Optimization of residential green space for environmental sustainability and property appreciation in metropolitan Phoenix, Arizona.

Cities in arid and semi-arid regions have been exploring urban sustainability policies, such as lowering the vegetation coverage to reduce residential outdoor water use. Meanwhile, urban residents express concerns that such policies could potentially impact home prices regardless of the reduced water costs because studies have shown that there is a positive correlation between vegetation coverage and home values. On the other hand, lower vegetation coverage in arid and semi-arid desert regions could increase surface temperatures, and consequently increases energy costs. The question is therefore where the point in which residential outdoor water use can be minimized without overly increasing surface temperatures and negatively impacting home values. This study examines the impacts of spatial composition of different vegetation types on land surface temperature (LST), outdoor water use (OWU), and property sales value (PSV) in 302 local residential communities in the Phoenix metropolitan area, Arizona using remotely sensed data and regression analysis. In addition, the spatial composition of vegetation cover was optimized to achieve a relatively lower LST and OWU and maintain a relatively higher PSV at the same time. We found that drought-tolerant landscaping that is composed of mostly shrubs and trees adapted to the desert environment is the most water efficient way to reduce LST, but grass contributes to a higher PSV. Research findings suggest that different residential landscaping strategies may be better suited for different neighborhoods and goal sets can be used by urban planners and city managers to better design urban residential landscaping for more efficient water conservation and urban heat mitigation for desert cities.

An overview of systematic reviews on the public health consequences of social isolation and loneliness.

OBJECTIVES: Social isolation and loneliness have been associated with ill health and are common in the developed world. A clear understanding of their implications for morbidity and mortality is needed to gauge the extent of the associated public health challenge and the potential benefit of intervention. STUDY DESIGN: A systematic review of systematic reviews (systematic overview) was undertaken to determine the wider consequences of social isolation and loneliness, identify any differences between the two, determine differences from findings of non-systematic reviews and to clarify the direction of causality. METHODS: Eight databases were searched from 1950 to 2016 for English language reviews covering social isolation and loneliness but not solely social support. Suitability for inclusion was determined by two or more reviewers, the methodological quality of included systematic reviews assessed using the a measurement tool to assess systematic reviews (AMSTAR) checklist and the quality of evidence within these reviews using the grading of recommendations, assessment, development and evaluations (GRADE) approach. Non-systematic reviews were sought for a comparison of findings but not included in the primary narrative synthesis. RESULTS: Forty systematic reviews of mainly observational studies were identified, largely from the developed world. Meta-analyses have identified a significant association between social isolation and loneliness with increased all-cause mortality and social isolation with cardiovascular disease. Narrative systematic reviews suggest associations with poorer mental health outcomes, with less strong evidence for behavioural and other physical health outcomes. No reviews were identified for wider socio-economic or developmental outcomes. CONCLUSIONS: This systematic overview highlights that there is consistent evidence linking social isolation and loneliness to worse cardiovascular and mental health outcomes. The role of social isolation and loneliness in other conditions and their socio-economic consequences is less clear. More research is needed on associations with cancer, health behaviours, and the impact across the life course and wider socio-economic consequences. Policy makers and health and local government commissioners should consider social isolation and loneliness as important upstream factors impacting on morbidity and mortality due to their effects on cardiovascular and mental health. Prevention strategies should therefore be developed across the public and voluntary sectors, using an asset-based approach.

Comparison of genome sequencing and clinical genotyping for pharmacogenes.

We compared whole exome sequencing (WES, n = 176 patients) and whole genome sequencing (WGS, n = 68) and clinical genotyping (DMET array-based approach) for interrogating 13 genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. We focused on 127 CPIC important variants: 103 single nucleotide variations (SNV), 21 insertion/deletions (Indel), HLA-B alleles, and two CYP2D6 structural variations. WES and WGS provided interrogation of nonoverlapping sets of 115 SNV/Indels with call rate >98%. Among 68 loci interrogated by both WES and DMET, 64 loci (94.1%, confidence interval [CI]: 85.6-98.4%) showed no discrepant genotyping calls. Among 66 loci interrogated by both WGS and DMET, 63 loci (95.5%, CI: 87.2-99.0%) showed no discrepant genotyping calls. In conclusion, even without optimization to interrogate pharmacogenetic variants, WES and WGS displayed potential to provide reliable interrogation of most pharmacogenes and further validation of genome sequencing in a clinical lab setting is warranted.

16(th) IHIW: global distribution of extended HLA haplotypes.

This report describes the project to identify the global distribution of extended HLA haplotypes, a component of 16th International HLA and Immunogenetics Workshop (IHIW), and summarizes the initial analyses of data collected. The project aims to investigate extended HLA haplotypes, compare their distribution among different populations, assess their frequency in hematopoietic stem cell unrelated donor registries and initiate an international family studies database and DNA repository to be made publicly available. HLA haplotypes compiled in immunogenetics laboratories during the evaluation of transplant candidates and related potential donors were analysed. Haplotypes were determined using the pedigree analysis tool publicly available from the National Marrow Donor Program (NMDP) website. Nineteen laboratories from 10 countries (11 laboratories from North America, five from Asia, two from Latin America and one from Australia) contributed data on a total of 1719 families comprised of 7474 individuals. We identified 10393 HLA haplotypes, of which 1682 haplotypes included high-resolution typing at HLA-A, B, C, DRB1 and DQB1 loci. We also present haplotypes containing MICA and other HLA loci and haplotypes containing rare alleles seen in these families. The project will be extended through the 17th IHIW, and investigators interested in joining the project may communicate with the first author.

16(th) IHIW: immunogenomic data-management methods. report from the immunogenomic data analysis working group (IDAWG).

SUMMARY: The goal of the immunogenomic data analysis working group (IDAWG) is to facilitate the consistent analysis of HLA and KIR data, and the sharing of those data among the immunogenomic and larger genomic communities. However, the data management approaches currently applied by immunogenomic researchers are not widely discussed or reported in the literature, and the effect of different approaches on data analyses is not known. With ASHI's support, the IDAWG developed a 45 question survey on HLA and KIR data generation, data management and data analysis practices. Survey questions detailed the loci genotyped, typing systems used, nomenclature versions reported, computer operating systems and software used to manage and transmit data, the approaches applied to resolve HLA ambiguity and the methods used for basic population-level analyses. Respondents were invited to demonstrate their HLA ambiguity resolution approaches in simulated data sets. By May 2012, 156 respondents from 35 nations had completed the survey. These survey respondents represent a broad sampling of the Immunogenomic community; 52% were European, 30% North American, 10% Asian, 4% South American and 4% from the Pacific. The project will continue in conjunction with the 17th Workshop, with the aim of developing community data sharing standards, ambiguity resolution documentation formats, single-task data Management tools and novel data analysis methods and applications. While additional project details and plans for the 17th IHIW will be forthcoming, we welcome the input and participation in these projects from the histocompatibility and immunogenetics community.

Distance Education as a Tool for Training Veterinarians in Laboratory Animal Medicine / 中国比较医学杂志

With increasing globalization and a trend towards international harmonization of standards for the care and use of animals in research and testing,there is a significant need to assist and support countries to develop training programs for laboratory animal veterinarians. Although formal educational opportunities for training laboratory animal veterinarians exist through well-established specialty colleges of laboratory animal medicine such as ACLAM,ECLAM,JCLAM,and KCLAM or through other professional organisations,such as the Federation of European Laboratory Animal Science Associations ( FELASA ),opportunities for participating in these programs are often limited to veterinarians in North America,Western Europe and specific regions of Asia. Creative thinking is required to develop cost-effective,practical,entry-level and advanced continuing education and applied training programs for veterinarians working in the field of laboratory animal medicine around the world.This paper will describe one potential solution for this issue,the use of a distance education program that provides theoretical information in a virtual classroom with applied training modules to deliver knowledge and practical skills to laboratory animal veterinarians.This type of program takes advantage of the online learning environment and can be an effective means to deliver training at the grassroots level to adult learners.

Effects of activating NK cell receptor expression and NK cell reconstitution on the outcomes of unrelated donor hematopoietic cell transplantation for hematologic malignancies.

Inhibitory NK cell receptors are recognized as important determinants of NK cell activity in hematopoietic cell transplantation (HCT). The role of activating receptors and their acquisition after HCT is less certain. Therefore, we comprehensively evaluated both inhibitory and activating receptors in 59 patients receiving unrelated donor HCT. NK cell numbers normalized quickly relative to B and T cells; however, the expression of both inhibitory and activating isoforms of killer immunoglobulin-like receptors (KIRs) was delayed. Most NK cells expressed an immature phenotype during the first 6 months post-HCT; however, we found high expression of activating NKp46 and NKp44 natural cytotoxicity receptors (NCRs), and cytotoxicity was preserved. Early reconstituting NK cells from unmanipulated grafts showed lower cytotoxicity than those from T-cell-depleted grafts. Differences in NK cell reconstitution had significant effects on clinical outcomes. Patients whose NK cells reconstituted earlier had better survival and lower relapse rates. The best survival group was recipients who possessed HLA-C2 but their donor lacked the cognate-activating KIR2DS1. Collectively, our data underscore the clinical relevance of reconstituting NK cells and their activating KIRs and NCRs. In addition to NK cell quantification and genotyping, comprehensive assessment of NK cell functions and phenotypes, including activating receptors, is essential.

Inhibitory KIR-HLA receptor-ligand mismatch in autologous haematopoietic stem cell transplantation for solid tumour and lymphoma.

Genes that encode killer Ig-like receptors (KIRs) and their HLA class I ligands segregate independently; thus, some individuals may express an inhibitory KIR gene but not its cognate ligand. We hypothesised that these patients with KIR-HLA receptor-ligand mismatch have a low risk of relapse after an autologous haematopoietic stem cell transplantation (HCT). Sixteen consecutive patients with lymphoma or solid tumour were enrolled onto a prospective study. They received high-dose busulphan and melphalan followed by autologous CD133(+) HCT. We found that 8 of the 16 patients experienced disease progression after autologous HCT, including 5 of the 6 patients (83%) with no inhibitory KIR-HLA mismatch and 3 of the 6 patients (50%) with 1 mismatched pair; none of the 4 (0%) patients with 2 mismatched pairs experienced disease progression. Survival analyses showed that inhibitory KIR-HLA mismatch was the only significant prognostic factor (P=0.01). The potential applicability of the receptor-ligand mismatch model to autologous HCTs and to patients with lymphoma or solid tumour is clinically significant because of the prevalence of the HCT procedure.

Twenty-three novel HLA-B alleles identified during intermediate-resolution testing.

Twenty-three novel human leukocyte antigen-B alleles are described: B*070204, *0738, *0742, *0821, *130202, *1312, *1575, *1598, *1599, *270507, *2728, *350104, *3558, *3811, *3931, *3932, *4045, *4107, *420501, *4812, *510106, *5520, and *5616. Thirteen of the variants are single-nucleotide substitutions from their most homologous allele, eight resulting in amino acid changes (B*0742, *1312, *1598, *1599, *3558, *3931, *4107, and *5616) and five with silent substitutions (B*070204, *130202, *270507, *350104, and *510106). Three alleles (B*0738, *4812, and *5520) differ by five nucleotide changes, altering four amino acids. The remaining seven alleles differ from their most similar alleles by two to three nucleotides, altering from one to two amino acids.

Effect of HLA class I or class II incompatibility in pediatric marrow transplantation from unrelated and related donors.

The degree of histoincompatibility that can be tolerated, and the relative importance of matching at individual HLA class I and class II locus in bone marrow transplantation (BMT) has not been established. We hypothesized that matching for HLA-DR may not be more important than matching for HLA-A or HLA-B in selection of a donor for successful BMT. We retrospectively analyzed the outcomes of 248 consecutive pediatric patients who received allogeneic BMT from related donors (RD, n = 119) or unrelated donors (URD, n = 129). HLA-A and HLA-B were serologically matched, and HLA-DRB1 were identical by DNA typing in 69% of donor-recipient pairs. Most patients (89%) had hematologic malignancies; the rest had aplastic anemia or a congenital disorder. One HLA-A antigen mismatch was associated with a decrease in survival (p = 0.003) and a delay in granulocyte engraftment (p = 0.02) in recipients of RD marrow; as well as a decrease in survival (p = 0.02) and the development of severe acute graft-versus-host disease (GVHD) (p = 0.03) in recipients of URD marrow. One HLA-B antigen mismatch was associated with a decrease in the survival (p = 0.05) and the development of severe GVHD (p = 0.0007) in recipients of RD marrow. One HLA-DRB1 allele mismatch was associated only with a decrease in the survival (p = 0.0003) of recipients of RD marrow. Results of this study suggest that disparity in HLA-A and HLA-B antigens may not be better tolerated than disparity in HLA-DR allele in allogeneic BMT. Further studies are warranted to confirm our results.

Tissue distribution of indoleamine 2,3-dioxygenase in normal and malaria-infected tissue.

An immunohistochemical method was developed, using a polyclonal antibody, to detect the enzyme indoleamine 2,3-dioxygenase (IDO) in normal and malaria-infected tissue. Plasmodium berghei ANKA, a cerebral malaria (CM) model, and P. berghei K173, a non-cerebral malaria (NCM) model, were used. It was found that vascular endothelial cells were the primary site of IDO expression in both models of malaria infection and that this response was systemic, with the vascular endothelium of brain, heart, lung, spleen and uterus all staining positive. These results suggest that IDO is part of a systemic host response to parasite infection. Although high levels of IDO production alone may not cause pathology, it is possible that when its production is combined with other features of CM, such as breakdown of the blood-brain barrier (BBB), metabolites of the kynurenine pathway may be able to influence the otherwise tightly regulated, immunologically privileged site of the CNS and cause some of the symptoms and pathology observed.

Growth arrest-specific gene 6 expression in proliferating rabbit vascular smooth muscle cells in vitro and in vivo.

Proliferation and migration of vascular smooth muscle cells (VSMCs) are involved in the processes of atherosclerosis and restenosis. The protein product of the growth arrest-specific gene 6 (Gas-6) has recently been identified as a ligand for the Axl/Rse/Mer tyrosine kinase receptor family, which may be involved in proliferation and migration of VSMCs. Here we show that Gas-6 gene expression is increased in proliferating VSMCs in tissue culture (2.5-fold increase by Northern blot) and following neointimal proliferation in a rabbit balloon-injury model (3-fold increase by Western blot). Neither platelet-derived growth factor (PDGF) nor thrombin stimulate the expression of Gas-6 in cultured VSMCs despite the ability of the PDGF, but not thrombin, to stimulate proliferation in growth-arrested cells. These data suggest a role for the Gas-6 regulatory system in VSMC proliferation, which may be a target for therapeutic interventions in the atherosclerotic process and restenosis after angioplasty.

A critical analysis of the pharmacology of AZT and its use in AIDS.

The triphosphorylated form of the nucleoside analogue 3'-azido-3'-deoxythymidine (Zidovudine, AZT) is claimed to interrupt the HIV replication cycle by a selective inhibition of viral reverse transcriptase, thereby preventing the formation of new proviral DNA in permissive, uninfected cells. Given that initial HIV infection of an individual instigates abundant HIV replication from inception until death, and that the life of infected T-cells is only several days, the administration of AZT should lead both in vitro and in vivo (i) to decreased formation of proviral DNA; and thus (ii) to decreased frequencies of 'HIV isolation' (detection of p24 or reverse transcription or both) in stimulated cultures/cocultures of T-cells from seropositive individuals; (iii) to decreased synthesis of HIV p24 and RNA ('antigenaemia', 'plasma viraemia', 'viral load') ultimately resulting in low or absent levels of all three parameters; and (iv) to a perfect and direct correlation between all these parameters. A critical analysis of the presently available data shows that no such evidence exists, an outcome not unexpected given the pharmacological data on AZT. HIV experts all agree that only the triphosphorylated form of AZT (AZTTP) and not the unphosphorylated form administered to patients, nor its mono- or diphosphate, is the active agent. Furthermore, the mechanism of action is the ability of AZTTP to halt the formation of HIV-DNA (chain termination). However, although this claim was posited from the outset, AZT underwent clinical trials and was introduced as a specific anti-HIV drug many years before there were any data proving that the cells of patients are able to triphosphorylate the parent compound to a level considered sufficient for its putative pharmacological action. Notwithstanding, from the evidence published since 1991 it has become apparent that no such phosphorylation takes place and thus AZT cannot possess an anti-HIV effect. However, the scientific literature does elucidate: (i) a number of biochemical mechanisms which predicate the likelihood of widespread, serious toxicity from use of this drug; (ii) in vitro data proving that AZT has significant antibacterial and antiviral properties which confound interpretation of its effects when administered to patients. Based on all these data it is difficult if not impossible to explain why AZT was introduced and still remains the most widely recommended and used anti-HIV drug.

Incidence estimates of late stages of trachoma among women in a hyperendemic area of central Tanzania.

The purpose of this study is to estimate 5-year incidences of conjunctival scarring and trichiasis, and 10-year incidence of corneal opacities due to trachoma, using prevalence data from a population sample of 6038 women living in a trachoma-hyperendemic area of central Tanzania. Previous surveys have documented the age-specific prevalence of scarring, trichiasis, and corneal opacities in women in hyperendemic areas. Using the age-stratified prevalences of these different clinical signs, corresponding incidence rates were estimated. Transition rates from one sign to the next were also obtained by restricting the risk group to only women with a specific trachoma sign. Thus, the 5-year incidence of trichiasis among women with conjunctival scarring, and the 10-year incidence of corneal opacities among women with trichiasis were estimated. Incidences of all the signs markedly increased with age. For scarring, 5-year incidence rates increased from 3.1% in the 15-19 age category to 14.3% for women between 55 and 59 years. The 5-year incidence of trichiasis ranged from 0.3% in the 15-19 age category to 7.5% in the age group 55-59. Corneal opacities due to trachoma were highest in the age group 45-54; the 10-year incidence increased to 2.8%. The 5-year incidence of trichiasis among only women with scars increased from 3.2% in the 15-19 age group to 15.1% in women in the 55-59 age group. Once trichiasis is present, almost one-third of the women below 35 and more than 40% of the women older than 45 will develop corneal opacities in a 10-year interval. These estimates are important in understanding the dynamics of progression of trachoma from conjunctival scarring to the potentially blinding signs of trichiasis and corneal opacities. They provide important information for planning adequate services in areas where trachoma is endemic and surgery for trichiasis is a key factor to avoid blindness from trachoma. They also provide clues to the pathogenesis that may be useful in the development of new methods of control.