Forecasting Urban Expansion in the Seven Lakes Area in San Pablo City, Laguna, the Philippines Using the Land Transformation Model

Managing urban growth is essential to the conservation of the Seven Lakes ecosystem in San Pablo City, Laguna province in the Philippines. This study simulates potential conversion of agricultural lands to built-up areas using the land transformation model (LTM), which integrates geographical information systems (GIS) and an artificial neural network (ANN). Historical drivers of the expansion of built-up areas are identified and validated through the application of LTM to land cover maps from 1988 to 2015. Identified drivers include distance to roads, distance to trails, distance to the Seven Lakes, distance to existing built-up areas, slopes and population density per barangay. Results from the percent correct matrix (PCM) were 79.88 per cent for the 1988–2003 runs and 66.42 per cent for the 2003–2015 runs, while the Kappa statistic for both time periods was higher than 0.60, which indicates high levels of agreement. Forecasted scenarios were business-as-usual (BAU) growth, doubled growth and strict law implementation protecting the vicinity around the Seven Lakes and other natural areas. In the BAU scenario, urban expansion spread out along the road networks. The doubled growth scenario showed that further expansion will likely extend around the proximity of the lakes, which may adversely affect the livelihoods of the local fishing communities. As such, it was recommended that preventive measures, such as strict implementation of buffer zones coupled with regular monitoring, be taken to manage land use in the surrounding lake areas

HumMeth27QCReport: an R package for quality control and primary analysis of Illumina Infinium methylation data

<p>Abstract</p> <p>Background</p> <p>The study of the human DNA methylome has gained particular interest in the last few years. Researchers can nowadays investigate the potential role of DNA methylation in common disorders by taking advantage of new high-throughput technologies. Among these, Illumina Infinium assays can interrogate the methylation levels of hundreds of thousands of CpG sites, offering an ideal solution for genome-wide methylation profiling. However, like for other high-throughput technologies, the main bottleneck remains at the stage of data analysis rather than data production.</p> <p>Findings</p> <p>We have developed <it>HumMeth27QCReport</it>, an R package devoted to researchers wanting to quickly analyse their Illumina Infinium methylation arrays. This package automates quality control steps by generating a report including sample-independent and sample-dependent quality plots, and performs primary analysis of raw methylation calls by computing data normalization, statistics, and sample similarities. This package is available at CRAN repository, and can be integrated in any Galaxy instance through the implementation of ad-hoc scripts accessible at Galaxy Tool Shed.</p> <p>Conclusions</p> <p>Our package provides users of the Illumina Infinium Methylation assays with a simplified, automated, open-source quality control and primary analysis of their methylation data. Moreover, to enhance its use by experimental researchers, the tool is being distributed along with the scripts necessary for its implementation in the Galaxy workbench. Finally, although it was originally developed for HumanMethylation27, we proved its compatibility with data generated with the HumanMethylation450 Bead Chip.</p

Influence of the Escherichia coli oxyR gene function on λ prophage maintenance

In Escherichia coli hosts, hydrogen peroxide is one of the factors that may cause induction of λ prophage. Here, we demonstrate that H2O2-mediated λ prophage induction is significantly enhanced in the oxyR mutant host. The mRNA levels for cI gene expression were increased in a λ lysogen in the presence of H2O2. On the other hand, stimulation of the pM promoter by cI857 overproduced from a multicopy plasmid was decreased in the ΔoxyR mutant in the presence of H2O2 but not under normal growth conditions. The purified OxyR protein did bind specifically to the pM promoter region. This binding impaired efficiency of interaction of the cI protein with the OR3 site, while stimulating such a binding to OR2 and OR1 sites, in the regulatory region of the pM promoter. We propose that changes in cI gene expression, perhaps in combination with moderately induced SOS response, may be responsible for enhanced λ prophage induction by hydrogen peroxide in the oxyR mutant. Therefore, OxyR seems to be a factor stimulating λ prophage maintenance under conditions of oxidative stress. This proposal is discussed in the light of efficiency of induction of lambdoid prophages bearing genes coding for Shiga toxins

Breast epithelial cell proliferation is markedly increased with short-term high levels of endogenous estrogen secondary to controlled ovarian hyperstimulation

Oocyte donors have high serum estradiol (E2) levels similar to the serum levels seen in the first trimester of pregnancy. We report in this article our studies comparing cell proliferation, Ki67 (MIB1), and estrogen and progesterone receptor levels (ERα, PRA, and PRB) in the breast terminal duct lobular units of oocyte donors, women in early pregnancy, and in normally cycling women. Breast tissue and blood samples were obtained from 10 oocyte donors, and 30 pregnant women at 5–18 weeks of gestation. Breast tissue samples were also obtained from 26 normally cycling women. In the oocyte donors: peak E2 (mean ~15,300 pmol/l) was reached on the day before oocyte (and tissue) donation; peak progesterone (P4; mean 36.3 nmol/l) was reached on the day of donation; Ki67 was positively associated with level of E2, and the mean Ki67 was 7.0% significantly greater than the mean 1.8% of cycling women. In the pregnant women: mean E2 rose from ~2,000 pmol/l at 5 weeks of gestation to ~27,000 pmol/l at 18 weeks; mean P4 did not change from ~40 nmol/l until around gestational week 11 when it increased to ~80 nmol/l; mean Ki67 was 15.4% and did not vary with gestational age or E2. Oocyte donors have greatly increased levels of E2 and of breast-cell proliferation, both comparable in the majority of donors to the levels seen in the first trimester of pregnancy. Whether their short durations of greatly increased E2 levels are associated with any long-term beneficial effects on the breast, as occurring in rodent models, is not known

Updates on radiotherapy-immunotherapy combinations: Proceedings of 6(th) annual ImmunoRad conference

Focal radiation therapy (RT) has attracted considerable attention as a combinatorial partner for immunotherapy (IT), largely reflecting a well-defined, predictable safety profile and at least some potential for immunostimulation. However, only a few RT-IT combinations have been tested successfully in patients with cancer, highlighting the urgent need for an improved understanding of the interaction between RT and IT in both preclinical and clinical scenarios. Every year since 2016, ImmunoRad gathers experts working at the interface between RT and IT to provide a forum for education and discussion, with the ultimate goal of fostering progress in the field at both preclinical and clinical levels. Here, we summarize the key concepts and findings presented at the Sixth Annual ImmunoRad conference

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Type 1 Fimbriae, a Colonization Factor of Uropathogenic Escherichia coli, Are Controlled by the Metabolic Sensor CRP-cAMP

Type 1 fimbriae are a crucial factor for the virulence of uropathogenic Escherichia coli during the first steps of infection by mediating adhesion to epithelial cells. They are also required for the consequent colonization of the tissues and for invasion of the uroepithelium. Here, we studied the role of the specialized signal transduction system CRP-cAMP in the regulation of type 1 fimbriation. Although initially discovered by regulating carbohydrate metabolism, the CRP-cAMP complex controls a major regulatory network in Gram-negative bacteria, including a broad subset of genes spread into different functional categories of the cell. Our results indicate that CRP-cAMP plays a dual role in type 1 fimbriation, affecting both the phase variation process and fimA promoter activity, with an overall repressive outcome on fimbriation. The dissection of the regulatory pathway let us conclude that CRP-cAMP negatively affects FimB-mediated recombination by an indirect mechanism that requires DNA gyrase activity. Moreover, the underlying studies revealed that CRP-cAMP controls the expression of another global regulator in Gram-negative bacteria, the leucine-responsive protein Lrp. CRP-cAMP-mediated repression is limiting the switch from the non-fimbriated to the fimbriated state. Consistently, a drop in the intracellular concentration of cAMP due to altered physiological conditions (e.g. growth in presence of glucose) increases the percentage of fimbriated cells in the bacterial population. We also provide evidence that the repression of type 1 fimbriae by CRP-cAMP occurs during fast growth conditions (logarithmic phase) and is alleviated during slow growth (stationary phase), which is consistent with an involvement of type 1 fimbriae in the adaptation to stress conditions by promoting biofilm growth or entry into host cells. Our work suggests that the metabolic sensor CRP-cAMP plays a role in coupling the expression of type 1 fimbriae to environmental conditions, thereby also affecting subsequent attachment and colonization of host tissues

Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression

Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression

Real-world data using mHealth apps in rhinitis, rhinosinusitis and their multimorbidities

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real-time, real-world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK-air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.Peer reviewe

GWAS of Suicide Attempt in Psychiatric Disorders Identifies Association With Major Depression Polygenic Risk Scores

Objective: Over 90% of suicide attempters have a psychiatric diagnosis, however twin and family studies suggest that the genetic etiology of suicide attempt (SA) is partially distinct from that of the psychiatric disorders themselves. Here, we present the largest genome-wide association study (GWAS) on suicide attempt using major depressive disorder (MDD), bipolar disorder (BIP) and schizophrenia (SCZ) cohorts from the Psychiatric Genomics Consortium. Method: Samples comprise 1622 suicide attempters and 8786 non-attempters with MDD, 3264 attempters and 5500 non-attempters with BIP and 1683 attempters and 2946 non-attempters with SCZ. SA GWAS were performed by comparing attempters to non-attempters in each disorder followed by meta-analyses across disorders. Polygenic risk scoring was used to investigate the genetic relationship between SA and the psychiatric disorders. Results: Three genome-wide significant loci for SA were found: one associated with SA in MDD, one in BIP, and one in the meta-analysis of SA in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with SA in MDD (R2=0.25%, P=0.0006), BIP (R2=0.24%, P=0.0002) and SCZ (R2=0.40%, P=0.0006). Conclusions: This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size hold potential to robustly identify genetic associations and gain biological insights into the etiology of suicide attempt