bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost analysis of pharmaceutical care provided to HIV-infected patients: an ambispective controlled study
Authors: Carnevale Renata Cavalcanti , de Godoi Rezende Costa Molino Caroline , Visacri Marília Berlofa , Mazzola Priscila Gava , Moriel Patricia
Published: February 2015

Background

Studies have shown that pharmaceutical care can result in favorable clinical outcomes in human immunodeficiency virus (HIV)-infected patients, however, few studies have assessed the economic impact. The objective of this study was to evaluate the clinical and economic impact of pharmaceutical care of HIV-infected patients.

Methods

A controlled ambispective study was conducted in Brazil from January 2009 to June 2012. Patients were allocated to either intervention or control group. The control group was followed according to standard care while the intervention group was also followed by a pharmacist at each physician appointment for one year. Effectiveness outcomes included CD4+ count, viral load, absence of co-infections and optimal immune response, and economic outcomes included expenses of physician and pharmaceutical appointments, laboratory tests, procedures, and hospitalizations, at six months and one year.

Results

Intervention and control groups included 51 patients each. We observed significant decreases in total pharmacotherapy problems during the study. At six months, the intervention group contained higher percentages of patients without co-infections and of patients with CD4+ >500 cells/mm3. None of the differences between intervention and control group considering clinical outcomes and costs were statistically significant. However, at one year, the intervention group showed higher percentage of better clinical outcomes and generated lower spending (not to procedures). An additional health care system daily investment of US$1.45, 1.09, 2.13, 4.35, 1.09, and 0.87 would be required for each additional outcome of viral load <50 copies/ml, absence of co-infection, CD4+ >200, 350, and 500 cells/mm3, and optimal immune response, respectively.

Conclusion

This work demonstrated that pharmaceutical care of HIV-infected patients, for a one-year period, was able to decrease the number of pharmacotherapy problems. However, the clinical outcomes and the costs did not have statistical difference but showed higher percentage of better clinical outcomes and lower costs for some items.
Optimization of upstream and downstream process parameters for cellulase-poor-thermo-solvent-stable xylanase production and extraction by Aspergillus tubingensis FDHN1
Authors: Adhyaru Dharmesh N , Bhatt Nikhil S , Modi Hasmukh A
Published: February 2015

Background

Xylanases are important members of the hemicellulolytic enzyme system. Xylanase plays a vital role in the hydrolysis of major hemicellulosic component xylan and converts it into xylooligosaccharides and ultimately yields xylose. Cellulase-lacking or cellulase-poor xylanase with high temperature and pH stability has gained special attention, especially in paper and pulp industries. Most of the available literature highlighted the fungal xylanase production by optimizing environmental and cultural parameters. However, the importance of enzyme recovery from fermented biomass still needs attention. In this study, upstream and downstream process parameters were studied for enhancing xylanase production and extraction by a newly isolatedAspergillus tubingensisFDHN1 under solid-state fermentation using low-cost agro-residues.

Results

In the present study,A. tubingensisFDHN1 was used for the xylanase, with very low level of cellulase, production under solid-state fermentation (SSF). Among various agro-residues, sorghum straw enhanced the xylanase production. Under optimized upstream conditions, the highest xylanase production 2,449 ± 23 U/g was observed. Upon characterization, crude xylanase showed stability over a broad range of pH 3.0 to 8.0 up to 24 h. The temperature stability revealed the nature of the xylanase to be thermostable. Native polyacrylamide gel electrophoresis (native PAGE) and zymogram analysis revealed the multiple forms of the xylanase. Due to the many industrially important characteristics of the xylanases, the study was elaborated for optimizing the downstream process parameters such as volume of extractant, extraction time, temperature and agitation speed to recover maximum xylanase from fermented sorghum straw. The highest amount of xylanase (4,105 ± 22 U/g) was recovered using 0.05 M sodium citrate buffer (pH 6.5) at 12:1 (v/w) extractant/solid ratio, 90-min extraction time, 150-rpm agitation speed and 40°C. Finally, detailed bioprocess optimization shows an overall 6.66-fold enhancement in the xylanase yield.

Conclusions

The present study consolidates the importance of upstream and downstream process optimization for the overall enhancement in the xylanase production. The xylanase fromA. tubingensisFDHN1 shows the stability at different pH and temperature, and it was also active in the presence of organic solvents. These properties of xylanase are very much important from an industrial application point of view.
Feasibility of time-lapse gravity and gravity gradiometry monitoring for steam-assisted gravity drainage reservoirs
Authors: Reitz Anya , Krahenbuhl Richard , Li Yaoguo
Published: February 2015

There is presently an increased need to monitor production efficiency as heavy oil reservoirs become more economically viable. We present a feasibility study of monitoring steam-assisted gravity drainage (SAGD) reservoirs using time-lapse gravimetry and gravity gradiometry. Even though time-lapse seismic has historically shown great success for SAGD monitoring, the gravimetry and gravity gradiometry methods offer a low-cost interseismic alternative that can complement the seismic method, increase the survey frequency, and decrease the cost of monitoring. In addition, both gravity-based methods are directly sensitive to the density changes that occur as a result of the replacement of heavy oil by steam. Advances in technologies have made both methods viable candidates for consideration in time-lapse reservoir monitoring, and we have numerically evaluated their potential application in monitoring SAGD production. The results indicate that SAGD production should produce a strong anomaly for both methods at typical SAGD reservoir depths. However, the level of detail for steam-chamber geometries and separations that can be recovered from the gravimetry and gravity gradiometry data is site dependent. Gravity gradiometry shows improved monitoring ability, such as better recovery of nonuniform steam movement due to reservoir heterogeneity, at shallower production reservoirs. Gravimetry has the ability to detect SAGD steam-chamber growth to greater depths than does gravity gradiometry, although with decreasing resolution of the expanding steam chambers.
Does Aggressive Surgery Improve Outcomes? Interaction Between Preoperative Disease Burden and Complex Surgery in Patients With Advanced-Stage Ovarian Cancer: An Analysis of GOG 182
Authors: Horowitz Neil S. , Miller Austin , Rungruang Bunja , Richard Scott D. , Rodriguez Noah , Bookman Michael A. , Hamilton Chad A. , Krivak Thomas C. , Maxwell G. Larry
Published: February 2015

Purpose

To examine the effects of disease burden, complex surgery, and residual disease (RD) status on progression-free (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and complete surgical resection (R0) or < 1 cm of RD (MR) after surgical cytoreduction.

Patients and Methods

Demographic, pathologic, surgical, and outcome data were collected from 2,655 patients with EOC or PPC enrolled onto the Gynecologic Oncology Group 182 study. The effects of disease distribution (disease score [DS]) and complexity of surgery (complexity score [CS]) on PFS and OS were assessed using the Kaplan-Meier method and multivariable regression analysis.

Results

Consistent with existing literature, patients with MR had worse prognosis than R0 patients (PFS, 15 v 29 months; P < .01; OS, 41 v 77 months; P < .01). Patients with the highest preoperative disease burden (DS high) had shorter PFS (15 v 23 or 34 months; P < .01) and OS (40 v 71 or 86 months; P < .01) compared with those with DS moderate or low, respectively. This relationship was maintained in the subset of R0 patients with PFS (18.3 v 33.2 months; DS moderate or low: P < .001) and OS (50.1 v 82.8 months; DS moderate or low: P < .001). After controlling for DS, RD, an interaction term for DS/CS, performance status, age, and cell type, CS was not an independent predictor of either PFS or OS.

Conclusion

In this large multi-institutional sample, initial disease burden remained a significant prognostic indicator despite R0. Complex surgery does not seem to affect survival when accounting for other confounding influences, particularly RD.
Health-Related Quality of Life in Stable, Long-Term Survivors of Low-Grade Glioma
Authors: Boele Florien W. , Douw Linda , Reijneveld Jaap C. , Robben Rianne , Taphoorn Martin J.B. , Aaronson Neil K. , Heimans Jan J. , Klein Martin
Published: February 2015

Purpose

Patients with low-grade glioma (LGG) often experience long periods of stable disease, emphasizing the importance of maintaining good health-related quality of life (HRQOL). We assessed the changes in HRQOL in long-term survivors of WHO grade I or II astrocytoma, oligodendroglioma, or oligoastrocytoma with clinically and radiologically stable disease.

Patients and Methods

Patients completed self-report measures of generic HRQOL (Short Form-36 [SF-36]) and disease-specific HRQOL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Brain Cancer Module). Assessments took place at midterm and long-term follow-up, on average 6 and 12 years after histologic diagnosis and initial treatment, respectively. Comparisons between patients with LGG and individually matched healthy controls were made, and change within the patients with LGG was calculated, as was minimal detectable change.

Results

Although no statistically significant differences between patients with LGG and healthy matched controls were found at midterm follow-up, patients with LGG had worse physical role functioning (P = .004) and general health perceptions (P = .004) than controls at long-term follow-up. Within patients with stable LGG (n = 65), physical HRQOL (the SF-36 physical component summary and the physical functioning subscale) was significantly worse at long-term than at midterm follow-up (both P < .001). Although 48% of patients improved or remained stable on all HRQOL scales, 38.5% of patients experienced detectable decline on one or more scales.

Conclusion

Although HRQOL remains mostly preserved in the majority of patients with LGG, a subset of patients experience detectable decline on one or more HRQOL scales despite long-term stable disease. For this subgroup, further research is recommended to better aid patients in dealing with the consequences of LGG.
Refining American Joint Committee on Cancer/Union for International Cancer Control TNM Stage and Prognostic Groups for Human Papillomavirus–Related Oropharyngeal Carcinomas
Authors: Huang Shao Hui , Xu Wei , Waldron John , Siu Lillian , Shen Xiaowei , Tong Li , Ringash Jolie , Bayley Andrew , Kim John , Hope Andrew , Cho John , Giuliani Meredith , Hansen Aaron , Irish Jonathan , Gilbert Ralph , Gullane Patrick , Perez-Ordonez Bayardo , Weinreb Ilan , Liu Fei-Fei , O'Sullivan Brian
Published: February 2015

Purpose

To refine stage and prognostic group for human papillomavirus (HPV) –related nonmetastatic (M0) oropharyngeal cancer (OPC).

Methods

All patients with nonmetastatic (M0) p16-confirmed OPC treated with radiotherapy with or without chemotherapy from 2000 to 2010 were included. Overall survival (OS) was compared among TNM stages for patients with HPV-related and HPV-unrelated OPC separately. For HPV-related OPC, recursive partitioning analysis (RPA) derived new RPA stages objectively. Cox regression was used to calculate adjusted hazard ratios (AHRs) to derive AHR stages. The performance of survival prediction of RPA stage and AHR stage was assessed against the current seventh edition TNM stages. Prognostic groups were derived by RPA, combining RPA stage and nonanatomic factors.

Results

The cohort comprised 573 patients with HPV-related OPC and 237 patients with HPV-unrelated OPC, with a median follow-up of 5.1 years. Lower 5-year OS with higher TNM stage was evident for patients with HPV-unrelated OPC (stage I, II, III, and IV 5-year OS: 70%, 58%, 50%, and 30%, respectively; P = .004) but not for patients with HPV-related OPC (stage I, II, III, and IV 5-year OS: 88%, 78%, 71%, and 74%, respectively; P = .56). RPA divided HPV-related OPC into RPA-I (T1-3N0-2b), RPA-II (T1-3N2c), and RPA-III (T4 or N3; 5-year OS: 82%, 76%, and 54%, respectively; P < .001). AHR also yielded a valid classification, but RPA stage demonstrated better survival prediction. A further RPA (including RPA stage, age, and smoking pack-years [PYs]) derived the following four valid prognostic groups for survival: group I (T1-3N0-N2c_≤ 20 PY), group II (T1-3N0-N2c_> 20 PY), group III (T4 or N3_age ≤ 70), and group IVA (T4 or N3_age > 70; 5-year OS: 89%, 64%, 57%, and 40%, respectively; P < .001).

Conclusion

An RPA-based TNM stage grouping (stage I/II/III: T1-3N0-N2b/T1-3N2c/T4 or N3, with M1 as stage IV) is proposed for HPV-related OPC as a result of significantly improved survival prediction compared with the seventh edition TNM, and prognostication is further improved by an RPA-based prognostic grouping within the American Joint Committee on Cancer/Union for International Cancer Control TNM framework for HPV-related OPC.
Overall Response Rate, Progression-Free Survival, and Overall Survival With Targeted and Standard Therapies in Advanced Non–Small-Cell Lung Cancer: US Food and Drug Administration Trial-Level and Patient-Level Analyses
Authors: Blumenthal Gideon M. , Karuri Stella W. , Zhang Hui , Zhang Lijun , Khozin Sean , Kazandjian Dickran , Tang Shenghui , Sridhara Rajeshwari , Keegan Patricia , Pazdur Richard
Published: February 2015

Purpose

To conduct analyses exploring trial-level and patient-level associations between overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in advanced non–small-cell lung cancer (NSCLC) trials.

Methods

We identified 14 trials (N = 12,567) submitted to US Food and Drug Administration since 2003 of treatments for advanced NSCLC. Only randomized, active-controlled trials with more than 150 patients were included. Associations between trial-level PFS hazard ratio (HR), OS HR, and ORR odds ratio were analyzed using a weighted linear regression model. Patient-level responder analyses comparing PFS and OS between patients with and without an objective response were performed using pooled data from all studies.

Results

In the trial-level analysis, the association between PFS and ORR was strong (R2 = 0.89; 95% CI, 0.80 to 0.98). There was no association between OS and ORR (R2 = 0.09; 95% CI, 0 to 0.33) and OS and PFS (R2 = 0.08; 95% CI, 0 to 0.31). In the patient-level responder analyses, patients who achieved a response had better PFS and OS compared with nonresponders (PFS: HR, 0.40; 95% CI, 0.38 to 0.42; OS: HR, 0.40; 95% CI, 0.38 to 0.43).

Conclusion

On a trial level, there is a strong association between ORR and PFS. An association between ORR and OS and between PFS and OS was not established, possibly because of cross-over and longer survival after progression in the targeted therapy and first-line trials. The patient-level analysis showed that responders have a better PFS and OS compared with nonresponders. A therapy in advanced NSCLC with a large magnitude of effect on ORR may have a large PFS effect.
Prostate Cancer Survivorship Care Guideline: American Society of Clinical Oncology Clinical Practice Guideline Endorsement
Authors: Resnick Matthew J. , Lacchetti Christina , Bergman Jonathan , Hauke Ralph J. , Hoffman Karen E. , Kungel Terrence M. , Morgans Alicia K. , Penson David F.
Published: February 2015

Purpose

The guideline aims to optimize health and quality of life for the post-treatment prostate cancer survivor by comprehensively addressing components of follow-up care, including health promotion, prostate cancer surveillance, screening for new cancers, long-term and late functional effects of the disease and its treatment, psychosocial issues, and coordination of care between the survivor's primary care physician and prostate cancer specialist.

Methods

The American Cancer Society (ACS) Prostate Cancer Survivorship Care Guidelines were reviewed for developmental rigor by methodologists. The American Society of Clinical Oncology (ASCO) Endorsement Panel reviewed the content and recommendations, offering modifications and/or qualifying statements when deemed necessary.

Results

The ASCO Endorsement Panel determined that the recommendations from the 2014 ACS Prostate Cancer Survivorship Care Guidelines are clear, thorough, and relevant, despite the limited availability of high-quality evidence to support many of the recommendations. ASCO endorses the ACS Prostate Cancer Survivorship Care Guidelines, with a number of qualifying statements and modifications.

Recommendations

Assess information needs related to prostate cancer, prostate cancer treatment, adverse effects, and other health concerns and provide or refer survivors to appropriate resources. Measure prostate-specific antigen (PSA) level every 6 to 12 months for the first 5 years and then annually, considering more frequent evaluation in men at high risk for recurrence and in candidates for salvage therapy. Refer survivors with elevated or increasing PSA levels back to their primary treating physician for evaluation and management. Adhere to ACS guidelines for the early detection of cancer. Assess and manage physical and psychosocial effects of prostate cancer and its treatment. Annually assess for the presence of long-term or late effects of prostate cancer and its treatment.
Napping Reverses the Salivary Interleukin-6 and Urinary Norepinephrine Changes Induced by Sleep Restriction
Authors: Faraut Brice , Nakib Samir , Drogou Catherine , Elbaz Maxime , Sauvet Fabien , De Bandt Jean-Pascal , Léger Damien
Published: February 2015

Context:

Neuroendocrine and immune stresses imposed by chronic sleep restriction are known to be involved in the harmful cardiovascular effects associated with poor sleep.

Objectives:

Despite a well-known beneficial effect of napping on alertness, its effects on neuroendocrine stress and immune responses after sleep restriction are largely unknown.

Design:

This study was a strictly controlled (sleep-wake status, light environment, caloric intake), crossover, randomized design in continuously polysomnography-monitored subjects.

Setting:

The study was conducted in a laboratory-based study.

Participants:

The subjects were 11 healthy young men.

Intervention:

We investigated the effects on neuroendocrine and immune biomarkers of a night of sleep restricted to 2 h followed by a day without naps or with 30 minute morning and afternoon naps, both conditions followed by an ad libitum recovery night starting at 20:00.

Main Outcome Measures:

Salivary interleukin-6 and urinary catecholamines were assessed throughout the daytime study periods.

Results:

The increase in norepinephrine values seen at the end of the afternoon after the sleep-restricted night was not present when the subjects had the opportunity to take naps. Interleukin-6 changes observed after sleep deprivation were also normalized after napping. During the recovery day in the no-nap condition, there were increased levels of afternoon epinephrine and dopamine, which was not the case in the nap condition. A recovery night after napping was associated with a reduced amount of slow-wave sleep compared to after the no-nap condition.

Conclusions:

Our data suggest that napping has stress-releasing and immune effects. Napping could be easily applied in real settings as a countermeasure to the detrimental health consequences of sleep debt.
Is Normocalcemic Primary Hyperparathyroidism Harmful or Harmless?
Authors: Chen Gang , Xue Ying , Zhang Qiongyao , Xue Ting , Yao Jin , Huang Huibin , Liang Jixing , Li Liantao , Lin Wei , Lin Lixiang , Shi Lidan , Cai Liangchun , Wen Junping
Published: February 2015

Context:

Primary hyperparathyroidism (PHPT) is reported to be associated with an increased frequency of hypertension, however, information in this regard is sparse in relation to normocalcemic primary hyperparathyroidism (NPHPT).

Objective:

The aim of this study was to determine the association between NPHPT and blood pressure.

Design, Setting, and Patients:

We retrospectively enrolled 940 patients who visited the Fujian Provincial Hospital between September 2010 and December 2013 with a measured serum parathyroid hormone (PTH) and calcium level. Among them, 11 patients were diagnosed with NPHPT, while 296 cases with normal PTH and albumin-adjusted serum calcium.

Main Outcomes Measures:

Systolic blood pressure (SBP), diastolic blood pressure (DBP), intact serum PTH, and serum calcium were recorded.

Results:

There were no significant differences between subjects identified with NPHPT and those with normal PTH in terms of age, sex, body mass index, serum calcium, 25-Hydroxyvitamin D, serum creatinine, fasting plasma glucose, triglycerides, total cholesterol, high density lipoprotein, and low density lipoprotein. The subjects with a diagnosis of NPHPT had higher levels of SBP (141.9 ± 20.2 vs 131.2 ± 16.5, P = .041) and DBP (85.2 ± 12.4 vs 76.8 ± 10.3, P = .026) than the subjects in the cohort with normal PTH. After adjustment for all potential confounders, risks (odds ratios and 95% confidence interval) of SBP and DBP in NPHPT patients were 1.035 (1.000, 1.071) and 1.063 (1.004, 1.125), respectively (P < .05).

Conclusions:

The NPHPT had higher risk of high blood pressure than subjects with normal PTH. It is worth considering the necessity of more aggressive therapeutic intervention aimed to normalize PTH even if patients with NPHPT continue to be normocalcemic.
Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells
Authors: Merkle Florian T. , Maroof Asif , Wataya Takafumi , Sasai Yoshiki , Studer Lorenz , Eggan Kevin , Schier Alexander F.
Published: February 2015

Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a ‘self-patterning’ strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases.
Akt1 signaling coordinates BMP signaling and β-catenin activity to regulate second heart field progenitor development
Authors: Luo Wen , Zhao Xia , Jin Hengwei , Tao Lichan , Zhu Jingai , Wang Huijuan , Hemmings Brian A. , Yang Zhongzhou
Published: February 2015

Second heart field (SHF) progenitors exhibit continued proliferation and delayed differentiation, which are modulated by FGF4/8/10, BMP and canonical Wnt/β-catenin signaling. PTEN-Akt signaling regulates the stem cell/progenitor cell homeostasis in several systems, such as hematopoietic stem cells, intestinal stem cells and neural progenitor cells. To address whether PTEN-Akt signaling is involved in regulating cardiac progenitors, we deleted Pten in SHF progenitors. Deletion of Pten caused SHF expansion and increased the size of the SHF derivatives, the right ventricle and the outflow tract. Cell proliferation of cardiac progenitors was enhanced, whereas cardiac differentiation was unaffected by Pten deletion. Removal of Akt1 rescued the phenotype and early lethality of Pten deletion mice, suggesting that Akt1 was the key downstream target that was negatively regulated by PTEN in cardiac progenitors. Furthermore, we found that inhibition of FOXO by Akt1 suppressed the expression of the gene encoding the BMP ligand (BMP7), leading to dampened BMP signaling in the hearts of Pten deletion mice. Cardiac activation of Akt also increased the Ser552 phosphorylation of β-catenin, thus enhancing its activity. Reducing β-catenin levels could partially rescue heart defects of Pten deletion mice. We conclude that Akt signaling regulates the cell proliferation of SHF progenitors through coordination of BMP signaling and β-catenin activity.
Integrin traffic – the update
Authors: De Franceschi Nicola , Hamidi Hellyeh , Alanko Jonna , Sahgal Pranshu , Ivaska Johanna
Published: February 2015

Integrins are a family of transmembrane cell surface molecules that constitute the principal adhesion receptors for the extracellular matrix (ECM) and are indispensable for the existence of multicellular organisms. In vertebrates, 24 different integrin heterodimers exist with differing substrate specificity and tissue expression. Integrin–extracellular-ligand interaction provides a physical anchor for the cell and triggers a vast array of intracellular signalling events that determine cell fate. Dynamic remodelling of adhesions, through rapid endocytic and exocytic trafficking of integrin receptors, is an important mechanism employed by cells to regulate integrin–ECM interactions, and thus cellular signalling, during processes such as cell migration, invasion and cytokinesis. The initial concept of integrin traffic as a means to translocate adhesion receptors within the cell has now been expanded with the growing appreciation that traffic is intimately linked to the cell signalling apparatus. Furthermore, endosomal pathways are emerging as crucial regulators of integrin stability and expression in cells. Thus, integrin traffic is relevant in a number of pathological conditions, especially in cancer. Nearly a decade ago we wrote a Commentary in Journal of Cell Science entitled ‘Integrin traffic’. With the advances in the field, we felt it would be appropriate to provide the growing number of researchers interested in integrin traffic with an update.
Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry
Authors: Long Jason , Wright Edward , Molesti Eleonora , Temperton Nigel , Barclay Wendy
Published: February 2015

Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achievedin vivo. We propose CQ as a priority candidate to consider for treatment of EBOV.
Optimization Methods for Multistage Freight Train Formation
Authors: Bohlin Markus , Gestrelius Sara , Dahms Florian , Mihalák Matúš , Flier Holger
Published: February 2015

This paper considers mathematical optimization for the multistage train formation problem, which at the core is the allocation of classification yard formation tracks to outbound freight trains, subject to realistic constraints on train scheduling, arrival and departure timeliness, and track capacity. The problem formulation allows the temporary storage of freight cars on a dedicated mixed-usage track. This real-world practice increases the capacity of the yard, measured in the number of simultaneous trains that can be successfully handled. Two optimization models are proposed and evaluated for the multistage train formation problem. The first one is a column-based integer programming model, which is solved using branch and price. The second model is a simplified reformulation of the first model as an arc-indexed integer linear program, which has the same linear programming relaxation as the first model. Both models are adapted for rolling horizon planning and evaluated on a five-month historical data set from the largest freight yard in Scandinavia. From this data set, 784 instances of different types and lengths, spanning from two to five days, were created. In contrast to earlier approaches, all instances could be solved to optimality using the two models. In the experiments, the arc-indexed model proved optimality on average twice as fast as the column-based model for the independent instances, and three times faster for the rolling horizon instances. For the arc-indexed model, the average solution time for a reasonably sized planning horizon of three days was 16 seconds. Regardless of size, no instance took longer than eight minutes to be solved. The results indicate that optimization approaches are suitable alternatives for scheduling and track allocation at classification yards.
‘Scenes of marvellous variety’: The work-in-progress screenplays of Maurice
Authors: Speidel Suzanne
Published: February 2015

This article examines the work-in-progress screenplays of Maurice by Ivory (1987), which was adapted from E. M. Forster’s novel, published posthumously in 1971. The article examines the creative processes revealed in the writers’ treatment, and three manuscripts of the screenplay, held at King’s College, Cambridge, all of which differ from the film as it has subsequently been released in cinemas and on DVD. Writers James Ivory and Kit Hesketh-Harvey restructured the narrative order of the story in several different ways, before the film was eventually edited to follow (almost) the chronology of the novel. The screenplay was also significantly shaped through the collaborative assistance of Ruth Prawer Jhabvala, who is not credited as a writer for the film. This article charts these hitherto hidden creative and authorial processes, and argues that the narrative’s journey from page to screen was not a straight trajectory, but instead constituted a move away from mainstream narrative genres, such as the Bildungsroman and the love story, and then a recommitment to them in the film’s ‘final’ cut. The multiple versions of the screenplay add to the palimpsetuous inscriptions of this already multi-layered, in-flux narrative, which was revised repeatedly by E. M. Forster over a 45-year period, and has also been reworked through new book editions, a re-release of the DVD that includes deleted scenes as ‘extras’, and fan activity on the Internet.
Reviews
Authors: Raw Laurence , Collard Christophe , Raw Laurence
Published: February 2015

Last Tape on Stage in Translation: Unwinding Beckett�s Spool in Turkey, Bur� Idem Din�el (2012) Newcastle-upon-Tyne: Cambridge Scholars, 131 pp., ISBN: 9781443835145, h/bk, �34.99

Bastard or Playmate? Adapting Theatre, Mutating Media, and the Contemporary Performing Arts, Robrecht Vanderbeeken, Christel Stalpaert, David Depestel and Boris Debackere (eds) (2012) Amsterdam: Amsterdam University Press, 264 pp., ISBN: 9789089642585, p/bk, �21.99

The Adaptations of the Mind: A Reply to Patrick Cattrysse
Remediations of Congolese urban dance music in Kinshasa
Authors: Pype Katrien
Published: February 2015

Following the continuing popularity of Congolese rumba music in the 1950s–1970s, I explore the technological spaces in which old songs appear more than 50 years later, and study the agency of those who initiate and actively contribute to the reinsertions of the old music in and on new media formats. By redefining the ‘repurposing’ of the remediations as strategies steered by human intentionality and occurring within social spaces, I investigate the kind of knowledge that an anthropological focus on remediation, repetition and circulation through electronic and digital media can offer about Kinshasa’s society at large. I propose to analyse the various purposes that direct Kinois (the inhabitants of Kinshasa), individual persons, media professionals and international corporations, to copy and insert old (and new) Congolese dance music into a particular media format, such as TV shows, USB sticks or mobile phone ring tones.
Targeting Urbanites: Nairobi-bred audio-visual narratives in Sheng
Authors: Overbergh Ann
Published: February 2015

In this article I analyse three cases of media production in Nairobi that target teenage and young adult audiences in the Sheng language. Despite large differences in terms of scale, style, financial strength and audience reach, my cases have a number of common characteristics, traits which I theorize by using elements of subcultural theory. The cases also show how the role and position of Sheng, an urban vernacular closely associated with youth and city life, is changing.
Crocodilites: retrato de um sofisma sem solução
Authors: Duarte Rui Miguel
Published: February 2015

Entre as anedotas e enigmas em circulação na Antiguidade, havia um género que os Estoicos designaram por ?????????????, em virtude de numa das suas variantes o protagonista ser um crocodilo. Característico deles era a impossibilidadede conclusão, de modo que, por onde quer que se procurasse abordá-los, resultavsempre o contrário. Examinar-se-ão as variantes conhecidas destas historietas. Em alguns casos só as personagens mudavam. Porém, embora artificiais, elas não eram meras anedotas. Pelo contrário, faziam, desde os Estoicos até a doutrina das ??????? de Hermógenes de Tarso e seus escoliastas, as delícias de dialécticos e retóricos, como ????? (inconclusivos). E nesses meios foram cultivadas como pretextos paraexercícios de escola. A sua popularidade e tradição são pois por assim dizer uma questão de recepção. Por outro lado, é porque geravam debates que não chegavam a sê-lo que se pode entendê-las como um problema de performance, ou da sua negação.
Attenuation in Superconducting Rectangular Waveguides
Authors: Yeap Kim Ho , Mei Teh Joyce Shu , Nisar Humaira , Yeong Kee Choon , Hirasawa Kazuhiro
Published: February 2015

We present an accurate analysis on the attenuation of waves, propagating in rectangular waveguides with superconducting walls. The wavenumbers
Retroflex consonant harmony: An areal feature in South Asia
Authors: Arsenault Paul
Published: February 2015

Retroflexion is a well-known areal feature of South Asia. Most South Asian languages, regardless of their genetic affiliation, contrast retroflex consonants with their non-retroflex dental counterparts. However, South Asian languages differ in the phonotactic restrictions that they place on retroflex consonants. This paper presents evidence that a large number of South Asian languages have developed a co-occurrence restriction on coronal obstruents that can be described as retroflex consonant harmony. In these languages, roots containing two non-adjacent coronal stops are primarily limited to those with two dentals (T…T) or two retroflexes (Ṭ…Ṭ), while those containing a combination of dental and retroflex stops are avoided (*T…Ṭ, *Ṭ…T). Historical-comparative evidence indicates that long-distance retroflex assimilation has contributed to the development of this phonotactic pattern (T…Ṭ → Ṭ…Ṭ). In addition, the paper demonstrates that the distribution of languages with and without retroflex consonant harmony is geographic in nature, not genetic. Retroflex consonant harmony is characteristic of most languages in the northern half of the South Asian subcontinent, regardless of whether they are Indo-Aryan, Dravidian or Munda (but not Tibeto-Burman). It is not characteristic of Indo-Aryan and Dravidian languages in the south. Thus, retroflex consonant harmony constitutes an areal feature within South Asia.
Two micro-areal developments in northwestern South Asia: Causative involuntatives and causee marking postpositions
Authors: Bashir Elena
Published: February 2015

This paper focuses on two language clusters in the region comprising the Hindu Kush mountains; Swat, Dir and Indus Kohistan (Pakistan); and the Himalayan foothills (HKKH region). The languages considered are Kalasha, Khowar, Palula, Dameli, Torwali, Kohistani, Shina, Kashmiri, Pashai and some of the Nuristani languages. One cluster of languages shares the expression of non-volitional semantics by derived transitive/causative verb forms, previously discussed as “causative involuntatives” or “impersonal causative expressions”. Two apparent subtypes are identified and mapped. A second, partially overlapping, cluster shares the use of a grammaticized conjunctive participle of a causative form of a reflex of the OIA √sañj as a postposition marking the secondary agent in causative constructions. The paper presents data illustrating these features, delimits the regions in which they appear, and characterizes these two microareas. The data indicate a clear geographical split between those languages in which reflexes of √sañj express this cluster of meanings, which seem to share descent from Gāndhārī Prakrit and possibly other unrecorded MIA varieties, and those which have developed words with similar meanings from √lag.
First person objects, antipassives, and the political history of the Southern Kirant
Authors: Bickel Balthasar , Gaenszle Martin
Published: February 2015

Several Kiranti languages (Tibeto-Burman, Nepal) from different genealogical sub-groups show multiple parallel developments from antipassive constructions with generic, non-specific objects into agreement markers registering first person objects. The developments span a relatively contiguous geographical area in the southernmost part of the family. We explain the developments by contact with politeness strategies of speaker-effacement in Maithili (Indo-Aryan) formal style, with which southern Kiranti elites have been in intense contact in about the same time frame as can be assumed for the emergence of the antipassive-based agreement forms. These findings illustrate a particularly tight interaction between natural (functional) strategies of politeness with specific historical contingencies.
The Northwest of South Asia and beyond: The issue of Indo-Aryan retroflexion yet again
Authors: Hock Hans Henrich
Published: February 2015

The Vedic Sanskrit contrast dental : retroflex is widely attributed to Dravidian substratum influence (starting with Pott 1833, 1836). An objection is that retroflexion is explainable by internal developments and that the phonological systems of Sanskrit and reconstructed Dravidian differ considerably (e.g. Bloch 1925; Hock 1975, 1982). Tikkanen (1987, 1988) raises the alternative possibility of a northwestern substrate.

I reexamine the evidence and arguments offered so far. The trigger for the internal development of Sanskrit retroflexion is the retroflex sibilant ṣ and its variant ẓ(h), segments absent in Proto-Dravidian. The Northwest, by contrast, has retroflex sibilants; in fact, a triple contrast s : ṣ : ś is widespread and occurs as early as the Prakrits, Eastern Middle Iranian Saka, and even Avestan (with s : š : ṣ̌ : š́). Significantly, it also occurs in Vedic. I argue that the retroflex sibilant, the trigger for Vedic retroflexion, arose in the Northwest, not by contact with Dravidian. The development of retroflex stops can be explained in terms of later convergent developments in peninsular South Asia, developments which in Dravidian also introduced alveolar stops.

In the concluding section I discuss the relevance of this account for convergence studies in general.
Transport Demand Forecast on Pan-European Road Corridor X. Methodology, Results and their Assessment Through Comparisons with Actual Demand
Authors: Miltiadou Marios D.
Published: February 2015

Transport demand forecast is a crucial parameter for transport planning. It defines the infrastructure dimensioning for a required level of service in a planning period, but moreover, it is determinative in the socioeconomic and financial feasibility study of transport projects. This paper presents the methodology and the results of the traffic flows forecasting exercise for the Pan-European Corridor X, which was elaborated to serve as a sound basis for documentation of the transport investments priorities, and the assessment of the results of the forecasted demand through comparisons with actual demand.
Asphalt Mixtures with Limestone Aggregate for Base Layer
Authors: Răcănel Carmen , Dicu Mihai , Lazăr Ştefan Marian , Burlacu Adrian
Published: February 2015

Asphalt mixtures are mixtures of mineral aggregates, filler, bitumen and eventually additives in proportions determined by recipe designed in the laboratory. Asphalt mixtures used as base course are bituminous concrete.

The natural aggregates are granular materials of mineral origin that come from natural or artificial crushing of the rocks. In our country there are the various rocks: eruptive or magmatic rocks, metamorphic rocks, sedimentary rocks.

To the category of sedimentary rocks belong limestone. Sedimentary rocks are characterized by relatively high porosity and a pronounced stratification, which causes mechanical resistance to be low and vary by direction of load. Due to the structure less dense and weaker mechanical resistance, the limestone are used less in heavy traffic pavement structures.

This paper presents an asphalt mixture recipe for the base layer developed in the Laboratory of Roads from Technical University of Civil Engineering Bucharest (TUCEB), using limestone aggregates extracted from Hoghiz Quarry. The paper contains laboratory test results to determine the recipe and laboratory findings leading to the schedule of product.
Application of GPR and FWD in Assessing Pavement Bearing Capacity
Authors: Domitrović Josipa , Rukavina Tatjana
Published: February 2015

The process of pavement maintenance and rehabilitation starts by collecting the data which will form the base for evaluation of pavement functional and structural condition. Collection of data can be performed by destructive and non-destructive testing. Usually preferred are the non-destructive methods, that do not damage the pavement, and the process of pavement evaluation is objective and repeatable. Non-destructive testing methods are becoming more and more popular, especially for assessing the structural condition of the pavement. Non-destructive testing by a Falling Weight Deflectometer (FWD) and the analysis of so collected data by the process of backcalculations is today the usual tool for assessing pavement bearing capacity. One of the basic input parameters for analysis of the data collected by FWD is pavement layers thickness.

The practice in Croatia is to determine pavement layers thickness by coring. This destructive method affects pavement integrity, so the number of such tests should be kept to the minimum. By coring the accurate thickness of all pavement layers is obtained on specific point locations. Thus, numerous deviations in layer thickness remain unnoticed, and in the end, use of such data for the process of backcalculations does not provide ac urate values of layer moduli. Coring can be replaced with non-destructive method of testing by Ground Penetrating Radar (GPR), which provides continuous information on thickness of all pavement layers.

The paper shows the method for assessing the bearing capacity of the pavement based on the data collected by FWD, GPR and coring. The calculation for layer moduli was performed by the ELMOD software, separately for the layers thickness data obtained by coring, and separately for the thickness obtained by GPR tests. Analysis and comparison of the results of calculated elasticity moduli obtained by using various methods for collecting layer thickness data were performed in the paper.
Balanced Cantilever Girder Bridge Over the Danube-Black Sea Channel
Authors: Giordano Aldo , Pedrazzi Giorgio , Voiro Giovanni
Published: February 2015

This paper describes the design and construction of a “balanced cantilever girder” bridge over the Danube-Black Sea channel, characterized by a central span of 155m with two symmetrical side spans of 77.5m. The total length of the bridge, including portions of the abutments support, is 312.0m.

The bridge main features, from calculation as well as construction points of view, are in particular the post-tensioning tendons, distributed both a top and bottom sides of the section along the bridge. The former ones play a key role in the construction phase, for the need of counterbalancing selfweight while subsequent segments are realized.

Tendons are symmetrical about midspan, with anchors positioned at the end of each segment.

Bridge deck is supported by two piers outfitted with friction pendulum seismic bearings, which develop friction both in static conditions to withstand static forces and small displacements, and in dynamic conditions, causing dissipation. Under severe earthquake load all structures (deck and piers) develop only elastic behavior.

This papers presents a detailed review of the design process as well as a time journey during construction
Increase the Safety of Road Traffic Accidents by Applying Clustering
Authors: Kos Goran , Brlek Predrag , Meic Kristijan , Vidovic Kresimir
Published: February 2015

In terms of continual increase of number of traffic accidents and alarming trend of increasing number of traffic accidents with catastrophic consequences for human life and health, it is necessary to actively research and develop methods to combat these trends. One of the measures is the implementation of advanced information systems in existing traffic environment. Accidents clusters, as databases of traffic accidents, introduce a new dimension in traffic systems in the form of experience, providing information on current accidents and the ones that have previously occurred in a given period. This paper proposes a new approach to predictive management of traffic processes, based on the collection of data in real time and is based on accidents clusters. The modern traffic information services collects road traffic status data from a wide variety of traffic sensing systems using modern ICT technologies, creating the most accurate road traffic situation awareness achieved so far. Road traffic situation awareness enhanced by accident clusters' data can be visualized and distributed in various ways (including the forms of dynamic heat maps) and on various information platforms, suiting the requirements of the end-users. Accent is placed on their significant features that are based on additional knowledge about existing traffic processes and distribution of important traffic information in order to prevent and reduce traffic accidents.