bluuebunny/crossref_metadata_2025 huggingface dataset:
Diseases Transmitted by Man’s Best Friend: The Dog
Authors: Jacob Jerry , Lorber Bennett
Published: July 2015

The relationship between dogs and humans is ancient and mutually beneficial. Dogs have served people well as companions, workmates, guides, and protectors. However, on occasion, dogs may injure humans through biting or may transmit pathogens resulting in a large number of problems ranging from a trivial rash to life-threatening bacteremia. Given that there are more than 80 million pet dogs in the United States, it is worth knowing the potential problems that can result from canine exposure. Annually, almost 5 million people in the United States suffer a dog bite. Dog bite wounds become infected up to 15% of the time. In those who have had a splenectomy, a dog bite may transmit the bacterium
Capnocytophaga canimorsus
, leading to life-threatening bacteremia. Other illnesses that humans can acquire from dog contact include ringworm, diarrheal disease (salmonellosis, campylobacteriosis, and intestinal parasites), leptospirosis, brucellosis, Q fever, visceral larva migrans, and echinococcosis. Evidence exists that the family dog may serve as a reservoir for uropathogenic
Escherichia coli
that can lead to urinary tract infections among human household contacts. In this article we discuss dog-related infectious diseases as well as measures to minimize dog-associated illness (e.g., do not disturb sleeping dogs; HIV-infected persons who wish to acquire a puppy should have the dog’s stool checked for
Cryptosporidium
).
Perinatal consequences of a category 1 caesarean section at term
Authors: Grace Leah , Greer Ristan M , Kumar Sailesh
Published: July 2015

Objective

To characterise maternal demographics, obstetric risk factors and neonatal outcomes associated with term category 1 caesarean sections (CS).

Design and setting and main outcome measures

Retrospective study of term singleton pregnancies delivering at a major tertiary unit in Brisbane, Australia. Category 1 CS were defined as one that required a decision-to-delivery time interval of <30 min when there was an immediate threat to the life of a woman or fetus. Neonatal outcomes analysed were gestation at delivery, birth weight, Apgar scores, acidosis at birth, need for resuscitation, admission to neonatal intensive care and neonatal seizures and death.

Results

A total of 30 719 women delivering at term were included. Of these, 1179 (3.8%) women required a category 1 CS. A further 3527 women underwent non-category 1 CS. Most category 1 CS were performed for non-reassuring fetal status (65.9%, 777/1179). The indications for non-category 1 CS were for failure to progress (46.5%, 1641/3527) and non-reassuring fetal status (19%, 671/3527). Maternal age, body mass index and medical disease did not differ significantly between the two cohorts. Caucasian women were equally as likely to undergo a category 1 CS as a non-category 1 CS, while indigenous women and women of Asian ethnicity were more likely to undergo a category 1 CS. Significantly higher (p<0.001) perinatal complications were seen in the category 1 CS cohort—Apgar scores <7 at 1 min (20.4%, 241/1179 vs 10.7%, 377/3527) and 5 min (5.8%, 68/1179 vs 1.9%, 67/3527), umbilical arterial pH<7.2 (23.7%, 279/1179 vs 9.1%, 321/3527), neonatal resuscitation (59.9%, 706/1179 vs 51.8%, 1828/3527), neonatal intensive care unit admission (9.8%, 116/1179 vs 2.5%, 87/3527) and seizures (0.8%, 10/1179 vs 0.3%, 9/3527), respectively.

Conclusions

These results demonstrate significantly poorer outcomes associated with term category 1 CS compared with non-category 1 emergency CS.
Global existence of solutions for a nonlinear size-structured population model with distributed delay in the recruitment
Authors: Bai Meng , Xu Shihe
Published: July 2015

In this paper, we study a nonlinear size-structured population model with distributed delay in the recruitment. The delayed problem is reduced into an abstract initial value problem of an ordinary differential equation in a Banach space by using the semigroup techniques. The local existence and uniqueness of solution as well as the continuous dependence on initial conditions are obtained by using the general theory of quasi-linear evolution equations in Banach spaces, while the global existence of solution is obtained by the estimates of the solution and the extension theorem.
Analysis of the effect of older drivers’ driving behaviors on traffic flow based on a modified CA model
Authors: Jian Mei-Ying , Shi Jing , Liu Yang
Published: July 2015

As the global population ages, there are more and more older drivers on the road. The decline in driving performance of older drivers may influence the properties of traffic flow and safety. The purpose of this paper is to investigate the effect of older drivers’ driving behaviors on traffic flow. A modified cellular automaton (CA) model which takes driving behaviors of older drivers into account is proposed. The simulation results indicate that older drivers’ driving behaviors induce a reduction in traffic flow especially when the density is higher than 15 vehicles per km per lane and an increase in Lane-changing frequency. The analysis of stability shows that a number of disturbances could frequently emerge, be propagated and eventually dissipate in this modified model. The results also reflect that with the increase of older drivers on the road, the probability of the occurrence of rear-end collisions increases greatly and obviously. Furthermore, the value of acceleration influences the traffic flow and safety significantly. These results provide the theoretical basis and reference for the traffic management departments to develop traffic management measure in the aging society.
The sensitization of laser-induced heat of Er3+ doped Y2O3 nanocrystals by codoped with Mn2+
Authors: Bai Yunfeng , Luan Minjie , Li Linjun , He Zhelong , Li Dongyu
Published: July 2015

Low threshold power density cw laser-induced heat has been observed in [Formula: see text] and [Formula: see text] codoped [Formula: see text] nanocrystals under excitation by a 980 nm IR laser. Codoped [Formula: see text] remarkably reduces the power density threshold of laser-induced heat compared with [Formula: see text] doped [Formula: see text] nanocrystals. When the excitation power density exceed [Formula: see text], [Formula: see text] codoped [Formula: see text] nanocrystals emit strong blackbody radiation. The thermal emission of [Formula: see text] should originate from the multiphonon relaxation between neighboring energy levels. One additional UC-PL enhancement is observed. The UC-PL intensity can be enhanced by an order of magnitude through high temperature calcination caused by light into heat.
Alternative classical force of gravitation: A study of the free fall motion
Authors: Guiot E.
Published: July 2015

The purpose of this work is to clarify the mathematical form of an alternative classical force of gravitation, which has been described in a previous paper. The purpose of this investigation is to find a solution to the problem of the velocity curve of spiral galaxies, without dark matter hypothesis. In the first part, we study the free fall motion, in the case of our force, and we determine a possible mathematical expression for it. In the second part, we discuss the validity of our assumptions.
A STUDY OF HEAD–DISK INTERACTION DETECTION IN THE HARD-DISK DRIVES
Authors: SEGU DAWIT ZENEBE , KHAN POLINA V. , HWANG PYUNG
Published: July 2015

The reliability and performance of precision mechanical components that experience sliding under contact depend heavily on the friction and wear characteristics at the sliding interface. In order to improve the reliability of the sliding interface, there is a need to predict, measure and monitor any physical interactions at the head–disk interface (HDI). In the present work, the basic tribological characteristics of HDI were analyzed. The HDI during start–stop and constant speed operation using acoustic emission (AE) were studied. The Fast Fourier Transform (FFT) analysis of the AE signal was used to understand the interaction between the AE signal and the state of contact. In addition, we developed laser textured (LT) disk and the contact start–stop (CSS) tests were performed to investigate the effect of dimples on the stiction performance of the HDI. Furthermore, numerical analysis between the slider and disk surface pressure were performed using the boundary coordinate system and divergence formulation for the nonlinear Reynold's equation solution.
Another note on smooth numbers in short intervals
Authors: Matomäki Kaisa
Published: July 2015

In this paper, we prove that, for any positive constants [Formula: see text] and [Formula: see text] and every large enough [Formula: see text], the interval [Formula: see text] contains numbers whose all prime factors are smaller than [Formula: see text].
On l-class groups of global function fields
Authors: Zhao Zhengjun , Hu Wanbao
Published: July 2015

Let [Formula: see text] be a finite geometric separable extension of the rational function field [Formula: see text], and let [Formula: see text] be a finite cyclic extension of [Formula: see text] of prime degree [Formula: see text]. Assume that the ideal class number of the integral closure [Formula: see text] of [Formula: see text] in [Formula: see text] is not divisible by [Formula: see text]. Using genus theory and Conner–Hurrelbrink exact hexagon for function fields, we study in this paper the [Formula: see text]-class group of [Formula: see text] (i.e. the Sylow [Formula: see text]-subgroup of the ideal class group of [Formula: see text]) as Galois module, where [Formula: see text] is the integral closure of [Formula: see text] in [Formula: see text]. The resulting conclusion is used to discuss the relations of class numbers for the biquadratic function fields with their quadratic subfields.
Benford’s Law for coefficients of newforms
Authors: Jameson Marie , Thorner Jesse , Ye Lynnelle
Published: July 2015

Let [Formula: see text] be a newform of even weight [Formula: see text] on [Formula: see text] without complex multiplication. Let [Formula: see text] denote the set of all primes. We prove that the sequence [Formula: see text] does not satisfy Benford’s Law in any integer base [Formula: see text]. However, given a base [Formula: see text] and a string of digits [Formula: see text] in base [Formula: see text], the set [Formula: see text] has logarithmic density equal to [Formula: see text]. Thus, [Formula: see text] follows Benford’s Law with respect to logarithmic density. Both results rely on the now-proven Sato–Tate Conjecture.
Shear Banding of Complex Fluids
Authors: Divoux Thibaut , Fardin Marc A. , Manneville Sebastien , Lerouge Sandra
Published: July 2015

Even in simple geometries, many complex fluids display nontrivial flow fields, with regions where shear is concentrated. The possibility for such shear banding has been known for several decades, but in recent years, we have seen an upsurge in studies offering an ever-more precise understanding of the phenomenon. The development of new techniques to probe the flow on multiple scales with increasing spatial and temporal resolution has opened the possibility for a synthesis of the many phenomena that could only have been thought of separately before. In this review, we bring together recent research on shear banding in polymeric and soft glassy materials and highlight their similarities and disparities.
Visuomotor Functions in the Frontal Lobe
Authors: Schall Jeffrey D.
Published: July 2015

This review surveys how vision becomes action through the frontal lobe. Signals from extrastriate areas create maps in frontal areas. These maps are shaped by visual features and shaded by goals, values, and experience, and they guide contingent activation of motor circuits to execute coordinated gaze, head, and limb movements. Frontal circuits also support the visual perception of learned objects, events, and actions. Other frontal circuits monitor consequences and exert executive control to improve the effectiveness of visually guided behavior.
The role of frataxin in doxorubicin-mediated cardiac hypertrophy
Authors: Mouli Shravanthi , Nanayakkara Gayani , AlAlasmari Abdullah , Eldoumani Haitham , Fu Xiaoyu , Berlin Avery , Lohani Madhukar , Nie Ben , Arnold Robert D. , Kavazis Andreas , Smith Forrest , Beyers Ronald , Denney Thomas , Dhanasekaran Muralikrishnan , Zhong Juming , Quindry John , Amin Rajesh
Published: July 2015

Doxorubicin (DOX) is a highly effective anti-neoplastic agent; however, its cumulative dosing schedules are clinically limited by the development of cardiotoxicity. Previous studies have attributed the cause of DOX-mediated cardiotoxicity to mitochondrial iron accumulation and the ensuing reactive oxygen species (ROS) formation. The present study investigates the role of frataxin (FXN), a mitochondrial iron-sulfur biogenesis protein, and its role in development of DOX-mediated mitochondrial dysfunction. Athymic mice treated with DOX (5 mg/kg, 1 dose/wk with treatments, followed by 2-wk recovery) displayed left ventricular hypertrophy, as observed by impaired cardiac hemodynamic performance parameters. Furthermore, we also observed significant reduction in FXN expression in DOX-treated animals and H9C2 cardiomyoblast cell lines, resulting in increased mitochondrial iron accumulation and the ensuing ROS formation. This observation was paralleled in DOX-treated H9C2 cells by a significant reduction in the mitochondrial bioenergetics, as observed by the reduction of myocardial energy regulation. Surprisingly, similar results were observed in our FXN knockdown stable cell lines constructed by lentiviral technology using short hairpin RNA. To better understand the cardioprotective role of FXN against DOX, we constructed FXN overexpressing cardiomyoblasts, which displayed cardioprotection against mitochondrial iron accumulation, ROS formation, and reduction of mitochondrial bioenergetics. Lastly, our FXN overexpressing cardiomyoblasts were protected from DOX-mediated cardiac hypertrophy. Together, our findings reveal novel insights into the development of DOX-mediated cardiomyopathy.
Murine and human CFTR exhibit different sensitivities to CFTR potentiators
Authors: Cui Guiying , McCarty Nael A.
Published: July 2015

Development of therapeutic molecules with clinical efficacy as modulators of defective CFTR includes efforts to identify potentiators that can overcome or repair the gating defect in mutant CFTR channels. This has taken a great leap forward with the identification of the potentiator VX-770, now available to patients as “Kalydeco.” Other small molecules with different chemical structure also are capable of potentiating the activity of either wild-type or mutant CFTR, suggesting that there are features of the protein that may be targeted to achieve stimulation of channel activity by structurally diverse compounds. However, neither the mechanisms by which these compounds potentiate mutant CFTR nor the site(s) where these compounds bind have been identified. This knowledge gap partly reflects the lack of appropriate experimental models to provide clues toward the identification of binding sites. Here, we have compared the channel behavior and response to novel and known potentiators of human CFTR (hCFTR) and murine (mCFTR) expressed in Xenopus oocytes. Both hCFTR and mCFTR were blocked by GlyH-101 from the extracellular side, but mCFTR activity was increased with GlyH-101 applied directly to the cytoplasmic side. Similarly, glibenclamide only exhibited a blocking effect on hCFTR but both blocked and potentiated mCFTR in excised membrane patches and in intact oocytes. The clinically used CFTR potentiator VX-770 transiently increased hCFTR by ∼13% but potentiated mCFTR significantly more strongly. Our results suggest that mCFTR pharmacological sensitivities differ from hCFTR, which will provide a useful tool for identifying the binding sites and mechanism for these potentiators.
Regulation of allergic lung inflammation by endothelial cell transglutaminase 2
Authors: Soveg Frank , Abdala-Valencia Hiam , Campbell Jackson , Morales-Nebreda Luisa , Mutlu Gökhan M. , Cook-Mills Joan M.
Published: July 2015

Tissue transglutaminase 2 (TG2) is an enzyme with multiple functions, including catalysis of serotonin conjugation to proteins (serotonylation). Previous research indicates that TG2 expression is upregulated in human asthma and in the lung endothelium of ovalbumin (OVA)-challenged mice. It is not known whether endothelial cell TG2 is required for allergic inflammation. Therefore, to determine whether endothelial cell TG2 regulates allergic inflammation, mice with an endothelial cell-specific deletion of TG2 were generated, and these mice were sensitized and challenged in the airways with OVA. Deletion of TG2 in endothelial cells blocked OVA-induced serotonylation in lung endothelial cells, but not lung epithelial cells. Interestingly, deletion of endothelial TG2 reduced allergen-induced increases in respiratory system resistance, number of eosinophils in the bronchoalveolar lavage, and number of eosinophils in the lung tissue. Endothelial cell deletion of TG2 did not alter expression of adhesion molecules, cytokines, or chemokines that regulate leukocyte recruitment, consistent with other studies, demonstrating that deletion of endothelial cell signals does not alter lung cytokines and chemokines during allergic inflammation. Taken together, the data indicate that endothelial cell TG2 is required for allergic inflammation by regulating the recruitment of eosinophils into OVA-challenged lungs. In summary, TG2 functions as a critical signal for allergic lung responses. These data identify potential novel targets for intervention in allergy/asthma.
The Clinical and Pathological Significance of Nectin-2 and DDX3 Expression in Pancreatic Ductal Adenocarcinomas
Authors: Liang Shan , Yang Zhulin , Li Daiqiang , Miao Xiongying , Yang Leping , Zou Qiong , Yuan Yuan
Published: July 2015

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, but the genetic basis of PDAC is still unclear. In this study, Nectin-2 and DDX3 expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic lesions, and 13 normal pancreatic tissues were measured by immunohistochemical methods. Results showed that the percentage of positive Nectin-2 and DDX3 expression was significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P<0.01). The percentage of cases with positive Nectin-2 and DDX3 expression was significantly lower in PDAC patients without lymph node metastasis and invasion and having TNM stage I/II disease than in patients with lymph node metastasis, invasion, and TNM stage III/IV disease (P<0.05orP<0.01). Positive DDX3 expression is associated with poor differentiation of PDAC. Kaplan-Meier survival analysis showed that positive Nectin-2 and DDX3 expression were significantly associated with survival in PDAC patients (P<0.001). Cox multivariate analysis revealed that positive Nectin-2 and DDX3 expression were independent poor prognosis factors in PDAC patients. In conclusion, positive Nectin-2 and DDX3 expression are associated with the progression and poor prognosis in PDAC patients.
ALindera obtusilobaExtract Blocks Calcium-/Phosphate-Induced Transdifferentiation and Calcification of Vascular Smooth Muscle Cells and Interferes with Matrix Metalloproteinase-2 and Metalloproteinase-9 and NF-κB
Authors: Freise Christian , Kim Ki Young , Querfeld Uwe
Published: July 2015

Vascular calcifications bear the risk for cardiovascular complications and have a high prevalence among patients with chronic kidney disease. Central mediators of vascular calcifications are vascular smooth muscle cells (VSMC). They transdifferentiate into a synthetic/osteoblast-like phenotype, which is induced, for example, by elevated levels of calcium and phosphate (Ca/P) due to a disturbed mineral balance. An aqueous extract fromLindera obtusiloba(LOE) is known to exert antifibrotic and antitumor effects or to interfere with the differentiation of preadipocytes. Using murine and rat VSMC cell lines, we here investigated whether LOE also protects VSMC from Ca/P-induced calcification. Indeed, LOE effectively blocked Ca/P-induced calcification of VSMC as shown by decreased VSMC mineralization and secretion of alkaline phosphatase. In parallel, mRNA expression of the calcification markers osterix and osteocalcin was reduced. Vice versa, the Ca/P-induced loss of the VSMC differentiation markers alpha smooth muscle actin and smooth muscle protein 22-alpha was rescued by LOE. Further, LOE blocked Ca/P-induced mRNA expressions and secretions of matrix metalloproteinases-2/-9 and activation of NF-κB, which are known contributors to vascular calcification. In conclusion, LOE interferes with the Ca/P-induced transdifferentiation/calcification of VSMC. Thus, LOE should be further analysed regarding a potential complementary treatment option for cardiovascular diseases including vascular calcifications.
Experimental Assessment of a Variable Orifice Flowmeter for Respiratory Monitoring
Authors: Tardi Giuseppe , Massaroni Carlo , Saccomandi Paola , Schena Emiliano
Published: July 2015

Accurate measurement of gas exchanges is essential in mechanical ventilation and in respiratory monitoring. Among the large number of commercial flowmeters, only few kinds of sensors are used in these fields. Among them, variable orifice meters (VOMs) show some valuable characteristics, such as linearity, good dynamic response, and low cost. This paper presents the characterization of a commercial VOM intended for application in respiratory monitoring. Firstly, two nominally identical VOMs were calibrated within ±10 L·min−1, to assess their metrological properties. Furthermore, experiments were performed by humidifying the air, to evaluate the influence of vapor condensation on sensor’s performances. The condensation influence was investigated during two long lasting trials (i.e., 4 hours) by delivering 4 L·min−1and 8 L·min−1. Data show that the two VOMs’ responses are linear and their response is comparable (sensitivity difference of 1.4%, RMSE of 1.50 Pa); their discrimination threshold is <0.5 L·min−1, and the settling time is about 66 ms. The condensation within the VOM causes a negligible change in sensor sensitivity and a very slight deterioration of precision. The good static and dynamic properties and the low influence of condensation on sensor’s response make this VOM suitable for applications in respiratory function monitoring.
Galectin-Binding O-Glycosylations as Regulators of Malignancy
Authors: Dimitroff Charles J.
Published: July 2015

Cancer cells commonly display aberrant surface glycans and related glycoconjugate scaffolds. Compared with their normal counterparts, cancer cell glycans are variably produced and often structurally distinct, serving as biomarkers of cancer progression or as functional entities to malignancy. The glycan signature of a cancer cell is created by the collaborative activities of glycosyltransferases, glycosidases, nucleotide-sugar transporters, sulfotransferases, and glycan-bearing protein/lipid scaffolds. In a coordinated fashion, these factors regulate the synthesis of cancer cell glycans and thus are considered correlates of cancer cell behavior. Functionally, cancer cell glycans can serve as binding targets for endogenous lectin effectors, such as C-type selectins and S-type galectins. There has been a recent surge of important observations of the role of glycosytransferases, specifically α2,6 sialyltransferases, in regulating the length and lectin-binding features of serine/threonine (O)-glycans found on cancer cells. The capping activity of O-glycan–specific α2,6 sialyltransferases, in particular, has been found to regulate cancer growth and metastasis in a galectin-dependent manner. These findings highlight the functional importance of cancer cell O-glycans and related galectin-binding features in the virulent activity of cancer and raise the prospect of targeting cancer cell glycans as effective anticancer therapeutics. Cancer Res; 75(16); 3195–202. ©2015 AACR.
A Threshold Level of Intratumor CD8+ T-cell PD1 Expression Dictates Therapeutic Response to Anti-PD1
Authors: Ngiow Shin Foong , Young Arabella , Jacquelot Nicolas , Yamazaki Takahiro , Enot David , Zitvogel Laurence , Smyth Mark J.
Published: July 2015

Despite successes, thus far, a significant proportion of the patients treated with anti-PD1 antibodies have failed to respond. We use mouse tumor models of anti-PD1 sensitivity and resistance and flow cytometry to assess tumor-infiltrating immune cells immediately after therapy. We demonstrate that the expression levels of T-cell PD1 (PD1lo), myeloid, and T-cell PDL1 (PDL1hi) in the tumor microenvironment inversely correlate and dictate the efficacy of anti-PD1 mAb and function of intratumor CD8+ T cells. In sensitive tumors, we reveal a threshold for PD1 downregulation on tumor-infiltrating CD8+ T cells below which the release of adaptive immune resistance is achieved. In contrast, PD1hi T cells in resistant tumors fail to be rescued by anti-PD1 therapy and remain dysfunctional unless intratumor PDL1lo immune cells are targeted. Intratumor Tregs are partly responsible for the development of anti-PD1–resistant tumors and PD1hi CD8+ T cells. Our analyses provide a framework to interrogate intratumor CD8+ T-cell PD1 and immune PDL1 levels and response in human cancer. Cancer Res; 75(18); 3800–11. ©2015 AACR.
The 1,2-Diaminocyclohexane Carrier Ligand in Oxaliplatin Induces p53-Dependent Transcriptional Repression of Factors Involved in Thymidylate Biosynthesis
Authors: Kiyonari Shinichi , Iimori Makoto , Matsuoka Kazuaki , Watanabe Sugiko , Morikawa-Ichinose Tomomi , Miura Daisuke , Niimi Shinichiro , Saeki Hiroshi , Tokunaga Eriko , Oki Eiji , Morita Masaru , Kadomatsu Kenji , Maehara Yoshihiko , Kitao Hiroyuki
Published: July 2015

Platinum-based chemotherapeutic drugs are widely used as components of combination chemotherapy in the treatment of cancer. One such drug, oxaliplatin, exerts a synergistic effect against advanced colorectal cancer in combination with 5-fluorouracil (5-FU) and leucovorin. In the p53-proficient colorectal cancer cell line HCT116, oxaliplatin represses the expression of deoxyuridine triphosphatase (dUTPase), a ubiquitous pyrophosphatase that catalyzes the hydrolysis of dUTP to dUMP and inhibits dUTP-mediated cytotoxicity. However, the underlying mechanism of this activity has not been completely elucidated, and it remains unclear whether factors other than downregulation of dUTPase contribute to the synergistic effect of 5-FU and oxaliplatin. In this study, we found that oxaliplatin and dachplatin, platinum-based drugs containing the 1,2-diaminocyclohexane (DACH) carrier ligand, repressed the expression of nuclear isoform of dUTPase (DUT-N), whereas cisplatin and carboplatin did not. Oxaliplatin induced early p53 accumulation, upregulation of primary miR-34a transcript expression, and subsequent downregulation of E2F3 and E2F1. Nutlin-3a, which activates p53 nongenotoxically, had similar effects. Introduction of miR-34a mimic also repressed E2F1 and DUT-N expression, indicating that this miRNA plays a causative role. In addition to DUT-N, oxaliplatin repressed, in a p53-dependent manner, the expression of genes encoding enzymes involved in thymidylate biosynthesis. Consequently, oxaliplatin significantly decreased the level of dTTP in the dNTP pool in a p53-dependent manner. These data indicate that the DACH carrier ligand in oxaliplatin triggers signaling via the p53–miR-34a–E2F axis, leading to transcriptional regulation that ultimately results in accumulation of dUTP and reduced dTTP biosynthesis, potentially enhancing 5-FU cytotoxicity. Mol Cancer Ther; 14(10); 2332–42. ©2015 AACR.
Pancreatic Cancer Metastases Harbor Evidence of Polyclonality
Authors: Maddipati Ravikanth , Stanger Ben Z.
Published: July 2015

Studies of the cancer genome have demonstrated that tumors are composed of multiple subclones with varied genetic and phenotypic properties. However, little is known about how metastases arise and evolve from these subclones. To understand the cellular dynamics that drive metastasis, we used multicolor lineage-tracing technology in an autochthonous mouse model of pancreatic cancer. Here, we report that precursor lesions exhibit significant clonal heterogeneity but that this diversity decreases during premalignant progression. Furthermore, we present evidence that a significant fraction of metastases are polyclonally seeded by distinct tumor subclones. Finally, we show that clonality during metastatic growth—leading to either monoclonal or polyclonal expansion—differs based on the site of metastatic invasion. These results provide an unprecedented window into the cellular dynamics of tumor evolution and suggest that heterotypic interactions between tumor subpopulations contribute to metastatic progression in native tumors.

Significance: Studies of tumor heterogeneity indicate that distinct tumor subclones interact during cancer progression. Here, we demonstrate by lineage tracing that metastases often involve seeding by more than one clone and that subsequent cellular outgrowth depends on the metastatic site. These findings provide insight into clonal diversity and evolution in metastatic disease. Cancer Discov; 5(10); 1086–97. ©2015 AACR.

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Auditing Neonatal Intensive Care: Is PREM a Good Alternative to CRIB for Mortality Risk Adjustment in Premature Infants?
Authors: Guenther Kilian , Vach Werner , Kachel Walter , Bruder Ingo , Hentschel Roland
Published: July 2015

Background: Comparing outcomes at different neonatal intensive care units (NICUs) requires adjustment for intrinsic risk. The Clinical Risk Index for Babies (CRIB) is a widely used risk model, but it has been criticized for being affected by therapeutic decisions. The Prematurity Risk Evaluation Measure (PREM) is not supposed to be prone to treatment bias, but has not yet been validated. Objectives: We aimed to validate the PREM, compare its accuracy to that of the original and modified versions of the CRIB and CRIB-II, and examine the congruence of risk categorization. Methods: Very-low-birth-weight (VLBW) infants with a gestational age (GA) <33 weeks, who were admitted to NICUs in Baden-Württemberg from 2003 to 2008, were identified from the German neonatal quality assurance program. CRIB, CRIB-II and PREM scores were calculated and modified. Omitting variables that directly reflected therapeutic decisions [the applied fraction of inspired oxygen (FiO2)] or that may have been prone to early-treatment bias (base excess and temperature), non-NICU-therapy-influenced scores were obtained. Score performance was assessed by the area under their ROC curve (AUC). Results: The CRIB showed the largest AUC (0.89), which dropped significantly (to 0.85) after omitting the FiO2. The PREM birth condition model, PREM(bcm) (AUC 0.86), and the PREM birth model, PREM(bm) (AUC 0.82), also demonstrated good discrimination. PREM(bm) was superior to other non-therapy-affected scores and to GA, particularly in infants with <750 g birth weight. Congruence of risk categorization was low, especially among higher-risk cases. Conclusions: The CRIB score had the largest AUC, resulting from its inclusion of FiO2. PREM(bm), as the most accurate score among those unaffected by early treatment, seems to be a good alternative for strict risk adjustment in NICU auditing. It could be useful to combine scores.
Worsening of Respiratory Status during Neutropenia Recovery in Noncritically Ill Hematological Patients: Results of a Prospective Multicenter Study
Authors: Balsat Marie , Xhaard Alienor , Lengline Etienne , Tavernier Emmanuelle , Cornillon Jérôme , Guyotat Denis , Darmon Michael
Published: July 2015

Background: Neutropenia recovery (NR) has been associated with worsening preexisting lung injury in up to 50% of critically ill cancer patients. However, only limited relevant data exist in the general population of hematological patients. Objectives: To assess the incidence of acute respiratory deterioration during NR in patients with hematological malignancies. Methods: Adult patients with neutropenia expected to last more than 7 days were included. Worsening of respiratory status (WRS) was defined as a decrease in oxygen saturation of ≥5%, the need for oxygen therapy for ≥24 h, an increase in oxygen flow of ≥50% in patients previously treated with oxygen, or the need for mechanical ventilation. NR was defined as the 3 days preceding or following a neutrophil count of >0.5 × 109/l. Results: A total of 16 of 50 patients included in this pilot study experienced WRS during NR (32%), and 13 patients had WRS during neutropenia (26%). The incidence density of WRS was 0.53 (±0.79) episodes per 10 days during NR and 0.20 (±0.39) episodes per 10 days during neutropenia (p = 0.004). Sepsis, stem cell transplantation, preexisting pneumonia, or the use of granulocyte colony-stimulating factor were not associated with WRS during NR. Conclusion: Up to one third of noncritically ill hematological patients with expected neutropenia of more than 7 days experience WRS during NR. Clinical consequences and risk factors for WRS during NR remain to be evaluated.
In vivo Tube Assay: An Optimised Protocol of the Directed in vivo Angiogenesis Assay by Implementing Immunohistochemistry
Authors: Unseld Matthias , Breuss Johannes M. , Pausz Clemens , Pablik Eleonore , Schabbauer Gernot , Zielinski Christoph C. , Uhrin Pavel , Prager Gerald W.
Published: July 2015

Background: Angiogenesis, the formation of new blood vessels, is an essential process under physiological and pathological conditions. Method: Here, we improved the directed in vivo angiogenesis assay (DIVAA®) test, which is based on the usage of small Matrigel-filled tubes that are implanted into mice subcutaneously for a period of up to 15 days. The subsequent ex vivo assessment of neoangiogenesis within the silicon tubes is then achieved by fluorometry. Results: We showed that the immunohistochemical quantification of the ingrowth of endothelial cells, based on CD31, was superior to the fluorometric quantification advised in the manufacturer's instructions. We optimised the explantation procedure, ensuring the complete recovery of the ingrown vessels. Using this modified protocol, we investigated the effect of the length of stay of the implanted tubes as well as of the concentration of the growth factors VEGF and FGF on the assay. Conclusion: Our improved protocol offered an effective and reliable alternative to the original assay, which is expected to facilitate in vivo research on angiogenesis and, thus, might drive the development of novel therapeutic agents.
Chromosomal Mapping of Repetitive DNAs in Characidium (Teleostei, Characiformes): Genomic Organization and Diversification of ZW Sex Chromosomes
Authors: Scacchetti Priscilla C. , Utsunomia Ricardo , Pansonato-Alves José C. , Vicari Marcelo R. , Artoni Roberto F. , Oliveira Claudio , Foresti Fausto
Published: July 2015

The speciose neotropical genus Characidium has proven to be a good model for cytogenetic exploration. Representatives of this genus often have a conserved diploid chromosome number; some species exhibit a highly differentiated ZZ/ZW sex chromosome system, while others do not show any sex-related chromosome heteromorphism. In this study, chromosome painting using a W-specific probe and comparative chromosome mapping of repetitive sequences, including ribosomal clusters and 4 microsatellite motifs - (CA)15, (GA)15, (CG)15, and (TTA)10 -, were performed in 6 Characidium species, 5 of which possessed a heteromorphic ZW sex chromosome system. The W-specific probe showed hybridization signals on the W chromosome of all analyzed species, indicating homology among the W chromosomes. Remarkably, a single major rDNA-bearing chromosome pair was found in all species. The 18S rDNA localized to the sex chromosomes in C. lanei, C. timbuiense and C. pterostictum, while the major rDNA localized to one autosome pair in C. vidali and C. gomesi. In contrast, the number of 5S rDNA-bearing chromosomes varied. Notably, minor ribosomal clusters were identified in the W chromosome of C. vidali. Microsatellites were widely distributed across almost all chromosomes of the karyotypes, with a greater accumulation in the subtelomeric regions. However, clear differences in the abundance of each motif were detected in each species. In addition, the Z and W chromosomes showed the differential accumulation of distinct motifs. Our results revealed variability in the distribution of repetitive DNA sequences and their possible association with sex chromosome diversification in Characidium species.
Identifying the generic limits of the Cheilanthoid genus Doryopteris
Authors: Yesilyurt Jovita Cislinski , BARBARÁ THELMA , SCHNEIDER HARALD , RUSSELL STEPHEN , CULHAM ALASTAIR , GIBBY MARY
Published: July 2015

Morphology-based delimitation of genera in the Cheilanthoid ferns has proved to be problematic and understanding of the phylogeny and relationships amongst Cheilanthoid ferns based on morphological characters has posed even further difficulties, owing perhaps in large part to adaptation by many taxa to xeric habitats, as well as convergent evolution. It is only now with the application of DNA sequence data that relationships of species and genera are becoming clear. Here, we present results of cpDNA sequence data from species that have been traditionally placed in the genus Doryopteris and, based on both these results, and morphological and distribution data, this study helps clarify the concept of the genus Doryopteris its position within the Cheilanthoid ferns and the status of Lytoneuron. As a result, three genera are redefined: Doryopteris, Lytoneuron and Ormopteris.
Typification of the marine siphonous green algae Caulerpa prolifera (Bryopsidales, Chlorophyta)
Authors: Boisset Fernando , Ferrer Gallego Pedro Pablo
Published: July 2015

The typification of the marine siphonous green algae Caulerpa prolifera (Forsskål) J.V. Lamouroux (≡ Fucus prolifer Forsskål) (Caulerpaceae), including f. obovata (J. Agardh) Weber-van Bosse and f. zosterifolia Børgesen, is discussed. Original material conserved in the Natural History Museum of Denmark (Copenhagen) at C (Herbarium Forsskålii) and in the Botanical Museum of Lund University at LD are designated as the corresponding lectotypes.
Dynamical Response to the QBO in the Northern Winter Stratosphere: Signatures in Wave Forcing and Eddy Fluxes of Potential Vorticity
Authors: White Ian P. , Lu Hua , Mitchell Nicholas J. , Phillips Tony
Published: July 2015

Wave–mean flow interactions associated with the Holton–Tan effect (HTE), whereby the tropical quasi-biennial oscillation (QBO) modulates the Northern Hemisphere wintertime stratospheric polar vortex, are studied using the ERA-Interim dataset. Significant evidence of the HTE in isentropic coordinates is found, with a weaker and warmer polar vortex present when the lower-stratospheric QBO is in its easterly phase (QBOe). For the first time, the authors quantify the QBO modulation of wave propagation, wave–mean flow interaction, and wave decay/growth via a calculation of potential vorticity (PV)-based measures, the zonal-mean momentum budget, and up-/downgradient eddy PV fluxes. The effect of the tropospheric subtropical jet on QBO modulation of the wave activity is also investigated. In the subtropical-to-midlatitude lower stratosphere, QBOe is associated with an enhanced upward flux of wave activity, and corresponding wave convergence and wave growth, which leads to a stronger poleward zonal-mean meridional circulation and consequently a warmer polar region. In the middle stratosphere, QBOe is associated with increased poleward wave propagation, leading to enhanced wave convergence and in situ wave growth at high latitudes and contributing to the weaker polar vortex. In agreement with recent studies, the results suggest that the critical-line effect cannot fully account for these wave anomalies associated with the HTE. Instead, it is suggestive of a new, additional mechanism that hinges on the QBO-induced meridional circulation effect on the latitudinal positioning of the subtropical jet. Under QBOe, the QBO-induced meridional circulation causes a poleward shift of the subtropical jet, encouraging more waves to propagate into the stratosphere at midlatitudes.
Predictive Skill for Regional Interannual Steric Sea Level and Mechanisms for Predictability*
Authors: Polkova Iuliia , Köhl Armin , Stammer Detlef
Published: July 2015

Based on decadal hindcasts initialized every five years over the period 1960–2000, the predictive skill of annual-mean regional steric sea level and associated mechanisms are investigated. Predictive skill for steric sea level is found over large areas of the World Ocean, notably over the subtropical Atlantic and Pacific Oceans, along the path of the North Atlantic Current, and over the Indian and Southern Oceans. Mechanisms for the predictability of the thermosteric and halosteric contributions to the steric signal are studied by separating these components into signals originating from processes within and beneath the mixed layer. Contributions originating from below the mixed layer are further decomposed into density-related (isopycnal motion term) and density-compensated (spice term) changes. In regions of the subtropical Pacific and Atlantic Oceans, predictive skill results from the interannual variability associated with the contribution from isopycnal motion to thermosteric sea level. Skill related to thermosteric mixed layer processes is found to be important in the subtropical Atlantic, while the spice contribution shows skill over the subpolar North Atlantic. In the subtropics, the high predictive skill can be rationalized in terms of westward-propagating baroclinic Rossby waves for a lead time of 2–5 yr, as demonstrated using an initialized Rossby wave model. Because of the low Rossby wave speed in high latitudes, this process is not separable from the persistence there.
Calibrated Forecasts of Extreme Windstorms Using the Extreme Forecast Index (EFI) and Shift of Tails (SOT)
Authors: Boisserie Marie , Descamps Laurent , Arbogast Philippe
Published: July 2015

This study presents a method that improves extreme windstorm early warning in regards to past events that hit France during the last 30 years. From a 21-member ensemble forecast, the extreme forecast index (EFI) and the shift of tails (SOT) are used to produce calibrated forecasts for a selection of 59 windstorm cases. The EFI and SOT forecasts are evaluated for windstorms of different levels of severity and for various forecast index thresholds using the Heidke skill score (HSS), hit rate (HR), and false alarm rate (FA). The HR and FA show that a “zero misses” level always goes conjointly with a high level of false alarms. The HSS shows maxima that are associated with EFI (or SOT) thresholds that could be used as a rationale for decision-makers to issue warnings. For most extreme events, it is found that a higher level of HR can be achieved using the SOT rather than the EFI. Overall, most of the windstorms are well anticipated 3–4 days ahead. To facilitate the use of EFI or SOT forecasts, it is suggested that extra information in the form of conditional probabilities be added, hence linking the EFI (or SOT) values to a risk of occurrence of a severe event. Finally, this anticipation of extreme events is illustrated by maps of EFI and SOT for four historical windstorms.
Aging, Social Developmental, and Cultural Factors in Changing Patterns of Religious Involvement Over a 32-Year Period
Authors: Hayward R. David , Krause Neal
Published: July 2015

Religious change has been studied from the perspectives of both individual development and societal progress, but a lack of long-term longitudinal data has limited the capacity to examine them simultaneously. This study uses repeated cross-sectional data from the World Values Survey/European Values Study, covering 80 nations over the period from 1981 to 2013 to estimate age, period, and cohort effects on mean changes in the subjective importance of God and attendance at religious services. A cross-classified mixed model approach was used, examining both random effects indicating between-country differences in these changes and fixed factors unifying them in a broader framework. Older age was associated with greater personal and organizational religious involvement in a large majority of societies, but the strength of this association differed by culture, with the largest mean effects occurring in Western nations. Period effects were detected in many cultural areas but were very heterogeneous in direction and magnitude. Period changes were related to national wealth, with increase in per capita gross domestic product being related to declines in mean religious involvement. Cohort effects were in evidence in relatively few societies. These results indicate that both individual aging processes and changes in the material environment may influence changes in religious involvement, in keeping with both psychological and sociological theory, but that culture also plays a role in the nature and speed of these changes.
A Hermeneutics of Love for Community-Based, Participatory Action Research
Authors: McInerney Robert Garfield
Published: July 2015

This article presents a broad humanistic-existential framework in support of community-orientated, participatory action research. Beginning with Pink Floyd’s The Wall as a pedagogic illustration of the aporia of community, three dispositions are offered for the community researcher: communitas, allopathy, and munificence. Each disposition is shown to be supported by particular shared burdens (hospitality, alterity, finitude, and supplementarity) within existence. From this theoretical framework, a model is provided for what is designated as a hermeneutics of love as a research practice in communities.
Laparoscopic colorectal surgery: Is it beneficial in the over 80s?
Authors: Tabbakh Y , Ihedioha U , Panteleimonitis S , Gevech Z , Evans J , Kang P
Published: July 2015

Introduction

Advanced age is often associated with higher incidence of co-morbidities, advanced cancer and post-operative complications. The aim of this study was to compare the differences in pre-operative, co-morbidities, cancer stage and surgical outcome measures between patients over the age of 80 and those below 80 undergoing elective laparoscopic colorectal resection.

Method

Data were analysed from a prospectively maintained database between February 2011 and June 2012 and patients were subdivided into two groups (over 80 and under 80). All patients underwent laparoscopic colorectal surgery. Their length of stay, high dependency unit/intensive therapy unit stay, American Society of Anaesthesiologists grade, co-morbidities, conversion rates, Dukes’ stage and post-operative complication rates were compared.

Results

Of the 67 patients in the study, 57 were <80 at the time of surgery. Their American Society of Anaesthesiologists grade prior to surgery, as expected, was better than that of the >80 group, with 23% having an American Society of Anaesthesiologists grade of 3 compared to 60% in the >80%. The prognosis of the patients in the two groups based on Dukes’ stage was similar, with 63% of the <80 s having a good prognosis, compared to 80% in the >80 s. (Good prognosis = Dukes’ A or B). The conversion rates were similar (26% of the <80 s compared to 20% of the > 80 s) Post-operative length of stay was also similar in both groups (<80 s vs. >80 s: median 5 vs. 5; p = 0.33). Post-operative complication rates were similar (17% of the <80 s vs. 20% of the >80 s).

Conclusion

The short-term outcomes following laparoscopic colorectal surgery in the elderly are similar to that of younger patients. Laparoscopic surgery should therefore be offered to all patients irrespective of age.