Molecular epidemiology of human cutaneous leishmaniasis in Jericho and its vicinity in Palestine from 1994 to 2015

Cutaneous leishmaniases (CL) are vector-borne parasitic diseases endemic inmany countries of the Middle East including Palestine. Between 1994 and 2015, 2160 clinically suspected human cases of CL from the Jericho District were examined. Stained skin tissue smears and aspirates were checked by microscopy and cultured for promastigotes, respectively. For leishmanial species identification, amplification products from a PCR-ITS1 followed by RFLP analysis using Hae III. Data were analyzed using Epi Info free-software. The overall infection rate was 41.4% (895/2160), 56.3% (504/895) of the cases were male, 43.7% (391/895) female, 60.5% (514/849) children under age 14, 41.3% (259/627) of the cases were caused by Leishmania major and 57.3% (359/627) by Leishmania tropica. The case numbers peaked in 1995, 2001, 2004, and 2012. Statistically-significant clusters of cases caused by L. major were restricted to the Jericho District; those caused by L. tropica were from the districts of Jericho, Bethlehem, Nablus and Tubas. CL is seasonal and trails the sand fly season. Distribution of cases was parabolicwith fewest in July. Themonthly total number of cases of CL and just those caused by L.major correlated significantly with temperature, rainfall, relative humidity, evaporation, wind speed and sunshine (P b 0.05, r2= 0.7–0.9 and P b 0.05, r2=0.5–0.8, respectively). Cases caused by L. tropica, significantly, had a single lesion compared to cases caused by L. major (P=0.0001), which, significantly, had multiple lesions (P=0.0001). This and previous studies showed that CL is present in all Palestinian districts. The surveillance of CL has increased public awareness and molecular biologicalmethodology for leishmanial species identification is an essential addition to classical diagnosis. The overall results are discussed, correlated to climatic and environmental changes and largescale human activities.This work received financial support from grants of the Deutsche Forschungsgemeinschaft (DFG), Scho 448/6-1-3, Scho 448/8-1, Scho 448/8-2 that extended from 1998 until 2015. It also received support fromEurNegVeg COST Action TD1303 (Cost 037/13). At one time during the study WHO Eastern Mediterranean Region (EMRO), Division of Communicable Diseases (DCD) and the WHO Special Programme for Research and Training in Tropical Diseases (TDR): the EMRO/DCD/TDR Small Grants Scheme for Operational Research in Tropical and Communicable Diseases financially supported this work. We thank Dr. L. F. Schnur for going over our manuscript

Continuity Culture: A Key Factor for Building Resilience and Sound Recovery Capabilities

This article investigates the extent to which Jordanian service organizations seek to establish continuity culture through testing, training, and updating of their business continuity plans. A survey strategy was adopted in this research. Primary and secondary data were used. Semistructured interviews were conducted with five senior managers from five large Jordanian service organizations registered with the Amman Stock Exchange. The selection of organizations was made on the basis of simple random sampling. Interviews targeted the headquarters only in order to obtain a homogenous sample. Three out of five organizations could be regarded as crisis prepared and have better chances for recovery. The other two organizations exhibited characteristics of standard practice that only emphasizes the recovery aspect of business continuity management (BCM), while paying less attention to establishing resilient cultures and embedding BCM. The findings reveal that the ability to recover following major incidents can be improved by embedding BCM in the culture of the organization and by making BCM an enterprise-wide process. This is one of few meticulous studies that have been undertaken in the Middle East and the first in Jordan to investigate the extent to which service organizations focus on embedding BCM in the organizational culture

The Politics of Pleasure: Promenading on the Corniche and Beachgoing

Can the pleasures of young Palestinian women from refugee camps in promenading on the Beirut seaside Corniche on a warm summer evening be political? Or days spent at women-only beaches? If so, how do we understand such pleasure as everyday practices, as a politics of the present moment, or conversely (or simultaneously) as mechanisms of being co-opted into a broader apparatus of consumerist ideology and capitalist complacency? Drawing on ethnographic research over 2 years I argue that these moments of pleasure are caesuras in the massive apparatus of power – welded from strands of work, neoliberal practice, nationalist certitudes and political exclusion – which binds these women. These acts of pleasure cannot easily be categorised as ‘resistance’ but I argue that they should not facilely be considered reinforcements of hegemonic control either. They are momentary and ephemeral recognitions of ordinary life lived in hard times, attempts at clawing back an instant of joy from the drudgery of the everyday, and a surrender to the enjoyment of conviviality in public and urban spaces. If they are at all political, they are so because such conviviality is ever harder to sustain in the calamity of hopelessness that characterises so much politics today

Splitting Arabic Texts into Elementary Discourse Units

International audienceIn this article, we propose the first work that investigates the feasibility of Arabic discourse segmentation into elementary discourse units within the segmented discourse representation theory framework. We first describe our annotation scheme that defines a set of principles to guide the segmentation process. Two corpora have been annotated according to this scheme: elementary school textbooks and newspaper documents extracted from the syntactically annotated Arabic Treebank. Then, we propose a multiclass supervised learning approach that predicts nested units. Our approach uses a combination of punctuation, morphological, lexical, and shallow syntactic features. We investigate how each feature contributes to the learning process. We show that an extensive morphological analysis is crucial to achieve good results in both corpora. In addition, we show that adding chunks does not boost the performance of our system

Ethnic differences in DNA methyltransferases expression in patients with systemic lupus erythematosus

Systemic lupus erythematous (SLE) is a systemic autoimmune inflammatory disease with both genetic and epigenetic etiologies. Evidence suggests that deregulation of specific genes through epigenetic mechanisms may be a contributing factor to SLE pathology. There is increasing evidence that DNA methyltransferase activity may be involved. This study demonstrated modulation in expression of DNA methyltransferases (DNMTs) according to ethnicity in patients diagnosed with SLE. Furthermore, differential expression in one of the DNMTs was found in a subset of lupus patients on dehydroepiandrosterone (DHEA) therapy. Real-time PCR analyses of DNMT1, DNMT3A and DNMT3B in peripheral blood mononuclear cells from a cohort of African American and European American lupus and non-lupus women were conducted. Also, global DNA methylation was assessed using the MethylFlash.sup.TM methylated quantification colorimetric assay. These findings suggest that epigenetic changes may play a critical role in the manifestations of the disease observed among ethnic groups, particularly African American women who often have a higher incidence of lupus. DHEA therapy effects on DNMT3A expression in AA women warrant further investigation in a larger population

Trans-Ancestral Studies Fine Map the SLE-Susceptibility Locus TNFSF4

We previously established an 80 kb haplotype upstream of TNFSF4 as a susceptibility locus in the autoimmune disease SLE. SLE-associated alleles at this locus are associated with inflammatory disorders, including atherosclerosis and ischaemic stroke. In Europeans, the TNFSF4 causal variants have remained elusive due to strong linkage disequilibrium exhibited by alleles spanning the region. Using a trans-ancestral approach to fine-map the locus, utilising 17,900 SLE and control subjects including Amerindian/Hispanics (1348 cases, 717 controls), African-Americans (AA) (1529, 2048) and better powered cohorts of Europeans and East Asians, we find strong association of risk alleles in all ethnicities; the AA association replicates in African-American Gullah (152,122). The best evidence of association comes from two adjacent markers: rs2205960-T (P = 1.71×10-34, OR = 1.43[1.26-1.60]) and rs1234317-T (P = 1.16×10-28, OR = 1.38[1.24-1.54]). Inference of fine-scale recombination rates for all populations tested finds the 80 kb risk and non-risk haplotypes in all except African-Americans. In this population the decay of recombination equates to an 11 kb risk haplotype, anchored in the 5′ region proximal to TNFSF4 and tagged by rs2205960-T after 1000 Genomes phase 1 (v3) imputation. Conditional regression analyses delineate the 5′ risk signal to rs2205960-T and the independent non-risk signal to rs1234314-C. Our case-only and SLE-control cohorts demonstrate robust association of rs2205960-T with autoantibody production. The rs2205960-T is predicted to form part of a decameric motif which binds NF-κBp65 with increased affinity compared to rs2205960-G. ChIP-seq data also indicate NF-κB interaction with the DNA sequence at this position in LCL cells. Our research suggests association of rs2205960-T with SLE across multiple groups and an independent non-risk signal at rs1234314-C. rs2205960-T is associated with autoantibody production and lymphopenia. Our data confirm a global signal at TNFSF4 and a role for the expressed product at multiple stages of lymphocyte dysregulation during SLE pathogenesis. We confirm the validity of trans-ancestral mapping in a complex trait. © 2013 Manku et al

Integration of sequence data from a consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10-6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. © 2014 Plenge et al

Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries

Objective: Systemic lupus erythematosus (SLE; OMIM 152700) is a chronic autoimmune disease for which the aetiology includes genetic and environmental factors. ITGAM, integrin ?M(complement component 3 receptor 3 subunit) encoding a ligand for intracellular adhesion molecule (ICAM) proteins, is an established SLE susceptibility locus. This study aimed to evaluate the independent and joint effects of genetic variations in the genes that encode ITGAM and ICAM. Methods: The authors examined several markers in the ICAM1-ICAM4-ICAM5 locus on chromosome 19p13 and the single ITGAM polymorphism (rs1143679) using a large-scale case-control study of 17 481 unrelated participants from four ancestry populations. The singlemarker association and gene-gene interaction were analysed for each ancestry, and a meta-analysis across the four ancestries was performed. Results: The A-allele of ICAM1-ICAM4-ICAM5 rs3093030, associated with elevated plasma levels of soluble ICAM1, and the A-allele of ITGAM rs1143679 showed the strongest association with increased SLE susceptibility in each of the ancestry populations and the trans-ancestry meta-analysis (ORmeta=1.16, 95% CI 1.11 to 1.22; p=4.88 × 10-10 and ORmeta=1.67, 95% CI 1.55 to 1.79; p=3.32 × 10-46, respectively). The effect of the ICAM single-nucleotide polymorphisms (SNPs) was independent of the effect of the ITGAM SNP rs1143679, and carriers of both ICAM rs3093030-AA and ITGAM rs1143679-AA had an OR of 4.08 compared with those with no risk allele in either SNP (95% CI 2.09 to 7.98; p=3.91 × 10-5). Conclusion: These findings are the first to suggest that an ICAM-integrin-mediated pathway contributes to susceptibility to SLE