bluuebunny/crossref_metadata_2025 huggingface dataset:
A Rare Case of Paclitaxel and/or Trastuzumab Induced Acute Hepatic Necrosis
Authors: Mandaliya Hiren , Baghi Pinky , Prawira Amy , George Mathew K.
Published: October 2015

Paclitaxel induced mild derangement of liver functions including bilirubin, alkaline phosphatase, and AST has been infrequently noticed in clinical trials. Contrary to Paclitaxel, hepatocellular injury, hepatitis, and liver tenderness are common laboratory and clinical findings with Trastuzumab. However, hepatic failure/necrosis secondary to Paclitaxel or Trastuzumab has never been reported in literature. A 62-year-old lady, previously healthy, was treated with adjuvant therapy for left breast stage II, high grade invasive ductal carcinoma which was node negative, oestrogen receptor negative, progesterone receptor positive, and HER2 receptor positive. After modified radical mastectomy and axillary clearance, she finished four cycles of Doxorubicin/Cyclophosphamide chemotherapy and then commenced on Paclitaxel/Trastuzumab combination chemotherapy. Within twelve hours of first dose of Paclitaxel/Trastuzumab therapy, patient required hospital admission for acute onset respiratory failure. Patient died within 36 hours of therapy and autopsy was suggestive of acute hepatic necrosis without any other significant findings. Detailed investigations were not carried out as event was quick with rapid deterioration. There was no history of prior liver pathology/injury and preliminary investigations for major organ involvement were unremarkable. As per our knowledge, Paclitaxel and/or Trastuzumab induced acute hepatic necrosis has never been reported in literature before, hence difficult to predict.
Stability-Indicating HPLC Assay for Determination of Idebenone in Pharmaceutical Forms
Authors: Kombath Sonoube , Balde Issa-Bella , Carret Sandra , Kabiche Sofiane , Cisternino Salvatore , Fontan Jean-Eudes , Schlatter Joël
Published: October 2015

A stability-indicating method was validated for the determination in pharmaceutical forms of idebenone a coenzyme Q10-like compound. The assay was achieved by liquid chromatography analysis using a reversed-phase C18 column and a detector set at 480 nm. The optimized mobile phase consisted of isocratic flow rate at 1.0 mL/min for 3 min with methanol. The linearity of the assay was demonstrated in the range of 3.0 to 8.0 mg/mL with a correlation coefficientr2>0.998. The limits of detection and quantification were 0.03 and 0.05 mg/mL, respectively. The intraday and interday precisions were less than 1.0%. Accuracy of the method ranged from 98.6 to 101.5% with RSD < 0.6%. Specificity of the assay showed no interference from tablets components and breakdown products formed by alkaline, acidic, oxidative, sunlight, and high temperature conditions. This method allows accurate and reliable determination of idebenone for drug stability assay in pharmaceutical studies.
PPARαIs Required for PPARδAction in Regulation of Body Weight and Hepatic Steatosis in Mice
Authors: Garbacz Wojciech G. , Huang Jeffrey T. J. , Higgins Larry G. , Wahli Walter , Palmer Colin N. A.
Published: October 2015

Peroxisome proliferator activated receptors alpha (PPARα) and delta (PPARδ) belong to the nuclear receptor superfamily. PPARαis a target of well established lipid-lowering drugs. PPARδ(also known as PPARβ/δ) has been investigated as a promising antidiabetic drug target; however, the evidence in the literature on PPARδeffect on hepatic lipid metabolism is inconsistent. Mice conditionally expressing human PPARδdemonstrated pronounced weight loss and promoted hepatic steatosis when treated with GW501516 (PPARδ-agonist) when compared to wild type mice. This effect was completely absent in mice with either a dominant negative form of PPARδor deletion of the DNA binding domain of PPARδ. This confirmed the absolute requirement for PPARδin the physiological actions of GW501516 and confirmed the potential utility against the human form of this receptor. Surprisingly the genetic deletion of PPARαalso abrogated the effect of GW501516 in terms of both weight loss and hepatic lipid accumulation. Also the levels of the PPARαendogenous agonist 16:0/18:1-GPC were shown to be modulated by PPARδin wild type mice. Our results show that both PPARδand PPARαreceptors are essential for GW501516-driven adipose tissue reduction and subsequently hepatic steatosis, with PPARαworking downstream of PPARδ.
Identifying User Interaction Patterns in E‐Textbooks
Authors: Saarinen Santeri , Heimonen Tomi , Turunen Markku , Mikkilä-Erdmann Mirjamaija , Raisamo Roope , Erdmann Norbert , Yrjänäinen Sari , Keskinen Tuuli
Published: October 2015

We introduce a new architecture for e‐textbooks which contains two navigational aids: an index and a concept map. We report results from an evaluation in a university setting with 99 students. The interaction sequences of the users were captured during the user study. We found several clusters of user interaction types in our data. Three separate user types were identified based on the interaction sequences: passive user, term clicker, and concept map user. We also discovered that with the concept map interface users started to interact with the application significantly sooner than with the index interface. Overall, our findings suggest that analysis of interaction patterns allows deeper insights into the use of e‐textbooks than is afforded by summative evaluation.
A Case of Simultaneous Unilateral Anterior and Posterior Stafne Bone Defects
Authors: Ozaki Hisashi , Ishikawa Shigeo , Kitabatake Kenichirou , Yusa Kazuyuki , Tachibana Hirohiko , Iino Mitsuyoshi
Published: October 2015

Stafne bone defects (SBDs) are asymptomatic mandibular lingual bone depressions mainly caused by soft tissue inclusions. The most common form of SBDs is posterior; the anterior variant of SBD is relatively uncommon. Although posterior SBD is easily diagnosed by the unique location on radiography, anterior SBD is sometimes misdiagnosed and confused with other pathological entities owing to the location. We report herein a case of simultaneous unilateral anterior and posterior SBDs. In the present case, definitive diagnosis for the anterior mandibular cavity was unclear, as in reported cases. Surgical exploration was thus performed for the lesion in the anterior mandibular cavity. Pathologic examination of the removed tissue showed salivary gland with chronic inflammation. Postoperatively, no functional disturbance has been observed. Management of the posterior SBD was conservative, with radiographic follow-up. To the best of our knowledge, this represents the first report of simultaneous unilateral anterior and posterior SBDs.
A Preclinical Model of Malignant Peripheral Nerve Sheath Tumor-like Melanoma Is Characterized by Infiltrating Mast Cells
Authors: Hölzel Michael , Landsberg Jennifer , Glodde Nicole , Bald Tobias , Rogava Meri , Riesenberg Stefanie , Becker Albert , Jönsson Göran , Tüting Thomas
Published: October 2015

Human melanomas exhibit considerable genetic, pathologic, and microenvironmental heterogeneity. Genetically engineered mice have successfully been used to model the genomic aberrations contributing to melanoma pathogenesis, but their ability to recapitulate the phenotypic variability of human disease and the complex interactions with the immune system have not been addressed. Here, we report the unexpected finding that immune cell–poor pigmented and immune cell–rich amelanotic melanomas developed simultaneously in Cdk4R24C-mutant mice upon melanocyte-specific conditional activation of oncogenic BrafV600E and a single application of the carcinogen 7,12-dimethylbenz(a)anthracene. Interestingly, amelanotic melanomas showed morphologic and molecular features of malignant peripheral nerve sheath tumors (MPNST). A bioinformatic cross-species comparison using a gene expression signature of MPNST-like mouse melanomas identified a subset of human melanomas with a similar histomorphology. Furthermore, this subset of human melanomas was found to be highly associated with a mast cell gene signature, and accordingly, mouse MPNST-like melanomas were also extensively infiltrated by mast cells and expressed mast cell chemoattractants similar to human counterparts. A transplantable mouse MPNST-like melanoma cell line recapitulated mast cell recruitment in syngeneic mice, demonstrating that this cell state can directly reconstitute the histomorphologic and microenvironmental features of primary MPNST-like melanomas. Our study emphasizes the importance of reciprocal, phenotype-dependent melanoma–immune cell interactions and highlights a critical role for mast cells in a subset of melanomas. Moreover, our BrafV600E-Cdk4R24C model represents an attractive system for the development of therapeutic approaches that can target the heterogeneous tumor microenvironment characteristic of human melanomas. Cancer Res; 76(2); 251–63. ©2015 AACR.
Cancer-Specific Production of N-Acetylaspartate via NAT8L Overexpression in Non–Small Cell Lung Cancer and Its Potential as a Circulating Biomarker
Authors: Lou Tzu-Fang , Sethuraman Deepa , Dospoy Patrick , Srivastva Pallevi , Kim Hyun Seok , Kim Joongsoo , Ma Xiaotu , Chen Pei-Hsuan , Huffman Kenneth E. , Frink Robin E. , Larsen Jill E. , Lewis Cheryl , Um Sang-Won , Kim Duk-Hwan , Ahn Jung-Mo , DeBerardinis Ralph J. , White Michael A. , Minna John D. , Yoo Hyuntae
Published: October 2015

In order to identify new cancer-associated metabolites that may be useful for early detection of lung cancer, we performed a global metabolite profiling of a non–small cell lung cancer (NSCLC) line and immortalized normal lung epithelial cells from the same patient. Among several metabolites with significant cancer/normal differences, we identified a unique metabolic compound, N-acetylaspartate (NAA), in cancer cells—undetectable in normal lung epithelium. NAA's cancer-specific detection was validated in additional cancer and control lung cells as well as selected NSCLC patient tumors and control tissues. NAA's cancer specificity was further supported in our analysis of NAA synthetase (gene symbol: NAT8L) gene expression levels in The Cancer Genome Atlas: elevated NAT8L expression in approximately 40% of adenocarcinoma and squamous cell carcinoma cases (N = 577), with minimal expression in all nonmalignant lung tissues (N = 74). We then showed that NAT8L is functionally involved in NAA production of NSCLC cells through siRNA-mediated suppression of NAT8L, which caused selective reduction of intracellular and secreted NAA. Our cell culture experiments also indicated that NAA biosynthesis in NSCLC cells depends on glutamine availability. For preliminary evaluation of NAA's clinical potential as a circulating biomarker, we developed a sensitive NAA blood assay and found that NAA blood levels were elevated in 46% of NSCLC patients (N = 13) in comparison with age-matched healthy controls (N = 21) among individuals aged 55 years or younger. Taken together, these results indicate that NAA is produced specifically in NSCLC tumors through NAT8L overexpression, and its extracellular secretion can be detected in blood. Cancer Prev Res; 9(1); 43–52. ©2015 AACR.
Methylseleninic Acid Superactivates p53-Senescence Cancer Progression Barrier in Prostate Lesions of Pten-Knockout Mouse
Authors: Wang Lei , Guo Xiaolan , Wang Ji , Jiang Cheng , Bosland Maarten C. , Lü Junxuan , Deng Yibin
Published: October 2015

Monomethylated selenium (MM-Se) forms that are precursors of methylselenol, such as methylseleninic acid (MSeA), differ in metabolism and anticancer activities in preclinical cell and animal models from seleno-methionine that had failed to exert preventive efficacy against prostate cancer in North American men. Given that human prostate cancer arises from precancerous lesions such as high-grade prostatic intraepithelial neoplasia (HG-PIN), which frequently have lost phosphatase and tensin homolog (PTEN) tumor suppressor permitting phosphatidylinositol-3-OH kinase (PI3K)–protein kinase B (AKT) oncogenic signaling, we tested the efficacy of MSeA to inhibit HG-PIN progression in Pten prostate-specific knockout (KO) mice and assessed the mechanistic involvement of p53-mediated cellular senescence and of the androgen receptor (AR). We observed that short-term (4 weeks) oral MSeA treatment significantly increased expression of P53 and P21Cip1 proteins and senescence-associated-β-galactosidase staining, and reduced Ki67 cell proliferation index in Pten KO prostate epithelium. Long-term (25 weeks) MSeA administration significantly suppressed HG-PIN phenotype, tumor weight, and prevented emergence of invasive carcinoma in Pten KO mice. Mechanistically, the long-term MSeA treatment not only sustained P53-mediated senescence, but also markedly reduced AKT phosphorylation and AR abundance in the Pten KO prostate. Importantly, these cellular and molecular changes were not observed in the prostate of wild-type littermates which were similarly treated with MSeA. Because p53 signaling is likely to be intact in HG-PIN compared with advanced prostate cancer, the selective superactivation of p53-mediated senescence by MSeA suggests a new paradigm of cancer chemoprevention by strengthening a cancer progression barrier through induction of irreversible senescence with additional suppression of AR and AKT oncogenic signaling. Cancer Prev Res; 9(1); 35–42. ©2015 AACR.
Zopolrestat Induced Suicidal Death of Human Erythrocytes
Authors: Bouguerra Ghada , Bissinger Rosi , Abbès Salem , Lang Florian
Published: October 2015

Background/Aims: The aldose reductase inhibitor zopolrestat has been shown to either decrease or increase apoptosis, the suicidal death of nucleated cells. Erythrocytes may similarly enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress, Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i), and ceramide formation. The present study explored, whether and how zopolrestat induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, oxidative stress from DCFDA dependent fluorescence, [Ca2+]i from Fluo3-fluorescence, and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to zopolrestat (≥ 150 µg/ml) significantly increased the percentage of annexin-V-binding cells, significantly decreased forward scatter (≥ 125 µg/ml), significantly increased Fluo3-fluorescence (200 µg/ml), significantly increased ceramide abundance (150 µg/ml), but did not significantly modify DCFDA fluorescence. The effect of zopolrestat on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusions: Exposure of human erythrocytes to zopolrestat triggers cell shrinkage and cell membrane scrambling, an effect in part due to Ca2+ entry and ceramide.
Prognostic Role of Tumor-Infiltrating Lymphocytes in Lung Cancer: a Meta-Analysis
Authors: Geng Yiting , Shao Yingjie , He Wenting , Hu Wenwei , Xu Yanjie , Chen Jun , Wu Changping , Jiang Jingting
Published: October 2015

Background/Aims: The role of Tumor-infiltrating lymphocytes (TILs) in the prognosis of patients with lung cancer is still controversial. We performed a meta-analysis to evaluate the prognostic role of TILs in lung cancer. Methods: Studies were recruited by searching PubMed, Embase and the Cochrane Library and assessed by further quality evaluation. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to investigate the association between TIL subsets and lung cancer patients' outcome. Results: A total of 29 articles including 8,600 patients were enrolled into the meta-analysis. Our results indicated that high level of CD8+ cells infiltration in tumor stroma (TS) or tumor nest (TN) was associated with better OS in lung cancer patients (HR = 0.76, 95% CI 0.62-0.93, P = 0.006; HR = 0.80, 95% CI 0.67-0.96; P = 0.018, respectively). Similar results could be also observed in CD3+ T cells infiltration. High CD4+ T lymphocytes infiltration in TS was explicitly accompanied by better OS (HR = 0.65, 95% CI 0.46-0.91; P = 0.013), rather than in TN. In contrast, high density of FOXP3+ T cells infiltration in TS showed a poor PFS (HR = 2.67, 95% CI, 1.74-4.08, P < 0.001). Conclusion: This meta-analysis clarified that high level of CD8+ and CD3+ T cells infiltration in TS or TN, and high CD4+ T lymphocytes infiltration in TS showed better OS in lung cancer patients, whereas high density of FOXP3+ T cells infiltration in TS could be recognized as a negative prognostic factor.
Lithium Interferes with the Urinary Excretion of Phenolsulfonphthalein in Rats: Involvement of a Reduced Content of α-Ketoglutarate, the Driving Force for Organic Anion Transporters OAT1 and OAT3, in the Kidney Cortex
Authors: Uwai Yuichi , Tsuge Misato , Tokai Yuta , Kawasaki Tatsuya , Nabekura Tomohiro
Published: October 2015

Aims: Lithium is effective in the treatment for bipolar disorder and is known to influence renal functions. The purpose of this study was to examine the effects of lithium on the renal organic anion transport system. Methods: Pharmacokinetic experiments using rats and Western blotting were conducted. Results: Until 60 min after the intravenous injection of phenolsulfonphthalein, a typical substrate of the renal organic anion transporters, as a bolus, 41.2% of the dose was recovered in the urine, and the infusion of lithium chloride dose-dependently interfered with its renal excretion. No significant changes were observed in the expression levels of rat organic anion transporters rOAT1 and rOAT3, and the content of α-ketoglutarate, the driving force for both transporters, was significantly decreased in the kidney cortex of rats administered lithium. Conclusion: These findings represented the dysfunction of the renal organic anion transport system in rats by lithium. As the mechanism, the reduced driving force for rOAT1 and rOAT3 was suggested to be involved at least in part.
Heat Shock Factor 1 Deficiency Affects Systemic Body Temperature Regulation
Authors: Ingenwerth Marc , Noichl Erik , Stahr Anna , Korf Horst-Werner , Reinke Hans , von Gall Charlotte
Published: October 2015

Introduction: Heat shock factor 1 (HSF1) is a ubiquitous heat-sensitive transcription factor that mediates heat shock protein transcription in response to cellular stress, such as increased temperature, in order to protect the organism against misfolded proteins. In this study, we analysed the effect of HSF1 deficiency on core body temperature regulation. Materials and Methods: Body temperature, locomotor activity, and food consumption of wild-type mice and HSF1-deficient mice were recorded. Prolactin and thyroid-stimulating hormone levels were measured by ELISA. Gene expression in brown adipose tissue was analysed by quantitative real-time PCR. Hypothalamic HSF1 and its co-localisation with tyrosine hydroxylase was analysed using confocal laser scanning microscopy. Results: HSF1-deficient mice showed an increase in core body temperature (hyperthermia), decreased overall locomotor activity, and decreased levels of prolactin in pituitary and blood plasma reminiscent of cold adaptation. HSF1 could be detected in various hypothalamic regions involved in temperature regulation, suggesting a potential role of HSF1 in hypothalamic thermoregulation. Moreover, HSF1 co-localises with tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, suggesting a potential role of HSF1 in the hypothalamic control of prolactin release. In brown adipose tissue, levels of prolactin receptor and uncoupled protein 1 were increased in HSF1-deficient mice, consistent with an up-regulation of heat production. Conclusion: Our data suggest a role of HSF1 in systemic thermoregulation.
Matrix metalloproteinase-2 enhances platelet deposition on collagen under flow conditions
Authors: Momi Stefania , Groot Philip G. de , Battiston Monica , Marco Luigi de , Falcinelli Emanuela , Guglielmini Giuseppe , Appolloni Viviana , Gresele Paolo
Published: October 2015

Platelets contain and release matrix metalloproteinase-2 (MMP-2) that in turn potentiates platelet aggregation. Platelet deposition on a damaged vascular wall is the first, crucial, step leading to thrombosis. Little is known about the effects of MMP-2 on platelet activation and adhesion under flow conditions. We studied the effect of MMP-2 on shear-dependent platelet activation using the O’Brien filtration system, and on platelet deposition using a parallel-plate perfusion chamber. Preincubation of human whole blood with active MMP-2 (50 ng/ml, i. e. 0.78 nM) shortened filter closure time (from 51.8 ± 3.6 sec to 40 ± 2.7 sec, p< 0.05) and increased retained platelets (from 72.3 ± 2.3 % to 81.1 ± 1.8 %, p< 0.05) in the O’Brien system, an effect prevented by a specific MMP-2 inhibitor. High shear stress induced the release of MMP-2 from platelets, while TIMP-2 levels were not significantly reduced, therefore, the MMP-2/TIMP-2 ratio increased significantly showing enhanced MMP-2 activity. Preincubation of whole blood with active MMP-2 (0.5 to 50 ng/ml, i.e 0.0078 to 0.78 nM) increased dose-dependently human platelet deposition on collagen under high shear-rate flow conditions (3000 sec-1) (maximum +47.0 ± 11.9 %, p< 0.05, with 50 ng/ml), while pre-incubation with a MMP-2 inhibitor reduced platelet deposition. In real-time microscopy studies, increased deposition of platelets on collagen induced by MMP-2 started 85 sec from the beginning of perfusion, and was abolished by a GPIIb/IIIa antagonist, while MMP-2 had no effect on platelet deposition on fibrinogen or VWF. Confocal microscopy showed that MMP-2 enhances thrombus volume (+20.0 ± 3.0 % vs control) rather than adhesion. In conclusion, we show that MMP-2 potentiates shear-induced platelet activation by enhancing thrombus formation.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Patient-Centered Decision Support in Acute Ischemic Stroke
Authors: Decker Carole , Chhatriwalla Emily , Gialde Elizabeth , Garavalia Brian , Summers Debbie , Quinlan Miriam E. , Cheng Eric , Rymer Marilyn , Saver Jeffrey L. , Chen Er , Kent David M. , Spertus John A.
Published: October 2015

Background—

National guidelines endorse recombinant tissue-type plasminogen activator (r-tPA) in eligible patients with acute ischemic stroke to improve patients’ functional recovery. However, 23% to 40% of ideal candidates with acute ischemic stroke for reperfusion are not treated, perhaps because of the difficulty in explaining the benefits and risks of r-tPA within the frenetic pace of emergency department care. To support better knowledge transfer and creation of a shared decision-making tool, we conducted qualitative interviews to define the information needs and preferred presentation format for stroke survivors, caregivers, and clinicians considering r-tPA treatment.

Methods and Results—

A multidisciplinary team used qualitative research methods to identify informational needs and strategies for describing the benefits and risks of r-tPA in a clinical setting. Through focus groups (n=10) of stroke survivors (n=39) and caregivers (n=24) and individual interviews with emergency physicians (n=23) and advanced practice nurses (n=20), several themes emerged. Survivors and caregivers preferred a broader definition of a good outcome (independence, rather than no significant disability), simpler graphs as compared with detailed pictographs, and presentation of both population and individualized benefits (framed positively) and risk of receiving r-tPA. Some physicians expressed skepticism with the data and the ability to present risk/benefit information emergently, whereas other physicians and most advanced practice nurses thought such information would improve care. Physicians stressed the importance of presenting the risk of thrombolytic-related intracranial hemorrhage.

Conclusions—

This study suggests that a positively framed risk–benefit tool with graphical presentations of general and patient-specific risk estimates could support patients and providers in considering r-tPA for acute ischemic stroke.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01864928.
Care Trajectories of Veterans in the 12 Months After Hospitalization for Acute Ischemic Stroke
Authors: Arling Greg , Ofner Susan , Reeves Mathew J. , Myers Laura J. , Williams Linda S. , Daggy Joanne K. , Phipps Michael S. , Chumbler Neale , Bravata Dawn M.
Published: October 2015

Background—

Recovery after a stroke varies greatly between individuals and is reflected by wide variation in the use of institutional and home care services. This study sought to classify veterans according to their care trajectories in the 12 months after hospitalization for ischemic stroke.

Methods and Results—

The sample consisted of 3811 veterans hospitalized for ischemic stroke in Veterans Health Administration facilities in 2007. Three outcomes—nursing home care, home care, and mortality—were modeled jointly >12 months using latent class growth analysis. Data on Veterans’ care use and cost came from the Veterans Administration and Medicare. Covariates included stroke severity (National Institutes of Health Stroke Scale), functional status (functional independence measure score), age, marital status, chronic conditions, and prestroke ambulation. Five care trajectories were identified: 49% of Veterans had Rapid Recovery with little or no use of care; 15% had a Steady Recovery with initially high nursing home or home care that tapered off; 9% had Long-Term Home Care; 13% had Long-Term Nursing Home Care; and 14% had an Unstable trajectory with multiple transitions between long-term and acute care settings. Care use was greatest for individuals with more severe strokes, lower functioning at hospital discharge, and older age. Average annual costs were highest for individuals with the Long-Term Nursing Home trajectory ($63 082), closely followed by individuals with the Unstable trajectory ($58 720). Individual with the Rapid Recovery trajectory had the lowest costs ($9271).

Conclusions—

Care trajectories after stroke were associated with stroke severity and functional dependency and they had a dramatic impact on subsequent costs.
Weak Third Parties and Ripening: Revisiting Norwegian Interventions in Guatemala and the Israeli-Palestinian Conflict
Authors: Nissen Ada , Waage Hilde Henriksen
Published: October 2015

Can weak third parties contribute to ripening conflicts for resolution despite their lack of leverage? According to the core principles of ripeness theory, mediators with leverage have a clear advantage when it comes to ripening. What is often overlooked in the literature, however, is the important ways a weak mediator can contribute to ripening as well. This article explores two noteworthy cases of weak third party ripening – the Norwegian roles in the Oslo channel between Israel and the Palestinians, and between the urng guerrilla and the government in Guatemala. These cases demonstrate how careful interventions by weak third parties can help disputants see negotiations as a way out both in preliminary and later phases of negotiations. However, we also argue that weak third parties should not get involved in ripening unless they can call on a mediator with more leverage once substantial negotiations begin.
Kofi Annan’s Multilateral Strategy of Mediation and the Syrian Crisis: The Future of Peacemaking in a Multipolar World?
Authors: Hill Tom H.J.
Published: October 2015

This article examines the multilateral mediation strategy attempted by Kofi Annan in Syria in 2012. In a world of fragmenting power, can international mediation in civil wars be effective at the new fault-lines of great power rivalries? If so, how? As territorial fault-lines between rival great power interests deepen with increasing multipolarity, this is set to become a growing minefield for civil war mediators. Addressing this question requires analysis of recent examples that are indicative of crises to come. Was the failure of the Annan mission in Syria inevitable because of the depth of international polarization? Or, did it fail for other reasons? This detailed examination reveals that the mission was fatally wounded most of all by a Western “illusion of unipolarity” over and above any inherent obstacles posed by geopolitical polarization. This suggests greater, not fewer, possibilities for peacemaking in the future in similar contexts – that is, if Western policy can be better calibrated for the emerging multipolar international system.
Being a Church through Religious Learning at the Street Level
Authors: de Kock A.
Published: October 2015

How can religious learning-processes found in the missionary context of youth work and the guidance of these learning processes be understood religious-pedagogically? To answer this question, the results of fieldwork carried out in two Dutch cases of Christian youth work outside the church are presented and given religious pedagogical reflection. Religious learning processes appear to be situated in the encounter between youngster and youth worker; that is the encounter through living and acting together as well as through shared discussing of personal, societal and religious questions. This article discusses how such an encounter is related to the position of the church, concerning Scripture and regarding youth workers. It is discussed that churches own social forces for renewing their own practices as well as for supporting communities outside the institute leading in the direction of tribal communities that can meet the challenges and needs of a new generation of Christian youth.
“I Belong! And I’m Here to Stay!” u.s. Black Catholics’ Faith and Faithfulness
Authors: Reed-Bouley Jennifer
Published: October 2015

This study attends closely to the faith and experiences of black Catholics. Two major themes emerged from semi-structured interviews with fifteen black Catholics in a midwestern u.s. city: First, participants experience the Catholic church simultaneously as both a loving home and a significant source of suffering because of racism. Second, participants engage in forgiveness of racism, which involves working for racial transformation of church and society. The analysis suggests a need for corporate conversion in that racism remains a major and pernicious barrier to the u.s. Catholic church’s ability to serve as a sacrament of God’s love.
Desmacella Schmidt, 1870 from Brazil: Description of two new species and a review of records (Desmacellida: Demospongiae: Porifera)
Authors: CAVALCANTI THAYNÃ , SANTOS GEORGE GARCIA , PINHEIRO ULISSES
Published: October 2015

Three species of Desmacella Schmidt, 1870 are described from the Brazilian coast: Desmacella microsigmata sp. nov., Desmacella tylovariabilis sp. nov. and Desmacella annexa Schmidt, 1870. The new species were compared with Desmacella species from the Atlantic Ocean, which differ by the size of their spicules and by the presence of microspined sigmas. Desmacella annexa was found to have microspined toxiform microxeas and sigmas. Desmacella now contains 31 species distributed worldwide.
Future Changes in Convective Storm Days over the Northeastern United States Using Linear Discriminant Analysis Applied to CMIP5 Predictions
Authors: Li Harrison , Colle Brian A.
Published: October 2015

Future changes in the frequency of environmental conditions conducive for convective storm days (“CE days”) are determined for the northeastern United States (NEUS) during the warm seasons (April–September) of the twenty-first century. Statistical relationships between historical runs of seven models in phase 5 of the Coupled Model Intercomparison Project (CMIP5) and radar-classified convective storm days are developed using linear discriminant analysis (LDA), and these relationships are then applied to analyze changes in the convective environment under the high-emissions representative concentration pathway 8.5 (RCP8.5) scenario over the period 2006–99. The 1996–2007 warm seasons are used to train the LDA thresholds using convective precipitation from two reanalysis datasets and radar data, and the 1979–95 and 2008–10 warm seasons are used to verify these thresholds. For the CMIP5 historical period (1979–2005), the frequency of warm season CE days averaged across the CMIP5 models is slightly greater than that derived using reanalysis data, although both methods indicate a slight increasing trend through the historical period. Between 2006 and 2099, warm season CE day frequency is predicted to increase substantially at an average rate of 4–5 days decade−1 (50%–80% increase over the entire period). These changes are mostly attributed to a predicted 30%–40% increase in midlevel precipitable water between the historical period and the last few decades of the twenty-first century. Consistent with previous studies, there is decreasing deep-layer vertical wind shear as a result of a weakening horizontal temperature gradient, but this is outweighed by increases in instability led by the moisture increases.
Latitudinal Dependence of Wind-Induced Near-Inertial Energy
Authors: Zhai Xiaoming
Published: October 2015

Midlatitude storms, accounting for the majority of wind energy input to near-inertial motions in the ocean, are known to shift their track significantly from one year to another. The consequence of such storm track shifts on wind-induced near-inertial energy (NIE) is yet unknown. Here, the latitudinal dependence of wind-induced NIE is first analyzed in the framework of the slab model and then tested using two numerical ocean models. It is found that the NIE input by pure inertial wind stress forcing, which dominates the wind energy input to near-inertial motions, is independent of latitude. As a consequence, the NIE generated by white-noise wind stress forcing is also latitudinally independent. In contrast, the NIE generated by red-noise wind stress forcing shows strong dependence on latitude owing to longer inertial periods at lower latitudes capable of sampling greater inertial wind stress forcing. Given that the observed surface wind stress spectra are red, results from this study suggest that an equatorward shift of the storm track is likely to result in an increase in wind-induced NIE in the ocean, while the opposite is true for a poleward shift.
Modifications to the Near-Storm Environment Induced by Simulated Supercell Thunderstorms
Authors: Nowotarski Christopher J. , Markowski Paul M.
Published: October 2015

This study investigates the changes that simulated supercell thunderstorms impart on their surroundings. Supercells are simulated in a strongly sheared convective boundary layer comprising horizontal roll vortices. In sensitivity tests, the effects of cloud shading on the near-storm environment are explored through the removal of cloud ice, water, and hydrometeor effects on parameterized radiation. All of the simulated supercells increase the low-level shear in their proximal environment; however, this effect is more pronounced when cloud shading is included. Shading stabilizes the boundary layer beneath the cirrus anvil, diminishes boundary layer rolls and their attendant thermodynamic perturbations, and reduces the intensity of resolved turbulent mixing in the convective boundary layer. Anvil shading also acts to reduce the buoyancy of inflow air and the horizontal buoyancy gradient along the forward-flank outflow boundary.
Recurrence of conversion disorder symptoms in a successfully treated 16-year-old female
Authors: Shapiro Michael , Mehta Anuja , Avila Jorge , Nguyen Mathew
Published: October 2015

We present a case of a 16-year-old Caucasian female with a history of major depressive disorder and post-traumatic stress disorder who was admitted to an inpatient adolescent psychiatric unit with symptoms of conversion disorder, including non-epileptic seizures, an inability to speak or walk, and not eating on her own. She has a history of multiple previous medical and psychiatric hospitalizations without any significant resolution of symptoms, and extensive medical workups have all been negative. Treatment ultimately involved reassuring the patient and family that there was no underlying medical condition and emphasizing the conversion disorder diagnosis. The patient participated daily in physical therapy to improve mobility, deconditioning, and functioning. Hospital staff was instructed on the nature of the non-epileptic seizures, which continued to occur during the hospitalization. After one month, the patient was discharged home fully functional: walking, speaking, and eating on her own. One week after discharge, the patient presented with the same symptoms and was readmitted to the psychiatric facility. She subsequently never regained her previous level of functioning, and she was ultimately transferred to a residential treatment facility. We will discuss factors that led to the initial improvement and the factors that led to recurrence and persistence of symptoms.
Parent–child positivity and romantic relationships in emerging adulthood
Authors: Kretschmer Tina , Vollebergh Wilma , Oldehinkel Albertine J.
Published: October 2015

Romantic relationship quality in adolescence and early adulthood has often been linked to earlier parent–child relationship quality but it is possible that these links are nonlinear. Moreover, the role of social skills as mediator of associations between parent–child and romantic relations has been discussed but not rigorously tested. Using data from 2,230 participants of the longitudinal TRAILS (TRacking Adolescents’ Individual Lives Survey) sample, this study examined whether parent–child positivity assessed at age 11 predicted romantic involvement, commitment and satisfaction in emerging adulthood. Moreover, indirect effects via cooperation, assertion and self-control were tested. Parent–child positivity did not predict romantic involvement as such. However, in those who were romantically involved, linear and, by trend, nonlinear associations between parent–child positivity and commitment were found, suggesting higher levels of commitment in those who had reported positive parent–child relationships but also in individuals with particularly low levels of parent–child positivity. Satisfaction was linearly linked to parent–child positivity. Little support was found for the assumption that the association between parent–child positivity and romantic relationship quality in emerging adulthood are partly explained by social skills. These results show that neither congruence nor compensation alone are sufficient to explain the associations between parent–child and romantic relationship quality.
When the “Golden Years” turn blue
Authors: Green Jennifer S. , Magee Joshua C. , Steiner Amanda R.W. , Teachman Bethany A.
Published: October 2015

Current treatments for disorders of emotion, such as pathological anxiety, are often less effective in older adults than in younger adults and have poorly understood mechanisms, pointing to the need for psychopathology models that better account for age-related changes in normative emotional functioning and the expression of disordered emotion. This article describes ways in which the healthy aging and emotion literature can enhance understanding and treatment of symptoms of anxiety and depression in later life. We offer recommendations on how to integrate the theories and findings of healthy aging literature with psychopathology research and clinical practice and highlight opportunities for future research.
Tailored Pig Models for Preclinical Efficacy and Safety Testing of Targeted Therapies
Authors: Klymiuk Nikolai , Seeliger Frank , Bohlooly-Y Mohammad , Blutke Andreas , Rudmann Daniel G. , Wolf Eckhard
Published: October 2015

Despite enormous advances in translational biomedical research, there remains a growing demand for improved animal models of human disease. This is particularly true for diseases where rodent models do not reflect the human disease phenotype. Compared to rodents, pig anatomy and physiology are more similar to humans in cardiovascular, immune, respiratory, skeletal muscle, and metabolic systems. Importantly, efficient and precise techniques for genetic engineering of pigs are now available, facilitating the creation of tailored large animal models that mimic human disease mechanisms at the molecular level. In this article, the benefits of genetically engineered pigs for basic and translational research are exemplified by a novel pig model of Duchenne muscular dystrophy and by porcine models of cystic fibrosis. Particular emphasis is given to potential advantages of using these models for efficacy and safety testing of targeted therapies, such as exon skipping and gene editing, for example, using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system. In general, genetically tailored pig models have the potential to bridge the gap between proof-of-concept studies in rodents and clinical trials in patients, thus supporting translational medicine.
Violent Fantasies in Young Men With Autism Spectrum Disorders: Dangerous or Miserable Misfits? Duty to Protect Whom?
Authors: Palermo Mark T. , Bogaerts Stefan
Published: October 2015

Predictability of dangerousness in association with mental disorders remains elusive, outside of a few relatively well-established risk factors for the prognostication of violence, such as male sex, the presence of a psychotic disorder, and comorbid substance abuse. In clinical practice, inquiry into the presence of aggressive or violent ideation, in the form of ideas of homicide or suicide, is part of a standard mental status examination. Nonetheless, fantasy life, when it concerns harm toward others, may not be as reliable an indicator of imminent danger as it may be in the case of self-harm. Five cases of young Italian men with Asperger syndrome and recurrent and extremely violent femicide fantasies are presented. While there is no direct correlation between autism spectrum conditions and violence, as other humans, persons with an autistic condition are capable of committing crimes, including homicide. All five had in common a number of characteristics and behaviors felt to be pathoplastic: All had been bullied, all had been romantically rejected, all were long-standing First Person Shooter (FPS) game players, and all were avid violent pornography consumers. The potential for an actual neurocognitive impact of violent video games, well documented in the literature, and its combination with personal life history and chronic habituation following long-standing violent pornography use is discussed in the context of social and emotional vulnerabilities. While aggressive fantasies cannot and should not be underestimated, in countries where duty to protect legislation does not exist, a clinical approach is imperative, as, incidentally, should be anywhere.
The Diagnostic Yield of Array Comparative Genomic Hybridization Is High Regardless of Severity of Intellectual Disability/Developmental Delay in Children
Authors: D’Arrigo Stefano , Gavazzi Francesco , Alfei Enrico , Zuffardi Orsetta , Montomoli Cristina , Corso Barbara , Buzzi Erika , Sciacca Francesca L. , Bulgheroni Sara , Riva Daria , Pantaleoni Chiara
Published: October 2015

Microarray-based comparative genomic hybridization is a method of molecular analysis that identifies chromosomal anomalies (or copy number variants) that correlate with clinical phenotypes. The aim of the present study was to apply a clinical score previously designated by de Vries to 329 patients with intellectual disability/developmental disorder (intellectual disability/developmental delay) referred to our tertiary center and to see whether the clinical factors are associated with a positive outcome of aCGH analyses. Another goal was to test the association between a positive microarray-based comparative genomic hybridization result and the severity of intellectual disability/developmental delay. Microarray-based comparative genomic hybridization identified structural chromosomal alterations responsible for the intellectual disability/developmental delay phenotype in 16% of our sample. Our study showed that causative copy number variants are frequently found even in cases of mild intellectual disability (30.77%). We want to emphasize the need to conduct microarray-based comparative genomic hybridization on all individuals with intellectual disability/developmental delay, regardless of the severity, because the degree of intellectual disability/developmental delay does not predict the diagnostic yield of microarray-based comparative genomic hybridization.
Flammability and mechanical properties of poly(styrene–butadiene–styrene) copolymer–containing intumescent flame retardants
Authors: Huang Yiren , Yang Jianwei , Wang Zhengzhou
Published: October 2015

Flame-retardant properties of ammonium polyphosphate (APP) and its two microcapsules, APP with a shell of melamine–formaldehyde (MF) resin (MFAPP) and APP with a shell of epoxy resin (EPAPP), were studied in styrene–butadiene–styrene (SBS). The results indicate that APP after the microencapsulation leads to an increase in limiting oxygen index in SBS compared with APP. When dipentaerythritol is incorporated into the SBS composites containing the APP microcapsules, a further improvement in flame retardancy of the composites is observed. The microencapsulation does not result in much improvement of mechanical properties. Moreover, the effect of a compatibilizer (SBS grafted with maleic anhydride) on flame-retardant and mechanical properties of SBS/APP composites was investigated.
Propagation characteristics of tunnel compression waves with multiple peaks in the waveform of the pressure gradient: Part 1: Field measurements and mathematical model
Authors: Miyachi Tokuzo , Saito Sanetoshi , Fukuda Takashi , Sakuma Yutaka , Ozawa Satoru , Arai Takakage , Sakaue Shoji , Nakamura Shinya
Published: October 2015

A high-speed train entering a tunnel generates a compression wave. When the compression wave reaches the exit portal of the tunnel, a micro-pressure wave radiates outward. The magnitude of the micro-pressure wave is approximately proportional to the pressure gradient of the compression wave arriving at the exit portal. As the micro-pressure wave can cause environmental problems, tunnel entrance hoods have been installed at many portals of long slab track tunnels on the Japanese high-speed railway, the Shinkansen to reduce the magnitude of the micro-pressure wave. In this study, field measurements were taken in a Shinkansen long slab track tunnel with a hood at its entrance. The compression wave distorts during its propagation through a long slab track tunnel. The dependence of the propagation characteristics on the initial compression waveform was clarified on the basis of field measurements on different trains and hood window configurations. It was shown that compression waves with a waveform of the pressure gradient that has shallow valleys tend to steepen more easily and that the optimum window pattern of the hood depends on the length of the tunnel. Furthermore, a mathematical model corresponding to the results of the field measurements was proposed to describe the distortion of the compression waves.
Prescription Drug Use Among Adults With Chronic Conditions in South Korea
Authors: Jung Youn , Byeon Jinok , Chung Haejoo
Published: October 2015

The aim of this study is to identify the social determinants of prescription drug use among adults with chronic diseases by examining the associations between socioeconomic position and prescription medicine use and perceived burden for pharmaceutical expenditure, using a sample of the Korean population from the 2008 Korea Health Panel, with 4 analytic models. Controlled with health status and the type of health insurance, the probability of using prescription drugs and overall spending on drugs significantly increased with rising income level, while perceived burden for out-of-pocket payment significantly decreased. These results imply that the poor are likely to underuse prescription drugs compared with their wealthier counterparts with the same need for health care, probably due to economic barriers.