bluuebunny/crossref_metadata_2025 huggingface dataset:
A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens
Authors: Jacobson Rebecca S. , Becich Michael J. , Bollag Roni J. , Chavan Girish , Corrigan Julia , Dhir Rajiv , Feldman Michael D. , Gaudioso Carmelo , Legowski Elizabeth , Maihle Nita J. , Mitchell Kevin , Murphy Monica , Sakthivel Mayurapriyan , Tseytlin Eugene , Weaver JoEllen
Published: December 2015

Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that are de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies, and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network. Cancer Res; 75(24); 5194–201. ©2015 AACR.
ALCHEMIST Trials: A Golden Opportunity to Transform Outcomes in Early-Stage Non–Small Cell Lung Cancer
Authors: Govindan Ramaswamy , Mandrekar Sumithra J. , Gerber David E. , Oxnard Geoffrey R. , Dahlberg Suzanne E. , Chaft Jamie , Malik Shakun , Mooney Margaret , Abrams Jeffrey S. , Jänne Pasi A. , Gandara David R. , Ramalingam Suresh S. , Vokes Everett E.
Published: December 2015

The treatment of patients with metastatic non–small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next-generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is an NCI-sponsored national clinical trials network (NCTN) initiative to address the needs to refine therapy for early-stage NSCLC. This program will screen several thousand patients with operable lung adenocarcinoma to determine whether their tumors contain specific molecular alterations [epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase rearrangement (ALK)], making them eligible for treatment trials that target these alterations. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively, after completion of their standard adjuvant therapy. ALCHEMIST will also contain a large discovery component that will provide an opportunity to incorporate genomic studies to fully understand the clonal architecture, clonal evolution, and mechanisms of resistance to therapy. In this review, we describe the concept, rationale, and outline of ALCHEMIST and the plan for genomic studies in patients with lung adenocarcinoma. Clin Cancer Res; 21(24); 5439–44. ©2015 AACR.
Prospective Validation of Pooled Prognostic Factors in Women with Advanced Cervical Cancer Treated with Chemotherapy with/without Bevacizumab: NRG Oncology/GOG Study
Authors: Tewari Krishnansu S. , Sill Michael W. , Monk Bradley J. , Penson Richard T. , Long Harry J. , Poveda Andrés , Landrum Lisa M. , Leitao Mario M. , Brown Jubilee , Reid Thomas J.A. , Michael Helen E. , Moore David H.
Published: December 2015

Purpose: In the randomized phase III trial, Gynecologic Oncology Group (GOG) protocol 240, the incorporation of bevacizumab with chemotherapy significantly increased overall survival (OS) in women with advanced cervical cancer. A major objective of GOG-240 was to prospectively analyze previously identified pooled clinical prognostic factors known as the Moore criteria.

Experimental Design: Potential negative factors included black race, performance status 1, pelvic disease, prior cisplatin, and progression-free interval <365 days. Risk categories included low-risk (0–1 factor), mid-risk (2–3 factors), and high-risk (4–5 factors). Each test of association was conducted at the 5% level of significance. Logistic regression and survival analysis was used to determine whether factors were prognostic or could be used to guide therapy.

Results: For the entire population (n = 452), high-risk patients had significantly worse OS (P < 0.0001). The HRs of death for treating with topotecan in low-risk, mid-risk, and high-risk subsets are 1.18 [95% confidence interval (CI), 0.63–2.24], 1.11 (95% CI, 0.82–1.5), and 0.84 (95% CI, 0.50–1.42), respectively. The HRs of death for treating with bevacizumab in low-risk, mid-risk, and high-risk subsets are 0.96 (95% CI, 0.51–1.83; P = 0.9087), 0.673 (95% CI, 0.5–0.91; P = 0.0094), and 0.536 (95% CI, 0.32–0.905; P = 0.0196), respectively.

Conclusions: This is the first prospectively validated scoring system in cervical cancer. The Moore criteria have real-world clinical applicability. Toxicity concerns may justify omission of bevacizumab in some low-risk patients where survival benefit is small. The benefit to receiving bevacizumab appears to be greatest in the moderate- and high-risk subgroups (5.8-month increase in median OS). Clin Cancer Res; 21(24); 5480–7. ©2015 AACR.
Heterogeneity of Programmed Cell Death Ligand 1 Expression in Multifocal Lung Cancer
Authors: Mansfield Aaron S. , Murphy Stephen J. , Peikert Tobias , Yi Eunhee S. , Vasmatzis George , Wigle Dennis A. , Aubry Marie Christine
Published: December 2015

Purpose: The expression of programmed cell death ligand 1 (PD-L1) provides limited predictive value in identifying patients most likely to respond to immunotherapy. As the heterogeneity of PD-L1 expression may lead to sampling error and the misclassification of PD-L1 status, we assessed the distribution of PD-L1 expression in paired, resected multifocal lung cancers.

Experimental Design: PD-L1 was assessed by IHC. Paired lesions were defined as independent primaries or related lesions using mate pair next-generation sequencing. Agreement statistics were used for analysis.

Results: Sixty-seven multifocal lung cancers from 32 patients were sequenced and stained for PD-L1. There was agreement of PD-L1 expression by the tumor cells in paired lesions of 20 patients and disagreement of PD-L1 expression by the tumor cells in paired lesions of 12 patients (κ = 0.01). Sequencing identified that 23 patients had independent primary lung cancers and that 9 patients had related cancers. In paired lesions of patients with independent cancers, there was agreement of PD-L1 expression by the tumor cells in 12 patients and disagreement in 11 patients (κ = 0.31). In paired lesions of patients with related lung cancers, there was agreement of PD-L1 expression by the tumor cells in 8 patients and disagreement in 1 patient (κ = 0.73).

Conclusions: The expression of PD-L1 is heterogeneous among paired independent lung cancers, but there are high levels of agreement in intrapulmonary metastasis. Clin Cancer Res; 22(9); 2177–82. ©2015 AACR.
Eradication of Large Solid Tumors by Gene Therapy with a T-Cell Receptor Targeting a Single Cancer-Specific Point Mutation
Authors: Leisegang Matthias , Engels Boris , Schreiber Karin , Yew Poh Yin , Kiyotani Kazuma , Idel Christian , Arina Ainhoa , Duraiswamy Jaikumar , Weichselbaum Ralph R. , Uckert Wolfgang , Nakamura Yusuke , Schreiber Hans
Published: December 2015

Purpose: Cancers usually contain multiple unique tumor-specific antigens produced by single amino acid substitutions (AAS) and encoded by somatic nonsynonymous single nucleotide substitutions. We determined whether adoptively transferred T cells can reject large, well-established solid tumors when engineered to express a single type of T-cell receptor (TCR) that is specific for a single AAS.

Experimental Design: By exome and RNA sequencing of an UV-induced tumor, we identified an AAS in p68 (mp68), a co-activator of p53. This AAS seemed to be an ideal tumor-specific neoepitope because it is encoded by a trunk mutation in the primary autochthonous cancer and binds with highest affinity to the MHC. A high-avidity mp68-specific TCR was used to genetically engineer T cells as well as to generate TCR-transgenic mice for adoptive therapy.

Results: When the neoepitope was expressed at high levels and by all cancer cells, their direct recognition sufficed to destroy intratumor vessels and eradicate large, long-established solid tumors. When the neoepitope was targeted as autochthonous antigen, T cells caused cancer regression followed by escape of antigen-negative variants. Escape could be thwarted by expressing the antigen at increased levels in all cancer cells or by combining T-cell therapy with local irradiation. Therapeutic efficacies of TCR-transduced and TCR-transgenic T cells were similar.

Conclusions: Gene therapy with a single TCR targeting a single AAS can eradicate large established cancer, but a uniform expression and/or sufficient levels of the targeted neoepitope or additional therapy are required to overcome tumor escape. Clin Cancer Res; 22(11); 2734–43. ©2015 AACR.

See related commentary by Liu, p. 2602
Piperlongumine Suppresses Growth and Sensitizes Pancreatic Tumors to Gemcitabine in a Xenograft Mouse Model by Modulating the NF-kappa B Pathway
Authors: Wang Yongwei , Wu Xiangsong , Zhou Yinan , Jiang Hongchi , Pan Shangha , Sun Bei
Published: December 2015

Pancreatic cancer is an aggressive malignancy, which generally respond poorly to chemotherapy. Hence, novel agents that are safe and effective are highly needed. The aim of this study was to investigate whether piperlongumine, a natural product isolated from the fruit of the pepper Piper longum, has any efficacy against human pancreatic cancer when used either alone or in combination with gemcitabine in vitro and in a xenograft mouse model. In vitro, piperlongumine inhibited the proliferation of pancreatic cancer cell lines, potentiated the apoptotic effects of gemcitabine, inhibited the constitutive and inducible activation of NF-κB, and suppressed the NF-κB–regulated expression of c-Myc, cyclin D1, Bcl-2, Bcl-xL, Survivin, XIAP, VEGF, and matrix metalloproteinase-9 (MMP-9). Furthermore, in an in vivo xenograft model, we found piperlongumine alone significantly suppressed tumor growth and enhanced the antitumor properties of gemcitabine. These results were consistent with the downregulation of NF-κB activity and its target genes, decreased proliferation (PCNA and Ki-67), decreased microvessel density (CD31), and increased apoptosis (TUNEL) in tumor remnants. Collectively, our results suggest that piperlongumine alone exhibits significant antitumor effects against human pancreatic cancer and it further enhances the therapeutic effects of gemcitabine, possibly through the modulation of NF-κB– and NF-κB–regulated gene products. Cancer Prev Res; 9(3); 234–44. ©2015 AACR.
Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens in Postmenopausal Women with Increased Breast Cancer Risk
Authors: López Ana Maria , Pruthi Sandhya , Boughey Judy C. , Perloff Marjorie , Hsu Chiu-Hsieh , Lang Julie E. , Ley Michele , Frank Denise , Taverna Josephine A. , Chow H-H. Sherry
Published: December 2015

Aromatase inhibitors (AI) profoundly suppress estrogen levels in postmenopausal women and are effective in breast cancer prevention among high-risk postmenopausal women. Unfortunately, AI treatment is associated with undesirable side effects that limit patient acceptance for primary prevention of breast cancer. A double-blind, randomized trial was conducted to determine whether low and intermittent doses of letrozole can achieve effective estrogen suppression with a more favorable side-effect profile. Overall, 112 postmenopausal women at increased risk for breast cancer were randomized to receive letrozole at 2.5 mg once daily (QD, standard dose arm), 2.5 mg every Monday, Wednesday, and Friday (Q-MWF), 1.0 mg Q-MWF, or 0.25 mg Q-MWF for 24 weeks. Primary endpoint was suppression in serum estradiol levels at the end of letrozole intervention. Secondary endpoints included changes in serum estrone, testosterone, C-telopeptide (marker of bone resorption), lipid profile, and quality-of-life measures (QoL) following treatment. Significant estrogen suppression was observed in all dose arms with an average of 75% to 78% and 86% to 93% reduction in serum estradiol and estrone levels, respectively. There were no differences among dose arms with respect to changes in C-telopeptide levels, lipid profile, adverse events (AE), or QoL measures. We conclude that low and intermittent doses of letrozole are not inferior to standard dose in estrogen suppression and resulted in a similar side-effect profile compared with standard dose. Further studies are needed to determine the feasibility of selecting an effective AI dosing schedule with better tolerability. Cancer Prev Res; 9(2); 142–8. ©2015 AACR.
Neurosurgical Treatments for Patients with Chronic, Treatment-Refractory Depression: A Retrospective, Consecutive, Case Series Comparison of Anterior Capsulotomy, Anterior Cingulotomy and Vagus Nerve Stimulation
Authors: Christmas David , Matthews Keith
Published: December 2015

Background: The evidence base to guide therapeutic choices for patients with chronic and treatment-refractory depression (TRD) remains weak. There is limited comparative information available to guide the choice of intervention for patients with the most severe and disabling forms of illness. Objectives: The aim of this work was to describe the 12-month clinical outcomes of patients with chronic TRD treated with anterior capsulotomy (ACAPS; n = 5), anterior cingulotomy (ACING; n = 5) or vagus nerve stimulation (VNS; n = 5). Methods: We performed a retrospective, consecutive, case series comparison. Results: With clinical response defined as a ≥50% reduction from the baseline MADRS score, response rates were 40% for ACAPS, 60% for ACING and 20% for VNS. Adverse effects from all three procedures were relatively mild, consistent with previous reports and, in most cases, transient. Adverse effects from VNS were related to active stimulation, and were modifiable and diminished in severity over time. There were no deaths. Conclusions: Although based on a small sample, our data represent a unique comparison of ACAPS, ACING and VNS for chronic TRD. The three cohorts were broadly equivalent in terms of baseline clinical characteristics, indices of chronicity, illness severity and estimates of previous failed treatments. ACING and ACAPS, but not VNS, were associated with favourable response rates at 12 months.
No Benefit of Complex Fractionated Atrial Electrogram Ablation in Addition to Circumferential Pulmonary Vein Ablation and Linear Ablation
Authors: Wong Kelvin C.K. , Paisey John R. , Sopher Mark , Balasubramaniam Richard , Jones Michael , Qureshi Norman , Hayes Chris R. , Ginks Matthew R. , Rajappan Kim , Bashir Yaver , Betts Timothy R.
Published: December 2015

Background—

The optimal ablation strategy for persistent atrial fibrillation (AF) remains unclear.

Methods and Results—

This multicentre randomized study compared circumferential pulmonary vein ablation+linear ablation (control arm) versus circumferential pulmonary vein ablation+linear ablation+complex fractionated atrial electrogram (CFAE) ablation (CFAE arm) in patients with persistent AF. Circumferential pulmonary vein ablation was performed followed by roof and mitral isthmus ablation, before CFAE ablation in the CFAE arm. Ablation strategy was maintained at the first redo procedure. Sixty-five patients were recruited in each arm. The mean age was 61±10 years, 75% were men, median AF duration was 2 years, 42% had long-lasting persistent AF, 68% had associated cardiovascular disease, mean left atrial dimension was 46±6 mm, and median CHA
2
DS
2
-VASc score was 2. Ablation and procedure times were significantly longer in the CFAE arm (70±20 versus 55±17; 201±35 versus 152±45 minutes;
P
<0.005). After a mean follow-up of 35±5 months, single-procedural success off antiarrhythmic drugs at 12 months (CFAE: 30/65 [46%] versus control: 37/65 [57%];
P
=0.29) and multiprocedural success (CFAE: 51/65 [78%] versus control: 52/65 [80%];
P
=1.0) were not significantly different. At the first redo procedure, patients in the CFAE arm had a higher incidence of organized atrial tachycardia/flutter (24/33 [73%] versus 11/31 [35%];
P
=0.005) and gap-related macro–re-entrant flutter (8/33[24%] versus 1/31[3%];
P
=0.03). Early recurrence of atrial arrhythmia was an independent predictor of late recurrence.

Conclusions—

CFAE ablation did not confer incremental benefit when performed in addition to circumferential pulmonary vein ablation and linear ablation. It was associated with a higher incidence of gap-related flutter.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01711047.
The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL
Authors: Nelson Jessica Kristine , Sorrentino Vincenzo , Avagliano Trezza Rossella , Heride Claire , Urbe Sylvie , Distel Ben , Zelcer Noam
Published: December 2015

Rationale:

The low-density lipoprotein (LDL) receptor (LDLR) is a central determinant of circulating LDL-cholesterol and as such subject to tight regulation. Recent studies and genetic evidence implicate the inducible degrader of the LDLR (IDOL) as a regulator of LDLR abundance and of circulating levels of LDL-cholesterol in humans. Acting as an E3-ubiquitin ligase, IDOL promotes ubiquitylation and subsequent lysosomal degradation of the LDLR. Consequently, inhibition of IDOL-mediated degradation of the LDLR represents a potential strategy to increase hepatic LDL-cholesterol clearance.

Objective:

To establish whether deubiquitylases counteract IDOL-mediated ubiquitylation and degradation of the LDLR.

Methods and Results:

Using a genetic screening approach, we identify the ubiquitin-specific protease 2 (USP2) as a post-transcriptional regulator of IDOL-mediated LDLR degradation. We demonstrate that both USP2 isoforms, USP2-69 and USP2-45, interact with IDOL and promote its deubiquitylation. IDOL deubiquitylation requires USP2 enzymatic activity and leads to a marked stabilization of IDOL protein. Paradoxically, this also markedly attenuates IDOL-mediated degradation of the LDLR and the ability of IDOL to limit LDL uptake into cells. Conversely, loss of USP2 reduces LDLR protein in an IDOL-dependent manner and limits LDL uptake. We identify a tri-partite complex encompassing IDOL, USP2, and LDLR and demonstrate that in this context USP2 promotes deubiquitylation of the LDLR and prevents its degradation.

Conclusions:

Our findings identify USP2 as a novel regulator of lipoprotein clearance owing to its ability to control ubiquitylation-dependent degradation of the LDLR by IDOL.
Ameliorating Endothelial Mitochondrial Dysfunction Restores Coronary Function via Transient Receptor Potential Vanilloid 1–Mediated Protein Kinase A/Uncoupling Protein 2 Pathway
Authors: Xiong Shiqiang , Wang Peijian , Ma Liqun , Gao Peng , Gong Liuping , Li Li , Li Qiang , Sun Fang , Zhou Xunmei , He Hongbo , Chen Jing , Yan Zhencheng , Liu Daoyan , Zhu Zhiming
Published: December 2015

Coronary heart disease arising from atherosclerosis is a leading cause of cardiogenic death worldwide. Mitochondria are the principal source of reactive oxygen species (ROS), and defective oxidative phosphorylation by the mitochondrial respiratory chain contributes to ROS generation. Uncoupling protein 2 (UCP2), an adaptive antioxidant defense factor, protects against mitochondrial ROS-induced endothelial dysfunction in atherosclerosis. The activation of transient receptor potential vanilloid 1 (TRPV1) attenuates vascular dysfunction. Therefore, whether TRPV1 activation antagonizes coronary lesions by alleviating endothelial mitochondrial dysfunction and enhancing the activity of the protein kinase A/UCP2 pathway warrants examination. ApoE
−/−
, ApoE
−/−
/TRPV1
−/−
, and ApoE
−/−
/UCP2
−/−
mice were fed standard chow, a high-fat diet (HFD), or the HFD plus 0.01% capsaicin. HFD intake profoundly impaired coronary vasodilatation and myocardial perfusion and shortened the survival duration of ApoE
−/−
mice. TRPV1 or UCP2 deficiency exacerbated HFD-induced coronary dysfunction and was associated with increased ROS generation and reduced nitric oxide production in the endothelium. The activation of TRPV1 by capsaicin upregulated UCP2 expression via protein kinase A phosphorylation, thereby alleviating endothelial mitochondrial dysfunction and inhibiting mitochondrial ROS generation. In vivo, dietary capsaicin supplementation enhanced coronary relaxation and prolonged the survival duration of HFD-fed ApoE
−/−
mice. These effects were not observed in ApoE
−/−
mice lacking the
TRPV1
or
UCP2
gene. The upregulation of protein kinase A /UCP2 via TRPV1 activation ameliorates coronary dysfunction and prolongs the lifespan of atherosclerotic mice by ameliorating endothelial mitochondrial dysfunction. Dietary capsaicin supplementation may represent a promising intervention for the primary prevention of coronary heart disease.
Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development
Authors: Tripathi Ranjana , Wang Dong , Sullivan Ryan , Fan Tai-Hwang M. , Gladysheva Inna P. , Reed Guy L.
Published: December 2015

Dilated cardiomyopathy is a major cause of heart failure (HF) that affects millions. Corin cleaves and biologically activates pro-atrial natriuretic peptide (pro-ANP) and pro–B-type natriuretic peptide (pro-BNP). High corin levels reduce the development of systolic dysfunction and HF in experimental dilated cardiomyopathy. Yet, patients with significant HF unexpectedly show low corin levels with high plasma ANP/BNP levels. Therefore, we examined the relationship between cardiac corin expression, ANP/BNP levels, and the stages of HF. We used a well-established, dilated cardiomyopathy model to evaluate gene and protein expression as mice longitudinally developed Stages A–D HF. Cardiac systolic function (ejection fraction) continuously declined over time (
P
<0.001). Cardiac corin transcripts were decreased at early Stage B HF and remained low through Stages C and D (
P
<0.001). Cardiac corin levels were positively correlated with systolic function (
r
=0.96,
P
=0.003) and inversely with lung water (
r
=−0.92,
P
=0.001). In contrast, cardiac pro-ANP/BNP transcripts increased later (Stages C and D) and plasma levels rose only with terminal HF (Stage D,
P
<0.001). Immunoreactive plasma ANP and BNP levels were positively associated with plasma cyclic guanosine monophosphate levels (
r
=0.82,
P
=0.01 and
r
=0.8,
P
=0.02, respectively). In experimental dilated cardiomyopathy, corin levels declined early with progressive systolic dysfunction before the development of HF, whereas significant increases in plasma ANP, BNP, and cyclic guanosine monophosphate levels were found only in later stage (C and D) HF. This dyssynchrony in expression of corin versus ANP/BNP may impair cleavage activation of pro-natriuretic peptides, and thereby promote the transition from earlier to later stage HF.
Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake
Authors: Lanzani Chiara , Gatti Guido , Citterio Lorena , Messaggio Elisabetta , Delli Carpini Simona , Simonini Marco , Casamassima Nunzia , Zagato Laura , Brioni Elena , Hamlyn John M. , Manunta Paolo
Published: December 2015

Circulating levels of endogenous ouabain (EO), a vasopressor hormone of adrenocortical origin, are increased by sodium depletion. Furthermore, lanosterol synthase, an enzyme involved in cholesterol biosynthesis, has a missense polymorphism (rs2254524 V642L) that affects EO biosynthesis in adrenocortical cells. Here, we investigated the hypothesis that lanosterol synthase rs2254524 alleles in vivo impact the blood pressure (BP) and EO responses evoked by a low dietary Na intake (<100 mEq/d, 2 weeks) among patients with mild essential hypertension. During the low salt diet, the declines in both systolic BP (SBP: −8.7±1.7 versus −3.0±1.5;
P
=0.013) and diastolic BP (DBP: −5.1±0.98 versus −1.4±0.94 mm Hg;
P
<0.05), and the slope of the long-term pressure–natriuresis relationship affected significantly the presence of the lanosterol synthase rs2254524 A variant (AA: 0.71±0.22, AC 0.09±0.13, and CC 0.04±0.11 mEq/mm Hg/24 h;
P
=0.028). In addition, BP rose in ≈25% of the patients in response to the low salt diet and this was associated with increased circulating EO. Lanosterol synthase gene polymorphisms influence both the salt sensitivity of BP and changes in circulating EO in response to a low salt diet. The response of BP and EO to the low salt diet is markedly heterogeneous. Approximately 25% of patients experienced adverse effects, that is, increased BP and EO when salt intake was reduced and may be at increased long-term risk. The augmented response of EO to the low salt diet further supports the view that adrenocortical function is abnormal in some essential hypertensives.
A ’Thorn in the Flesh’: The Appropriation of Textual Meaning
Authors: Powers Janet Everts
Published: December 2015

One of the central issues in Pentecostal hermeneutics is how the reader enters into the biblical narrative and appropriates the meaning of the biblical text. The issue of how a reader is to appropriate the biblical text is clearly raised in discussions of Paul’s ’thorn in the flesh’ (2 Cor. 12.10). Does the meaning of this ’thom in the flesh’ apply to Paul alone or does he urge his readers to appropriate that meaning for themselves? After various meanings of the ’thom in the flesh’ are examined, it becomes clear that Paul’s account of his experience is a ’testimony’ that invites his readers to enter into the world of the biblical text. When they do this, they allow their lives to be shaped by the same understanding which has illuminated the meaning of the ’thom in the flesh’ for Paul: ’My grace is sufficient for you, for my power is made perfect in weakness’ (2 Cor. 12.10).
On the Consumption of Antarctic Bottom Water in the Abyssal Ocean
Authors: de Lavergne Casimir , Madec Gurvan , Le Sommer Julien , Nurser A. J. George , Naveira Garabato Alberto C.
Published: December 2015

The abyssal ocean is primarily filled by cold, dense waters formed around Antarctica and collectively referred to as Antarctic Bottom Water (AABW). At steady state, AABW must be consumed in the ocean interior at the same rate it is produced, but how and where this consumption is achieved remains poorly understood. Here, estimates of abyssal water mass transformation by geothermal heating and parameterized internal wave–driven mixing are presented. This study uses maps of the energy input to internal waves by tidal and geostrophic motions interacting with topography combined with assumptions about the distribution of energy dissipation to evaluate dianeutral transports induced by breaking internal tides and lee waves. Geothermal transformation is assessed based on a map of geothermal heat fluxes. Under the hypotheses underlying the constructed climatologies of buoyancy fluxes, the authors calculate that locally dissipating internal tides and geothermal heating contribute, respectively, about 8 and 5 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) of AABW consumption (upwelling), mostly north of 30°S. In contrast, parameterized lee wave–driven mixing causes significant transformation only in the Southern Ocean, where it forms about 3 Sv of AABW, decreasing the mean density but enhancing the northward flow of abyssal waters. The possible role of remotely dissipating internal tides in complementing AABW consumption is explored based on idealized distributions of mixing energy. Depending mostly on the chosen vertical structure, such mixing could drive 1 to 28 Sv of additional AABW upwelling, highlighting the need to better constrain the spatial distribution of remote dissipation. Though they carry large uncertainties, these climatological transformation estimates shed light on the qualitative functioning and key unknowns of the diabatic overturning.
An Impact Study of GPS Radio Occultation Observations on Frontal Rainfall Prediction with a Local Bending Angle Operator
Authors: Huang Ching-Yuang , Chen Shu-Ya , Rao Anisetty S. K. A. V. Prasad , Yang Shu-Chih , Hsiao Ling-Feng
Published: December 2015

The impact of global positioning system (GPS) radio occultation (RO) soundings on the prediction of severe mei-yu frontal rainfall near Taiwan in June 2012 was investigated in this study using a developed local bending angle (LBA) operator. Two operators for local refractivity (REF) and nonlocal refractivity [excess phase (EPH)] were also used for comparisons. The devised LBA simplifies the calculation of the Abel transform in inverting model local refractivity without a loss of accuracy. These operators have been implemented into the three-dimensional variational data assimilation system of the Weather Research and Forecasting (WRF) Model to assimilate GPS RO soundings available from the Formosa Satellite Mission 3/Constellation Observing Systems for Meteorology, Ionosphere and Climate (FORMOSAT-3/COSMIC). The RO data are found to be beneficial to the WRF forecast of local severe rainfall in Taiwan. Characteristics of assimilation performance and innovation for the three operators are discussed. Both of the local operators performing assimilation at observation levels appear to produce mostly larger positive moisture increments than do the current nonlocal operators performing assimilation on the mean height of each model vertical level. As the information of the initial increments has propagated farther south with the frontal flow, the simulation for LBA shows better prediction of rainfall peaks in Taiwan on the second day than both REF and EPH, with a maximum improvement of about 25%. The positive impact of the RO data results partially from several RO observations near Mongolia and north China. This study provides an intercomparison among the three RO operators, and shows the feasibility of regional assimilation with LBA.
Psychological Repair
Authors: Gobodo-Madikizela Pumla
Published: December 2015

The possibility of psychological repair after mass trauma is considered here in the context of the global trend of dialogue between survivors and perpetrators in the aftermath of mass atrocities. Stories of remorse and forgiveness illustrate and allow reflection on the last two decades’ experience in dealing with the past, as exemplified by truth commissions in countries like South Africa and Rwanda. Three aspects of this experience are stressed. First, it is argued that the Truth and Reconciliation Commission (TRC) of South Africa was a unique dialogic space that enabled the emergence of new subjectivities in the encounter between survivors and perpetrators. Second, concepts of intersubjectivity are used to explore how a psychoanalytic perspective might contribute to understanding the process of trauma testimony, and to examine the different ways in which empathy plays out in survivors’ and perpetrators’ responses as witnesses to trauma testimony. A key element here is the aspect of concern and care for the other that is linked to the empathy-remorse-forgiveness cycle in the dialogue between victim and perpetrator. Finally, remorse and its relation to forgiveness are explored. Contextually rich case study material from research on forgiveness illustrates this discussion.
Knowledge leadership: Mobilizing management research by becoming the knowledge object
Authors: Fischer Michael D , Dopson Sue , Fitzgerald Louise , Bennett Chris , Ferlie Ewan , Ledger Jean , McGivern Gerry
Published: December 2015

This article explores contrasting forms of ‘knowledge leadership’ in mobilizing management research into organizational practice. Drawing on a Foucauldian perspective on power–knowledge, we introduce three axes of power–knowledge relations, through which we analyse knowledge leadership practices. We present empirical case study data focused on ‘polar cases’ of managers engaged in mobilizing management research in six research-intensive organizations in the UK healthcare sector. We find that knowledge leadership involves agentic practices through which managers strive to actively become the knowledge object – personally transposing, appropriating or contending management research. This article contributes to the literature by advancing the concept of knowledge leadership in the work of mobilizing management research into organizational practice.
Local challenges and national concerns: municipal level responses to national refugee settlement policies in Denmark and Sweden
Authors: Myrberg Gunnar
Published: December 2015

This article investigates how Danish and Swedish national policies vis-à-vis refugees and asylum seekers are perceived, and responded to, at the municipal level in the cities of Aarhus and Malmö. As will be spelled out in the article, municipal representatives raised their voices in both Denmark and Sweden during the middle of the 1990s, arguing that their municipalities had to carry a larger ‘burden of reception’ than they could manage, and they thus urged for changes in the national dispersal and migration policies. The response at the national level was dramatically different in Denmark than in Sweden, however. This is today apparent not only in the sheer numbers of newcomers but also in municipal introduction practices as well as in the institutional memories of municipal officials.

Points for practitioners

The findings presented in this study point both to the possibility for municipalities to have a direct impact on national policies, in this case mainly on refugee settlement policies, but also to how policy decisions at one point in time shapes the political opportunity structures at national as well as local levels at later points in time.
Influencing public sector performance: studying the impact of ability-, motivation- and opportunity-enhancing human resources practices on various performance outcomes in the public sector
Authors: Vermeeren Brenda
Published: December 2015

Background

In response to recent calls in the literature to decompose both the human resources system and performance, this study has examined the effects of ability-, motivation- and opportunity-enhancing human resources practices on the effectiveness, efficiency and fairness of public organizations, with job satisfaction considered as a mediating variable.

Aim

Insights from Human Resource Management and performance research, mostly conducted in the private sector, have been combined with public management literature in order to gain insight into the Human Resource Management–performance relationship in the public sector.

Method

Regression analysis with a bootstrapping method was used to test the mediating effects.

Results

The analysis showed that the three human resources components heterogeneously impact upon the three performance outcomes. Further, the results showed that ability-enhancing and opportunity-enhancing human resources practices are more strongly related to performance outcomes than motivation-enhancing human resources practices.

Conclusion

Decomposing Human Resource Management and performance provides greater insight into the Human Resource Management–performance relationship.

Points for practitioners

The results show that investing in Human Resource Management positively influences performance outcomes. Moreover, our results show that various aspects of public performance require different human resources approaches. Investing in ability-enhancing human resources practices seems to be particularly relevant if one wants to enhance effectiveness. All the human resources practices, but especially ability-enhancing ones, are relevant to enhancing efficiency. However, investing in motivation-enhancing human resources practices seems to make little sense if one is seeking to enhance fairness.
Simulating police containment of a protest crowd
Authors: Posadas Vector Ion , Teknomo Kardi
Published: December 2015

This paper presents an agent-based computational model of the crowd containment tactic known as kettling, which involves cordons of police officers surrounding a crowd of protesters in order to restrict its movement. Our model uses steering behavior techniques to simulate a series of simple scenarios in which an unorganized group of protester agents clash with an opposing group of police agents holding position in a stationary, multiple-rank line formation. We investigate the stability and penetrability of the police formation and how they are influenced by the formation’s thickness (number of layers) as well as the specific behavioral strategy employed by individual police agents—whether using global or local references, or combinations of both. Our results show that a strategy using purely global references produces optimal performance, while increasing the number of formation layers enables strategies using combined references to approach this optimum to different degrees.
The Link between Money Supply and Tourism Demand Cycles
Authors: Ridderstaat Jorge , Croes Robertico
Published: December 2015

This study investigates whether money supply cycles in Canada, United Kingdom, and United States affect tourism demand cycles for Aruba and Barbados. Money supply data are, generally, more easily available than business cycle data (gross domestic product) and have the potential to influence tourism demand cycles. The study contributes to the literature by presenting an economically detailed and sophisticated approach for further understanding the dynamics of tourism demand, using money supply cycles as the explanatory factor. In addition, the study advances the theory through new propositions. The methodology involves data decomposition together with unit root, cointegration, and causality testing. The results show that money supply cycles can impact the cyclical movements of tourism demand and that the impacts are asymmetric, depending on the stage of development of the cycles. These findings implicate the need for adequate policies to counter expected tourism performances below their trend.
Does the Factor Structure of the Aggression Questionnaire Hold for Sexual Offenders?
Authors: Pettersen Cathrine , Nunes Kevin L. , Cortoni Franca
Published: December 2015

The Buss-Perry Aggression Questionnaire (AQ) is often used with sexual offenders, but its factor structure has never been examined in this population. The primary aim of this study was to assess the fit of the proposed four-factor model of the AQ reported in previous studies on a sample of incarcerated sexual offenders ( N = 293). Results of a series of confirmatory factor analyses did not clearly support the four-factor structure of the full or short version of the AQ. Specifically, very large latent factor correlations suggested that the AQ may not measure a four-dimensional construct in the current sample. Only the physical aggression subscale was independently associated with estimated risk of sexual recidivism. Our findings suggest that the AQ is relevant to risk of sexual recidivism but call into question the appropriateness of the established subscales and their interpretation for sexual offenders.
A Dubious Distinction? The BA Versus the BS in Psychology
Authors: Pfund Rory A. , Norcross John C. , Hailstorks Robin , Aiken Leona S. , Stamm Karen E. , Christidis Peggy
Published: December 2015

Previous studies have documented small differences between the bachelor of arts (BA) and the bachelor of science (BS) psychology degrees in their general education core requirements, particularly mathematics and science courses. But are there differences between the BA and BS degrees within the psychology curriculum? Using data from the Undergraduate Study in Psychology, we examined the psychology curriculum of 329 accredited, nonprofit institutions awarding bachelors’ degrees in psychology. We investigated potential differences between BA and BS programs as well as programs awarding both the BA and the BS. Overall, we discovered relatively few differences. The largest contributor to differences in baccalaureate degrees was not the type of degree but the level of the degrees awarded at an educational institution. Implications center on correcting student perceptions, faculty advising, and curricula planning regarding the differences between the BA and the BS in psychology.
A Comparison of Active Student Responding Modalities in a General Psychology Course
Authors: Zayac Ryan M. , Ratkos Thom , Frieder Jessica E. , Paulk Amber
Published: December 2015

Research on teaching has shown that incorporating active student responding (ASR) into classroom instruction facilitates learning and should be considered best practice. Nevertheless, few published studies have examined ASR using a within-participant design across a semester. Using a counterbalanced alternating treatment design, a direct comparison of three ASR methods (clickers, response cards, and hand-raising) and a control condition was conducted across four sections of a general psychology course. Students scored almost 5% higher on exams after utilizing an ASR approach than during control conditions. However, no statistically significant differences were found between experimental conditions. These data suggest that meaningful gains in exam performance are most likely due to the presentation of review questions rather than the use of specific ASR modalities.
Increasing the Efficiency of Data Collection With a Research Participation Night
Authors: Kilb Angela , Herzig Kathleen
Published: December 2015

Data collection can be a frustrating experience for student researchers due to difficulty in scheduling appointments with participants. To increase the efficiency of research project data collection, we organized a Research Participation Night in which volunteers were incentivized to participate in as many experiments as time allowed. By offering course credit, pizza, and other prizes, we attracted 95 participants who completed over 250 experimental sessions, accounting for 35% of the experimental sessions completed during that semester. We have outlined here how to organize such an event, which is particularly suitable for collecting data for a variety of relatively short experiments. It is highly recommended for student researchers struggling to recruit research participants in a short period of time.
“I Don’t Like Being Good!” Changing Behavior With Technology-Based Self-Monitoring
Authors: Bruhn Allison Leigh , Vogelgesang Kari , Schabilion Katherine , Waller LaNeisha , Fernando Josephine
Published: December 2015

Self-monitoring has a well-established literature base for improving the behavior of students with a range of ages and abilities. Whereas self-monitoring often involves technology for prompting self-monitoring procedures, to date, only a few studies have examined the use of technology for recording self-monitored behavior. To extend the literature in this area, the effects of technology-based self-monitoring were examined using an iPad application called SCORE IT in which students and teachers rate students’ behavior and view automated graphs of progress toward goals. Using a baseline and intervention (ABAB) design to measure outcomes, improvements in behavior were established for both middle school participants—one with attention deficit hyperactivity disorder and another receiving noncategorical special education services for reading, math, and behavioral deficits. Findings, limitations, and recommendations for future research are discussed.
Effects of Digital Navigation Aids on Adults With Intellectual Disabilities
Authors: McMahon Don D. , Smith Cate C. , Cihak David F. , Wright Rachel , Gibbons Melinda M.
Published: December 2015

The purpose of this study was to compare the effects of three different navigation aids with students with intellectual disability. Participants included six college-aged students with intellectual disability who attended a postsecondary education program. An adapted alternating treatment design was used to compare a paper map, Google Maps on a mobile device, and an augmented reality navigation application. The results indicated that the augmented reality navigation application was functionally the most effective condition. Conclusions are discussed in the context of supporting people with intellectual disability by teaching navigation skills.
Procedures, Considerations, and Recommendations for the Development of an Assistive Technology Demonstration and Lending Sites
Authors: Moody Amelia K.
Published: December 2015

The purpose of this article is to provide a description of procedures, considerations, and recommendations for developing an assistive technology demonstration and lending site to serve individuals with disabilities. This is accomplished through an examination of patterns of consumer use of the site within the first 3 years. We discuss demographics, utilization of resources, and professional development attendance in an effort to guide future efforts in offering assistive technology services. When looking at the data collected, we found slow and consistent growth over a 3-year period. These trends also suggest that individuals diagnosed with moderate to severe disabilities and their service providers utilize services at a higher rate than those with mild disabilities, as evidenced by high levels of communication, leisure, and daily living aids.
Neighborhood Predictors of Cognitive Training Outcomes and Trajectories in ACTIVE
Authors: Meyer Oanh L. , Sisco Shannon M. , Harvey Danielle , Zahodne Laura B. , Glymour M. Maria , Manly Jennifer J. , Marsiske Michael
Published: December 2015

We examined the influence of neighborhood socioeconomic position (SEP), racial/ethnic composition, and living in a major city on cognitive trajectories and intervention outcomes. Data came from the Advanced Cognitive Training for Independent and Vital Elderly study ( N = 2,438). Mixed effects analyses examined the associations between neighborhood variables and memory, reasoning, speed of processing, and everyday cognition, estimating differences in initial gains (potentially related to practice) and long-term rate of change over 10 years. The effect of reasoning training on initial gain was weaker for individuals in a major city. For everyday cognition, there was a stronger initial gain for memory-trained and control participants in areas with more racial/ethnic minorities and for speed-trained and control individuals in higher SEP areas. The racial/ethnic minority effect was no longer significant after adjustment for multiple comparisons. Neighborhood factors may be more important in practice-related improvement than in long-term change.