Human papillomavirus infection in women with and without cervical cancer in Karachi, Pakistan

BACKGROUND: No data exist on the population prevalence of, or risk factors for, human papillomavirus (HPV) infection in predominantly Muslim countries in Asia. METHODS: Cervical specimens were obtained from 899 married women aged 15-59 years from the general population of Karachi, Pakistan and from 91 locally diagnosed invasive cervical cancers (ICCs). HPV was detected using a GP5+/6+ PCR-based assay. RESULTS: The prevalence of HPV in the general population was 2.8%, with no evidence of higher HPV prevalence in young women. The positivity of HPV was associated with women's lifetime number of sexual partners, but particularly with the age difference between spouses and other husbands' characteristics, such as extramarital sexual relationships and regular absence from home. The HPV16/18 accounted for 24 and 88% of HPV-positive women in the general population and ICC, respectively. CONCLUSION: Cervical cancer prevention policies should take into account the low HPV prevalence and low acceptability of gynaecological examination in this population

Litterfall production in a tropical mangrove of Sarawak, Malaysia

Assessment of litterfall production is essential to ascertain the status of nutrient cycling and forest health. Sarawak, Malaysia, is endowed with numerous pristine and estuarine mangroves; however, research on primary productivity of these forests is scanty. Therefore, litterfall production in a pristine Sibuti mangrove of Sarawak was estimated using litter traps for one year (January–December 2013), and forest structure was studied through tree census. The forest was dominated by Rhizophora apiculata (relative density [RD] was 77.11%), followed by Xylocarpus granatum (RD was 16.92%) and other species (RD was only 5.97%). The annual dry weight of litterfalls was estimated to be 1640.82 g m−2, of which R. apiculata contributed 92.94%, followed by X. granatum (4.01%) and other species (3.05%). Leaves were the most abundant (57.21%) contributory component of litters, followed by propagules (11.89%), flowers (10.85%), twigs (8.56%), and stipules (8.45%). No significant correlations were found for total litterfall and its major components with climatic variables and forest structure. Total litterfall of R. apiculata and X. granatum did not show any seasonal variations. However, leaf litter of R. apiculata showed a significant seasonal variation between intermediate (January–April) and wet (September–December) seasons. The litterfall production of Sibuti mangrove forest is higher in comparison to other tropical mangroves of the world. The higher productivity of the forest could be due to nutrient availability, pristine nature, and stand maturity of the forest rather than climatic influences. The findings of the study suggest that litterfall production of the pristine Sibuti mangrove is not influenced by the variability of climatic factors

Low-flow analysis of the rivers in the Ljubljanica watershed

Methanol is the second most abundant volatile organic compound in the troposphere and plays a significant role in atmospheric chemistry. While there is consensus about the dominant role of living plants as the major source and the reaction with OH as the major sink of methanol, global methanol budgets diverge considerably in terms of source/sink estimates reflecting uncertainties in the approaches used to model, and the empirical data used to separately constrain these terms. Here we compiled micrometeorological methanol flux data from eight different study sites and reviewed the corresponding literature in order to provide a first cross-site synthesis of the terrestrial ecosystem-scale methanol exchange and present an independent data-driven view of the land–atmosphere methanol exchange. Our study shows that the controls of plant growth on the production, and thus the methanol emission magnitude, and stomatal conductance on the hourly methanol emission variability, established at the leaf level, hold across sites at the ecosystem-level. Unequivocal evidence for bi-directional methanol exchange at the ecosystem scale is presented. Deposition, which at some sites even exceeds methanol emissions, represents an emerging feature of ecosystem-scale measurements and is likely related to environmental factors favouring the formation of surface wetness. Methanol may adsorb to or dissolve in this surface water and eventually be chemically or biologically removed from it. Management activities in agriculture and forestry are shown to increase local methanol emission by orders of magnitude; they are however neglected at present in global budgets. While contemporary net land methanol budgets are overall consistent with the grand mean of the micrometeorological methanol flux measurements, we caution that the present approach of simulating methanol emission and deposition separately is prone to opposing systematic errors and does not allow taking full advantage of the rich information content of micrometeorological flux measurements

Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium

BACKGROUND: Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited. METHODS AND FINDINGS: The European consortium ABIRISK (Anti-Biopharmaceutical Immunization: prediction and analysis of clinical relevance to minimize the RISK) conducted a clinical and genomic multicohort prospective study of 560 patients with multiple sclerosis (MS, n = 147), rheumatoid arthritis (RA, n = 229), Crohn's disease (n = 148), or ulcerative colitis (n = 36) treated with 8 different biopharmaceuticals (etanercept, n = 84; infliximab, n = 101; adalimumab, n = 153; interferon [IFN]-beta-1a intramuscularly [IM], n = 38; IFN-beta-1a subcutaneously [SC], n = 68; IFN-beta-1b SC, n = 41; rituximab, n = 31; tocilizumab, n = 44) and followed during the first 12 months of therapy for time to ADA development. From the bioclinical data collected, we explored the relationships between patient-related factors and the occurrence of ADAs. Both baseline and time-dependent factors such as concomitant medications were analyzed using Cox proportional hazard regression models. Mean age and disease duration were 35.1 and 0.85 years, respectively, for MS; 54.2 and 3.17 years for RA; and 36.9 and 3.69 years for inflammatory bowel diseases (IBDs). In a multivariate Cox regression model including each of the clinical and genetic factors mentioned hereafter, among the clinical factors, immunosuppressants (adjusted hazard ratio [aHR] = 0.408 [95% confidence interval (CI) 0.253-0.657], p < 0.001) and antibiotics (aHR = 0.121 [0.0437-0.333], p < 0.0001) were independently negatively associated with time to ADA development, whereas infections during the study (aHR = 2.757 [1.616-4.704], p < 0.001) and tobacco smoking (aHR = 2.150 [1.319-3.503], p < 0.01) were positively associated. 351,824 Single-Nucleotide Polymorphisms (SNPs) and 38 imputed Human Leukocyte Antigen (HLA) alleles were analyzed through a genome-wide association study. We found that the HLA-DQA1*05 allele significantly increased the rate of immunogenicity (aHR = 3.9 [1.923-5.976], p < 0.0001 for the homozygotes). Among the 6 genetic variants selected at a 20% false discovery rate (FDR) threshold, the minor allele of rs10508884, which is situated in an intron of the CXCL12 gene, increased the rate of immunogenicity (aHR = 3.804 [2.139-6.764], p < 1 × 10-5 for patients homozygous for the minor allele) and was chosen for validation through a CXCL12 protein enzyme-linked immunosorbent assay (ELISA) on patient serum at baseline before therapy start. CXCL12 protein levels were higher for patients homozygous for the minor allele carrying higher ADA risk (mean: 2,693 pg/ml) than for the other genotypes (mean: 2,317 pg/ml; p = 0.014), and patients with CXCL12 levels above the median in serum were more prone to develop ADAs (aHR = 2.329 [1.106-4.90], p = 0.026). A limitation of the study is the lack of replication; therefore, other studies are required to confirm our findings. CONCLUSION: In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: Recommendations of the innovative medicines initiative ABIRISK consortium

Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies, and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry, and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk, and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices, and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium (Anti-Biopharmaceutical [BP] Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu), was formed by leading clinicians, academic scientists, and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation, and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp). This article is protected by copyright. All rights reserved

7th Drug hypersensitivity meeting: part two

No abstract availabl