A Combined Trip Generation, Trip Distribution, Modal Split and Traffic Assignment Model

Revised and submitted to Transportation Science February 1985.We introduce a transportation equilibrium model that simultaneously predicts trip generation, trip distribution, modal split, and traffic assignment by algorithms that are guaranteed to converge to an equilibrium and are computationally efficient for large-scale systems. The model is formulated as an equivalent optimization problem, yet it allows realistic, flexible and behaviorally acceptable demand models

Diatomite alleviates the adverse effects of salinity stress on growth and yield of Stevia rebaudiana

ABSTRACT The present study was planned to investigate the role of diatomitein salt tolerance of Stevia rebaudiana using pot experimental. Diatomite increased the growth characters of plants, hence resulted in higher yields. In contrast, the seawater treatments alone significantly decreased these parameters in both seasons. While, treating Stevia rebaudianaplants with diatomite prior to salinity stress decreased the detrimental effectof salt stress on growth and yield.The Esterase isoenzymesprofiles has indicated that salinity, diatomite and their combinations has caused biochemical changes in Steviar. plants. On the other hand, saline water irrigation decreased Rebaudioside A concentration at the second harvest as estimated by HPLC analysis in both seasons .The effect of the interaction between salinity and diatomite was the mosteffective treatments for Rebaudioside A when Stevia rebaudianaplants treated by salt concentration 4000 ppm and 2.5 g/kgsoil diatomite

Surveillance on A/H5N1 virus in domestic poultry and wild birds in Egypt

The endemic H5N1 high pathogenicity avian influenza virus (A/H5N1) in poultry in Egypt continues to cause heavy losses in poultry and poses a significant threat to human health. Here we describe results of A/H5N1 surveillance in domestic poultry in 2009 and wild birds in 2009-2010. Tracheal and cloacal swabs were collected from domestic poultry from 22024 commercial farms, 1435 backyards and 944 live bird markets (LBMs) as well as from 1297 wild birds representing 28 different types of migratory birds. Viral RNA was extracted from a mix of tracheal and cloacal swabs media. Matrix gene of avian influenza type A virus was detected using specific real-time reverse-transcription polymerase chain reaction (RT-qPCR) and positive samples were tested by RT- qPCR for simultaneous detection of the H5 and N1 genes. In this surveillance, A/H5N1 was detected from 0.1% (n = 23/) of examined commercial poultry farms, 10.5% (n = 151) of backyard birds and 11.4% (n = 108) of LBMs but no wild bird tested positive for A/H5N1. The virus was detected from domestic poultry year- round with higher incidence in the warmer months of summer and spring particularly in backyard birds. Outbreaks were recorded mostly in Lower Egypt where 95.7% (n = 22), 68.9% (n = 104) and 52.8% (n = 57) of positive commercial farms, backyards and LBMs were detected, respectively. Higher prevalence (56%, n = 85) was reported in backyards that had mixed chickens and waterfowl together in the same vicinity and LBMs that had waterfowl (76%, n = 82). Our findings indicated broad circulation of the endemic A/H5N1 among poultry in 2009 in Egypt. In addition, the epidemiology of A/H5N1 has changed over time with outbreaks occurring in the warmer months of the year. Backyard waterfowl may play a role as a reservoir and/or source of A/H5N1 particularly in LBMs. The virus has been established in poultry in the Nile Delta where major metropolitan areas, dense human population and poultry stocks are concentrated. Continuous surveillance, tracing the source of live birds in the markets and integration of multifaceted strategies and global collaboration are needed to control the spread of the virus in Egypt

Protective efficacy of recombinant turkey herpes virus (rHVT-H5) and inactivated H5N1 vaccines in commercial Mulard ducks against the highly pathogenic avian influenza (HPAI) H5N1 clade 2.2.1 virus

In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/ Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/ dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/ chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge.S1 Table. Weekly mean HI titres (log2 ± SD) using A/Swan/Hungary/4999/2006) rHVT/Ag that indicate the immune response to the rHVT-H5 vaccination. S1 Table legend: Different upper case letters in a row denote the presence of statistically significant (p 0.05) differences. Group I (vaccinated with rHVT-H5 vaccine at 1 day old), Group II (vaccinated with inactivated KV-H5 vaccine at 8 days old), Group III (unvaccinated control).S2 Table. Weekly mean HI titres (log2 ± SD) measured using (A/chicken/Egypt/Q1995D/ 2010) V/H5N1/Ag that indicates the immune response to the KV-H5 vaccination. S2 Table legend: Different upper case letters in a row denote the presence of statistically significant (p 0.05) differences. Group 1 (vaccinated with rHVT-H5 vaccine at 1 day old), Group II (vaccinated with inactivated KV-H5 vaccine at 8 days old), Group III (unvaccinated control).S3 Table. Weekly mean HI titres (log2 ± SD) measured using (A/chicken/Egypt/128S/2012) C/H5N1/Ag that indicates the immune response to the challenge virus. S3 Table legend: Different upper case letters in a row denote the presence of statistically significant (p 0.05) differences. Group 1 (vaccinated with rHVT-H5 vaccine at 1 day old), Group II (vaccinated with inactivated KV-H5 vaccine at 8 days old), Group III (unvaccinated control).This work was supported by the United States Agency for International Development (USAID) under a grant (AID-263-IO-11-00001, Mod. #3) and within the framework of OSRO/EGY/101/ USA, which applies to projects jointly implemented by the FAO, GOVS and NLQP.http://www.plosone.orgam2016Production Animal StudiesVeterinary Tropical Disease

Protective efficacy of recombinant turkey herpes virus (rHVT-H5) and inactivated H5N1 vaccines in commercial Mulard ducks against the highly pathogenic avian influenza (HPAI) H5N1 clade 2.2.1 virus

In Egypt, ducks kept for commercial purposes constitute the second highest poultry population, at 150 million ducks/year. Hence, ducks play an important role in the introduction and transmission of avian influenza (AI) in the Egyptian poultry population. Attempts to control outbreaks include the use of vaccines, which have varying levels of efficacy and failure. To date, the effects of vaccine efficacy has rarely been determined in ducks. In this study, we evaluated the protective efficacy of a live recombinant vector vaccine based on a turkey Herpes Virus (HVT) expressing the H5 gene from a clade 2.2 H5N1 HPAIV strain (A/Swan/ Hungary/499/2006) (rHVT-H5) and a bivalent inactivated H5N1 vaccine prepared from clade 2.2.1 and 2.2.1.1 H5N1 seeds in Mulard ducks. A 0.3ml/dose subcutaneous injection of rHVT-H5 vaccine was administered to one-day-old ducklings (D1) and another 0.5ml/ dose subcutaneous injection of the inactivated MEFLUVAC was administered at 7 days (D7). Four separate challenge experiments were conducted at Days 21, 28, 35 and 42, in which all the vaccinated ducks were challenged with 106EID50/duck of H5N1 HPAI virus (A/ chicken/Egypt/128s/2012(H5N1) (clade 2.2.1) via intranasal inoculation. Maternal-derived antibody regression and post-vaccination antibody immune responses were monitored weekly. Ducks vaccinated at 21, 28, 35 and 42 days with the rHVT-H5 and MEFLUVAC vaccines were protected against mortality (80%, 80%, 90% and 90%) and (50%, 70%, 80% and 90%) respectively, against challenges with the H5N1 HPAI virus. The amount of viral shedding and shedding rates were lower in the rHVT-H5 vaccine groups than in the MEFLUVAC groups only in the first two challenge experiments. However, the non-vaccinated groups shed significantly more of the virus than the vaccinated groups. Both rHVT-H5 and MEFLUVAC provide early protection, and rHVT-H5 vaccine in particular provides protection against HPAI challenge.S1 Table. Weekly mean HI titres (log2 ± SD) using A/Swan/Hungary/4999/2006) rHVT/Ag that indicate the immune response to the rHVT-H5 vaccination. S1 Table legend: Different upper case letters in a row denote the presence of statistically significant (p 0.05) differences. Group I (vaccinated with rHVT-H5 vaccine at 1 day old), Group II (vaccinated with inactivated KV-H5 vaccine at 8 days old), Group III (unvaccinated control).S2 Table. Weekly mean HI titres (log2 ± SD) measured using (A/chicken/Egypt/Q1995D/ 2010) V/H5N1/Ag that indicates the immune response to the KV-H5 vaccination. S2 Table legend: Different upper case letters in a row denote the presence of statistically significant (p 0.05) differences. Group 1 (vaccinated with rHVT-H5 vaccine at 1 day old), Group II (vaccinated with inactivated KV-H5 vaccine at 8 days old), Group III (unvaccinated control).S3 Table. Weekly mean HI titres (log2 ± SD) measured using (A/chicken/Egypt/128S/2012) C/H5N1/Ag that indicates the immune response to the challenge virus. S3 Table legend: Different upper case letters in a row denote the presence of statistically significant (p 0.05) differences. Group 1 (vaccinated with rHVT-H5 vaccine at 1 day old), Group II (vaccinated with inactivated KV-H5 vaccine at 8 days old), Group III (unvaccinated control).This work was supported by the United States Agency for International Development (USAID) under a grant (AID-263-IO-11-00001, Mod. #3) and within the framework of OSRO/EGY/101/ USA, which applies to projects jointly implemented by the FAO, GOVS and NLQP.http://www.plosone.orgam2016Production Animal StudiesVeterinary Tropical Disease

CLaRO: a Controlled Language for Authoring Competency Questions

Competency Questions (CQs) assist in the development and maintenance of ontologies and similar knowledge organisation systems. The absence of tools to support the authoring of CQs has hampered their effective use. The few existing question templates have limited coverage of sentence constructions and are restricted to OWL. We aim to address this by proposing the \cqcnl~template-based CNL to author CQs. For its design, we exploited a new dataset of 234 CQs that had been processed automatically into 106 patterns, which we analysed and used to design a template-based CNL, with an additional CNL model and XML serialisation. The CNL was evaluated, showing coverage of about 90\% with the 93 templates and their 41 variants. \cqcnl~has the potential to facilitate streamlining formalising ontology content requirements and, given that about one third of the CQs in the test sets turned out to be invalid questions, assist in writing good questions

A classification of grammar-infused templates for ontology and model verbalisation

Involving domain-experts in the development, maintenance, and use of knowledge organisation systems can be made easier through the introduction of easy-to-use interfaces that are based on natural language. Well resourced languages make use of natural language generation techniques to provide such interfaces. In particular, they often make use of templates combined with computational grammar rules to generate grammatically complex text. However, there is no model of pairing templates and computational grammar rules to ensure suitability for less-resourced languages. These languages require a modular design that ensures grammar detachability so as to allow grammar re-use across domains and applications. In this paper, we present a model and classification scheme for grammar-infused templates suited for less-resourced languages and classify existing systems that make use of them. We have found that of the 15 systems that pair templates and grammar rules, and their 11 distinct template types, 13 have support for detachable grammars

Diagnosis and management of tropomyosin receptor kinase (TRK) fusion sarcomas : expert recommendations from the World Sarcoma Network

Sarcomas are a heterogeneous group of malignancies with mesenchymal lineage differentiation. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions as tissue-agnostic oncogenic drivers has led to new personalized therapies for a subset of patients with sarcoma in the form of tropomyosin receptor kinase (TRK) inhibitors. NTRK gene rearrangements and fusion transcripts can be detected with different molecular pathology techniques, while TRK protein expression can be demonstrated with immunohistochemistry. The rarity and diagnostic complexity of NTRK gene fusions raise a number of questions and challenges for clinicians. To address these challenges, the World Sarcoma Network convened two meetings of expert adult oncologists and pathologists and subsequently developed this article to provide practical guidance on the management of patients with sarcoma harboring NTRK gene fusions. We propose a diagnostic strategy that considers disease stage and histologic and molecular subtypes to facilitate routine testing for TRK expression and subsequent testing for NTRK gene fusions.Peer reviewe

Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial

Background We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. Methods EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1–5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. Findings Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6–76·6); 62·3 months (IQR 46·9–77·1) for the MAP group and 61·1 months (IQR 46·5–75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78–1·23]); hazards were non-proportional (p=0·0003). The most common grade 3–4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. Funding UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre