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// Sara Strese 1 , Saadia Bashir Hassan 1 , Ebba Velander 2 , Caroline Haglund 1 , Martin Hoglund 3 , Rolf Larsson 1 , Joachim Gullbo 1, 2 1 Department of Medical Sciences, Division of Cancer Pharmacology and Computational Medicine, Uppsala University, Uppsala, Sweden 2 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden 3 Department of Medical Sciences, Division of Hematology, Uppsala University, Uppsala, Sweden. Correspondence to: Joachim Gullbo, email: Joachim.Gullbo@medsci.uu.se Keywords: melflufen, drug development, alkylator, pre-clinical, acute myeloid leukemia Received: May 20, 2016 Accepted: November 06, 2016 Published: December 10, 2016 ABSTRACT The novel aminopeptidase potentiated alkylating agent melflufen, was evaluated for activity in acute myeloid leukemia in a range of in vitro models, as well as in a patient derived xenograft study. All tested AML cell lines were highly sensitive to melflufen while melphalan was considerably less potent. In the HL-60 cell line model, synergy was observed for the combination of melflufen and cytarabine, an interaction that appeared sequence dependent with increased synergy when melflufen was added before cytarabine. Also, in primary cultures of AML cells from patients melflufen was highly active, while normal PBMC cultures appeared less sensitive, indicating a 7-fold in vitro therapeutic index. Melphalan, on the other hand, was only 2-fold more potent in the AML patient samples compared with PBMCs. Melflufen was equally active against non-malignant, immature CD34 + progenitor cells and a more differentiated CD34 + derived cell population (GM14), whereas the stem cell like cells were less sensitive to melphalan. Finally, melflufen treatment showed significant anti-leukemia activity and increased survival in a patient derived xenograft of AML in mice. In conclusion, melflufen demonstrates high and significant preclinical activity in AML and further clinical evaluation seem warranted in this disease.

The study aimed to identify the necessary requirements needed for employing eLearning in the physical learning environment from the point of view of the teaching staff. In this study the researcher employed the analytical descriptive method and the size of the sample in which the study was applied was (127) individuals from the teaching staff with a degree of a teaching assistant and above, The researcher has employed questionnaire technique as a study tool, and the most important findings of the study are: The study has come to the fact that the majority of the researchers managed to answer the study areas which are summarized in the requirements needed for employing e. learning by the educational environment which was specified by this study، these requirements are vitally important from the point of view of the teaching staff. And the most important recommendations of the study are: Providing all the requirements needed to put e. learning into practice in the physical educational environment which was determine by the study to employ eLearning in the institutions of the higher education in Sudan.

Increased urbanization in Vietnam disturbing land use efficiency related to natural resources and quality of human life and development. Therefore, land use efficiency become an inherent requirement under growing population and land resources for national and regional sustainable development. This study presents an evaluation of land use efficiency in Vietnam using DEA (Data Envelopment Analysis) and Super-Efficiency DEA model. In general, Vietnam land use efficiency is low, only 8 among 63 provinces have high land use efficiency. The results show that Super-efficiency DEA model can effectively rank the efficiency DMU completely, by thatHo Chi Minh City tops the list of land use efficiency of Vietnam in 2017, followed by Ba Ria-Vung-Tau, BacNinh, NinhThuan, Da Nang, Vinh Long, AnGiang and Lai Chau. NgheAn andThanhHoa, the two largest provinces of Vietnam located get the lowest land use efficiency value. There is no certain relation between the efficiency of land use and the grade of the province. This study may provide a reference for the decision maker in land use planning to get high efficiency and sustainable land resources. Introduction Land is an essential natural resource for the survival and prosperity of humanity, and for the maintenance of all terrestrial ecosystem(FAO/UNEP, 1999). From economic perspective land is the primary means of production used to generate a livelihood for a family in most of the developing countries. Land use is defined as the link between land cover and the actions of human being in their environment. By this way, it is characterized by the arrangements, activities and inputs by people to produce, change or maintain a certain land cover type (Di Gregorio, 1998). Demand of multiple land uses leads to increase in land competition, therefore, size of the holdings affects the household's income(Power, 2010), (Harvey & Pilgrim, 2011). Vietnam-one developing country in Southeast Asia heavily depending on agriculture experiencing the high urbanization growth with around 700 square kilometers of land incorporated into towns and cities annually("Vietnam needs more effective urban land use," 2018). Furthermore, therapid urbanization bringsfast economic development, industrialization and the increase in urban population(J. Wang, Zhou, Pickett, Yu, & Li, 2019). According to World Bank (Bank, 2019) , Vietnam’s urbanization rate increased from 28.5% (2007) to 35.2% (2017). On the other hand, urban land use pattern caused land use problems such as traffic congestion, insufficient water use, shortage electricity supplies, deterioration of living environment and reduced social stability. The socioeconomic development of Vietnam mainly depends on the land and forestresources used for agricultural growth and rural development.In fact, urban land use efficiency in Vietnam remain relatively low withpopulation density of 2100 people per square kilometer compared to other Asian countries have about 10000 people per square kilometer("Viet Nam land use efficiency remains low," 2017). Land use efficiency is an important indicator for the level of urban land use(Songqing Jin, 2013). Recently, various studies have investigated land use efficiency in term of urban land use efficiencyconsidering ecology, regional economic, social behavior and political economics by different methodologies.Pauleit, Ennos, and Golding (2005),Mouri and Aisaki (2015) andM. Mirzaei (2016) explored the effect of urban land use on the environment, while Lin and Ho (2003),Kumar, Merwade, Rao, and Pijanowski (2013) examined the status of urban land use in different countries and regions.Some studies have examined land use efficiency in terms of development density, population density and employment density Glaeser and Kahn (2004) andPeiser (1989). YEH and WU (1996)analyzed the important factors of land use efficiency in Guangzhou-China by using logistic regression. Herold, Couclelis, and Clarke (2005) studied the urban land use change by applying spatial measurement. Furthermore Aguilera, Valenzuela, and Botequilha-Leitão (2011) focused on spatial measurement applied to access urban land use Land use efficiency has been traditionally analyzed using economic efficiency and primarily focused on economic intensification of land use and its spatial differentiation.Jiang C Y (2008) analyzed the spatial-temporal variation of landuse economic efficiency of the 40 districts and counties based on the land use status along with the natural and socio-economic situation in Chongqing City from 1999 to 2006.Yang et al., 2009; Liang L T (2013)investigated the spatial disparity characters of urban land use efficiency in the prefectural-level cities in China focused on how to optimize the urban land use efficiency. Moreover, due to diverse land resource functions, land use efficiency is essentially a comprehensive efficiency that integrates economic, social, and ecological outputs. There are several parametric and nonparametric techniques to measuring land use efficiency, among them, data envelopment analysis (DEA) is the most adopted as a nonparametric technique(Raheli, Rezaei, Jadidi, &Mobtaker, 2017). The advantage of nonparametric technique over parametric is that it supposes neither a predetermined functional relationship between inputs and outputs, nor a prior information about weights of inputs and outputs. DEA was applied to evaluate energy use efficiency by Nassiri and Singh (2009), AghaAlikhani, Kazemi-Poshtmasari, and Habibzadeh (2013), Mobtaker, Akram, Keyhani, and Mohammadi (2012).Toma, Dobre, Dona, and Cofas (2015) have study been applied DEA to assess the agriculture efficiency on areas with similar geographically patterns.The notion of land use efficiency refers to an optimal situation, it can be understood as the ability to achieve maximum output for a given level of input for a given level of output. To measure land use efficiency, Data Envelopment Analysis (DEA) has been widely used by many researchers. DEAhave ability to adopt the optimization method to determine the weight of each input element. The unique advantage of DEA model is that it doesn’t need to determine the specific functional relation between input/output and avoid the errors because of function relationship as well as the inaccuracy caused by the subjectivity of determining each index weigh effectively(Charnes, Cooper, & Rhodes, 1978). Various studies have investigated application ofDEA in land use efficiency evaluation such as X. Wang (2005) applied the CCR-DEA to evaluate land use efficiency of 17 cities in Shandong-China; Zhang (2009) made an empirical analysis on land use efficiency of prefecture city in China; Wu (2011) evaluated the land use efficiency of 33 cities in China and made an analysis on the input-output elements. Yang, Wu, and Dang (2017) also used DEA model to study the urban land use efficiency and coordination on 33 provincial capital cities and municipalities of China. Vietnam cities are now facing severe environmental pressure due to environmental destruction, hazardous pollutants emission and consumption of natural resources. Therefore, land use efficiency become an inherent requirement under growing population and land resources for national and regional sustainable development. Moreover, land use policy in developing countries is considered as an important factor of the overall development policy that government needs to stress on for rapid economic growth and poverty alleviation. Despite the large literatures on the application of DEA on land use efficiency, to the best of our knowledge, empirical studies of low-income countries like Vietnam are almost non-existent. In this study, land use efficiency was analyzed from an economic perspective. Firstly, we used Data envelopment analysis (DEA) to compute efficiency scores of each province/municipality, by that we could assess the proportion of both inputs and outputs in the process of land use. After that the Super-efficiency DEA model was used to distinguish and compare the efficiency difference between the effective DMU (which has efficiency value is 1).Specifically, the purpose of this study to investigate the land use efficiency of low income and under developing country for the decision making in natural resources management. The remainder of the paper is organized as follow: section 2 described the study area and methodology; section 3 showed a presentation and an analysis of the results; section 4 offers a demonstrative conclusion to the study and policy implication of the findings. 2. Material and method 2.1. Study area Vietnam located in Southeast Asia, at latitude 140 3’ 30’’ N and longitude 108016’9’’. It has common borders with Laos and Cambodia in the west and with the People’s Republic of China in the north. Vietnam also has a long coastline along the Gulf of Tonkin, the South China Sea and the Gulf of Thailand with 3.444 kilometers.Due to geographical location stretches across many latitudes, Vietnam’s climate changes significantly from north to south, with four distinct seasons in the north and tropical in central and southern.The area of natural land resources in Vietnam is about 33 million hectares or 330.000 square kilometers (km2), ranked 65/194 of countries over the world.Total area of the country composed of land area, 82.3% or about 27,28 million hectares is agricultural land, 11.24% is non-agricultural land and the remaining is unused land(GSO, 2018).The structure of land use in Vietnam also tends to be like the world: increasing agricultural land, decreasing forest land, and increasing specialized land and barren hills. Officially, Vietnam has63provinces,municipalities(hereafter refer as provinces)and is divided into 6 socio-economic regions as follows: Red river delta, Northern midlands and Mountain areas, North central and Central coastal areas, Central Highlands, South East and Mekong river delta. The socio-economic regions are divided based on the geographical location of the provinces and the national development strategy. Figure 1 shows the structure of land area and proportional contribution into national GDP of 6 socio-economic regions. The disparity between the land area and the ratio of GDP contribution can be seen. Both Northern midlands and Mountain areas region and North central and Coastal areas region accounting for 29% of the territory but GDP contribution was only 8% and 15%, respectively. TheCentral Highlands region also occupies a large area in the territory (17%) but the region’s GDP was the lowest value among 6 regions (4%). Mekong river delta region has the same proportion in both land area and the contribution to national GDP (12%). Total land area of two regions Red river delta and South East accounting for 13% of total country but contributed 61% for national GDP. Results shows that Red river delta and South East region utilize land resources with higher economic efficiency than the rest. However, for evaluating whether land use is appropriate or not, it’s not only based on the value of gross domestic product in the region, but also a reasonable combination of inputs such as land area, labor and investment capital, to create outputs like GDP, average income. In this paper, we evaluated the land use efficiency of each province/municipality, and then we made a comparison among 6 socio-economic regions to understand the land use circumstance of the country. Fig. 1. Structure of land area and proportional contribution into national GDP of 6 socio-economic regions 2.2. Research method Data envelopment analysis (DEA) is a non-parametric method to evaluate the relative performance of decision-making units (DMU), which was put forward byCharnes et al. (1978). It was originally designed to study the relative efficiencies of different firms or managerial units assumed to have available a common best practice production technology. DEA can provide a method to compare firms based on the extent to which inputs are used efficiency in the production of output, given the technology. Similarly, the econometric frontier production function literature originally took the technology as given. Let Xj= (X1j, X2j, … ,Xmj), Yj=(Y1j , Y2j , … , YSj), j = 1,2,3,…,n, the XijandYijrespectively are vectors of input and output. The slack vectors s- and s+ correspond to input excesses (input slack) and output shortfalls (output slacks) and θ is DMU’s efficiency value. Commonly used DEA models are as follow: min s.t. Ifθ=1 and s+=s-=0, DMU¬¬¬0 is considered efficiency. It means in the system composed of n DMU, the output Y0 that obtained from the input X0 has reached the optimal. If θ=1 and s+≠0 or s-≠0,DMU¬¬¬0is considered low efficiency. It means the system consisting of n decision making units in the case of input X0,s-can be reduced while the original output Y0 remains unchanged or increase the output s+ if the input X0 is unchanged. If θs. t. + = ,i = 1,2 ,…,m = ,r = 1,2,…, s , , 0, j = 1, 2,… n, j Where ε> 0 is the non-Archimedean infinitesimal. 2.3. Data sources DEAP 2.1 software was used to conduct land use efficiency analysis. Based on existing literature, we chose acreage of land, the number of employed-population at 15 years of age and above, and capital investment to represent input indicators. In term of output indicators, we selected regional gross domestic product (GDP) and regional per capita disposable income.From the perspective of scientific analysis, to evaluate land use efficiency, the outputs should include environment factor. In this paper we didn’t consider this factor due the lack of data available in this country. All data were collected from the Statistic yearbook of Vietnam 2017 which were confirmed by Vietnam General Statistics Office. The administrative zoning map of Vietnam is shown in Figure2. Fig. 2.The administrative zoning map of Vietnam 3. Results and discussions We used DEAP 2.1 to calculate the land use efficiency value in Vietnam. The results are shown in Table 1. Table 1. Land use efficiency data envelopment analysis Province Firm CRSTE VRSTE Scale Ha Noi VinhPhuc BacNinh QuangNinh Hai Duong HaiPhong Hung Yen Thai Binh Ha Nam Nam Dinh NinhBinh Ha Giang Cao Bang BacKan TuyenQuang Lao Cai Yen Bai Thai Nguyen Lang Son BacGiang PhuTho Dien Bien Lai Chau Son La HoaBinh ThanhHoa Nghe An Ha Tinh QuangBinh Quang Tri ThuaThien Hue Da Nang Quang Nam QuangNgai BinhDinh Phu Yen KhanhHoa NinhThuan BinhThuan Kon Tum Gia Lai DakLak DakNong Lam Dong BinhPhuoc TayNinh Binh Duong Dong Nai Ba Ria-Vung Tau Ho Chi Minh City Long An TienGiang Ben Tre TraVinh Vinh Long Dong Thap AnGiang KienGiang Can Tho HauGiang SocTrang Bac Lieu Ca Mau 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 0.632 0.827 1 0.702 0.689 0.865 0.891 0.529 0.969 0.732 0.871 0.622 0.680 0.946 0.851 0.586 0.589 0.530 0.594 0.488 0.548 0.515 1 0.469 0.723 0.183 0.280 0.405 0.612 0.829 0.606 1 0.552 0.520 0.429 0.642 0.562 1 0.572 0.903 0.513 0.503 0.882 0.584 0.775 0.788 0.703 0.582 1 1 0.669 0.684 0.787 0.645 1 0.773 1 0.418 0.669 0.978 0.978 0.802 0.827 0.686 0.914 1 0.719 0.707 0.868 0.957 0.586 1 0.743 0.896 0.738 0.718 1 0.893 0.661 0.627 0.612 0.629 0.495 0.602 0.669 1 0.535 0.803 0.217 0.304 0.506 0.626 0.870 0.612 1 0.566 0.584 0.450 0.660 0.588 1 0.615 0.946 0.513 0.503 0.890 0.678 0.964 0.936 1 0.601 1 1 0.744 0.712 0.800 0.776 1 0.778 1 0.427 0.713 1 0.985 0.874 0.831 0.922 0.904 1 0.976 0.974 0.996 0.930 0.903 0.969 0.985 0.972 0.842 0.947 0.946 0.952 0.886 0.940 0.866 0.944 0.984 0.910 0.770 1 0.875 0.900 0.844 0.918 0.801 0.977 0.952 0.991 1 0.975 0.891 0.952 0.973 0, {"references":["AghaAlikhani, M., Kazemi-Poshtmasari, H., andHabibzadeh, F., 2013, Energy use pattern in rice production: A case study from Mazandaran province, Iran. Energy Conversion and Management, v. 69, p. 157-162. doi:https://doi.org/10.1016/j.enconman.2013.01.034","Aguilera, F., Valenzuela, L. M., andBotequilha-Leitão, A., 2011, Landscape metrics in the analysis of urban land use patterns: A case study in a Spanish metropolitan area. Landscape and Urban Planning, v. 99, no. 3, p. 226-238.doi:https://doi.org/10.1016/j.landurbplan.2010.10.004","Liang L.T. Z. Q. L., Chen C et al., 2013, Analysis on the characters of spatial disparity of urban land use efficiency and its optimization in China. China Land Sciences, v. 27, no. 7, p. 48-54."]}

Background:Tuberculous lymphadenopathy is an extremely common condition in developing countries; however, vocal cord paralysis secondary to compression by enlarged tuberculous lymph node is an extremely rare presentation. Case Presentation:In this paper, we present the case of a 72-year-old male patient who came to us with concerns of hoarseness of voice for the last eight months with fever and chills. He had been treated previously at ear, nose and throat (ENT) clinics and on evaluation, we discovered he had left vocal cord paralysis. Imaging showed multiple enlarged mediastinal and right hilar lymph nodes. Management & Results:Mediastinoscopy with biopsy was done and after histopathologic confirmation of tuberculosis, the patient was prescribed antituberculous treatment. Conclusion:Antituberculous treatment in such patients shows signs of clinical and radiologic improvement. Link: http://aeirc-edu.com/ojs14/index.php/IJEHSR/article/view/390/522

Background: Although T-cell cytokine’s role in the long-term control of chronic myeloid leukemia (CML) is well established, previous studies showed contradicting results regarding imatinib (IM) effect on the endogenous T-cell function by IM. The purpose of this study was to determine the relation between the endogenous T-cell function prior to therapy and the degree of response to IM therapy in CP CML. In addition, modulation of the endogenous T-cell function during IM therapy was studied. Methods: We evaluated Th1 (gamma interferon (IFN-γ)), Th2 (interleukin (IL-4)) and tumor necrosis factor (TNF)-α cytokine synthesis by activated T-cell subsets in 20 patients with newly diagnosed CML in chronic phase (CP CML) using flow cytometry before and during IM therapy compared to patients with IM resistance (IM Res) and healthy donors. Results: Patients with optimal response (CML OR) to IM demonstrated a lower pre-treatment Th1 cytokine compared to that of healthy donors, and a higher percentage of Th2 and TNF-α producing T cells compared to that of healthy donors, non-optimal responders (CML nOR) and those with IM Res. A shift from Th2 profile to Th1 profile and initial decline of TNF-α producing T cells was detected early during therapy in optimal responders which was coinciding with complete hematological remission with a significant increase in the percentages of CD4+ve/IFN-γ+ve cells (P = 0.01) and a significant drop of in CD8+ve/IL-4+ve T cells (P = 0.04). Conclusion: We believe that pre-treatment levels of IL-4 and/or TNF-α may have a role in identifying CP CML patients who may respond to IM therapy; however, further investigation is needed. J Hematol. 2018;7(3):96-106 doi: https://doi.org/10.14740/jh410w

Identity Document (ID) forgery is a process by which authorized identity document is modified and\or copied by unauthorized party or parties to be used illegally. The rapid development of personal computers, scanners, and color printers a long with their affordability raises up the risk of identity document forgery. They represent rich tools and techniques that highly support the creation of faked identities. This review paper investigates the current techniques for countering document forgery threats long with their achievements and limitations. These techniques are insufficient to mitigate ID forgery threats. New methods and techniques need to be developed to reduce or eliminate the risk of the Identity documents forgery.

Although acute promyelocytic leukemia (APL) is a curable hematologic malignancy, early death (ED) remains a significant cause of treatment failure especially in developing countries. In a retrospective data analysis of 67 adult APL patients diagnosed in United Arab Emirates we report an ED rate of 11.9% which is comparable to that reported from more developed countries. We identified the following parameters at presentation as significant predictor of increased ED: Age >40 years (P = 0.015), fever (P = 0.030), WBC count >20 × 109/L (P = 0.010), the breakpoints other than bcr1 (P = 0.043) and fibrinogen level 10 × 109/L and expression of HLA-DR (P = 0.018) or CD2 (P = 0.017) were significant predictors for differentiation syndrome (DS) which was found to be a predictor of ED (P = 0.002). Reducing the APL related ED rate in centers with limited resources is feasible provided early initiation of ATRA administration and early correction of coagulopathy in high-risk patients in addition to prompt treatment of DS. To our knowledge this is the first report from the Arabian Gulf describing ED in APL.

Background and aim The plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) can reflect the cardiac functions in patients with cardiac diseases. Our aim is to assess the value of NT-proBNP in the diagnosis of heart failure and evaluation of cardiac functions in pediatric patients with ventricular septal defect (VSD). Patients and method The study comprised 40 children with VSD (mean age 12 ± 5 months) and 20 healthy children as a control group. Detailed echocardiographic examination was performed and the level of NT-proBNP level was measured. Results The plasma level of NT-proBNP was significantly higher in patients with VSD than in control subjects (P

Dette er en bacheloroppgave i økonomi og administrasjon hvor jeg undersøker hva som påvirker kundetilfredshet og kundelojalitet. Jeg handler selv veldig mye hos Dressman og derfor falt valget på å studere hvilke faktorer som fremmer kundetilfredshet og kundelojalitet hos Dressmann sine kunder. Oppgavens problemstilling er ”Hva legger kunder hos Dressmann i begrepene kundetilfredshet og kundelojalitet”, og oppgavens formål er å beskrive hvilke faktorer som fremmer kundetilfredshet og kundelojalitet ved handel hos Dressmann. Studien er basert på en kvalitativ metode hvor jeg brukte intervjuer som datainnsamlingsmetode. Et av kravene for å kunne delta i undersøkelsen var at kundene var lojale hos Dressmann. For å kunne svare tilfredsstillende på problemstillingen min valgte jeg å intervjue 8 informanter. Som forskningsdesign ble casedesign brukt. Basert på teorien som ble fremlagt dannet jeg teoretiske antakelser som jeg baserte min datainnsamling på. Funnene viser at de fleste kundene fokuserer på pris, kvalitet og service. Kundene er avhengig av å vurderer priser med andre konkurrenter. Dessuten er man veldig opptatt av bra produkter med kunnskapsrike ansatte som er serviceinnstilte. Samtidig er det viktig å understreke at høye priser, dårlige produkter og dårlig service også er faktorer som sørger for at kunder velger andre konkurrenter fremfor Dressmann. I tillegg til pris, kvalitet og service er det også viktig å ha godt omdømme og gi regelmessige fordeler for å skape kundetilfredshet og kundelojalitet.

A high-throughput screen of the cytotoxic activity of 2000 molecules from a commercial library in three human colon cancer cell lines and two normal cell types identified the acridine acriflavin to be a colorectal cancer (CRC) active drug. Acriflavine was active in cell spheroids, indicating good drug penetration and activity against hypoxic cells. In a validation step based on primary cultures of patient tumor cells, acriflavine was found to be more active against CRC than ovarian cancer and chronic lymphocytic leukemia. This contrasted to the activity pattern of the CRC active standard drugs 5-fluorouracil, irinotecan and oxaliplatin. Mechanistic studies indicated acriflavine to be a dual topoisomerase I and II inhibitor. In conclusion, the strategy used seems promising for identification of new diagnosis-specific cancer drugs.

Purpose: The study was carried out to investigate the prevalence of refractive errors in al Bahar Alahmar province in Sudan. The aim was to identify the prevalence in the province and to help in improving the health strategic plans in the area as well as reviewing the eye care services provided in the region. Materials and Methods: Eye testing had been executed on 790 patients with ages ranged between 10 and 59 years and means of 41.7 standard deviation ± 10.1. All patients tested for distance vision using (tumbling E chart) and near vision using (tumbling E chart). The battery kept simple at the beginning of the test; however, noncycloplegic objective refraction followed using a streak retinoscope to refract and prescribe the required optical correction. Results: Decreased in vision was more common in the age group of (40–49) years old, right eye (RE); 38% and left eye (LE); 34% (χ2 = 20.83/df = 20/P = 0.04). Spectacles could improve the vision to 6/6 from 45.8% (unaided) in RE to 91.5% aided and from 44.4% to 90.6% for LE. The prevalence of refractive error was 37.1% for the total; of which 19.6% hypermetropia, 6.6%, myopia and 10.9% astigmatism, respectively. The prevalence of hypermetropia increased in those age (40–49) RE; 38% and LE; 39.4% with highly association with age (χ2 = 58.41/df = 12/probability P = 0.001). Myopia found in the age group (50–59) years old RE; 40.4% and LE; 37.8%, but without any significant association between myopia and age (χ2 = 46.28/df = 12/P = 0.74). In examination site, 66.8% of the ametropes were not wearing correction, but 12.4% wearing distance correction, 15.1% using near correction, and 5.7% wearing distance and near correction. Conclusion: Hypermetropia was the most common type of refractive errors. Refractive errors affect a sizable portion of these three towns, a substantial number of uncorrected refractive errors individuals were waiting for help. Thus, awareness and services must be dramatically improved to meet the needs.

15 cases of HCL were studied with a panel of monoclonal antibodies against different leukocyte antigens. A B-cell phenotype different from that of B-CLL was observed (CD10-, CD19+, CD20+, CD21-, CD22+, CD37+, CD38-, FMC7+, LN1+, PCA-1+, BLy7+ and CD5-). As expected, CD11c and CD25 were positive and, in addition, a My7 and My9 positivity in varying degree was noted. 3 weeks of in vitro incubation did not significantly alter the phenotype. We conclude that HCL exhibits a unique phenotype among chronic B-cell leukemias, which is closer to the plasma cell stage of differentiation than that of B-CLL. The BLy7 monoclonal antibody seems to be a promising marker for HCL.

14 patients with HCL were started on alpha-interferon (IFN) treatment. Bone marrow changes were followed in trephine biopsies every 3rd month. Differential counting was performed according to the point counting method and fiber content was evaluated. At the start of treatment all patients had 80% or more of tumor cells in the bone marrow. The reduction of granulopoiesis was more pronounced than for erythropoiesis. During treatment cellularity decreased in 6/13 patients already after 3 months; later, cellularity was normalized in most patients. Only 1 patient showed a complete remission. 12/14 patients showed a significant but slow reduction of tumor cells. Also, between 12 and 18 months an improvement was seen in some patients. The megakaryocytes improved rapidly and the erythropoiesis was normalized before the granulopoiesis. Only 1 patient did not show a bone marrow response. 5/14 patients showed a reduction of bone marrow fibers, first seen after 6 months of treatment. IFN was discontinued in 9/14 patients. 7 of these relapsed during the observation period (18 months).

There is no published data regarding adult acute leukemia (AL) in the United Arab Emirates (UAE). Our objectives were to determine the distribution and incidence of adult AL in UAE (nationals and non-nationals). This epidemiological survey recovered 263 adult patients with AL diagnosed between January 2000 and December 2006 with a median age of 34 years. Twenty-four percent were UAE nationals and 63% were males. Acute lymphoblastic leukemia (ALL) was more frequently diagnosed (32%) than in western countries. This clearly reflects the population structure of the UAE which consists of predominantly young males. There is a tendency for lower crude and age-specific incidence rates of AL, acute myeloid leukemia (AML) and ALL in the UAE when compared with those in western countries. We found a statistically significant higher incidence of AML among national females than in national males (p = 0.04). This is reflected in a significantly higher incidence of AL (p = 0.02) and AML (p = 0.02) among the females when compared with the males in the total population of the UAE. This result contradicts the generally known finding that AML and ALL are more common in males. The implication of cumulative risk factors to which females could be exposed, such as vitamin D deficiency as a result of sunlight deprivation and direct exposure to benzene and color enhancement chemicals in henna, could not be excluded and warrant further investigation.

Bone marrow trephine biopsies from 30 healthy volunteers, 10 men and 20 women aged 18-60 yr were obtained for identification and localisation of hyaluronan (HYA). Fixation, decalcification and embedding were performed by two different methods, with identical results in both. For comparison bone marrow trephine biopsies from three patients with different haematological diseases and known fibrosis were studied. All bone marrow specimens were also stained for reticulin grading. HYA was found in the bone marrow specimens from healthy individuals in a pattern that was concordant with the reticulin staining, the common way of visualising bone marrow fibrosis. In bone marrow from the patients with known fibrosis the HYA and reticulin staining were both more intense and abundant. Interestingly, HYA was also found intracellularly in eosinophilic cells in normal bone marrow. HYA is a polysaccharide unique both in structural and biological properties, and in excess it may predict bone marrow fibrosis.

CHS 828 is a pyridyl cyanoguanidine that has shown promising preclinical anticancer activity against various experimental tumor models and is presently being tested in a phase II trial in man. In the present study the fluorometric microculture cytotoxicity assay was used for in vitro evaluation of CHS 828 activity in primary cell cultures from hematological and solid tumors. In total, 156 samples from various diagnoses were tested with 72-h continuous drug exposure. CHS 828 showed high relative in vitro activity against tumor cells from chronic lymphocytic leukemia as well as from acute leukemia and high-grade lymphoma. Activity was also observed in several solid tumor cell samples, although the group as a whole appeared less responsive. CHS 828 was significantly more active against hematological malignancies compared to normal lymphocytes. Correlation analysis with standard drugs revealed low to moderate correlation coefficients. The results show that CHS 828 has potent antitumor activity against primary cultures of human tumor cells from patients and might have a unique mechanism of action.

Fresh human tumour cells from patients with ovarian cancer and chronic lymphocytic leukaemia were cultured in semipermeable hollow fibres. The fibres were implanted on immunocompetent rats, which were treated with the cyanoguanidine N -(4-chlorophenoxyhexyl)- N ′-cyano- N ″-4-pyridylguanidine (CHS 828). CHS 828 showed high antitumour activity against all eight tumour samples; the fibres from control animals had a mean net growth of 73% while CHS 828 treatment induced a 37% mean reduction of cell density, without observable haematological toxicity. The results show a feasibility of using tumour cells directly from patients in the hollow-fibre rat model.

Based on the previously published hollow-fibre assay mainly used for early in vivo anticancer drug screening, we wanted to develop an extended hollow-fibre model in which antitumour activity, haematological toxicity and pharmacokinetics could be studied in the same animal.The breast cancer cell lines MDA-MB-231 and MCF-7 were cultured in semipermeable hollow fibres. The fibres were implanted subcutaneously into immunocompetent male Sprague Dawley rats, and the rats were treated with 5-fluorouracil (5-FU, 125 mg/kg), epirubicin (EPI, 10 mg/kg) or cyclophosphamide (CP, 120 mg/kg) intraperitoneally, the new cyanoguanidine CHS 828 (375 mg/kg or 75 mg/kg x 5) orally, or vehicle only. After 6 days the fibres were retrieved and the cell density was evaluated. Haematological parameters were monitored and two to four samples per animal were drawn to determine the pharmacokinetic parameters in NONMEM.Drug treatment had generally low effects on the tumour cells. Of the standard drugs (5-FU, EPI and CP), only CP exerted a statistically significant antiproliferative effect. CHS 828 had only a minor effect as a single dose, but divided into five daily doses had a pronounced effect on both cell lines. 5-FU, EPI and CP all caused a marked decrease in leucocytes, platelets and haemoglobin, while CHS 828 did not seem to affect these parameters. The pharmacokinetics of 5-FU and EPI were in accordance with previously established pharmacokinetic models. The pharmacokinetics of CP and CHS 828 were both described by one-compartment models.This study illustrates the possibility of measuring antitumour effect, haematological toxicity and pharmacokinetics in the same animal using the hollow-fibre model.

This retrospective data analysis examined the outcome of 99 acute lymphoblastic leukemia (ALL) patients treated at Tawam Hospital between January 2000 and December 2009. Sixteen patients were treated before June 2002, and 83 patients were treated from June 2002. A modified form of UKALL XII/ECOG E2993 with pulsed dexamethasone in induction phase one (modified UKALL) was the main therapy from June 2002 (71/83). The median age was 28 years. Fifty-eight percent had pre-B ALL where 36 % of them were Philadelphia chromosome-positive (Ph+). Overall, complete remission (CR) rate was 86.7 % which was significantly inferior for patients with white blood cell count 30–100 × 109/l (p = 0.009), therapy before June 2002 (p = 0.02), pregnancy (p = 0.005), CNS leukemia (p = 0.028), and unknown karyotype (p = 0.004). With a median follow-up of 11.8 months (0.49–126 months), the estimated overall survival (OS) and event-free survival (EFS) at 3 years were 50.6 and 28.7 %, respectively. OS and EFS were significantly inferior for patients not in CR after induction, age >20 years, Ph+, unknown karyotype and therapy before June 2002. In addition, CR, OS and EFS were significantly superior (p = 0.004, p

Background: Acute promyelocytic leukemia (APL) is a highly curable subtype of acute myeloid leukemia (AML). APL has unique morphological, cytogenetic and molecular characteristics. Although extensive data regarding APL are available from developed countries only few studies have been published from developing countries. They describe higher early death rates with lower complete remission rate compared to patients from developed countries. In a retrospective analysis, we evaluated the characteristics features at presentation and predictor of early death in 67 patients with APL diagnosed between 2000 and 2015 at two centers in UAE. To our knowledge there are no published data on APL early death rates from the United Arab Emirates (UAE) Patients and Methods: All patients age >15 years with a newly diagnosis of APL between January 2000 and January 2013 at Tawam hospital and Sheikh Khalifa Medical City (SKMC) were included. The initial diagnosis was typically based on clinical, morphological & phenotypic (negative expression of CD34 and HLA-DR but positive expression of CD2 and CD9) suspicion of APL. Subsequently the diagnosis was confirmed with genetic study for detection of t(15:17). Oral ATRA was immediately started at the standard dose 45 mg/m2 per day in addition to supportive care to correct the coagulopathy (fresh-frozen plasma, cryoprecipitate to maintain fibrinogen at >1.5 g/l, and platelets was maintained at >30x109/l). Early death was defined as death within 30 days of a patient being diagnosed with APL. Data were analyzed using SPSS version 21 (IBM SPSS Inc., Chicago, IL). Results: The median age was 33 years (15 - 57) with only 18 (26.9%) of the patients were older than 40 years. Patients were more likely to be male (42, 62.7%), present with bleeding (53, 80.3%) at the time of diagnosis, have a WBC count greater than 10x109/L in 59.9% while in 40% of the patients it was < 5 x109/L. They tend to have platelet count < 30x109/L in 76.1%, high INR in 66.7% and < 1.5g/L fibrinogen in two third of them. 69.2% of them had bcr1 and 10 of the patients (14.9%) had t(15:17) with additional chromosomal abnormalities include monosomy7 (2 patients), trisomy 8 (1 patients), del 9 (1 patients), ring chromosome 6 (2 patients), der 21 (1 patients) and complex karyotype (3 patients). Early death rate was 11.9%(8/67 patients). In a univariate analysis of the prognostic factors, early-deaths occurred significantly more frequent in patients who were >40 years of age (27.8% versus 6.1%; p= 0.015), those who presented with fever (21.2% versus 2.3%; p=0.030), WBC count >20 x 109/L (26.1% versus 4.5%; p=0.010), high INR (17.7% versus 0.0%; p=0.047), high APTT (40% versus 7.4%; p=0.021) at the time of diagnosis. Although fibrinogen level 24h versus within 24h) therapy failed to show statistical significance (13.3% versus 12.5%; p=0.9). Patients with WBC count Conclusion: The patient characteristics of UAE APL patients at presentation are similar to other published data. Early death rate is comparable to that published from developed countries. Our data support that coagulopathy at presentation is a major contributor to early death and that treatment of APL with improvement of early death rate is feasible at centers in developing countries provided access to facilities for aggressive supportive care. Disclosures No relevant conflicts of interest to declare.

The sage components linalyl acetate (Ly) and alpha-terpineol (Te) exhibit synergistic anti-proliferative effects. We investigated the effects of Ly and Te on NF-kappaB signaling in HCT-116 colon cancer cells. Ly and Te combinations dose-dependently reduced HCT-116 viability at non-cytotoxic concentrations. Combination treatment induced 30%-60% increase in PreG1 through induction of apoptosis and necrosis. DNA binding assays revealed that combination treatment suppressed both basal and TNF-alpha-induced NF-kappaB activation. This suppression correlated with the inhibition of p65 nuclear translocation and IkappaB-alpha degradation. The lack of change in IKK expression levels or inhibition in IkappaB-alpha phosphorylation suggest the involvement of an IKK-independent mechanism. Ly and Te combination was found to downregulate the expression of NF-kappaB-regulated antiapoptotic and proliferative gene products. Separate treatments and drug combinations significantly decreased DNA binding activity of NF-kappaB which led to the potentiation of cell death induced by the colon cancer drugs oxaliplatin and 5-FU. These results indicate that Ly and Te anticancer activities are partly mediated through the suppression of NF-kappaB activation, suggesting their use in combination with chemotherapeutic agents to induce apoptosis.

Background Cancer cells are characterised by uncontrolled replication involving loss of control of cyclin-dependent kinases (CDKs) and cyclins, and by abolished differentiation. In this study we introduce KGI, a nanoparticle with a Quillaja saponin as an active molecule. Methods By the use of RNA array analysis and confirmation at the protein level, we studied the effects of KGI on myeloid leukaemia cells. Findings KGI affects myeloid leukaemia cells (particularly the U937 monoblast cancer cell) by the following mechanisms: ceasing cell replication via proteasome degradation; down-regulation of key molecules at check points between G 1 /S and G 2 /M phases; reduction of thymidine kinase activity; followed by exit to differentiation and production of IL-8, eventually leading to apoptosis. Leukaemia cell lines (U937 and HL-60 cells) were exposed to KGI for 8 h, after which the drug was removed. The cancer cells did not revert to replication over the following 10 days. Interpretation Our findings suggest that the nanoparticle KGI inhibits proliferation and promotes differentiation in leukaemic cells by interfering with the cell cycle process.

Alpha terpineol is a bioactive component of Salvia libanotica essential oil extract and has shown antitumour activity.The cytotoxicity of alpha terpineol towards different tumour cell lines was evaluated in vitro. Mechanistic characterization was performed using analysis of drug activity in a cell line panel and drug-induced gene expression perturbation using the connectivity map approach.The small cell lung carcinoma was the cell line most sensitive to alpha terpineol. The results proposed alpha terpineol as an NF-kappaB inhibitor, which was confirmed by the observed dose-dependent inhibition of NF-kappaB translocation and activity using two NF-kappaB assays, and by the down-regulation of the expression of several NF-kappaB-related genes such as IL-1 beta and IL1R1.The results suggest that alpha terpineol inhibits the growth of tumour cells through a mechanism that involves inhibition of the NF-kappaB pathway.

Lebanese sage essential oil possesses antitumor properties, however, the bioactive components and antitumor mechanisms are not known. Here we show that combining the three sage bioactive compounds, Linalyl acetate (Ly), Terpeniol (Te) and Camphor (Ca), caused synergistic inhibition of the growth of two isogenic human colon cancer cell lines HCT-116 (p53(+/+) and p53(-/-)) and had no effect on growth of FHs74Int normal human intestinal cell line. In p53(+/+) cells, the combination of Ly + Te + Ca (10(-3) M of each) caused significant accumulation of cells in PreG(1) (64% at 48 hours); less preG(1) increase was observed in response to Ly + Te (25%) or Ly + Ca (14%). In p53(-/-) cells, Ly + Te + Ca caused cell accumulation in PreG(1) and G(2)/M phases. In response to the three components, 58% apoptosis occurred in p53(+/+) cells and 38% in p53(-/-) cells. Apoptosis by Ly + Te + Ca, in p53+/+ cells, was associated with increased Bax/Bcl-2 ratio and pp53/p53 ratio, cleavage and activation of caspase-3, loss of mitochondrial membrane potential and cytochrome c release. In p53(-/-) cells, the disruption of mitochondrial membrane potential was observed but to a lesser extent than in p53(+/+) cells and caspase activation or cleavage did not appear to be involved in drug-induced apoptosis. Sage components induced poly(ADP-ribose)-polymerase (PARP) cleavage in both p53(+/+) and p53(-/-) cell lines. Pretreatment with the caspase-3 inhibitor and pan caspase inhibitor abrogated drug-mediated apoptosis and blocked procaspase-3 activation and partially blocked PARP cleavage in p53(+/+) cells. Conversely, in p53(-/-) cells, pre-incubation with caspase inhibitors potentiated drug-induced cell death. It appears that apoptosis in p53(+/+) cells is through the mitochondrial-mediated, caspase-dependent pathway, while in p53(-/-) cells apoptosis is mostly caspase independent despite the presence and features indicating caspase-dependent cell death, such as cytochrome c release and PARP cleavage. Our findings encourage further studies of sage oil components as promising chemotherapeutic agents against colon cancer.

The title reagent (TDH2) has been used to precipitate cadmium from aqueous solution. The rate of extraction is rapid ( 1 2 ca. 2 min ). A Scatchard plot has two clear regions which have values K1 = 7.2 × 106 ( n 1 0.038 ) and K1 3.2 × 106 ( n 2 0.29 ). The first region is probably associated with (Cd TDH)+NO3 solid− formation and the second with (Cd TD)n (a polymer). Clear regions are seen even though the equilibrium constants are comparable. Related polymeric and amine compounds are unable to extract cadmium efficiently and it appears likely that polymer (CdTD)n formation is crucial to the extraction process.

فإنَّ البحث في اللغة وذاكرتها الجمعيّة ميدانٌ وعرٌ تقع فيه اختلافات بسبب حصول التطوّر والاتسّاع، وظهور الاشتقاق وغير ذلك؛ إذ تتطوّر اللغة بطريقة معقّدة يصعب رصدها، بيد أنَّ الخصوصية التي تتمتع بها اللغة العربية حفّزت الباحثين لتأمّل الأصالة التي تتمتع بها هذه اللغة بسبب عمرها المقروء، وتأثير البيئة والدين والايديولوجيات وغير ذلك ممّا أدّى إلى إظهار نوع من (التضمين اللغوي) ذي طابع كنائي يرتبط بالخزين اللاوعي للفرد الناطق باللغة العربية. شرع البحث بتمهيد وضح فيه مفهوم (الذاكرة الجمعيّة)، وبعض مقولات علماء اللغة في ذلك، ثُمَّ اكتفى بعرض ٍ يحسبُهُ وافيًا لعينات كشف فيها عن المعاني الجمعيّة التي تُظهرها بعض الألفاظ ويعتقد أنّها تعطي تصوّرًا عن الموضوع، من هذه الألفاظ: (النسيان، والنور والظلام، واليد، والماء). وأحال البحث في ثنيّات تطبيقه على عدد من الأمثلة التي تُظهر (الأصالة) من خلال عرض جانب من المنجز الأسلوبي للغة العربية وذاكرتها الجمعيّة. إنَّ هذا البحث نواة لتأصيل معنى (الذاكرة الجمعيّة) على أساس أنَّ اكتساب اللغة وتعلمها يرتبط بهذه الذاكرة، فضلا عن علاقتها المباشرة بعوالم التصوير واللغة الشعرية. وهو محاولة يُتمنى أن تكون قد حقَّـقتْ قدرًا من الفائدة، ووضعت نواةً لدراسات أخرى تُطَوِّرُ الفكرة التي قام عليها. والله الموفق

N-(6-Chlorophenoxyhexyl)-N'-cyano-N''-4-pyridylguanidine (CHS 828) is a novel anticancer agent that shows schedule-dependent effects in vitro and in vivo, as well as in Phase I clinical trials. A rat hollow fibre model was used to investigate whether this dependency is due to pharmacokinetic and/or pharmacodynamic factors. The effect on two cell lines, MDA-MB-231 (breast cancer) and CCRF-CEM (leukaemia) were studied after CHS 828 was administered orally as a single dose or in a 5-day schedule, at different total dose levels. The 5-day schedules were associated with greater effects on both cell lines compared with single doses. A one-compartment pharmacokinetic model, with a half-life of 2.3h and a consecutive zero- and first-order process to describe dissolution and absorption, fit the concentration data. Pharmacokinetics were dose-dependent, as the fraction absorbed decreased with increasing dose. Clearance increased with accumulative exposure. Twenty hours after administration, concentrations started to increase again, probably due to coprophagy. Pharmacokinetic-pharmacodynamic models characterized the cell growth and cell kill over time and showed that schedule-dependent antitumour effects were present also when the dose-dependent pharmacokinetics were accounted for. The prolonged schedules of CHS 828 were therefore associated with greater antitumour effects than single doses of the same total exposure.

The paclitaxel formulation, Taxol (Bristol-Myers Squibb), is one of the most effective anticancer agents used today. However; it is associated with serious side effects believed to be caused by the Cremophor EL used for its formulation.To evaluate the cytotoxic activity of a new paclitaxel formulation, Pacliex (developed by Oasmia Pharmaceutical, Uppsala, Sweden), a mixed micelles preparation in which an amphiphilic synthetic derivative of retinoic acid replaced Cremophor EL/ethanol vehicle.In this study, three model systems were used to evaluate the cytotoxic activity of Pacliex and other paclitaxel preparations. The cytotoxic activities of Pacliex, Taxol and paclitaxel in ethanol were investigated against a panel of ten human tumor cell lines using the fluorometric microculture cytotoxicity assay (FMCA). Low- and high- proliferating in vitro hollow fiber model of two cell lines, the leukemia CCRF-CEM and the myeloma RPMI 8226/S cell lines, were used to assess the cytotoxic activity of the three formulations. The in vivo hollow fiber model of the two cell lines was used for assessment of Pacliex and Taxol activity. The [3-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to analyze the in vitro and in vivo hollow fiber data.Pacliex was somewhat more effective than Taxol in the more sensitive cell lines. The activity of Taxol was more pronounced in the resistant cell lines due to an additive effect of the vehicle used. The three formulations showed similar activity in both the low- and high-proliferating in vitro hollow fiber cultures. The in vivo hollow fiber cytotoxic activity of Pacliex was similar to that of Taxol. Putting all the results together, it was found that all the three formulations had similar in vitro and in vivo activity.The three in vitro and in vivo models confirmed the similarity of the cytotoxic activities of Pacliex and Taxol. Considering the above, Pacliex could be an interesting alternative Cremophor EL-free formulation of paclitaxel.