Edwards, 1894), M. heiseles Kuoh, 1981 = M. guttatus (Matsumura, 1915); M. huangxionis Kuoh, 1981 = M. heitiacus Kuoh, 1981; M. latiaedeagus Dai et al., 2008 = M. cristatus Ribaut, 1927; and M. serrata Dai et al., 2011 = M. striifrons Anufriev, 1968 and also a junior homonym of M. serratus Kwon, 2010; and M. symphorosus Yang, 1996 = M. viridigriseus (Edwards, 1924). A checklist to the Macrosteles species from China is provided together with a key for separation of males.
Epiplatys atratus (Cyprinodontiformes: Nothobranchiidae), a new species of the E. multifasciatus species group from the Lulua Basin (Kasaï drainage), Democratic Republic of Congo
Authors: ZEE JOUKE R. VAN DER , MUNENE JOSÉ J. MBIMBI MAYI , SONNENBERG RAINER
Published: August 2013

Epiplatys atratus, a new species of the E. multifasciatus group, is described from specimens collected from several tributaries of the middle Lulua River, a tributary of the Kasaï River, south of Kananga (Democratic Republic of the Congo, Kasaï Occidental Province). Epiplatys atratus is the south-eastern most representative of the genus. Large adult E. atratus males differ from all congeners in displaying a dark grey to black pigmentation of body and fins. In contrast to other Epiplatys species, with a fully exposed laterosensory system of the head, the lobes surrounding the supra-orbital part of the laterosensory system almost completely cover the system in large males of E. atratus. Also in males of E. atratus the dorsal fin is positioned on average more anteriorly than in other members of the E. multifasciatus group. Small males and females show a unique pattern of three fine oblique dark bars just behind the pectoral fin.
Does An ENSO-Conditional Skill Mask Improve Seasonal Predictions?
Authors: Pegion Kathy , Kumar Arun
Published: August 2013

The National Centers for Environmental Prediction Climate Prediction Center uses statistical tools together with the Climate Forecast System (CFS) to produce forecasts for seasonal outlooks of U.S. temperature and precipitation. They are combined using an optimal weighting procedure that depends on a skill mask consisting of the average historical forecast skill of each tool. However, it is likely that skill during El Niño–Southern Oscillation events is higher and the use of this information in developing forecasts could lead to improved seasonal predictions. This study explores the potential to improve the skill of seasonal predictions by developing an ENSO-conditional skill mask. The conditional masks are developed in a perfect-model framework using the CFS version 2 hindcasts and two indices of ENSO. The skill of the indices in forecasting variations in conditional skill is evaluated. The ENSO-conditional skill masks provide improvements in correlation skill over the unconditional mask when averaged over the globe. The masks are applied to tercile forecasts of seasonal temperature and precipitation during the spring and forecasts are verified in a perfect-model context. Application of the conditional masks to tercile forecasts results in modified Heidke skill scores of more than 10% less than using the average mask for temperature and little difference in skill for precipitation. This is attributed to the larger number of equal chances forecasts when using the conditional masks, particularly for temperature. For precipitation, the skill predicted by the average and conditional masks is frequently below 0.3, leading to low skill regardless of which mask is used.
A Strategy for Verifying Near-Convection-Resolving Model Forecasts at Observing Sites
Authors: Mittermaier Marion P.
Published: August 2013

Routine verification of deterministic numerical weather prediction (NWP) forecasts from the convection-permitting 4-km (UK4) and near-convection-resolving 1.5-km (UKV) configurations of the Met Office Unified Model (MetUM) has shown that it is hard to consistently demonstrate an improvement in skill from the higher-resolution model, even though subjective comparison suggests that it performs better. In this paper the use of conventional metrics and precise matching (through extracting the nearest grid point to an observing site) of the forecast to conventional synoptic observations in space and time is replaced with the use of inherently probabilistic metrics such as the Brier score, ranked probability, and continuous ranked probability scores applied to neighborhoods of forecast grid points. Three neighborhood sizes were used: ~4, ~12, and ~25 km, which match the sizes of the grid elements currently used operationally. Six surface variables were considered: 2-m temperature, 10-m wind speed, total cloud amount (TCA), cloud-base height (CBH), visibility, and hourly precipitation. Any neighborhood has a positive impact on skill, either in reducing the skill deficit or enhancing the skillfulness over and above the single grid point. This is true for all variables. An optimal neighborhood appears to depend on the variable and threshold. Adopting this probabilistic approach enables easy comparison to future near-convection-resolving ensemble prediction systems (EPS) and also enables the optimization of postprocessing to maximize the skill of forecast products.
Therapeutic drug monitoring of ciclosporin A and tacrolimus in heart lung transplant patients using dried blood spots
Authors: Hinchliffe Edward , Adaway Joanne , Fildes James , Rowan Anna , Keevil Brian G
Published: August 2013

Background

Therapeutic drug monitoring of ciclosporin A (CsA) and tacrolimus is traditionally performed using venous whole blood sampling. A number of reports have described development of ultra high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) methods for the quantitation of CsA and tacrolimus from dried blood spots (DBS), which may offer a convenient alternative. As yet, no such reports have validated this methodology using fingerprick capillary DBS samples collected from transplant patients.

Methods

Capillary fingerprick DBS were collected from heart and lung transplant patients in a specialist cardiothoracic transplant centre. We utilized our previously published method for the extraction and simultaneous quantitation of CsA and tacrolimus from DBS using UPLC-MS/MS. Drug concentrations measured from DBS were compared to concentrations measured in venous whole blood by our routine clinical UPLC-MS/MS assay.

Results

In total, 91 heart or lung transplant patients were enrolled onto the study; 46 patients were on CsA therapy and 45 on tacrolimus therapy. Passing–Bablock analysis demonstrated excellent agreement between capillary fingerprick DBS samples and venous whole blood samples. There was a mean positive bias of 2.6  µg/L (95% confidence interval (CI) −2.2 to 7.5  µg/L) for CsA ( n = 45) and mean negative bias of −0.7  µg/L (95% CI −1.1 to −0.3  µg/L) for tacrolimus ( n = 42).

Conclusions

We demonstrate utility of DBS for serial monitoring of CsA and tacrolimus using UPLC-MS/MS in heart and lung transplant patients. This may offer significant advantages for these patients including the ability to take capillary DBS samples in the community prior to clinic visits.
Scientists and the 3Rs: attitudes to animal use in biomedical research and the effect of mandatory training in laboratory animal science
Authors: Franco NH , Olsson IAS
Published: August 2013

The 3Rs principle of replacement, reduction, and refinement has increasingly been endorsed by legislators and regulatory bodies as the best approach to tackle the ethical dilemma presented by animal experimentation in which the potential benefits for humans stand against the costs borne by the animals. Even when animal use is tightly regulated and supervised, the individual researcher’s responsibility is still decisive in the implementation of the 3Rs. Training in laboratory animal science (LAS) aims to raise researchers’ awareness and increase their knowledge, but its effect on scientists’ attitudes and practice has not so far been systematically assessed. Participants ( n = 206) in eight LAS courses (following the Federation of European Laboratory Animal Science Associations category C recommendations) in Portugal were surveyed in a self-administered questionnaire during the course. Questions were related mainly to the 3Rs and their application, attitudes to animal use and the ethical review of animal experiments. One year later, all the respondents were asked to answer a similar questionnaire (57% response rate) with added self-evaluation questions on the impact of training. Our results suggest that the course is effective in promoting awareness and increasing knowledge of the 3Rs, particularly with regard to refinement. However, participation in the course did not change perceptions on the current and future needs for animal use in research.
A low-cost banding device for oesophageal varices using Foley catheters
Authors: Jacob Tarun JK , Manoharan Ravikumar , Kumar Ashok , Kirishnan Sumonth , Cherian Anne George
Published: August 2013

Our institution has devised a low cost method of banding oesophageal varices by loading cut Foley catheters on to a banding apparatus.
Men’s Hostile Sexism and Biased Perceptions of Intimate Partners
Authors: Hammond Matthew D. , Overall Nickola C.
Published: August 2013

Hostile sexism (HS) expresses attitudes that characterize women who challenge men’s power as manipulative and subversive. Does endorsing HS negatively bias perceptions of women’s behavior and, in turn, create animosity within intimate relationships? Committed heterosexual couples reported on their own behavior and perceptions of their partner’s behavior five times across a year (Study 1) and daily for 3 weeks (Study 2). Men who more strongly endorsed HS perceived their partner’s behavior as more negative than was justified by their partner’s reports. Furthermore, more negative perceptions of the partner’s behavior mediated the links between men’s HS and feeling more manipulated by their partners, behaving more negatively toward their partners, and lower relationship quality. This indicates that men who endorse HS behave more negatively toward intimate partners and experience lower relationship satisfaction because their antagonistic attitudes toward women in general permeate the way they perceive those partners.
Use of a non-navigational, non-verbal landmark task in children
Authors: Overman William , Pierce Allison , Watterson Lucas , Coleman Jennifer K.
Published: August 2013

Two hundred and twenty two children (104 females), 1–8 years of age and young adults, were tested for up to 25 days on five versions of a non-verbal, non-navigational landmark task that had previously been used for monkeys. In monkeys, performance on this task is severely impaired following damage to the parietal cortex. For the basic task, the positive of two identical stimuli concealed a food reward and was designated by spatial proximity of a salient landmark. None of the 1- and 2-year-old children learned the task, i.e., they failed to consistently reach for and displace the positive stimulus in 25 test days. Of the 3-, 4-, and 5- year-old groups, 56%, 70%, and 77% of the children, respectively, mastered the task within 25 days. Children older than 5 and adults rapidly mastered the task. In Experiment #2, all subjects, 1–6 years of age, rapidly mastered a non-relational task when the choice stimulus was attached to the landmark, but the youngest children failed to transfer performance when the landmark was subsequently detached. Children under the age of 5 did not tolerate relational ambiguity as well as adults did. Replications of the first two experiments produced virtually identical results and indicated that the tests have a high degree of reliability. In Experiment #5, there were two distinct proximal landmarks, one of which always designated the positive stimulus. This manipulation did not improve performance of younger children. As compared to results from navigational landmark tasks, results obtained in the Wisconsin General Testing Apparatus (WGTA) indicate a very narrow focus of attention on the response site. Thus, small separations between discriminative cue and response site significantly affect performance, especially in younger children. By comparing the present results with those from monkeys, we speculate that components of the parietal pathways involved with attention and reaching mature between 1 and 5 years of age in children.
Decentralisation and political participation: An empirical analysis in Western and Eastern Europe
Authors: Spina Nicholas
Published: August 2013

A major justification for bringing government “closer to the people” is that it improves the opportunities for and frequency of citizen participation in the political system. This article first reviews the major arguments for decentralisation and why it is credited with increasing participation. I then perform statistical analyses in 22 states with country-level decentralisation data and public opinion data drawn from the 2006 European Social Survey. The findings generally fail to support the conventional wisdom that decentralisation improves political participation.
Teaching improvisation and the pedagogical history of the Jimmy Giuffre 3
Authors: Johnston Peter
Published: August 2013

Improvisation pedagogy has presented a challenge to music educators since jazz courses began being offered in North American universities in the 1950s, a development which has raised important pedagogical questions ranging from ‘Can improvisation be taught?’ to ‘Should it be taught?’ Following on the increase in academic writing on improvisation over the past decade, in this article I draw on practice-based and ethnographic research on the under-documented yet influential American jazz ensemble the Jimmy Giuffre 3 to propose alternative approaches to teaching improvisation at the post-secondary level. The remembrances of these master improvisers offer an accessible entryway into free improvisation for educators and students who have been either resistant to this part of the jazz tradition, or simply unsure of where to start exploring collectively improvised music-making. I argue that if properly presented, improvisation pedagogy can aid students in developing a disposition for creative thinking, potentially enabling them to become critical, engaged citizens and productive participants in the cultural field.
Prediction of axial compressive strength of reinforced concrete circular short columns confined with carbon fiber reinforced polymer wrapping sheets
Authors: Farghal Omar Ahmed , Diab Hesham Mohamed Ahmed
Published: August 2013

External confinement of concrete columns by means of carbon fiber reinforced polymer (CFRP) sheets can be considered as an efficient technique for their structural strengthening. An experimental research program including 18 circular short column specimens were tested under axial compression load, to investigate the gain strength of reinforced concrete (RC) columns confined with CFRP sheets. The parameters studied were both the volume and configurations of CFRP sheets, the size of cross-section, the percentage of main reinforcement, and the volume of internal stirrups. On the basis of the obtained results, mathematical models (Egyptian code and American Concrete Institute code) proposed to predict the axial compressive strength of non-slender RC column strengthened by means of CFRP sheets are evaluated. These codes showed an underestimation in predicting the axial compressive strength of RC strengthened columns. This, from the authors' point of view, is attributed mainly to the fact that the proposed models overlooked the amount of internal stirrups when calculating the strength of strengthened columns. Therefore, modifications in the studied models were considered. The modifications take the effective lateral confining pressure due to presence of internal steel stirrups into account. The modified codes showed an acceptable approach to the experimental results.
Increasing Use of Less-Invasive Hemodynamic Monitoring in 3 Specialty Surgical Intensive Care Units
Authors: Kirton Orlando C. , Calabrese Rebecca C. , Staff Ilene
Published: August 2013

Introduction:

Less-invasive hemodynamic monitoring (eg, esophageal doppler monitoring [EDM] and arterial pressure contour analysis, FloTrac) is increasingly used as an alternative to pulmonary artery catheters (PACs) in critically ill intensive care unit (ICU).

Hypothesis:

The decrease in use of PACs is not associated with increased mortality.

Methods:

Five-year retrospective review of 1894 hemodynamically monitored patients admitted to 3 surgical ICUs in a university-affiliate, tertiary care urban hospital. Data included the number of admissions, diagnosis-related group discharge case mix, length of stay, insertion of monitoring devices (PAC, EDM, and FloTrac probes), administered intravenous vasoactive agents (β-predominant agonists—dobutamine, epinephrine, and dopamine; vasopressors—norepinephrine and phenylephrine), and mortality. Data from hospital administrative databases were compiled to create patient characteristic and monitoring variables across a 5-year time period, 2005 to 2009 inclusive. Chi-square for independent proportions, 1-way analysis of variance, and Kruskal-Wallis tests were used; tests for trend were conducted. An α level of .05 was considered significant. Statistical Package for the Social Sciences v14 was used for all statistical testing.

Results:

There was a significant change in the type of hemodynamic monitors inserted in 2 of the 3 surgical ICUs (in the general surgery and neurointensive care but not in the cardiac ICU) from PACs to less-invasive devices (FloTrac or EDM) during the 5-year study period ( P < .001). There was no change in mortality rate over the time period ( P = .492). There was an overall increase in the proportion of monitored patients who received intravenous vasoactive agents ( P < .001) with a progressive shift from β-agonists to vasopressors ( P < .002). Multivariate analyses indicated that age, case mix, and use of vasoactive agents were all independent predictors of inhospital mortality ( P = .001) but that type of monitoring was not ( P = .638).

Conclusions:

In a 5-year period, the decreased insertions of PACs were replaced by increased utilization of less-invasive hemodynamic monitoring devices. This change in practice did not adversely impact mortality.