bluuebunny/crossref_metadata_2025 huggingface dataset:
Decision analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer
Authors: Boyd Kathleen A , Jones Rob J , Paul Jim , Birrell Fiona , Briggs Andrew H , Leung Hing Y
Published: October 2015

Objective

To determine the cost-effectiveness of salvage cryotherapy (SC) in men with radiation recurrent prostate cancer (RRPC).

Design

Cost-utility analysis using decision analytic modelling by a Markov model.

Setting and methods

Compared SC and androgen deprivation therapy (ADT) in a cohort of patients with RRPC (biopsy proven local recurrence, no evidence of metastatic disease). A literature review captured published data to inform the decision model, and resource use data were from the Scottish Prostate Cryotherapy Service. The model was run in monthly cycles for RRPC men, mean age of 70 years. The model was run over the patient lifetime, to assess changes in patient health states and the associated quality of life, survival and cost impacts. Results are reported in terms of the discounted incremental costs and discounted incremental quality-adjusted life years (QALYs) gained between the 2 alternative interventions. Probabilistic sensitivity analysis used a 10 000 iteration Monte Carlo simulation.

Results

SC has a high upfront treatment cost, but delays the ongoing monthly cost of ADT. SC is the dominant strategy over the patient lifetime; it is more effective with an incremental 0.56 QALY gain (95% CI 0.28 to 0.87), and less costly with a reduced lifetime cost of £29 719 (€37 619) (95% CI −51 985 to −9243). For a ceiling ratio of £30 000, SC has a 100% probability to be cost-effective. The cost neutral point was at 3.5 years, when the upfront cost of SC (plus any subsequent cumulative cost of side effects and ADT) equates the cumulative cost in the ADT arm. Limitations of our model may arise from its insensitivity to parameter or structural uncertainty.

Conclusions

The platform for SC versus ADT cost-effective analysis can be employed to evaluate other treatment modalities or strategies in RRPC. SC is the dominant strategy, costing less over a patient's lifetime with improvements in QALYs.

Trial registration number

This economic analysis was undertaken as part of the CROP RCT study ISRCTN:72677390; it was a pre-trial economic model developed and analysed during the pre-results stage of the RCT.
Sympathetic autonomic dysfunction and impaired cardiovascular performance in higher risk surgical patients: implications for perioperative sympatholysis
Authors: Whittle John , Nelson Alexander , Otto James M , Stephens Robert C M , Martin Daniel S , Sneyd J Robert , Struthers Richard , Minto Gary , Ackland Gareth L
Published: October 2015

Objective

Recent perioperative trials have highlighted the urgent need for a better understanding of why sympatholytic drugs intended to reduce myocardial injury are paradoxically associated with harm (stroke, myocardial infarction). We hypothesised that following a standardised autonomic challenge, a subset of patients may demonstrate excessive sympathetic activation which is associated with exercise-induced ischaemia and impaired cardiac output.

Methods

Heart rate rise during unloaded pedalling (zero workload) prior to the onset of cardiopulmonary exercise testing (CPET) was measured in 2 observation cohorts of elective surgical patients. The primary outcome was exercise-evoked, ECG-defined ischaemia (>1 mm depression; lead II) associated with an exaggerated increase in heart rate (EHRR ≥12 bpm based on prognostic data for all-cause cardiac death in preceding epidemiological studies). Secondary outcomes included cardiopulmonary performance (oxygen pulse (surrogate for left ventricular stroke volume), peak oxygen consumption (VO2peak), anaerobic threshold (AT)) and perioperative heart rate.

Results

EHRR was present in 40.4–42.7% in both centres (n=232, n=586 patients). Patients with EHRR had higher heart rates perioperatively (p<0.05). Significant ST segment depression during CPET was more common in EHRR patients (relative risk 1.7 (95% CI 1.3 to 2.1); p<0.001). EHRR was associated with 11% (95%CI 7% to 15%) lower predicted oxygen pulse (p<0.0001), consistent with impaired left ventricular function.

Conclusions

EHRR is common and associated with ECG-defined ischaemia and impaired cardiac performance. Perioperative sympatholysis may further detrimentally affect cardiac output in patients with this phenotype.
Coenzyme Q10 for the treatment of heart failure: a review of the literature
Authors: DiNicolantonio James J , Bhutani Jaikrit , McCarty Mark F , O'Keefe James H
Published: October 2015

Coenzyme Q10 (CoQ10) is an endogenously synthesised and diet-supplied lipid-soluble cofactor that functions in the mitochondrial inner membrane to transfer electrons from complexes I and II to complex III. In addition, its redox activity enables CoQ10 to act as a membrane antioxidant. In patients with congestive heart failure, myocardial CoQ10 content tends to decline as the degree of heart failure worsens. A number of controlled pilot trials with supplemental CoQ10 in heart failure found improvements in functional parameters such as ejection fraction, stroke volume and cardiac output, without side effects. Subsequent meta-analyses have confirmed these findings, although the magnitude of benefit tends to be less notable in patients with severe heart failure, or within the context of ACE inhibitor therapy. The multicentre randomised placebo-controlled Q-SYMBIO trial has assessed the impact of supplemental CoQ10 on hard endpoints in heart failure. A total of 420 patients received either CoQ10 (100 mg three times daily) or placebo and were followed for 2 years. Although short-term functional endpoints were not statistically different in the two groups, CoQ10 significantly reduced the primary long-term endpoint—a major adverse cardiovascular event—which was observed in 15% of the treated participants compared to 26% of those receiving placebo (HR=0.50, CI 0.32 to 0.80, p=0.003). Particularly in light of the excellent tolerance and affordability of this natural physiological compound, supplemental CoQ10 has emerged as an attractive option in the management of heart failure, and merits evaluation in additional large studies.
The effect of captivity on the oral health of the critically endangered black-footed ferret (Mustela nigripes)
Authors: Antonelli T.S. , Leischner C.L. , Ososky J.J. , Hartstone-Rose A.
Published: October 2015

Black-footed ferrets (Mustela nigripes (Audubon and Bachman, 1851)), a North American species of mustelid, faced near extinction after westward expansion during the 20th century destroyed a majority of the population of prairie dogs (genus Cynomys Rafinesque, 1817), their primary food source. Fearing extinction of the black-footed ferret, the U.S. Fish and Wildlife Service captured the entire population between 1985 and 1987 and began a captive breeding program. While in captivity, the fertility and genetic diversity of the species was closely monitored; however, there is little information about other health consequences of this breeding program. For instance, the black-footed ferrets have been fed a diet that is very different than what they consume in the wild. How did the composition of this diet affect the oral health of these animals? An analysis of dentition of wild and captive black-footed ferrets reveals that calculus accumulation and periodontal diseases occurred with greater severity in captive black-footed ferrets, suggesting that such oral pathologies arose from the unnaturally soft diet fed to them. These findings offer insight into how mechanical properties of diet can affect oral health and how these dietary properties should be considered, not only in regard to the health of black-footed ferrets but also to the health of all mammals including humans.
Particle Dark Matter in the galactic halo
Authors: Bernabei R. , Belli P. , d’Angelo S. , Di Marco A. , Montecchia F. , d’Angelo A. , Incicchitti A. , Cappella F. , Caracciolo V. , Cerulli R. , Dai C. J. , He H. L. , Kuang H. H. , Ma X. H. , Sheng X. D. , Wang R. G. , Ye Z. P.
Published: October 2015

The DAMA/LIBRA–phase1 and the former DAMA/NaI data (cumulative exposure 1.33 ton [Formula: see text] yr, corresponding to 14 annual cycles) give evidence at 9.3[Formula: see text] C.L. for the presence of Dark Matter (DM) particles in the galactic halo, on the basis of the exploited model independent DM annual modulation signature by using highly radio-pure NaI(Tl) target. Results and comparisons will be shortly recalled. Recent analyses on possible diurnal effects and on the Earth shadowing effect (the latter holds only for some DM candidates) will be mentioned. The analysis of the time distribution of the low-energy single-hit events in DAMA/LIBRA–phase1 is reported for the first time. Finally, some perspectives of the presently running DAMA/LIBRA–phase2 will be mentioned.
Probing the nature of dark energy
Authors: Wang Yun
Published: October 2015

The cause for the observed acceleration in the expansion of the Universe is unknown, and referred to as “dark energy” for convenience. Dark energy could be an unknown energy component, or a modification of Einstein’s general relativity. This dictates the measurements that are optimal in unveiling the nature of dark energy: the cosmic expansion history, and the growth history of cosmic large scale structure. Type Ia supernovae, galaxy clustering, and weak lensing are generally considered the most powerful observational probes of dark energy. I will examine Type Ia supernovae and galaxy clustering as dark energy probes, and discuss the recent results and future prospects.
The development of ground based gravitational wave astronomy and opportunities for Australia–China collaboration
Authors: Blair David , Ju Li , Zhao Chunnong , Wen Linqing , Chu Qi , Ma Yiqiu , Page Michael , Blair Carl , Fang Qi , Miao Haixing
Published: October 2015

This paper begins by reviewing the development of gravitational wave astronomy from the first predictions of gravitational waves to development of technologies across the entire gravitational wave spectrum, and then focuses on the current status of ground based gravitational wave detectors. With substantial improvements already demonstrated in early commissioning it is emphasised that Advanced detectors are on track for first detection of gravitational waves. The importance of a worldwide array of detectors is emphasised, and recent results are shown that demonstrate the continued advantage of a southern hemisphere detector. Finally it is shown that a north–south pair of 8 km arm length detectors would give rise to a dramatic improvement in event rate, enabling a pair of detectors to encompass a 64-times larger volume of the universe, to conduct a census on all stellar mass black hole mergers to [Formula: see text] and to observe neutron star mergers to a distance of [Formula: see text][Formula: see text]800 Mpc.
Microstructure Models with Short-Term Inertia and Stochastic Volatility
Authors: Kouritzin Michael A.
Published: October 2015

Partially observed microstructure models, containing stochastic volatility, dynamic trading noise, and short-term inertia, are introduced to address the following questions: (1) Do the observed prices exhibit statistically significant inertia? (2) Is stochastic volatility (SV) still evident in the presence of dynamical trading noise? (3) If stochastic volatility and trading noise are present, which SV model matches the observed price data best? Bayes factor methods are used to answer these questions with real data and this allows us to consider volatility models with very different structures. Nonlinear filtering techniques are utilized to compute the Bayes factor on tick-by-tick data and to estimate the unknown parameters. It is shown that our price data sets all exhibit strong evidence of both inertia and Heston-type stochastic volatility.
Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus
Authors: Wong-Baeza Carlos , Tescucano Alonso , Astudillo Horacio , Reséndiz Albany , Landa Carla , España Luis , Serafín-López Jeanet , Estrada-García Iris , Estrada-Parra Sergio , Flores-Romo Leopoldo , Wong Carlos , Baeza Isabel
Published: October 2015

Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR) signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK) cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice.
Serum Cystatin C, Markers of Chronic Kidney Disease, and Retinopathy in Persons with Diabetes
Authors: Wong Chee Wai , Teo Boon Wee , Lamoureux Ecosse , Ikram Mohammad Kamran , Wang Jie Jin , Tai E. Shyong , Sethi Sunil , Wong Tien Yin , Sabanayagam Charumathi
Published: October 2015

Purpose.We examined the association of CKD defined by serum creatinine, serum cystatin C, and albuminuria with moderate diabetic retinopathy (DR).Methods.We examined 1,119 Indian adults with diabetes, aged 40–80 years, who participated in the Singapore Indian Eye Study (2007–2009), a population-based cross-sectional study. The associations of CKD defined by each of the three markers alone and in combination with moderate DR were examined using logistic regression models adjusted for potential confounding factors including duration of diabetes, smoking, body mass index, systolic blood pressure, and HbA1c.Results.The prevalence of moderate DR was significantly higher among those with CKD defined by triple markers (41.1%) compared to CKD defined separately by creatinine (26.6%), cystatin C (20.9%), and albuminuria (23.4%). People with CKD defined by triple markers had a fourteenfold higher odds of moderate DR (OR (95% CI) = 13.63 (6.08–30.54)) compared to those without CKD by any marker. Nearly half (48.7%) of participants with cystatin C ≥ 1.12 mg/L have moderate DR.Conclusions.CKD defined by a triple marker panel was strongly associated with moderate DR in this Asian population with diabetes.
Evaluation of Humoral Immunity toMycobacterium tuberculosis-Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development
Authors: Niki Mamiko , Suzukawa Maho , Akashi Shunsuke , Nagai Hideaki , Ohta Ken , Inoue Manabu , Niki Makoto , Kaneko Yukihiro , Morimoto Kozo , Kurashima Atsuyuki , Kitada Seigo , Matsumoto Sohkichi , Suzuki Koichi , Hoshino Yoshihiko
Published: October 2015

Although tuberculosis remains a major global health problem, Bacille Calmette-Guérin (BCG) is the only available vaccine. However, BCG has limited applications, and a more effective vaccine is needed. Cellular mediated immunity (CMI) is thought to be the most important immune response for protection againstMycobacterium tuberculosis(Mtb). However, the recent failure of a clinical trial for a booster BCG vaccine and increasing evidence of antibody-mediated immunity prompted us to evaluate humoral immunity to Mtb-specific antigens. Using Enzyme-Linked ImmunoSpot and Enzyme-Linked ImmunoSorbent Assays, we observed less correlation of both CMI and IgG titers with patient clinical status, including serum concentration of C reactive protein. However, IgA titers against Mtb were significantly correlated with clinical status, suggesting that specific IgA antibodies protect against Mtb proliferation. In addition, in some cases, IgA antibody titers were significantly associated with the serum concentration of total albumin, which supports the idea that humoral immunity can be influenced by the nutritional status. Based on these observations, we propose that the induction of humoral immunity should be included as an option in TB vaccine development strategies.
Acoustic Coordinated Reset Neuromodulation in a Real Life Patient Population with Chronic Tonal Tinnitus
Authors: Hauptmann Christian , Ströbel Armin , Williams Mark , Patel Nitesh , Wurzer Hannes , von Stackelberg Tatjana , Brinkmann Uwe , Langguth Berthold , Tass Peter A.
Published: October 2015

Purpose. Primary tinnitus has a severe negative influence on the quality of life of a significant portion of the general population. Acoustic coordinated reset neuromodulation is designed to induce a long-lasting reduction of tinnitus symptoms. To test acoustic coordinated reset neuromodulation as a treatment for chronic, tonal tinnitus under real life conditions, an outpatient study “RESET Real Life” was commissioned by ANM GmbH. Herein we present the results of this study.Methods. In a prospective, open-label, nonrandomized, noncontrolled multicenter clinical study with 200 chronic tinnitus patients, tinnitus questionnaire TBF-12 and Global Clinical Improvement-Impression Scale (CGI-I7) are used to study the safety and efficacy of acoustic coordinated reset neuromodulation. 189 patients completed the last 12-month visit, 11 patients dropped out (8 because of nontreatment related reasons; 2 because tinnitus did not change; and 1 because tinnitus got louder).Results. Acoustic coordinated reset neuromodulation caused a statistically and clinically significant decrease in TBF-12 scores as well as in CGI-I7 after 12 months of therapy under real life conditions. There were no persistent adverse events reported that were related to the therapy.Conclusion. The field study “RESET Real Life” provides evidence for safety and efficacy of acoustic coordinated reset neuromodulation in a prospective, open-label, real life setting.
Medications and Nutritional Supplements in Athletes during the 2000, 2004, 2008, and 2012 FIFA Futsal World Cups
Authors: Pedrinelli André , Ejnisman Leandro , Fagotti Lorenzo , Dvorak Jiri , Tscholl Philippe M.
Published: October 2015

Objective. To examine the use of medications and nutritional supplements among top-level male futsal players during international tournaments.Materials and Methods. This retrospective survey of the four consecutive 2000 to 2012 FIFA (Fédération Internationale de Football Association) Futsal World Cup tournaments analyzes data about the use of medications and nutritional supplements by each player prior to every match. A total of 5264 reports on 1064 futsal players were collected from the 188 matches played.Results. A total of 4237 medications and 8494 nutritional supplements (0.8 and 1.6 per player per match, resp.) were prescribed, and 64% of the players used at least one type of medication over the four tournaments. The most frequently prescribed medication was nonsteroidal anti-inflammatory drugs (NSAIDs) (41.1%), whereby 45.7% of all players consumed at least one NSAID during the tournament and 27.4% did so prior to every match.Conclusions. The intake of medications, particularly of NSAIDs, is frequently high among top-level futsal players and follows a similar pattern to that found in FIFA Football World Cups. Campaigns should be instituted to understand this prescription practice by team physicians involving professional football players, with the aim to decrease its use and to prevent athletes from potential short- and long-term risks.
Migrating Polyarthritis as a Feature of Occult Malignancy: 2 Case Reports and a Review of the Literature
Authors: Watson Geoffrey Alan , O’Neill Lorraine , Law Ruth , McCarthy Geraldine , Veale Douglas
Published: October 2015

Malignant disease may be associated with a wide variety of musculoskeletal syndromes. Rarely the musculoskeletal system can be indirectly affected by paraneoplastic phenomena, such as carcinomatous polyarthritis (CP). The differential diagnosis for CP is broad and is often a diagnosis of exclusion. CP often presents similarly to other forms of inflammatory arthritis, and a detailed history and physical examination can often distinguish CP from other more common causes of polyarticular arthritis. However serological tests such as rheumatoid factor (RF) and anti-citrullinated peptide (anti-CCP) antibody positivity, while rare, can be misleading. Clinical awareness and suspicion are paramount in achieving an accurate diagnosis and early detection of an occult neoplasm is critical for prompt management and therapy. We report two cases presenting with this unique clinical phenotype associated with paraneoplastic polyarthropathy and review the literature.
CCL9 Induced by TGFβ Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Organ
Authors: Yan Hangyi H. , Jiang Jian , Pang Yanli , Achyut B.R. , Lizardo Michael , Liang Xinhua , Hunter Kent , Khanna Chand , Hollander Christine , Yang Li
Published: October 2015

Tumor cell survival in the hostile distant organ is a rate-limiting step in cancer metastasis. Bone marrow–derived myeloid cells can form a premetastatic niche and provide a tumor-promoting microenvironment. However, it is unclear whether these myeloid cells in the premetastatic site have any direct effect on tumor cell survival. Here, we report that chemokine CCL9 was highly induced in Gr-1+CD11b+ immature myeloid cells and in premetastatic lung in tumor-bearing mice. Knockdown of CCL9 in myeloid cells decreased tumor cell survival and metastasis. Importantly, CCL9 overexpression in myeloid cells lacking TGFβ signaling rescued the tumor metastasis defect observed in mice with myeloid-specific Tgfbr2 deletion. The expression level of CCL23, the human orthologue for CCL9, in peripheral blood mononuclear cells correlated with progression and survival of cancer patients. Our study demonstrates that CCL9 could serve as a good candidate for anti-metastasis treatment by targeting the rate-limiting step of cancer cell survival. In addition, targeting CCL9 may avoid the adverse effects of TGFβ-targeted therapy. Cancer Res; 75(24); 5283–98. ©2015 AACR.
RETRACTED: Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells
Authors: Yoon Changhwan , Cho Soo-Jeong , Aksoy Bülent Arman , Park Do Joong , Schultz Nikolaus , Ryeom Sandra W. , Yoon Sam S.
Published: October 2015

Purpose: The Lauren diffuse type of gastric adenocarcinoma (DGA), as opposed to the intestinal type (IGA), often harbors mutations in RHOA, but little is known about the role of RhoA in DGA.

Experimental Design: We examined RhoA activity and RhoA pathway inhibition in DGA cell lines and in two mouse xenograft models. RhoA activity was also assessed in patient tumor samples.

Results: RhoA activity was higher in DGA compared with IGA cell lines and was further increased when grown as spheroids to enrich for cancer stem-like cells (CSCs) or when sorted using the gastric CSC marker CD44. RhoA shRNA or the RhoA inhibitor Rhosin decreased expression of the stem cell transcription factor, Sox2, and decreased spheroid formation by 78% to 81%. DGA spheroid cells had 3- to 5-fold greater migration and invasion than monolayer cells, and this activity was Rho-dependent. Diffuse GA spheroid cells were resistant in a cytotoxicity assay to 5-fluorouracil and cisplatin chemotherapy, and this resistance could be reversed with RhoA pathway inhibition. In two xenograft models, cisplatin inhibited tumor growth by 40% to 50%, RhoA inhibition by 32% to 60%, and the combination by 77% to 83%. In 288 patient tumors, increased RhoA activity correlated with worse overall survival in DGA patients (P = 0.017) but not in IGA patients (P = 0.612).

Conclusions: RhoA signaling promotes CSC phenotypes in DGA cells. Increased RhoA activity is correlated with worse overall survival in DGA patients, and RhoA inhibition can reverse chemotherapy resistance in DGA CSC and in tumor xenografts. Thus, the RhoA pathway is a promising new target in DGA patients. Clin Cancer Res; 22(4); 971–83. ©2015 AACR.
Transthoracic Needle Biopsies: It's More than Just Hitting the Bull's-eye
Authors: Aerts Joachim G.
Published: October 2015

Spectroscopy has shown to be of value in determining benign from malignant tissue. Incorporation of spectroscopic measurements may increase the diagnostic yield of transthoracic needle biopsies. Given the increasing amount of incidentally found lung lesions, such a technique may prevent unnecessary invasive procedures and uncertainty for the patient. Clin Cancer Res; 22(2); 273–4. ©2015 AACR.

See related article by Spliethoff et al., p. 357
Abstract B45: c-MYC is a potential therapeutic target for cisplatin-resistant ovarian cancer
Authors: Vivas-Mejia Pablo E. , Reyes jeyshka , Sood Anil K.
Published: October 2015

Ovarian cancer accounts for approximately 3% of all cancers in women. However, it is the deadliest cancer of the female reproductive system. Due to its non-specific symptoms, ovarian cancer is diagnosed at advanced stages of the disease. The most common standard treatment for advanced ovarian cancer is the platinum-based drugs such as cisplatin. However, over 70% of women relapse due to chemoresistance. Several mechanisms of cisplatin resistance have been described. However, the exact mechanism is not known. Evidence indicates that activation of the transcription factor c-MYC and its regulated genes could be involved in such resistance. Furthermore, it has been found that there is a significant association between increasing c-MYC expression and poor survival. Our previous findings showed that c-MYC messenger (mRNA) levels were similar in a panel of resistant and sensitive ovarian cancer cells. However, cispaltin resistant cells expressed higher levels of c-MYC protein when compared to their sensitive counterparts. We found that specific microRNAs (miRNAs) could be involved in the post-transcriptional regulation of c-MYC in cisplatin resistant ovarian cancer cells. Importantly, targeting of c-MYC with small interference RNA (siRNA) in the cispaltin resistant ovarian cancer cells, A2780CP20 induced a significant cell growth arrest and inhibition of cell proliferation. These data suggests c-MYC as a potential therapeutic target for overcoming cisplatin resistance in ovarian cancer. Supported by: NIH-NCI 1K22CA166226-01A1 (PEVM), and the UPR-MDACC Partnership in Cancer Research Training Program.

Citation Format: Pablo E. Vivas-Mejia, jeyshka Reyes, Anil K. Sood. c-MYC is a potential therapeutic target for cisplatin-resistant ovarian 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 B45.
Abstract PR03: Serine 62 phosphorylated MYC associates with nuclear lamins and its regulation by CIP2A is essential for proliferation induction in vivo
Authors: Myant Kevin , Qiao Xi , Halonen Tuuli , Come Christophe , Laine Anni , Partanen Johanna I. , Ogg Erinn-Lee , Laiterä Tiina , Janghorban Mahnaz , Okkeri Juha , Klefström Juha , Sears Rosalie C. , Sansom Owen J. , Westermarck Jukka
Published: October 2015

Targeting MYC function would be highly desirable for hyperproliferative diseases. As MYC itself is refractory to direct chemical inhibition, understanding of the mechanisms determining MYC's transcriptional and proliferation promoting activities in vivo would be critical for generation of alternative targeting strategies. However, despite 30 years of research, it is very poorly documented what post-translational mechanisms control MYC function in vivo. Here we demonstrate for the first time that Lamin A/C association is critical for MYC phosphorylation regulation. MYC phosphorylation at serine 62 enhances MYC recruitment to Lamin A/C-associated nuclear structures and the Protein Phosphatase 2A (PP2A) inhibitor protein CIP2A is required for retaining this phosphorylation and localization. CIP2A is also critical for serum induced MYC phosphorylation, and for MYC-elicited proliferation induction in vitro. Critically, using complementary transgenic approaches, and intestinal regeneration model, we demonstrate the in vivo importance of this mechanism for MYC´s transcriptional and proliferation promoting activities. However, targeting of this mechanism does not influence basal proliferation, or differentiation of intestinal crypt cells or mouse well-being. Together we discover unprecedented importance of nuclear organization of MYC for its phosphorylation regulation; leading to in vivo demonstration of a strategy for targeting of MYC activity without detrimental physiological effects.

Citation Format: Kevin Myant, Xi Qiao, Tuuli Halonen, Christophe Come, Anni Laine, Johanna I. Partanen, Erinn-Lee Ogg, Tiina Laiterä, Mahnaz Janghorban, Juha Okkeri, Juha Klefström, Rosalie C. Sears, Owen J. Sansom, Jukka Westermarck. Serine 62 phosphorylated MYC associates with nuclear lamins and its regulation by CIP2A is essential for proliferation induction in vivo. [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 PR03.
Isolated Superior Mesenteric Artery Dissection with Small Intestine Ischemia
Authors: Aimi Masahito , Amano Chika , Yoshida Rika , Matsubara Takeshi , Mikami Hironobu , Izumi Daisuke , Okimoto Eiko , Ishimura Norihisa , Ishihara Shunji , Kinoshita Yoshikazu
Published: October 2015

Superior mesenteric artery (SMA) dissection without aortic dissection is a rare condition, and its diagnosis is considered to be difficult. Intestinal infarction is a severe complication of the disease, which may require resection of the intestine. We present a case of isolated SMA dissection. A 53-year-old man experienced sudden pain in the abdomen while playing Japanese pinball and was admitted to our hospital due to acute abdominal symptoms of uncertain cause. Enhanced CT revealed a defect of the root of the SMA, while angiography and intravascular ultrasound findings showed dissection of the SMA wall. Conservative treatment was chosen at the time, while a part of the small intestine was eventually resected because of progressive ischemia. Although SMA dissection is a rare occurrence in cases with acute abdominal symptoms, awareness of the condition is important for differential diagnosis.
Admirandus multicavus and Adoncholaimus ussuriensis sp. n. (Nematoda: Enoplida: Oncholaimidae) from the Sea of Japan
Authors: Mordukhovich Vladimir , Atopkin Dmitry , Fadeeva Natalia , Yagodina Victoria , Zograf Julia
Published: October 2015

A description of one new, and redescription of one known, species of the subfamily Adoncholaiminae (Nematoda: Oncholaimidae) from Peter the Great Bay (Sea of Japan) are provided. Adoncholaimus ussuriensis sp. n. is characterised by relatively large body size (L = 4.3-5.8 mm in male, 4.4-6.2 mm in female), a pair of terminal pores of the Demanian system opening dorsally at 147-189 μm (2.3-3.0 abd) anterior to the anus, excretory pore located posterior to buccal cavity region, absence of a ventral swelling on tail, long spicules (190-230 μm), presence of a gubernaculum (32-40 μm), presence of a complicated sensory field in the male with a complex supplementary organ and two sets of pilose filaments (5-10 μm long) on the posterior cloacal lobe and four rows of subventral and subdorsal postcloacal sensilla. We provide a redescription of Admirandus multicavus illustrated by light and scanning electron micrographs and propose Adoncholaimus chinensis as a junior synonym of Admirandus multicavus. The diagnoses of both genera are emended. Partial sequences of the mitochondrial gene cytochrome oxidase c subunit I (COI) and D2-D3 region of the 28S rDNA for both species were obtained. A dichotomous key to Adoncholaimus species is provided.
Decentralizing for performance? A quantitative assessment of functional reforms in the German Länder
Authors: Ebinger Falk , Richter Philipp
Published: October 2015

In the last 10 years, the governments of most of the German Länder initiated administrative reforms. All of these ventures included the municipalization of substantial sets of tasks. As elsewhere, governments argue that service delivery by communes is more cost-efficient, effective and responsive. Empirical evidence to back these claims is inconsistent at best: a considerable number of case studies cast doubt on unconditionally positive appraisals. Decentralization effects seem to vary depending on the performance dimension and task considered. However, questions of generalizability arise as these findings have not yet been backed by more ‘objective’ archival data. We provide empirical evidence on decentralization effects for two different policy fields based on two studies. Thereby, the article presents alternative avenues for research on decentralization effects and matches the theoretical expectations on decentralization effects with more robust results. The analysis confirms that overly positive assertions concerning decentralization effects are only partially warranted. As previous case studies suggested, effects have to be looked at in a much more differentiated way, including starting conditions and distinguishing between the various relevant performance dimensions and policy fields.

Points for practitioners

In multi-level systems, reformers of public administration have to decide which level is most appropriate for the implementation of a certain task. In the last years, reformers have often decided to decentralize state functions in the hope of creating an effective and efficient government. Yet, in reality, the claim to deliver public tasks better and, at the same time, cheaper in decentralized units proves unfeasible. We provide empirical evidence on the performance effects of decentralization and show that it has other advantages and other disadvantages compared to state service delivery. Reformers of public administration have to ponder these pros and cons in each particular case.
Luke 9:18–27: “Daily” cross-bearing for Jesus’ sake
Authors: Dowd Sharyn
Published: October 2015

This article explores Luke 9:18–27 by first understanding its placement in the greater narrative of Luke’s gospel. In the passage, Jesus makes a statement about his identity that Peter misunderstands. Jesus explains in 9:23 by applying what is about to happen to him to his followers. The act of self-denial is akin to one’s daily execution—an idea that is found in Luke 14:15–24 as well as 9:57–62. Elements of self-denial are also found in the summary statements that describe the early church in Acts 2 and 4. Ultimately, to deny oneself meant to the ancient audience what it means in the modern context: one’s identity is determined solely by the fact that one is a follower of Jesus. The article concludes by providing examples of what this may look like for a twenty-first century Christ-follower.
Encountering snakes in early Victorian London: The first reptile house at the Zoological Gardens
Authors: Hall James R.
Published: October 2015

This paper examines the first reptile house (1849) at the Zoological Gardens in London as a novel site for the production and consumption of knowledge about snakes, stressing the significance of architectural and material limitations on both snakes and humans. Snakes were familiar and ambiguous, present at every level of British society through the reading of Scripture and as recurrent characters in imperial print culture. For all that snakes engendered feelings of disgust as the most distinctive representatives of a lowly class of animals, they exerted an equivalent fascination over diverse publics spanning the social spectrum. Building on work showing a consideration for the multi-sensory nature of visits to menageries, this paper considers animal display beyond the visual. It explores the emotional economy of encountering snakes in person and the bodily phenomena this engendered. Vicarious visits were offered up to readers of periodicals and newspapers and the reptile house was harnessed as a controversial pedagogical resource for teaching moral, as well as scientific, lessons.
Multi-objective optimization of a mixture inventory system using a MOPSO–TOPSIS hybrid approach
Authors: Srivastav Achin , Agrawal Sunil
Published: October 2015

This paper studies a multi-objective mixture inventory problem for a pharmaceutical distributor. The work starts with a discussion of a mixture inventory model and three objectives, namely the minimization of: 1) ordering and holding costs, 2) number of units that stockout and 3) frequency of stockout occasions. Multi-objective particle swarm optimization (MOPSO) is used to determine the non-dominated solutions and generate Pareto curves for the inventory system. Two variants of MOPSO are proposed, based on the selection of inertia weight. The performance of the proposed MOPSO algorithms is evaluated in comparison with two robust algorithms like non-dominated sorting genetic algorithm II (NSGA-II) and multi-objective cuckoo search (MOCS). The metrics that are used for the performance measurement of the algorithms are error ratio, spacing and maximum spread. Furthermore, the technique of order preference by similarity to ideal solution (TOPSIS) is used to rank the non-dominated solutions and determine the best compromise solution among them. A factorial analysis develops the linear regression expressions of optimal cost, service level measures, lot size and safety stock factor for practitioners. Lastly, the results of the regression equations are compared using a MOPSO–TOPSIS approach and the validity of the developed equations are checked.
Malnutrition in Mumbai Slums
Authors: Choudhary Neetu
Published: October 2015

Despite strong constitutional safeguards and promises, malnutrition persists in major Indian conurbations such as Mumbai and manifests as a group phenomenon concentrated in certain slum pockets that remain institutionally isolated. Based on a detailed study of four slums in Mumbai, this article uses the entitlement approach developed by Amartya Sen to examine how group identity affects group differentials in achievement of basic capabilities. Irrespective of similar initial endowments, some groups were found able to achieve upward mobility over time, whereas others remained constantly vulnerable. This may be because the access to various resources and the ability to translate them into functioning assets are mediated in various ways, depending on people’s multiple identities, which sometimes constitute barriers. The article concludes that to alleviate malnutrition, proactive state agency and public transfers are needed to enhance deprived groups’ prospects to build on their basic capabilities to improve their lives.
Oil prices and interstate conflict
Authors: Hendrix Cullen S.
Published: October 2015

Anecdotal evidence suggests that high oil prices embolden oil-rich states to behave more aggressively. This article contends that arguments linking oil-exporter status to interstate conflict are implicitly price contingent, and tests this via a reanalysis of works by Colgan and Weeks. It finds a contingent effect of oil prices on interstate disputes, with high oil prices associated with significant increases in dispute behavior in petrostates, for which oil exports constitute more than 10% of GDP, while having a null effect in non-petrostates. Directed-dyadic tests indicate that this is due to petrostates initiating disputes, rather than becoming more attractive targets for conquest or coercion.
Reference interval for rectal temperature in healthy confined adult cats
Authors: Levy Julie K , Nutt Kelly R , Tucker Sylvia J
Published: October 2015

Objectives:

Despite the common use of rectal temperature for assessing health and identifying infectious diseases in cats, there is little evidence to support frequently cited feline reference intervals for rectal temperature. Body temperature measurements are most commonly performed indoors in animal shelters and veterinary clinics. In these facilities, cats are often inactive and housed in small enclosures in a climate-controlled environment. The purpose of this study was to establish a new reference interval for rectal temperature in healthy confined adult cats.

Methods:

Rectal temperatures were measured in 200 healthy adult indoor cats in animal shelters, veterinary clinics and private homes. The reference interval was established using the method of the Clinical and Laboratory Standards Institute.

Results:

The reference interval for healthy adult cat rectal temperature was determined to range from 36.7°C (confidence interval [CI] = 36.6–36.8°C; 98.1°F [CI = 97.9–98.3°F]) at the lower limit to 38.9°C (CI = 38.8–39.1°C; 102.1°F [CI = 101.9–102.3°F]) at the upper limit. The ambient temperature ranged from 20.3–30.8°C (68.5–87.5°F). Rectal temperature was not significantly correlated with ambient temperature.

Conclusions and relevance:

A range of 36.7–38.9°C (98.1–102.1°F) should be considered the new reference interval for healthy adult cats for rectal temperature measured indoors in climate-controlled conditions. This range is lower than commonly reported. Use of previously published ranges could lead to overdiagnosis of hypothermia or underdiagnosis of mild pyrexia.
Student Characteristics and Collegiate Environments that Contribute to the Overall Satisfaction With Academic Advising Among College Students
Authors: DeLaRosby Hal R.
Published: October 2015

Academic advising satisfaction is highly correlated with retention in higher education. Thriving Quotient survey responses were collected from undergraduate students at a private, liberal arts college in the Pacific Northwest. Using a multiple regression analysis, this study examined what student characteristics and collegiate environments affect student satisfaction with academic advising. The results indicate that campus residency, amount of time spent in student–faculty interaction, and the quality of student–faculty interaction are statistically significant factors in academic advising satisfaction.
Minireview: Familiar Faces in Unfamiliar Places: The Emerging Role of Nuclear Receptors in Lung Cancer
Authors: Yenerall Paul , Kittler Ralf
Published: October 2015

Nuclear hormone receptors (NRs) are a superfamily of 48 transcription factors that are frequently modulated by ligands and control various cancer-relevant cellular pathways, such as differentiation, proliferation, migration, and metabolism. These properties make them excellent therapeutic targets in cancers dependent upon their activity, and as such, 3 NRs, estrogen receptor-α, androgen receptor, and retinoic acid receptor-α (more specifically, the promyelocytic leukemia-retinoic acid receptor-α translocation), have been targeted clinically in breast cancer, prostate cancer, and acute promyelocytic leukemia, respectively. Recently, a number of studies have highlighted a putative role for NRs in nonsmall cell lung cancer (NSCLC), a highly lethal type of lung cancer with relatively few targeted agents. Here, we review the potential roles of selected NRs in NSCLC and offer insights on how NRs may be leveraged in NSCLC to improve patient outcomes.
Instability of periodic traveling waves for the symmetric regularized long wave equation
Authors: Pava Jaime Angulo , Brango Carlos Alberto Banquet
Published: October 2015

We prove the linear and nonlinear instability of periodic traveling wave solutions for a generalized version of the symmetric regularized long wave (SRLW) equation. Using analytic and asymptotic perturbation theory, we establish sufficient conditions for the existence of exponentially growing solutions to the linearized problem and so the linear instability of periodic profiles is obtained. An application of this approach is made to obtain the linear/nonlinear instability of cnoidal wave solutions for the modified SRLW (mSRLW) equation. We also prove the stability of dnoidal wave solutions associated to the equation just mentioned.
Human stem cells from single blastomeres reveal pathways of Embryonic or trophoblast fate specification
Authors: Zdravkovic Tamara , Nazor Kristopher L. , Larocque Nicholas , Gormley Matthew , Donne Matthew , Hunkapillar Nathan , Giritharan Gnanaratnam , Bernstein Harold S. , Wei Grace , Hebrok Matthias , Zeng Xianmin , Genbacev Olga , Mattis Aras , McMaster Michael T. , Krtolica Ana , Valbuena Diana , Simón Carlos , Laurent Louise C. , Loring Jeanne F. , Fisher Susan J.
Published: October 2015

Mechanisms of initial cell fate decisions differ among species. To gain insights into lineage allocation in humans, we derived ten human embryonic stem cell lines from single blastomeres of four 8-cell embryos and one 12-cell embryo from a single couple (UCSFB1-10). Versus numerous conventional lines from blastocysts, they had unique gene expression and DNA methylation patterns, in part, indicative of trophoblast competence. At a transcriptional level, UCSFB lines from different embryos were often more closely related than those from the same embryo. As predicted by the transcriptomic data, immunolocalization of EOMES, BRACHYURY, GDF15 and active β-catenin revealed differential expression among blastomeres of 8-10-cell human embryos. The UCSFB lines formed derivatives of the three germ layers and CDX2-positive progeny, from which we derived the first human trophoblast stem cell line. Our data suggest heterogeneity among early-stage blastomeres and that the UCSFB lines have unique properties, indicative of a more immature state than conventional lines.
P114RhoGEF governs cell motility and lumen formation during tubulogenesis via ROCK-myosin II pathway
Authors: Kim Minji , Shewan Annette , Ewald Andrew J. , Werb Zena , Mostov Keith E.
Published: October 2015

Tubulogenesis is fundamental to the development of many epithelial organs. Although lumen formation in cysts has received considerable attention, less is known about lumenogenesis in tubes. Here we utilized hepatocyte growth factor induced tubulogenesis in MDCK cells, which form tubes enclosing a single lumen. We report the mechanism that controls tubular lumenogenesis and limits each tube to a single lumen. Knockdown of 114RhoGEF, a guanine nucleotide exchange factor for RhoA, did not perturb the early stages of tubulogenesis induced by hepatocyte growth factor. However, this knockdown impaired later stages of tubulogenesis, resulting in multiple lumens in a tube. Inhibition of Rho Kinase or myosin IIA, which are downstream of RhoA, led to formation of multiple lumens. We studied lumen formation by live cell imaging, which revealed that inhibition of this pathway blocked cell movement, suggesting that cell movement is necessary for consolidating multiple lumens into a single lumen. Lumen formation in tubules is mechanistically quite different from lumenogenesis in cysts. Thus, we demonstrate a novel pathway that regulates directed cell migration and single lumen formation in epithelial tube morphogenesis.