bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel point mutations and mutational complexes in the enhancer II, core promoter and precore regions of hepatitis B virus genotype D1 associated with hepatocellular carcinoma in Saudi Arabia
Authors: Khan Anis , Al Balwi Mohammed A. , Tanaka Yasuhito , Hajeer Ali , Sanai Faisal M. , Al Abdulkarim Ibrahim , Al Ayyar Latifah , Badri Motasim , Saudi Dib , Tamimi Waleed , Mizokami Masashi , Al Knawy Bandar
Published: June 2013

In this study, a cohort of 182 patients [55 hepatocellular carcinoma (HCC) and 127 non‐HCC] infected with hepatitis B virus (HBV) in Saudi Arabia was investigated to study the relationship between sequence variation in the enhancer II (EnhII), basal core promoter (BCP) and precore regions of HBV genotype D (HBV/D) and the risk of HCC. HBV genotypes were determined by sequencing analysis and/or enzyme‐linked immunosorbent assay. Variations in the EnhII, BCP and precore regions were compared between 107 non‐HCC and 45 HCC patients infected with HBV/D, followed by age‐matched analysis of 40 cases versus equal number of controls. Age and male gender were significantly associated with HCC (p = 0.0001 and p = 0.03, respectively). Serological markers such as aspartate aminotransferase, albumin and anti‐HBe were significantly associated with HCC (p = 0.0001 for all), whereas HBeAg positivity was associated with non‐HCC (p = 0.0001). The most prevalent HBV genotype was HBV/D (94%), followed by HBV/E (4%), HBV/A (1.6%) and HBV/C (0.5%). For HBV/D1, genomic mutations associated with HCC were T1673/G1679, G1727, C1741, C1761, A1757/T1764/G1766, T1773, T1773/G1775 and C1909. Age‐ and gender‐adjusted stepwise logistic regression analysis indicated that mutations G1727 [odds ratio (OR) = 18.3; 95% confidence interval (CI) = 2.8–118.4; p = 0.002], A1757/T1764/G1766 (OR = 4.7; 95% CI = 1.3–17.2; p = 0.01) and T1773 (OR = 14.06; 95% CI = 2.3–84.8; p = 0.004) are independent predictors of HCC development. These results implicate novel individual and combination patterns of mutations in the X/precore region of HBV/D1 as predictors of HCC. Risk stratification based on these mutation complexes would be useful in determining high‐risk patients and improving diagnostic and treatment strategies for HBV/D1.
Tumor‐infiltrating CD14‐positive myeloid cells and CD8‐positive T‐cells prolong survival in patients with cervical carcinoma
Authors: de Vos van Steenwijk P.J. , Ramwadhdoebe T.H. , Goedemans R. , Doorduijn E.M. , van Ham J.J. , Gorter A. , van Hall T. , Kuijjer M.L. , van Poelgeest M.I.E. , van der Burg S.H. , Jordanova E.S.
Published: June 2013

One of the hallmarks of cancer is the influx of myeloid cells. In our study, we investigated the constitution of tumor‐infiltrating myeloid cells and their relationship to other tumor‐infiltrating immune cells, tumor characteristics and the disease‐specific survival of patients with cervical cancer (CxCa). Triple‐color immunofluorescence confocal microscopy was used to locate, identify and quantify macrophages (CD14), their maturation status (CD33) and their polarization (CD163) in a cohort of 86 patients with cervical carcinoma. Quantification of the numbers of myeloid cells revealed that a strong intraepithelial infiltration of CD14+ cells, and more specifically the population of CD14+CD33−CD163− matured M1 macrophages, is associated with a large influx of intraepithelial T lymphocytes (p = 0.008), improved disease‐specific survival (p = 0.007) and forms an independent prognostic factor for survival (p = 0.033). The intraepithelial CD8+ T‐cell and regulatory T‐cell (Treg) ratio also forms an independent prognostic factor (p = 0.010) and combination of these two factors reveals a further increased benefit in survival for patients whose tumor displays a dense infiltration with intraepithelial matured M1 macrophages and a high CD8 T‐cell/Treg ratio, indicating that both populations of immune cells simultaneously improve survival. Subsequently, we made a heatmap including all known immune parameters for these patients, whereby we were able to identify different immune signatures in CxCa. These results indicate that reinforcement and activation of the intratumoral M1 macrophages may form an attractive immunotherapeutic option in CxCa.
Light‐Activated Metal Complexes that Covalently Modify DNA
Authors: Glazer Edith C.
Published: June 2013

Many drugs in current clinical use rely on mechanisms of action that involve damage to nucleic acids. While this has been a successful therapeutic approach for many years, the major limitation of these agents is systemic cytotoxicity, resulting from damage caused to healthy cells. Photoactive metal complexes offer the possibility of combining two successful treatment modalities for cancer and other diseases by providing DNA damage similar to that obtained with cisplatin, but in a spatially and temporally controlled manner, as with phototherapy. Recent progress in the field has provided metal complexes that can be triggered to create covalent adducts with nucleic acids both in vitro and in cells. Furthermore, several of these agents have been shown to induce cytotoxicity in cancer cell lines, in vitro tumor models, and in vivo animal models. In the last year, new compounds have been reported that can be activated with low energy light within the “therapeutic window,” where light penetration through tissue is sufficient to access larger volume tumors. This review highlights the advances that demonstrate the potential of light‐activated metal complexes as therapeutics and research tools for biomedical applications.
N‐hexane inhalation during pregnancy alters DNA promoter methylation in the ovarian granulosa cells of rat offspring
Authors: Li Hong , Liu Jin , Sun Yan , Wang Wenxiang , Weng Shaozheng , Xiao Shihua , Huang Huiling , Zhang Wenchang
Published: June 2013

The N‐hexane‐induced impact on the reproductive system of the offspring of animals exposed to n‐hexane has caused great concern. Pregnant Wistar rats inhaled 500, 2 500 or 12 500 ppm n‐hexane during gestational days 1–20. Clinical characteristics and developmental indices were observed. Ovarian granulosa cells were extracted from F1 rats, the number of follicles was determined in ovarian slices and promoter methylation was assessed using MeDIP‐Chip. Several methods were used to analyze the scanned genes, including the Gene Ontology Consortium tools, the DAVID Functional Annotation Clustering Tool, hierarchical clustering and KEGG pathway analysis. The results indicated that the live pups/litter ratio was significantly lowest in the 12 500 ppm group. A significant decrease in secondary follicles and an increase in atresic follicles were observed in the 12 500 ppm group. The number of shared demethylated genes was higher than that of the methylated genes, and the differentially methylated genes were enriched in cell death and apoptosis, cell growth and hormone regulation. The methylation profiles of the offspring from the 500 ppm and control groups were different from those of the 2500 and 12 500 ppm groups. Furthermore, the methylation status of genes in the PI3K‐Akt and NF‐kappa B signaling pathways was changed after n‐hexane exposure. The Cyp11a1, Cyp17a1, Hsd3b1, Cyp1a1 and Srd5a1 promoters were hypermethylated in the n‐hexane‐exposed groups. These results indicate that the developmental toxicity of n‐hexane in F1 ovaries is accompanied by the altered methylation of promoters of genes associated with apoptotic processes and steroid hormone biosynthesis. Copyright © 2013 John Wiley & Sons, Ltd.
Cbl‐family proteins as regulators of cytoskeleton‐dependent phenomena
Authors: Lee Hojin , Tsygankov Alexander Y.
Published: June 2013

Although the role of Cbl‐family proteins as key cellular regulators has been established, phenomena regulated in a Cbl‐dependent fashion are multiple and the mechanisms mediating the effects of Cbl proteins are diverse. This finding makes it important to consider different phenomena affected by functions of Cbl proteins individually. Among effects of Cbl on various biological functions there are many cases of regulation of cellular phenomena related to cytoskeletal rearrangements, such as cell adhesion, motility and invasion. Some of these regulatory functions are mediated by adaptor‐type interactions of Cbl, especially by Cbl‐dependent modulation of phosphatidyl‐inositol‐3′ kinase (PI3K), while others are caused by Cbl‐dependent ubiquitylation of various cytoskeletal and regulatory proteins, identified and unidentified. The role of Cbl in regulation of cytoskeleton‐dependent cellular functions is discussed in this review. J. Cell. Physiol. 228: 2285–2293, 2013. © 2013 Wiley Periodicals, Inc.
Iron Chelation in the Treatment of Cancer: A New Role for Deferasirox?
Authors: Bedford Matthew R. , Ford Samuel J. , Horniblow Richard D. , Iqbal Tariq H. , Tselepis Chris
Published: June 2013

Iron plays a crucial role in a number of metabolic pathways including oxygen transport, DNA synthesis, and ATP generation. Although insufficient systemic iron can result in physical impairment, excess iron has also been implicated in a number of diseases including ischemic heart disease, diabetes, and cancer. Iron chelators are agents which bind iron and facilitate its excretion. Experimental iron chelators have demonstrated potent anti‐neoplastic properties in a number of cancers in vitro. These agents have yet to be translated into clinical practice, however, largely due to the significant side effects encountered in pre‐clinical models. A number of licenced chelators, however, are currently in clinical use for the treatment of iron overload associated with certain non‐neoplastic diseases. Deferasirox is one such agent and the drug has shown significant anti‐tumor effects in a number of in vitro and in vivo studies. Deferasirox is orally administered and has demonstrated a good side effect profile in clinical practice to date. It represents an attractive agent to take forward into clinical trials of iron chelators as anti‐cancer agents.
Unusual parotid gland lesions: A pictorial review
Authors: Cho C.M. , Tong S.L. , Bhatia K.S. , Wong K.T. , Yuen H.Y. , Lee Y.P. , Ahuja A.T.
Published: June 2013

This is a pictorial essay of unusual parotid gland lesions that may be encountered in routine clinical practice. © 2013 Wiley Periodicals, Inc. J Clin Ultrasound, 41:501–508, 2013;
Modeling cosmic ray proton induced terrestrial neutron flux: A look‐up table
Authors: Overholt Andrew C. , Melott Adrian L. , Atri Dimitra
Published: June 2013

Neutrons contribute a significant radiation dose at commercial passenger airplane altitudes. With cosmic ray energies > 1 GeV, these effects could, in principle, be propagated to ground level. Under current conditions, the cosmic ray spectrum incident on the Earth is dominated by particles with energies < 1 GeV. Astrophysical shocks from events such as supernovae accelerate high‐energy cosmic rays (HECRs) well above this range. The Earth is likely episodically exposed to a greatly increased HECR flux from such events. Solar events of smaller energies are much more common and short lived but still remain a topic of interest due to the ground level enhancements they produce. The air showers produced by cosmic rays (CRs) ionize the atmosphere and produce harmful secondary particles such as muons and neutrons. Although the secondary spectra from current day terrestrial cosmic ray flux are well known, this is not true for spectra produced by many astrophysical events. This work shows the results of Monte Carlo simulations quantifying the neutron flux due to CRs at various primary energies and altitudes. We provide here look‐up tables that can be used to determine neutron fluxes from proton primaries with kinetic energies of 1 MeV–1 PeV. By convolution, one can compute the neutron flux for any arbitrary CR spectrum. This contrasts with all other similar works, which are spectrum dependent. Our results demonstrate the difficulty in deducing the nature of primaries from the spectrum of ground level neutron enhancements.
Impact of aerosols on tropical cyclones: An investigation using convection‐permitting model simulation
Authors: Hazra Anupam , Mukhopadhyay P. , Taraphdar S. , Chen J.‐P. , Cotton William R.
Published: June 2013

The role of aerosols' effect on two tropical cyclones over the Bay of Bengal is investigated using a convection‐permitting model with a two‐moment mixed‐phase bulk cloud microphysics scheme. The simulation results show the role of aerosol on the microphysical and dynamical properties of the cloud and bring out the change in efficiency of the clouds in producing precipitation. The tracks of the tropical cyclones (TCs) are hardly affected by the changing aerosol concentrations, but the intensity exhibits significant sensitivity due to the change in aerosol concentration. It is also clearly seen from the analyses that higher heating in the middle troposphere within the cyclone center is in response to latent heat release as a consequence of greater graupel formation. Greater heating in the middle level is particularly noticeable for the clean aerosol regime which causes enhanced divergence in the upper level, which, in turn, forces lower level convergence. As a result, the cleaner aerosol perturbation is more unstable within the cyclone core and produces a more intense cyclone as compared to the other two aerosol perturbations. This study, along with previous simulations, shows the robustness of the concept of TC weakening by storm ingestion of high concentrations of cloud condensation nuclei (CCN). The consistency of these model results gives us confidence in stating that there is a high probability that ingestion of high CCN concentrations in a TC will lead to weakening of the storm but has little impact on storm direction. Moreover, as pollution is increasing over the Indian subcontinent, this study suggests that pollution may be weakening TCs over the Bay of Bengal.
Near‐surface air temperature lapse rates in the mainland China during 1962–2011
Authors: Li Xiuping , Wang Lei , Chen Deliang , Yang Kun , Xue Baolin , Sun Litao
Published: June 2013

Land surface hydrological modeling is sensitive to near‐surface air temperature, which is especially true for the cryosphere. The lapse rate of near‐surface air temperature is a critical parameter when interpolating air temperature from station data to gridded cells. To obtain spatially distributed, fine‐resolution near‐surface (2 m) air temperature in the mainland China, monthly air temperature from 553 Chinese national meteorological stations (with continuous data from 1962 to 2011) are divided into 24 regional groups to analyze spatiotemporal variations of lapse rate in relation to surface air temperature and relative humidity. The results are as follows: (1) Evaluation of estimated lapse rate shows that the estimates are reasonable and useful for temperature‐related analyses and modeling studies. (2) Lapse rates generally have a banded spatial distribution from southeast to northwest, with relatively large values on the Tibetan Plateau and in northeast China. The greatest spatial variability is in winter with a range of 0.3°C–0.9°C · 100 m−1, accompanied by an inversion phenomenon in the northern Xinjiang Province. In addition, the lapse rates show a clear seasonal cycle. (3) The lapse rates maintain a consistently positive correlation with temperature in all seasons, and these correlations are more prevalent in the north and east. The lapse rates exhibit a negative relationship with relative humidity in all seasons, especially in the east. (4) Substantial regional differences in temporal lapse rate trends over the study period are identified. Increasing lapse rates are more pronounced in northern China, and decreasing trends are found in southwest China, which are more notable in winter. An overall increase of air temperature and regional variation of relative humidity together influenced the change of lapse rate.
A new high‐resolution central and western Saharan summertime dust source map from automated satellite dust plume tracking
Authors: Ashpole Ian , Washington Richard
Published: June 2013

In this paper, we outline a new objective dust source detection method for the central and western Sahara (CWS), based on the automated tracking of individual dust plumes in data from the Spinning Enhanced Visible and Infrared Imager, available every 15 mins. at ~0.03° spatial resolution. The method is used to map the origin of summertime dust storms in the CWS for June – August 2004 – 2010. It reveals the sources of these events in unprecedented detail, allowing for the identification of specific, highly active source areas. The study of collocated surface features reveals that many of the dominant sources are likely associated with paleolakes and outwash plains, many in close proximity to the Saharan mountains. Extensive nonsource areas are associated with low albedo and elevated terrain, pointing to the mountainous regions of the Sahara. Additionally, sand seas are not identified as important source areas, but their margins sometimes are. The automated tracking method also facilitates analysis of the transport direction of dust plumes from key source regions and the inference of emission mechanisms. It is found that there are two broad domains within the CWS: one in southwest Algeria and northwest Mali, characterized primarily by transport toward the southwest and very likely dominated by low‐level jets embedded in the northeasterly Harmattan winds; and a second in southern Algeria, northwest Niger, and northeast Mali where there is no preferred transport direction and a strong potential association between dust events and deep convection, pointing toward cold pool outflows as the likely deflation mechanism.
Laboratory measurements of charge separation in low liquid water content conditions and low impact velocity
Authors: Ávila Eldo E. , Lighezzolo Rafael A. , Castellano Nesvit E. , Pereyra Rodolfo G. , Bürgesser Rodrigo E.
Published: June 2013

A laboratory investigation of the electric charge separated in collisions between vapor‐grown ice crystals and a target growing by riming is presented in this work, with the goal of studying the performance of the noninductive mechanism under microphysical conditions similar to some of those which occur in the stratiform regions of the mesoscale convective systems. A series of experiments were conducted by using a target of 2 mm in diameter, for ambient temperatures between −7°C and −13°C, effective liquid water content between 0.05 and 0.5 g m−3, and air speeds between 1 and 3 m s−1. Charge diagrams of the sign of the electric charge transfer on the rimer as a function of the ambient temperature and the effective liquid water content for each velocity are presented. The results show that the riming target charges positive for temperatures above −10°C. For temperatures below −10°C, the charging is positive for high liquid water content and negative for low liquid water content. The magnitude of the charge transfer per collision under the studied conditions ranges from 0.01 to 0.2 fC. The implications of these results to the electrification processes are discussed.
The Common Language of Leadership
Authors: Seemiller Corey , Murray Thomas
Published: June 2013

As our complex society continues to call for leadership across all career fields, preparing leaders at the college level can be challenging. This article outlines the results of a comprehensive examination of learning outcomes of 475 academic programs within 72 academic accrediting organizations in regard to student leadership development. The purpose of the current study was twofold: (a) to understand better what competencies college students need to develop in order to engage in leadership in their respective career fields and (b) to use research findings to develop a list of leadership competencies across academic disciplines, serving as a “common language” for use in program planning, course development, as well as individual student advising and mentoring. The Student Leadership Competencies have been translated to contemporary leadership models such as the Relational Leadership Model, the Social Change Model of Leadership Development, the Five Practices of Exemplary Leadership, Emotionally Intelligent Leadership, and the CAS Standards. Implications for the use of the Student Leadership Competencies in program development, program assessment, and the development of strategic partnerships are also discussed.
A prospective pilot study to evaluate combined topical photodynamic therapy and surgery for extramammary paget's disease
Authors: Wang Hong‐wei , Lv Ting , Zhang Ling‐lin , Lai Yong‐xian , Tang Li , Tang Yi‐chen , Huang Zheng , Wang Xiu‐li
Published: June 2013

Background and objective

Extramammary Paget's disease (EMPD) is a rare intra‐epithelial neoplasm. Surgical excision is the treatment of choice. The usefulness of topical photodynamic therapy (PDT) in the treatment of EMPD has been reported. The objective of this prospective pilot study was to investigate the feasibility of combined PDT and surgery in the treatment of EMPD.

Subjects and Methods

A total of 13 patients with 19 large EMPD lesions were recruited and assigned to surgery (n = 5) or PDT + surgery (n = 8) group. For the PDT + surgery group, four sessions of topical PDT mediated with 20% 5‐aminolevulinic acid (ALA‐PDT) were applied prior to surgery. Patients were followed up for 12 months. Treatment outcomes, adverse reactions and recurrence were compared.

Results

In the surgery group, recurrence was seen in 2 out of 8 lesions (25%). In the combination group, over 58% reduction in lesion size was achieved after 4‐sessions of PDT and recurrence was seen in 1 out of 11 lesions (9.1%) after surgery.

Conclusions

Multiple ALA‐PDT could be applied to reduce the severity of EMPD lesion and improve the success of surgery. Lasers Surg. Med. 45:296–301, 2013. © 2013 Wiley Periodicals, Inc.
Microphase Separation in the Bulk inABATriblock Copolymer‐based Model Conetworks: Effects of Core Crowding and Loop Formation
Authors: Karbarz Marcin , Stojek Zbigniew , Patrickios Costas S.
Published: June 2013

The microphase separation in the bulk, in the strong segregation limit, of model conetworks based on end‐linked ABA triblock copolymers was investigated by calculating and minimizing the total Gibbs free energy for the various possible morphologies. The results of this study comprise a phase diagram with the prevailing morphologies mapped against junction functionality and conetwork composition, and the various geometrical parameters of the system at equilibrium, including the domain sizes and the aspect ratios. In the free‐energy calculations for the assembly of the anisotropic morphologies, cylinders and lamellae, two important characteristics of the system were taken into consideration: core crowding at high core functionality, and topological loop formation upon self‐assembly. The former leads to an increase in the elastic energy of the core‐forming chains, whereas the latter results in a reduction in the stretching energy of the chains. The results of this study suggest that spheres are favored by a high core functionality (100–200) and a low volume fraction (≤0.15) of the A end‐block, whereas lamellae are promoted by an intermediate core functionality (20–100) and a relatively high A‐block volume fraction (≥0.30).
Analysis of video‐polysomnographic sleep findings in dementia with Lewy bodies
Authors: Terzaghi Michele , Arnaldi Dario , Rizzetti Maria Cristina , Minafra Brigida , Cremascoli Riccardo , Rustioni Valter , Zangaglia Roberta , Pasotti Chiara , Sinforiani Elena , Pacchetti Claudio , Manni Raffaele
Published: June 2013

Knowledge of sleep architecture and disorders of nocturnal sleep in dementia with Lewy bodies (DLB) is limited by a lack of systematic video‐polysomnographic (video‐PSG) investigations. We describe video‐PSG findings in 29 consecutive subjects diagnosed with DLB. All the patients underwent a clinical interview and overnight video‐PSG monitoring. Twenty‐nine nondemented patients with Parkinson's disease (PD) matched for age and sex with the DLB cases were selected for comparison. The DLB subjects showed less 1NREM sleep (P = .000) and more 2NREM sleep (P = .000) than the PD subjects. Sleep apnea (30.7% vs. 34.8%) and periodic limb movements (60.9% versus 50.0%) were frequent in both groups. Disruptive motor behavioral manifestations were more frequent in subjects with DLB (69.6% vs. 26.9%, P = .008) and consisted of not only REM sleep behavior disorder (RBD) but also confusional events (30.3% vs. 3.8%, P = .020) and arousal‐related episodes mimicking RBD. Subjects with DLB in whom a sleep disturbance had been the presenting symptom performed better than those with other onset symptoms on both the Mini–Mental State Examination (22.2 ± 4.1 vs. 18.1 ± 4.6, P = .019) and the Frontal Assessment Battery (15.8 vs. 10.3, P = .010). Polysomnographic findings in DLB show a complex mix of overlapping sleep alterations: impaired sleep structure, sleep comorbidities, and various motor‐behavioral events (not restricted to RBD). Clinicians should be aware of the possibility of misleading symptoms and of the risk of overlooking sleep comorbidities, and consider performing polysomnographic sleep investigations in selected cases. We found evidence that a sleep disturbance as the presenting symptom might indicate a different phenotype of the disease, characterized by milder cognitive impairment. © 2013 International Parkinson and Movement Disorder Society
Coexistence of peripheral myelin protein 22 and dystrophin mutations in a chinese boy
Authors: Wang Zhanjun , Cui Fang , Chen Dajun , Pu Chuanqiang , Chen Zhaohui , Yang Fei , Wu Honghu , Huang Xusheng
Published: June 2013

Introduction: We describe a 10‐year‐old Chinese boy with features of Charcot–Marie–Tooth disease (CMT) and Duchenne muscular dystrophy (DMD). Methods: Case report. Results: Weakness and mild sensory loss in the distal extremities, pes cavus, and nerve conduction findings suggested demyelinating neuropathy, while moderate calf pseudohypertrophy, proximal muscle weakness, a myopathic pattern on electromyography, and deficiency of dystrophin immunohistochemical staining on muscle biopsy indicated DMD. Genetic testing revealed a large deletion spanning exon 50 in the gene coding for dystrophin and duplications in the gene coding for peripheral myelin protein 22. Conclusions: This is an interesting and very rare case of CMT type 1A comorbid with DMD. This results in an unusual phenotype and rapid deterioration of motor function. Usage of both target region capture and next generation sequencing is a powerful tool for predicting precisely the range of the large DNA fragment deletion in DMD. Muscle Nerve 48: 979–983, 2013
Effect of amitriptyline in treatment interstitial cystitis or bladder pain syndrome according to two criteria: Does ESSIC criteria change the response rate?
Authors: Sun Yaofei , Fang Zujun , Ding Qiang , Zheng Jie
Published: June 2013

Aims

The European Society for the Study of Interstitial Cystitis (ESSIC) recommended that interstitial cystitis (IC) should be replaced by bladder pain syndrome (BPS), which focused more attention on the painful or discomfort feeling related to bladder and weakened the importance of cystoscopy in diagnosis process. Our study aimed to explore whether this alteration changed the treatment outcomes of amitriptyline and whether cystoscopy was meaningful for the treatment of this disease.

Methods

We conducted a retrospective study including 25 IC patients fulfilled the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) criteria and 42 BPS patients diagnosed according to ESSIC criteria. All the patients received amitriptyline with a self‐uptitration protocol. We compared the response rates of two groups by a patient reported global response assessment after 3 months and reclassified all the 67 patients according to ESSIC criteria, the response rates of different BPS types were also assessed.

Results

There was no significant difference of response rate between IC patients (12/25, 48%) and BPS patients (19/42, 45.2%) according to different criteria (P = 0.337). The response rate of BPS type 1 (13/30, 43.3%) was similar to that of type 2 or 3 (18/37, 48.6%) (P = 0.664).

Conclusions

ESSIC criteria did not decrease the response rate of amitriptyline treatment for BPS patients compared to IC patients with complaint of bladder pain or discomfort. Cystoscopy showed no predictive effect for the treatment outcome of amitriptyline. Neurourol. Urodynam. 33:341–344, 2014. © 2013 Wiley Periodicals, Inc.
Nonoblivious 2‐Opt heuristics for the traveling salesman problem
Authors: Levin Asaf , Yovel Uri
Published: June 2013

The k‐opt heuristics are among the most common techniques for approaching the traveling salesman problem (TSP). They are used either directly or as subroutines in more sophisticated heuristics, such as the celebrated Lin–Kernighan heuristic. The value of k is typically 2 or 3. In this article, we modify the 2‐opt heuristic to be based on a function f of the distances rather than the distances solely. This may be viewed as modifying the local search with the 2‐change neighborhood to be nonoblivious. We denote the corresponding heuristic by (2, f)‐opt. We provide theoretical performance guarantees for it: both lower and upper bounds based on the ones given by Chandra et al. [SIAM J Comput 28 (1999), 1998–2029], obtained originally for the standard 2‐opt heuristic. By a tighter analysis of the neighborhood size, we improve their upper bound for the standard 2‐opt by a factor of , and we show that these bounds hold for (2, f)‐opt for any nonnegative, increasing function f. We then provide experimental evidence based on TSPLIB benchmark problems, showing that (2, f)‐opt with for various values of significantly outperforms 2‐opt. These values of r also depend on the method chosen for constructing the initial tours. Specifically, when the initial tours are random permutations, the improvement over 2‐opt is more than 35% for ; when they are generated by the Nearest Neighbor heuristic, it is about 10% for r = 0.5, 0.55, 0.6. We also see that the average length of the tour generated by (2, f)‐opt is relatively close to the optimum or the known bound. © 2013 Wiley Periodicals, Inc. NETWORKS, Vol. 62(3), 201–219 2013
To share or not to share: the role of content and emotion in viral marketing
Authors: Botha Elsamari , Reyneke Mignon
Published: June 2013

One of the most recent influential trends in the global environment has been the rise of social media. Stakeholders have found a strong voice in social media, and messages are spread among social media users at an astounding speed across a global landscape. As a result of this phenomenon and in an effort to use this viral spread of messages across social media, companies are increasingly making use of viral marketing. Viral messages are playing an increasingly important role in influencing and shifting public opinion on corporate reputations, brands, and products as well as political parties and public personalities to name but a few.

Very little is known about the motivations, attitudes, and behavior of the people who forward viral messages to their online networks. Through in‐depth interviews with college‐going Generation Y consumers, we explore this relationship between viral media and emotions. We look at two very specific components of online videos that have gone viral: first, the relevance of the video's content and, second, participants' emotional reaction to these videos to try and better explain the viral spread of online video messages. The paper concludes by proposing a decision tree that interusers might subconsciously experience when deciding whether to share a video with their friends or not. The article concludes with a discussion about future research avenues in the area of emotions and viral marketing. Copyright © 2013 John Wiley & Sons, Ltd.
Is there a need for a universal benefit–risk assessment framework for medicines? Regulatory and industry perspectives
Authors: Leong James , McAuslane Neil , Walker Stuart , Salek Sam
Published: June 2013

Purpose

To explore the current status and need for a universal benefit–risk framework for medicines in regulatory agencies and pharmaceutical companies.

Methods

A questionnaire was developed and sent to 14 mature regulatory agencies and 24 major companies. The data were analysed using descriptive statistics, for a minority of questions preceded by manual grouping of the responses.

Results

Overall response rate was 82%, and study participants included key decision makers from agencies and companies. None used a fully quantitative system, most companies preferring a qualitative method. The major reasons for this group not using semi‐quantitative or quantitative systems were lack of a universal and scientifically validated framework. The main advantages of a benefit–risk framework were that it provided a systematic standardised approach to decision‐making and that it acted as a tool to enhance quality of communication. It was also reported that a framework should be of value to both agencies and companies throughout the life cycle of a product. They believed that it is possible to develop an overarching benefit–risk framework that should involve relevant stakeholders in the development, validation and application of a universal framework. The entire cohort indicated common barriers to implementing a framework were resource limitations, a lack of knowledge and a scientifically validated and acceptable framework.

Conclusions

Stakeholders prefer a semi‐quantitative, overarching framework that incorporates a toolbox of different methodologies. A coordinating committee of relevant stakeholders should be formed to guide its development and implementation. Through engaging the stakeholders, these outcomes confirm sentiments and need for developing a universal benefit–risk assessment framework. Copyright © 2013 John Wiley & Sons, Ltd.
Antidepressant Use During Early Pregnancy and the Risk of Congenital Anomalies
Authors: Vasilakis‐Scaramozza Catherine , Aschengrau Ann , Cabral Howard , Jick Susan S.
Published: June 2013

Study Objective

To estimate and compare the prevalence of congenital anomalies among the offspring of women exposed and not exposed to antidepressants during early pregnancy.

Design

Matched cohort study.

Data Source

United Kingdom's General Practice Research Database.

Subjects

Women exposed to tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants during the first trimester of pregnancy (3276 women) and a sample of women matched in a 2:1 ratio who had no exposure to any antidepressant during the first trimester of pregnancy (6617 women).

Measurements and Main Results

The prevalence of any congenital anomaly was 31.0 (95% confidence interval [CI] 27.0–35.5) per 1000 pregnancies among women not exposed to antidepressants and 27.2 (95% CI 22.1–33.4) per 1000 pregnancies among women exposed to antidepressants. The relative risk of having a child with an anomaly in mothers who were exposed to tricyclics and SSRIs during the first trimester compared with mothers not exposed to these drugs was 0.9 (95% CI 0.7–1.1). The relative risks for any anomaly among women exposed to antidepressants were 0.9 (95% CI 0.6–1.2) for tricylics and 0.9 (95% CI 0.7–1.2) for SSRIs. We found no statistically significant, stable increases in the risk of specific anomaly subtypes among women exposed to these antidepressants; however, the number of exposed cases was small.

Conclusion

Exposure to tricyclics and SSRIs during the first trimester of pregnancy was not associated with a statistically significant increased risk of congenital anomalies in the offspring of mothers exposed to these drugs.
Association Between Statin Adherence and Cholesterol Level Reduction from Baseline in a Veteran Population
Authors: Kazerooni Rashid , Watanabe Jonathan H. , Bounthavong Mark
Published: June 2013

Study Objective

To investigate the association between statin adherence and changes in lipid panel outcomes from baseline in a veteran population.

Design

Retrospective cohort study using multiple linear regression models.

Setting

Veterans Affairs health care system within the Veterans Integrated Service Network 22, a network of Veterans Affairs facilities in the southwest region of the United States that includes Los Angeles, San Diego, Loma Linda, and Long Beach, California, and Las Vegas, Nevada, with an enrollment of approximately 1.4 million veterans.

Patients

A total of 5365 patients who were new statin users between December 1, 2006, and November 30, 2007; 2674 patients were in the adherent group and 2691 were in the nonadherent group.

Measurements and Main Results

Adherence was determined by the medication possession ratio. Patients were categorized as adherent if the medication possession ratio at follow‐up was 0.80 or more. Adherent patients exhibited significant differences in baseline demographic and clinical characteristics than nonadherent patients in our study sample. Baseline laboratory values for adherent patients were significantly lower for low‐density lipoprotein cholesterol (LDL), high‐density lipoprotein cholesterol (HDL), non–high‐density lipoprotein cholesterol (non‐HDL), and total cholesterol levels. The primary outcome was change in LDL level from baseline at 12 months. Secondary outcomes were changes in non‐HDL and total cholesterol levels from baseline at 12 months. Independent variables controlled for in the multiple linear regression included age, sex, body mass index, race‐ethnicity, baseline lipid panel (LDL, HDL, total cholesterol, and triglycerides), statin copayment status, income quintile (according to ZIP code median household income), baseline medication count, statin prescribed, and comorbidities. Multiple linear regression revealed that adherent patients demonstrated significantly greater reductions in LDL of 20.98 mg/dl versus nonadherent patients (p<0.0001). Adherent patients similarly demonstrated larger reductions of 24.31 mg/dl in non‐HDL and 24.06 mg/dl in total cholesterol versus nonadherent patients (p<0.0001 for both comparisons).

Conclusion

Patients adherent to statin therapy had significant associations with clinically relevant reductions in LDL, non‐HDL, and total cholesterol from baseline at 12 months compared with nonadherent patients when controlling for potential confounders. Adherence to statin therapy may have important consequences in decreasing clinical outcomes such as myocardial infarctions, strokes, and mortality due to large reductions in lipid panel outcomes from baseline at 12 months.
Correlation of Pharmacokinetic/Pharmacodynamic–Derived Predictions of Antibiotic Efficacy with Clinical Outcomes in Severely Ill Patients with Pseudomonas aeruginosa Pneumonia
Authors: Fish Douglas N. , Kiser Tyree H.
Published: June 2013

Study Objective

To use pharmacokinetic/pharmacodynamic (PK/PD) modeling to correlate predicted antibiotic efficacy with actual clinical outcomes in patients with serious infections.

Design

Retrospective cohort analysis.

Setting

University medical center.

Patients

A total of 182 adult intensive care patients with Pseudomonas aeruginosa pneumonia during a 5‐year period from 2000 to 2004.

Measurements and Main Results

The primary study end point was correlation of predicted antibiotic efficacy as determined by PK/PD modeling with actual clinical outcomes in individual patients. PK/PD analyses were conducted by determination of PD indexes using calculated patient‐specific PK parameters and known pathogen minimum inhibitory concentrations, and by determination of predicted PD target attainment by using Monte Carlo simulation. Patients achieving PD targets were predicted to have clinically responded to therapy; patients not achieving PD targets were predicted to have failed therapy. A total of 128 patients (70%) apparently achieved desired PD targets; however, PK/PD modeling correctly predicted actual clinical outcome in only 47% of patients (86 of 182) with sensitivity of 49% and specificity of 43%. Percentages of patients apparently achieving PD targets were similar among those experiencing clinical response or clinical failure (67% vs 74%, respectively; p=0.344). Predicted achievement of PD targets was significantly associated only with reduction in intensive care unit and hospital lengths of stay. Achievement of PD targets was not significantly associated with clinical response by univariate or multivariate analysis, but factors related to severity of illness were significantly associated with clinical response.

Conclusion

PK/PD modeling did not accurately predict clinical or microbiologic success in patients with P. aeruginosa pneumonia. This study highlights the difficulties in applying PK/PD modeling at the level of the individual patient due to extreme PK variability and issues such as severity of illness. Antibiotic dosing based on sound PK/PD principles is strongly advocated, but additional studies are needed to confirm the role of PK/PD modeling in optimizing outcomes of patients with serious bacterial infections.
Synthesis of highly sulfonated polybenzimidazoles by direct copolymerization and grafting
Authors: Kulkarni Mahesh P. , Peckham Timothy J. , Thomas Owen D. , Holdcroft Steven
Published: June 2013

A series of highly sulfonated, ether‐containing polybenzimidazoles (SOPBI) with controlled sulfonation degrees were synthesized from various stoichiometric ratio mixtures of sodium 6,6'‐oxybis(3‐carboxybenzenesulfonate) (SODBA), 4,4'‐oxydibenzoic acid (ODBA), and 3,3'‐diaminobenzidine (DAB) by solution copolycondensation in poly(phosphoric acid). The resulting sulfonated polymers were further sulfonated by grafting of pendant sulfonic acid chains via a reaction of 1,3‐propane sultone with lithiated‐N of the imidazole rings in the polymer backbone, yielding materials with high, absolute IEC values (3.42–4.15 meq g−1). Due to self‐neutralization, the solid state polymers possessed “free” acid content of 1.40 to 2.15 meq g−1, were soluble in organic solvents yet insoluble in aqueous solution, while displaying proton conductivites (11–47 mS cm−1) at elevated temperatures (80 °C, 95% RH). © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3654–3666
The role of tyrosine sulfation in the dimerization of the CXCR4:SDF‐1 complex
Authors: Rapp Chaya , Snow Sara , Laufer Talya , McClendon Christopher L.
Published: June 2013

Oligomerization of G protein‐coupled receptors is a recognized mode of regulation of receptor activities, with alternate oligomeric states resulting in different signaling functions. The CXCR4 chemokine receptor is a G protein‐coupled receptor that is post‐translationally modified by tyrosine sulfation at three sites on its N‐terminus (Y7, Y12, Y21), leading to enhanced affinity for its ligand, stromal cell derived factor (SDF‐1, also called CXCL12). The complex has been implicated in cancer metastasis and is a therapeutic target in cancer treatment. Using molecular dynamics simulation of NMR‐derived structures of the CXCR4 N‐terminus in complex with SDF‐1, and calculations of electrostatic binding energies for these complexes, we address the role of tyrosine sulfation in this complex. Our results show that sulfation stabilizes the dimeric state of the CXCR4:SDF‐1 complex through hydrogen bonding across the dimer interface, conformational changes in residues at the dimer interface, and an enhancement in electrostatic binding energies associated with dimerization. These findings suggest a mechanism through which post‐translational modifications such as tyrosine sulfation might regulate downstream function through modulation of the oligomeric state of the modified system.
Surface Tamm states in a photonic crystal slab with asymmetric termination
Authors: Li Galina V. , Astrova Ekaterina V. , Dyakov Sergey A. , Baldycheva Anna , Perova Tatiana S. , Tikhodeev Sergey G. , Gippius Nikolay A.
Published: June 2013

The reflection and transmission spectra of a finite thickness 2D photonic crystal slab (PCS) based on macroporous silicon are investigated. Periodic photonic crystal region is separated from air by homogeneous silicon interfacial layers. These interfacial layers at the silicon/air boundary being defects of the photonic crystal lattice, define the properties of surface Tamm states in the photonic stop‐bands (PSBs). It is demonstrated experimentally and theoretically that the reflection spectra of a structure with different thicknesses of the interfacial layers on both sides of the PCS depend on the illuminated side. At the same time, the transmission spectra are identical for both light directions in agreement with the reciprocity principle. Analysis shows that the dependence of the reflection spectrum on the side of light entrance is due to scattering losses in the real structure. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fitting and interpreting continuous‐time latent Markov models for panel data
Authors: Lange Jane M. , Minin Vladimir N.
Published: June 2013

Multistate models characterize disease processes within an individual. Clinical studies often observe the disease status of individuals at discrete time points, making exact times of transitions between disease states unknown. Such panel data pose considerable modeling challenges. Assuming the disease process progresses accordingly, a standard continuous‐time Markov chain (CTMC) yields tractable likelihoods, but the assumption of exponential sojourn time distributions is typically unrealistic. More flexible semi‐Markov models permit generic sojourn distributions yet yield intractable likelihoods for panel data in the presence of reversible transitions. One attractive alternative is to assume that the disease process is characterized by an underlying latent CTMC, with multiple latent states mapping to each disease state. These models retain analytic tractability due to the CTMC framework but allow for flexible, duration‐dependent disease state sojourn distributions. We have developed a robust and efficient expectation–maximization algorithm in this context. Our complete data state space consists of the observed data and the underlying latent trajectory, yielding computationally efficient expectation and maximization steps. Our algorithm outperforms alternative methods measured in terms of time to convergence and robustness. We also examine the frequentist performance of latent CTMC point and interval estimates of disease process functionals based on simulated data. The performance of estimates depends on time, functional, and data‐generating scenario. Finally, we illustrate the interpretive power of latent CTMC models for describing disease processes on a dataset of lung transplant patients. We hope our work will encourage wider use of these models in the biomedical setting. Copyright © 2013 John Wiley & Sons, Ltd.
The Wave Motion of the Rolling Force during Variable Gauge Rolling
Authors: Yu Hai‐Liang , Tieu Kiet , Lu Cheng , Zhu Hongtao , Liu Xiang‐Hua
Published: June 2013

The variable gauge rolling process is a new technology designed to produce flat products of different thicknesses such as longitudinal profile (LP) plates and tailor rolled blanks (TRB), which are used in bridge building, shipbuilding, and automobile manufacturing, etc., to decrease the weight and the welding times, etc. In this paper, a series of numerical studies on the wave motion of rolling force in variable gauge rolling (in three stages: down rolling, flat rolling, and upper rolling) were carried out using the finite element method to obtain the deformation of the work piece at different stages of rolling. The rolling force and its wave motion during rolling were analyzed under a variety of reduction ratios, including the coefficient of friction, initial thickness of the plates, and diameters of the rolls. The rolling force obviously increases as the reduction in the down rolling process increases, and then decreases during upper rolling. The rolling force consists of two abrupt wave motions in the transitional zones during the down to flat rolling stage, and the flat to upper rolling stage. These results are significant with regards to precisely controlling the deformation of workpiece in the transition zone during variable gauge rolling.