bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B07: Expression of MYCS62A in thymocytes is anti-proliferative, but promotes the later emergence of tumorigenic cells
Authors: Daniel Colin J. , Link Jason Michael , Byers Sarah , Sears Rosalie C.
Published: October 2015

Oncogenic alterations that promote stability of MYC proteins are common in several human tumor types, and expression of stabilized MYC in mice promotes tumorigenesis from breast, pancreas, and thymus. Mutations that inhibit phosphorylation of T58 in MYC limit proteasomal degradation and enhance S62 phosphorylation and protein stability. Physiologically low expression of MycT58A from the ROSA26 locus (ROSA-MYCT58A) causes robust tumorigenesis, whereas tumor development in ROSA-MYCWT expressing cells is rare. Mice with T cell-specific expression of MYCT58A (LckCre ROSA-MYCT58A) typically succumb to thymomas within six months, whereas survival of LckCre ROSA-MYCWT mice is unaltered from control. In contrast to T58A mutation, S62A mutation stabilizes MYC but decreases cell production in breast tissue. Unexpectedly, LckCre ROSA-MYCS62A mice develop tumors and have significantly shorter lifespans than LckCre ROSA-MYCWT mice. However, unlike LckCre ROSA-MYCT58A mice, tumors in LckCre ROSA-MYCS62A mice are not exclusively thymomas and tumorigenesis takes significantly longer. Analysis of tumors from LckCre ROSA-MYCS62A mice revealed abundant S62-phosphorylated MYC indicating elevated expression and activation of endogenous MYC, despite suppression of endogenous Myc transcription in thymocytes and splenic T cells from young LckCre ROSA-MYCS62A mice. In order to test possible tumorigenic effects of S62A mutation apart from the effects of endogenous MYC, we developed mice that would simultaneously delete endogenous Myc and express ectopic ROSA-Myc in developing T cells. CRE-mediated deletion of endogenous Myc decreased the median survival of LckCre ROSA-MYCS62A mice and caused very early onset thymomas in a subset of young mice. Although LckCre ROSA-MYCT58A mice provide another classic example connecting increased MYC expression to tumor development, LckCre ROSA-MYCS62A mice demonstrate that limitations on MYC function can also promote tumorigenesis; likely by selecting for mutant cells that have escaped deletion or suppression of endogenous Myc. Strong, constitutive, mitogenic signals in developing thymocytes may increase the chance that MYC-suppression-escapees will be tumorigenic.

Citation Format: Colin J. Daniel, Jason Michael Link, Sarah Byers, Rosalie C. Sears. Expression of MYCS62A in thymocytes is anti-proliferative, but promotes the later emergence of tumorigenic cells. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B07.
Abstract B42: Therapeutic effects of an anti-myc drug on mouse pancreatic cancer
Authors: Stellas Dimitris , Szabolcs Matthias , Koul Sanjay , Li Zhe , Polyzos Alexander , Anagnostopoulos Constantinos , Cournia Zoe , Tamvakopoulos Constantin , Klinakis Apostolos , Efstratiadis Argiris
Published: October 2015

Background: Pancreatic ductal adenocarcinoma (PDA) is frequently driven by oncogenic KRAS(KRAS*) mutations. We developed a mouse model of KRAS*-induced PDA and, based on genetic results demonstrating that KRAS* tumorigenicity depends on Myc activity, we evaluated the therapeutic potential of an orally administered anti-Myc drug.

Methods: We tested the efficacy of Mycro3, a small-molecule inhibitor of Myc-Max dimerization, in the treatment of mouse PDA (n = 9) and also of xenografts of human pancreatic cancer cell lines (NOD/SCID mice, n = 3–12). Tumor responses to the drug were evaluated by PET/CT imaging, and histological, immunohistochemical, molecular and microarray analyses. The Student's t test was used for differences between groups. All statistical tests were two-sided.

Results: Transgenic overexpression of KRAS* in the pancreas resulted in pancreatic intraepithelial neoplasia in two-week old mice, which developed invasive PDA a week later and became moribund at one month. However, this aggressive form of pancreatic tumorigenesis was effectively prevented by genetic ablation of Myc specifically in the pancreas. We then treated moribund, PDA-bearing mice daily with the Mycro3 Myc-inhibitor. The mice survived until killed at two months. PET/CT image analysis (n = 5) demonstrated marked shrinkage of PDA, while immunohistochemical analyses showed an increase in cancer cell apoptosis and reduction in cell proliferation (treated/untreated proliferation index ratio: 0.29, P < .001, n = 3, each group). Tumor growth was also drastically attenuated in Mycro3-treated NOD/SCID mice (n = 12) carrying orthotopic or heterotopic xenografts of human pancreatic cancer cells (eg, mean tumor weight ± SD of treated heterotopic xenografts vs vehicle-treated controls: 15.2 ± 5.8 mg vs 230.2 ± 43.9 mg, P < .001).

Conclusion: These results provide strong justification for eventual clinical evaluation of anti-Myc drugs as potential chemotherapeutic agents for the treatment of PDA.

Citation Format: Dimitris Stellas, Matthias Szabolcs, Sanjay Koul, Zhe Li, Alexander Polyzos, Constantinos Anagnostopoulos, Zoe Cournia, Constantin Tamvakopoulos, Apostolos Klinakis, Argiris Efstratiadis. Therapeutic effects of an anti-myc drug on mouse pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B42.
Abstract B47: Incomplete RFA-generated heat shock response provokes colorectal cancer liver metastases (CRLMs) recurrence by inducing cancer cell stemness and invasion
Authors: Zhang Zhan-Guo , Zhang Wan-Guang , Wu Yan-Hui , Liang Hui-Fang , Zhang Bi-Xiang , Chen. Xiao-Ping
Published: October 2015

Even now, radiofrequency ablation (RFA) is accepted as a curative therapy for colorectal cancer liver metastasis (CRLMs). Accumulating data have shown that incomplete radiofrequency ablation (ICR) associates with increase of tumor recurrence and more aggressive malignant phenotype. We determined the mechanisms of this progression, including effectively predict biologic behaviors.We established a mouse model highly mimicking the process of RFA treatment. Functional studies were performed in vitro and in vivo. Our xenograft model unveiled ICR increases the risk in CRLMs recurrence. Here we focused on the heat shock (HS)-induced CRC malignance. Sublethal HS in CRC cell lines provoked cell growth, invasion, and tumor initiation in vitro. Consistently, the xenograft mouse model also confirmed the effects of HS in promoting tumor growth. With Western blot analysis, we found that Fra-1, which is a typical down-stream of the transcription factor ERK1/2, was significantly increased by heat shock stimuli compared with the untreated CRC cells. Furthermore, we demonstrated that silence of Fra-1 in HS treated cells could abolish the effects of HS in promoting malignant phenotype. Significantly, proliferation markers (Ki67, c-Myc, CyclinD1, CDK2), stem cell markers (Sox-2, Sox-9, Oct3/4, Lgr5) and invasion related MMP1 were up-regulated in the HS treated cells and in xenograft model. Taken together, this study established a novel mouse model to study the effect of ICR in CRLM. HS induces CRC proliferation and metastasis by targeting Fra-1, which is a potential prognostic marker and a promising therapeutic strategy for CRC recurrence after RFA treatment.

Citation Format: Zhan-Guo Zhang, Wan-Guang Zhang, Yan-Hui Wu, Hui-Fang Liang, Bi-Xiang Zhang, Xiao-Ping Chen. Incomplete RFA-generated heat shock response provokes colorectal cancer liver metastases (CRLMs) recurrence by inducing cancer cell stemness and invasion. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B47.
Abstract B49: Using small molecule activators of PP2A to negatively regulate c-myc in small cell lung cancer
Authors: Wolpaw Benjamin Jonathan , Narla Goutham , Cheemalavagu Shashank
Published: October 2015

Treatment for small cell lung cancer (SCLC) is based on combination chemotherapy with a five-year survival of just 10-13% for patients with limited disease. A common molecular alteration in SCLC is the overexpression of MYC family oncogenes, occurring in 18-31% of SCLCs, and more commonly in chemo-refractory disease. Several FDA approved tricyclic antidepressants were recently shown to have efficacy in SCLC cell lines based on G-protein coupled receptor (GPCR) mediated effects, and a phase IIa trial is testing one of these compounds. A reverse chemical engineering approach was employed to remove GPCR pharmacology from the tricyclic family of compounds, generating a novel class known as SMAPs, small molecule activators of protein phosphatase 2A (PP2A). PP2A is a tumor suppressor with an established negative regulatory action on c-myc. Thus, it was hypothesized that SMAPs could represent a novel treatment approach in SCLC via activation of PP2A with downstream effects on targets including c-myc. A genetic signature score for SMAP efficacy predicted broad activity of these compounds in SCLC and identified myc family pathways as strongly correlated to IC50 in a panel of tumor cell lines. Incubation with the SMAP TRC-794 was shown to induce apoptosis in the SCLC cell lines H82 and H69 as seen by induction of annexin V as well as parp and caspace-3 cleavage. Loss of c-myc in the c-myc amplified cell line H82 was observed in a dose dependent manner at 24hrs. Loss of c-myc was observed by 6 hours of drug treatment in H82 and H2081 cells. Supporting a PP2A dependent mechanism, molecular effects on c-myc in H82 were partially reversed with the phosphatase inhibitor okadaic acid. IC50s for these cell lines were similar to those for a lung adenocarcinoma line with established in vivo sensitivity to TRC-794. TRC-1154, a more potent SMAP, was shown to produce statistically significant tumor growth inhibition compared to vehicle control in a xenograft model when orally dosed at 100mg/kg daily. In summary, SMAPs may represent a viable treatment approach in SCLC, possibly via a PP2A mediated negative regulation of c-myc.

Citation Format: Benjamin Jonathan Wolpaw, Goutham Narla, Shashank Cheemalavagu. Using small molecule activators of PP2A to negatively regulate c-myc in small cell lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B49.
Abstract IA08: MYC and mitochondrial metabolism in childhood neuroblastoma
Authors: Arsenian-Henriksson Marie
Published: October 2015

Neuroblastoma, which arises from the sympathetic nervous system is one of the most aggressive solid tumors of early childhood. Amplification of the MYCN oncogene has been found in around 30% of neuroblastoma patients and it is associated with rapid tumor progression and poor prognosis. New treatment options are urgently needed for this group of patients. As metabolic adaptations are crucial for cancer cell survival during tumor progression, identifying metabolic discrepancies of aggressive tumors may be central in order to find new treatment strategies. We have recently highlighted the importance MYC driven mitochondrial metabolism in neuroblastoma pathogenesis. Our findings suggest that a small chemical molecule, 10058-F4, previously identified as a c-MYC inhibitor also targets the MYCN/MAX complex resulting in apoptosis and neuronal differentiation in MYCN-amplified neuroblastoma cells. Importantly, we found that inhibition of MYCN results in changes in neuroblastoma cell metabolism including mitochondrial dysfunction leading to accumulation of intracellular lipid droplets. Taken together, our results highlight that MYCN regulates important metabolic pathways in MYCN-amplified neuroblastoma, which may be the basis for development future therapies for this patient group.

Citation Format: Marie Arsenian-Henriksson. MYC and mitochondrial metabolism in childhood neuroblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr IA08.
Abstract PR07: Myc-dependent translation makes an impact: Tailor-made protein expression for cancer development
Authors: Stumpf Craig , Cunningham Tom , Ruggero Davide
Published: October 2015

Our research delineates how the “cancer translatome” can reprogram gene expression at the post-transcriptional level, by controlling the translation of specific subsets of mRNAs during distinct steps of cancer progression. Here, we have genetically engineered a novel mouse model in which two of the most commonly perturbed oncogenes, MYC and KRAS, are stochastically activated in a small number of hepatocytes resulting in a dramatic increase in metastatic tumors, recapitulating the process of liver tumor development in human cancers. Therefore, we have used this model to detail the evolution of gene expression from primary tumor initiation to metastasis at both the transcriptional and translational levels. We used a genome-wide ribosome profiling approach to assess changes in gene expression at the earliest possible time point after oncogenic activation to metastasis formation in order to develop the first functional comprehensive network of widespread changes in translational regulation that occur during the course of tumor development. We characterized networks of translational regulation unique to each individual oncogene, as well as networks that are synergistically regulated upon activation of both oncogenes. For example, we have identified common networks that are translationally induced upon activation of either MYC or KRAS (e.g. protein synthesis, energy metabolism). We discovered that each oncogene also regulates the translation of unique mRNA networks. MYC induces the translation of genes involved in cell proliferation, mRNA splicing, and lipid metabolism, while KRAS specifically induces the translation of stress response genes, especially the pathway that responds to hypoxia. In addition to the additive effects of regulating their cognate mRNA networks, the combination of MYC and KRAS activation in the same cells can also induce a synergistic effect on the translation of new networks including genes involved in integrin signaling, which may partially explain the increased metastasis observed in this mouse model. Additionally, we uncovered independent regulatory mechanisms that may allow for temporal regulation of discrete oncogenic processes, either at the level of transcription or translation, required at different times during the course of tumor development. Understanding the mechanisms and specific targets of translational regulation downstream of MYC and KRAS activation will provide a novel platform from which to develop therapeutic strategies targeting cancers possessing two of the most common and currently “undruggable” oncogenic lesions.

Citation Format: Craig Stumpf, Tom Cunningham, Davide Ruggero. Myc-dependent translation makes an impact: Tailor-made protein expression for cancer development. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr PR07.
Abstract PR12: Selective targeting of MYC mRNA by chemically stabilized antisense oligonucleotides
Authors: Ott Christopher J. , Bandaru Raj , Gill Taylor , Tao Junyan , Chen Xin , Zhang Yixian , Bradner James E.
Published: October 2015

Despite its well-characterized properties as a proto-oncogene in numerous cancers, direct potent and selective inhibition of MYC or its protein product c-Myc with cell-permeable synthetic agents remains a significant challenge. Systemic inhibition of c-Myc activity in mice by expression of dominant negative MYC transgenes has been shown to dramatically decrease tumor burden with apparently tolerable side effects (Soucek et al, Nature 2008). In order to ultimately realize the goal of therapeutic MYC inhibition in cancer, we have initiated discovery chemistry efforts aimed at inhibiting MYC at the transcriptional, translational, and post-translational level. Here we describe the application of synthetic antisense oligonucleotides designed to target specific sequences of the MYC mRNA (MYCASOs). We have incorporated several chemical features into MYCASOs, including the addition of locked nucleic acid (LNA) bases at the 5' and 3' ends, phosphorothioate linkers, and internal DNA bases in order to increase mRNA target affinity and cleavage, cellular permeability, stability, and systemic distribution in vivo. Treatment of MYC¬-expressing cancer cells with MYCASOs leads to a potent decrease in MYC mRNA and c-Myc protein levels. Cleaved MYC mRNA in MYCASO-treated cells is detected with a sensitive 5' rapid amplification of cDNA ends (RACE) assay. MYCASO-treatment of cancer cell lines leads to significant inhibition of cellular proliferation and induces apoptosis in c-Myc-dependent myeloma and leukemia cell lines while decreasing c-Myc-mediated gene expression. In vivo administration of MYCASOs simply dissolved in saline was performed in mice by tail vein injection. MYCASOs are well tolerated up to 25 mg per kg on a twice-weekly dosing regimen. In a MYC-induced model of hepatocellular carcinoma, MYCASO treatment leads to detectable cleavage of the MYC transcript, decreases c-Myc levels within tumors, and significantly decreases tumor burden. MYCASOs represent a new chemical tool for in vitro and in vivo modulation of c-Myc activity, and promising therapeutic agents for MYC-driven tumors.

Citation Format: Christopher J. Ott, Raj Bandaru, Taylor Gill, Junyan Tao, Xin Chen, Yixian Zhang, James E. Bradner. Selective targeting of MYC mRNA by chemically stabilized antisense oligonucleotides. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr PR12.
Reducing Transitional Hypothermia in Outborn Very Low Birth Weight Infants
Authors: Leng Haiqing , Wang Haiyan , Lin Biyun , Cheng Guoqiang , Wang Laishuan
Published: October 2015

Background: Transitional hypothermia (TH) is associated with increased morbidity and mortality in very low birth weight (VLBW) infants worldwide. Objectives: To assess the effect of a quality improvement project (QIP) on outborn TH and the associated mortality/morbidity among VLBW neonates. Methods: We conducted a multi-intervention QIP to reduce TH (<36°C) among outborn VLBW neonates. This cohort study compared a historical group (group I, n = 86) to a prospective group (group II, established after QIP implementation, n = 86). The primary outcome was axillary temperature measured in the delivery room (DR) and upon admission to the neonatal intensive care unit (NICU). Results: The baseline characteristics of the two groups were similar. After introducing the QIP, the mean DR and NICU admission temperatures of the patients rose from 35.5 to 36.1°C and from 34.6 to 36.2°C, respectively (p < 0.01), and the percentage of patients with temperatures <36°C in the DR and NICU decreased from 80 to 40% and from 81 to 42% (p < 0.01), respectively. Meanwhile, the percentage of patients with a normal temperature in the DR and NICU rose from 20 to 58% and from 19 to 56% (p < 0.01), respectively, which was accompanied by significantly decreased mortality (p < 0.02) and other improvements. Conclusion: Implementation of a QIP resulted in a decrease in the number of moderately hypothermic VLBW neonates and a sustained improvement in normothermia rates during DR stabilization and transfer to the NICU in outborn VLBW neonates.
Quantitative Electroencephalography as a Diagnostic Tool for Alzheimer's Dementia in Adults with Down Syndrome
Authors: Salem Lise Cronberg , Sabers Anne , Kjaer Troels W. , Musaeus Christian , Nielsen Martin N. , Nielsen Anne-Grete , Waldemar Gunhild
Published: October 2015

Background: Assessment of dementia in individuals with intellectual disability is complex due to great inter-individual variability in cognitive function prior to dementia and a lack of standardized instruments. Studies have indicated that quantitative electroencephalography (qEEG) results may be used as a diagnostic marker for dementia. The aim of this study was to examine the value of qEEG in the diagnostic evaluation of dementia in patients with Down syndrome (DS). Method: The study included 21 patients with DS and mild-to-moderate dementia due to Alzheimer's disease (DS-AD) and 16 age-matched adults with DS without cognitive deterioration assessed by the informant-based Dementia Screening Questionnaire in Intellectual Disability (DSQIID). Conventional EEG was performed and analysed quantitatively using fast Fourier transformation. Outcomes were centroid frequency, peak frequency, absolute power, and relative power. Results: In several regions of the brain, a significant decrease in the theta-1 band (4-7 Hz) was identified for the centroid frequency. A significant negative correlation was demonstrated between the mean of the centroid frequency of the theta-1 band and the total DSQIID score. Conclusion: We found that qEEG can detect a significant decrease in centroid frequency in a sample of patients with DS-AD as compared to a sample of adults with DS and no cognitive deterioration.
Application of the Mimic Valsalva Maneuver with the Help of a Saccule in Cerebrospinal Fluid Rhinorrhea Reconstruction Surgery
Authors: Cheng Peng , Tang Shi-Xiong , Qing Jing , Wang Yao-Wen , Yao Shou-Guo , Ouyang Tian-Bin , Kong De-Qiu
Published: October 2015

Objective: To explore the mimic Valsalva maneuver with the help of a saccule handled by an anesthesiologist in order to locate the leakage channel and repair the fistula during intranasal endoscopic reconstruction surgery of cerebrospinal fluid rhinorrhea. Methods: From 2012 to 2014, 8 patients were diagnosed with cerebrospinal fluid rhinorrhea by medical histories, physical and biochemical examination. All patients were treated with intranasal endoscopic reconstruction surgery of cerebrospinal fluid rhinorrhea. During the surgery, the mimic Valsalva maneuver with the help of a saccule was carried out once or twice by an anesthetist during the operation. Intranasal endoscopy was used to accurately locate the leakage site as shown by the exact fistula. Temporal fascia, fascia lata, middle turbinate mucosa and nasal septum mucosa were all used to repair the fistula. Results: After the surrounding mucosa was removed, the exact leakage sites were accurately found. Fascia materials were used in all 8 patients. All patients were successfully treated after their first operation, and 1 patient was successfully treated by two operations with no complications and recurrences. All the patients were followed up for 1 month to 2 years. Conclusion: The convenient method of the mimic Valsalva maneuver with the help of a saccule handled by an anesthesiologist has a good prospect in cerebrospinal fluid rhinorrhea reconstruction surgery.
Cancer Therapeutic Effects of Titanium Dioxide Nanoparticles Are Associated with Oxidative Stress and Cytokine Induction
Authors: Fujiwara Rina , Luo Yi , Sasaki Takamitsu , Fujii Kiyomu , Ohmori Hitoshi , Kuniyasu Hiroki
Published: October 2015

Nanoparticles (NPs) are considered to influence the inflammatory process; however, the precise mechanism and the significance in tumors are still not clear. In this study, when CT26 and LL2 mouse cancer cells were treated with 6-nm anatase titanium dioxide NPs (TDNPs) without ultraviolet irradiation, oxidative stress and induction of inflammatory cytokines were observed. Oxidative stress was further increased by disease-associated conditions such as high glucose concentrations and hypoxia. Inhaled or orally administered TDNPs generated granulomatous lesions in the lungs and colon of the rodent models tested, with increased oxidative stress and inflammatory cytokines. Oxidative stress and inflammatory cytokines were also found in cancer cells treated with gold or carbon black NPs. Treatment of CT26 cells with 10- to 70-nm rutile TDNPs showed that smaller NPs produced more oxidative stress and inflammatory cytokines than larger ones did. To avoid diffusion of TDNPs and to minimize toxicity, 10-nm TDNPs were suspended in a collagen gel inserted into a subcutaneous tumor in a CT26 mouse. A single TDNP treatment via this method inhibited tumor growth in a size- and dose-dependent manner, and resulted in lower levels of urinary 8-OHdG when compared to systemically administered TDNPs. These findings suggest that TDNPs might be useful for the local treatment of tumors.
An Autopsied Case of Malignant Sarcomatoid Pleural Mesothelioma in Which Chest Pain Developed Several Months Earlier without Abnormality on Imaging
Authors: Yaguchi Daizo , Ichikawa Motoshi , Inoue Noriko , Kobayashi Daisuke , Matsuura Akinobu , Shizu Masato , Imai Naoyuki , Watanabe Kazuko
Published: October 2015

The patient experienced chest pain for about 7 months, but a diagnosis could not be made until after death. He was diagnosed with malignant sarcomatoid pleural mesothelioma on autopsy. In this case report, difficult aspects of the diagnosis are discussed. The 70-year-old Japanese man was a driver who transported ceramic-related products. Right chest pain developed in July 2013, but no abnormality was detected on a chest computed tomography (CT) performed in September 2013, and the pain was managed as right intercostal neuralgia. A chest CT performed in late October 2013 revealed a right pleural effusion, and the patient was referred to our hospital in early November 2013. Thoracentesis was performed, but the cytology was negative, and no diagnosis could be made. Close examination was postponed because the patient developed a subarachnoid hemorrhage. He underwent 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) after discharge from the neurosurgery department, and extensive right pleural thickening and 18F-FDG accumulation in this region were observed. Based on these findings, malignant pleural mesothelioma was suspected, and a thoracoscopy was performed under local anesthesia in early December 2013, but no definite diagnosis could be made. The patient selected best supportive care and died about 7 months after the initial development of right chest pain. The disease was definitively diagnosed as malignant sarcomatoid pleural mesothelioma by a pathological autopsy. When chronic chest pain of unknown cause is observed and past exposure to asbestos is suspected, actions to prevent delay in diagnosis should be taken, including testing for suspicion of malignant pleural mesothelioma.
Robotic Mitral Valve Repair for Simple and Complex Degenerative Disease
Authors: Suri Rakesh M. , Taggarse Amit , Burkhart Harold M. , Daly Richard C. , Mauermann William , Nishimura Rick A. , Li Zhuo , Dearani Joseph A. , Michelena Hector I. , Enriquez-Sarano Maurice
Published: October 2015

Background—

Severe primary (degenerative) mitral regurgitation (MR) is repaired with durable results when simple single-scallop disease is addressed. The midterm quality outcomes of minimally invasive repair for complex disease are unknown, however.

Methods and Results—

From January 2008 to January 2015, 487 patients (56±11 years, 360 men, ejection fraction 65±6%, 98.8% complete follow-up) underwent robotic mitral valve repair for severe nonischemic degenerative MR. Simple pathology was addressed in 289 of 487 (59%) patients, and complex repair (all others) was performed in 198 of 487 (41%). Four patients died during follow-up with a 5-year survival rate 99.5% (99.4% simple; 99.5% complex; hazard ratio, 0.48; 95% confidence interval, 0.05–4.59); and New York Heart Association functional class I/II was documented in 97.9% (477/487). Eight patients had recurrence of moderate-to-severe MR (4 simple, 4 complex), with a 5-year freedom from MR of 94.6% (96.2% simple; 92.7%, complex;
P
=0.67; hazard ratio, 1.36; 95% confidence interval, 0.34–5.43). Seven patients (2 simple, 5 complex), underwent mitral reoperation, with a 5-year freedom from reoperation of 97.7% (99.1% simple; 95.7% complex;
P
=0.13; hazard ratio, 3.35; 95% confidence interval, 0.65–17.32).

Conclusions—

At a large tertiary care referral center, midterm quality outcomes after robotic correction of degenerative MR are excellent, with very high survival, infrequent complications, and a low likelihood of MR recurrence, regardless of mitral valve repair complexity. Awareness of these improvements in outcome is important to inform contemporary decisions regarding high-quality alternatives to conventional and percutaneous mitral repair.
Ecumenism and the Visible Unity of the Church
Authors: Chapman David M.
Published: October 2015

This paper traces the origins and subsequent use of the concepts of ‘organic union’ and ‘reconciled diversity’ as alternative descriptions of the visible unity of the Church and the method and goal of ecumenism, with special reference to the documents of the World Council of Churches and a select number of related texts emanating from theological dialogue at a world level. The paper argues: (1) that each of these concepts preserves valuable insights into the unity and diversity of the Church; (2) that the corresponding approaches to inter-church relations and dialogue need not be incompatible as ecumenical method; (3) but that ‘reconciled diversity’, as it is usually described, is only a temporary state on the way to ‘organic union’ and not itself a sufficient expression of the full visible unity of the Church.
A new species of Varronia (Cordiaceae) and a checklist of Boraginales for the State of Sergipe, Brazil
Authors: Miranda de Melo José Iranildo , Vieira Diego Daltro
Published: October 2015

Varronia johnstoniana, a new species of Cordiaceae is described for Sergipe State, Brazil. This new taxon is characterized principally by having sessile, shiny leaves, corolla with rufescent indumentum, and verrucose fruits. Illustrations, data concerning its habitats, distribution, reproductive phenology, and comments about taxonomic affinities based on morphology are presented. A checklist of Boraginales in Sergipe State is presented, comprising three families, seven genera, and 28 species, of which ten species constituting new occurrences, with their respective vegetation types.
New records for the Kosovo caddisfly fauna with the description of a new species, Drusus dardanicus sp. nov. (Trichoptera: Limnephilidae)
Authors: IBRAHIMI HALIL , KUČINIĆ MLADEN , VITECEK SIMON , WARINGER JOHANN , GRAF WOLFRAM , PREVIŠIĆ ANA , BÁLINT MIKLÓS , KERESZTES LUJZA , PAULS STEFFEN U.
Published: October 2015

The Balkan Peninsula is one of the most important European hotspots of freshwater biodiversity. The region is, however, to a large extent insufficiently investigated. Here we present data on distribution of caddisflies in one particularly understudied area, the Republic of Kosovo. Our data include the first records of Adicella altandroconia Botosaneanu & Novak and Halesus tessellatus (Rambur) for the Kosovo caddisfly fauna, and a new locality for the recently described Ecclisopteryx keroveci Previšić, Graf, & Vitecek. Further, we describe the new caddisfly species Drusus dardanicus sp. nov. from the Kopaonik Mountains. The new species belongs to the D. discophorus Species Group and differs morphologically from its most similar congeners (D. discophorus Radovanović, D. balcanicus Kumanski, and D. bureschi Kumanski) mainly in exhibiting (1) subtrianglar superior appendages; (2) a narrow, dorsal spinate area of tergite VIII; and (3) evenly rounded tips of intermediate appendages in caudal view. In phylogenetic analysis, D. dardanicus sp. nov. is well delineated and recovered as a sister taxon to D. osogovicus Kumanski, a species recorded from Bulgaria. The recent discovery of a new species and other rare or microendemic species presents important contributions to the knowledge on the rich freshwater biodiversity in Kosovo. These species face increasing anthropogenic pressure and threats to their conservation.
Redescription of late-instar larva of Scydmoraphes sparshalli (Denny) Coleoptera: Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ
Published: October 2015

The larva of Scydmoraphes sparshalli is redescribed. This is the first complete description of an immature Scydmoraphes with special focus on the chaetotaxic characters. The larva is unique among Cyrtoscydmini in having three pairs of stemmata, a very long sensory appendage of the antennomere II, mandibles with mesal row of microserrations interrupted by smooth portion of mandibular margin; maxillary mala with asetose apex and a row of very long, modified setae on mesal margin, and extremely elongate maxillary palpomere III and labium. A comparative study of previous descriptions resulted in recognizing a misidentification of a Scydmoraphes larva (the "Typ 2-Larve" of Schmid) as a putative Neuraphes (Pararaphes). The serial homology of chaetotaxic structures in the larva of Scydmoraphes sparshalli is discussed, and comparative notes on the larvae of Scydmoraphes, Neuraphes and Stenichnus are given, with an identification key.
A new species of Pseudophoxinus (Teleostei: Cyprinidae) from Southwestern Anatolia, Turkey
Authors: EKMEKÇİ F. GÜLER , ATALAY M. ALTUĞ , YOĞURTÇUOĞLU BARAN , TURAN DAVUT , KÜÇÜK FAHRETTİN
Published: October 2015

Pseudophoxinus mehmeti, new cyprinid species from the Alanköy basin in south-western Turkey, is distinguished from all species of Pseudophoxinus in adjacent regions by the combination of the following characters: body slender, its length 1.3–1.5 times its depth; caudal peduncle length 1.6–2.0 times its depth; mouth almost superior, with the tip of the mouth-cleft approximately level with the middle of the pupil; snout with a pointed tip, its length markedly greater than eye diameter; lateral line not complete, with 30–50 perforated scales and 48–60+2 scale rows in lateral series; 11½–13½ scale rows between lateral line and dorsal-fin origin, 3½–5½ scale rows between lateral line and anal-fin origin; dorsal-fin with 6½–7½ branched rays; anal-fin with 6½–7½ branched rays; a distinct black epidermal stripe from eye to caudal-fin base in preserved individuals.
A novel species of Euspondylus (Squamata: Gymnophthalmidae) from the Andes Mountains of central Peru
Authors: DOAN TIFFANY M. , ADAMS GRANT
Published: October 2015

The South American gymnophthalmid genus Euspondylus is distributed from Venezuela through Peru, with its highest diversity occurring in Peru. Euspondylus paxcorpus sp. nov. is a new species from Junín, Peru possessing prefrontal scales and represented by 60 specimens. The new species differs from all other species by the combination of four supraoculars with supraocular/supraciliary fusion, 5–7 occipitals, a single palpebral scale, five supralabials and infralabials, quadrangular dorsal scales with low keels arranged in transverse series only, 40–45 in a longitudinal count and 22–28 in a transverse count, 12 rows of ventrals in a transverse count and 23–25 in a longitudinal count, and no sexual dimorphism in coloration. The discovery of E. paxcorpus increases the known number of Euspondylus species to 13. Because the coloration patterns of the specimens were greatly different after preservation in alcohol, caution should be used when identifying Euspondylus species from museum specimens.
A Few GIS Clarifications on Tornado Density Mapping
Authors: Deng Yongxin , Wallace Brendan , Maassen Derek , Werner Johnathan
Published: October 2015

A geographical information system (GIS) perspective is taken to examine conceptual and methodological complications present in tornado density and probability mapping. Tornado density is defined as the inverse-distance-weighted count of tornado touchdown points or tornado-affected cells within a neighborhood area. The paper first adds a few geographic elements into the tornado definition and then characterizes tornado density as a density field in GIS that depends on predefined, modifiable areas to exist. Tornado density is therefore conceptually distinguished from both individual tornadoes and tornado probability. Three factors are identified to be vital in tornado density mapping: the neighborhood size, the distance decay function, and the choice of tornado properties. Correspondingly, 12 neighborhood sizes ranging from 20 to 360 km are tested, four distance decay functions are compared, and two tornado properties—tornado touchdown locations and pathlengths—are separately incorporated in mapping. GIS interpretations, clarifications, and demonstrations are provided for these factors to reach a thorough understanding of how the factors function and affect the resultant tornado density maps. Historical tornado data of the eastern half of the United States from 1973 to 2013 are used in these demonstrations. Uncertainty and propagation analyses are recommended for future tornado density and probability mapping, and a Monte Carlo simulation using tornado pathlength data is conducted as an example of uncertainty modeling. In all, tornado density mapping is diagnosed as a largely subjective activity, and the mapper needs to make multiple choices according to the mapping purpose, scale, and the involved tornado record data.
The M2 Internal Tide Simulated by a 1/10° OGCM
Authors: Li Zhuhua , Storch Jin-Song von , Müller Malte
Published: October 2015

Using a concurrent simulation of the ocean general circulation and tides with the ° Max Planck Institute Ocean Model (MPI-OM), known as STORMTIDE, this study provides a near-global quantification of the low-mode M2 internal tides. The quantification is based on wavelengths and their near-global distributions obtained by applying spectral analysis to STORMTIDE velocities and on comparisons of the distributions with those derived by solving the Sturm–Liouville eigenvalue problem. The simulated wavelengths, with respect to both their magnitudes and their geographical distributions, compare well with those obtained by solving the eigenvalue problem, suggesting that the STORMTIDE internal waves are, to a first approximation, linear internal waves satisfying local dispersion relations. The simulated wavelengths of modes 1 and 2 range within 100–160 and 45–80 km, respectively. Their distributions reveal, to different degrees for both modes, a zonal asymmetry and a tendency of a poleward increase with stratification N and the Coriolis parameter f being responsible for these two features, respectively. Distributions of mode 1 wavelengths are found to be determined by both N and f, but those of mode 2 are mainly controlled by variations in N. Larger differences between the STORMTIDE wavelengths and those of the eigenvalue problem occur, particularly for mode 2, primarily in high-latitude oceans and the Kuroshio and Gulf Stream and their extensions.
The cultural grammar of governance: The UK Code of Corporate Governance, reflexivity, and the limits of ‘soft’ regulation
Authors: Veldman Jeroen , Willmott Hugh
Published: October 2015

We identify limits of ‘reflexive governance’ by examining the UK Code of Corporate Governance that is celebrated for its ‘reflexivity’. By placing the historical genesis of the Code within its politico-economic context, it is shown how its scope and penetration is impeded by a shallow, ‘single loop’ of reflexivity. Legitimized by agency theory, the Code is infused by a ‘cultural grammar’ that perpetuates relations of shareholder primacy as it restricts accountability to narrow forms of information disclosure directed exclusively at shareholders. Engagement of a deeper, ‘double loop’ reflexivity allows account to be taken of the historical conditions and theoretical conceptions that shape practices and outcomes of corporate governance. Only then is it possible to disclose, challenge and reform narrow conceptions, boundaries and workings of ‘reflexive governance’.
The implementation trap: the local level and diversity policies
Authors: Schiller Maria
Published: October 2015

There is widespread agreement that the local level has become more self-confident and self-reliant in formulating its own immigrant policies and sometimes developing distinct philosophies of immigrant incorporation. However, to date we know little about the actual capacities of cities to implement these philosophies consistently. This article offers a level-specific study of the governance of immigrant incorporation by European municipalities. It focuses on cities with diversity policies and it compares the meaning of diversity in formulated policies with policy implementation. Identifying an implementation gap of diversity policies in Antwerp, Amsterdam and Leeds, it argues that cities may have become more self-reliant and self-confident in coming up with their own ideas and concepts for governing immigration, but this may not mean that they also consistently implement these ideas. This article identifies two explanations for an implementation gap and different capacities across cities to consistently implement such policies.

Points for practitioners

The article establishes two explanations for the inconsistent implementation of policies, focusing on the case of local diversity policies, and delineates how this plays out across different cities. These findings are relevant as they allow us to define the conditions for consistent policy implementation.
The rhetorical power of death and possessions in Luke’s Gospel
Authors: Rindge Matthew S.
Published: October 2015

Luke’s Gospel displays a thorough and keen interest in the interplay of death and possessions. Although much attention has been paid to the role of wealth and possessions in Luke, hardly any studies have examined these themes in light of death. This article explores the frequent interlacing of these motifs in Luke with special attention to two parables, “The Rich Fool” and “Lazarus and the Rich Man.” Luke’s interest in these twinned themes was part of a broader cross-cultural, contested conversation on the juxtaposition of death and possessions in the ancient world. Many Egyptian, Jewish, and Greco-Roman texts inquired about whether and how a person could use wealth and possessions meaningfully in light of death’s inevitability and uncertain timing. Luke’s Gospel both participates in this disputed conversation and reconfigures certain aspects of it. Luke’s attention to the interweaving of death and possessions is evident not only in his unfolding narrative, but also in specific rhetorical strategies he employs in order to transform the lives of his readers and hearers.
“I will give you a mouth and wisdom”: Prudent speech in Luke 21:15
Authors: Shiell William D.
Published: October 2015

Luke 21:15 is normally translated to the effect that Jesus will give his disciples “words and wisdom.” The ancient audience, however, when hearing this text from a lector, likely would have understood this phrase to be directed to them and to mean that Jesus would provide them with “a mouth and wisdom.” In the ancient world, the mouth functioned to organize one’s thoughts, provide a window on the character of the one speaking, and to provide a potential source of wisdom. When on trial, defendants needed to know what to say, and when to speak. Thus, this text, as heard by the ancient audience, would have served as Jesus’ promise of enabling them to speak prudently when standing trial for their faith.
Shining a light on Harriot and Galileo: On the mechanics of reflection and projectile motion
Authors: Smith Russell
Published: October 2015

Decades before Newton’s Principia ushered in the age of modern science, Aristotelian physics faced a serious challenge against its weakest point, in the quest to construct a new theory of projectile motion. Yet how were such new principles of motion conceived, without reference to an established theory of mechanics? This paper explores the conceptual space between the rejection of Aristotle’s physics and the appearance of Newton’s physics in which people such as Harriot and Galileo sought new ways to understand mechanical phenomena. This paper seeks to show that both Harriot and Galileo looked to the (early seventeenth-century) zeitgeist of accepting the law of reflection as a law of oblique projection-rebound for all material bodies, for their foundational (non-Aristotelian) conceptual resource. The kinematics and dynamics of light’s compound, oblique motion had been developed over centuries within optics, and constituted the ‘ideal’ resource for novel analyses of oblique projectile motion. Whereas Harriot’s inclusion of air resistance restricted the generalizability of optical principles to his simplest case, the upright parabola, Galileo’s idealized analysis of projectile motion in a vacuum represented all cases of projectile motion as upright parabolas. He was thus able to generalize these optical principles to projectile motion per se.
Privileging Naturals Over Strivers
Authors: Tsay Chia-Jung
Published: October 2015

A preference for “naturals” over “strivers” in performance judgments was investigated to test whether the effect is generalizable across domains, as well as to ascertain any costs imposed on decision quality by favoring naturals. Despite being presented with entrepreneurs equal in achievement, participants judged the natural and his business proposal to be superior to the striver and his proposal on multiple dimensions of performance and success (Study 1a and Study 1b). These findings were extended in Study 2, which quantified the costs of the naturalness bias using conjoint analysis to measure specific decision tradeoffs. Together, these three studies show that people tend to pass over better-qualified individuals in favor of apparent naturals.
Arabic tweets sentiment analysis – a hybrid scheme
Authors: Aldayel Haifa K. , Azmi Aqil M.
Published: October 2015

The fact that people freely express their opinions and ideas in no more than 140 characters makes Twitter one of the most prevalent social networking websites in the world. Being popular in Saudi Arabia, we believe that tweets are a good source to capture the public’s sentiment, especially since the country is in a fractious region. Going over the challenges and the difficulties that the Arabic tweets present – using Saudi Arabia as a basis – we propose our solution. A typical problem is the practice of tweeting in dialectical Arabic. Based on our observation we recommend a hybrid approach that combines semantic orientation and machine learning techniques. Through this approach, the lexical-based classifier will label the training data, a time-consuming task often prepared manually. The output of the lexical classifier will be used as training data for the SVM machine learning classifier. The experiments show that our hybrid approach improved the F-measure of the lexical classifier by 5.76% while the accuracy jumped by 16.41%, achieving an overall F-measure and accuracy of 84 and 84.01% respectively.
Should we worry about sex offenders who deny their offences?
Authors: Craissati Jackie
Published: October 2015

This paper reviews the literature on total and partial denial in sex offenders, considering the prevalence of denial, some explanations for the motives underpinning denial, and the research evidence examining the relationship between denial and the risk of sexual recidivism. The implications of the findings for treatment, and the dilemmas posed for ethical and professional practice, are discussed.
Understanding desistance from sexual offending
Authors: Farmer Mark , McAlinden Anne-Marie , Maruna Shadd
Published: October 2015

Although there is a substantial body of work on desistance from crime in general, comparatively little is known about desistance from sexual crime. The broad aim of this paper is to provide an overview of the research methodology and preliminary findings from a recent empirical study on desistance from sexual offending conducted by the authors.1 Such findings have potentially important implications for policy and practice concerning sex offender risk assessment, treatment and management.