Perinatal Gene Transfer to the Liver

The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable. In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer

Accuracy assessment and position correction for low-cost non-differential GPS as applied on an industrial peat bog

A low-cost, non-differentially corrected hand-held GPS receiver was tested on an industrial peat production bog. A correction procedure (‘pseudo-differential correction’) was derived that corrected data points to the nearest position on a line defining the centre of each 15-m wide field. The result was a corrected log of track points for each field for all points lying along the field. It was found that the mean orthogonal distance from a field centreline was linearly correlated with mean uncorrected GPS data error (r2=0.99) such that as GPS error increased so the accuracy obtained by correction decreased. For a signal with a mean uncorrected error of 30 m it was possible to reduce the error to 12 m. The results are discussed within the design requirements of a precision peat production system for peat energy. It is concluded that low-cost GPS could be used without differential correction as part of a precision peat production system because over 80% of the time positional error could be constrained to within 15 m. When compared with the perceived patterns of variability and the 30-m resolution of Landsat imagery which can be used for making application maps, this is acceptable

Adherence to antiretroviral therapy in adolescents living with HIV: systematic review and meta-analysis

OBJECTIVE: Adolescent and young adult (AYA) populations (12–24 years) represent over 40% of new HIV infections globally. Adolescence is sometimes characterized by high-risk sexual behaviour and a lack of engagement with healthcare services that can affect adherence to antiretroviral therapy (ART). Despite adherence to ART being critical in controlling viral replication, maintaining health and reducing onward viral transmission, there are limited data on ART adherence amongst AYA globally. We undertook a systematic review and meta-analysis of published studies reporting adherence to ART for AYA living with HIV. DESIGN AND METHODS: Searches included Embase, Medline and PsychINFO databases up to 14 August 2013. Eligible studies defined adequate adherence as at least 85% on self-report or undetectable blood plasma virus levels. A random effects meta-analysis was performed and heterogeneity examined using meta-regression. RESULTS: We identified 50 eligible articles reporting data from 53 countries and 10 725 patients. Using a pooled analysis of all eligible studies, 62.3% [95% confidence interval (CI) 57.1–67.6; I(2) : 97.2%] of the AYA population were adherent to therapy. The lowest average ART adherence was in North America [53% (95% CI 46–59; I(2) : 91%)], Europe [62% (95% CI 51–73; I(2) : 97%)] and South America [63% (95% CI 47–77; I(2) : 85%] and, with higher levels in Africa [84% (95% CI 79–89; I(2) : 93%)] and Asia [84% (95% CI 77–91; I(2) : 0%]. CONCLUSION: Review of published literature from Africa and Asia indicate more than 70% of HIV-positive AYA populations receiving ART are adherent to therapy and lower rates of adherence were shown in Europe and North America at 50–60%. The global discrepancy is probably multifactorial reflecting differences between focused and generalised epidemics, access to healthcare and funding

Differential gene expression profile in the small intestines of mice lacking pacemaker interstitial cells of Cajal

BACKGROUND: We previously identified eight known and novel genes differentially expressed in the small intestines of wild type and W/W(V )mice, which have greatly reduced populations of the interstitial cells of Cajal, that are responsible for the generation of electrical slow waves, by using a differential gene display method. METHODS: By using the same method we isolated additional candidate genes that were specifically down- or up-regulated in W/W(V )mice. Novel transcripts were designated as DDWMEST. RESULTS: We isolated seven candidates that were specifically down- or up-regulated in W/W(V )mice. Two novel transcripts, DDWMEST 1 and -91 were increased in both fed and fasted W/W(V )mice. Expression of another five genes was suppressed in W/W(V )mice: ARG2 (Arginase II), ONZIN (encoding leukemia inhibitory factor regulated protein), and three novel transcripts: DDWMEST62, -84, and -100. Together with the previous report, we identified fifteen differentially expressed genes in total in the small intestines of W/W(V )mice. Eight of these genes were reduced in the jejunums of W/W(V )mice compared to age matched wild type mice, whereas the other seven genes showed an increase in expression. Differential expression was the same in fasted and fed animals, suggesting that the differences were independent of the dietetic state of the animal. CONCLUSIONS: Several known and novel genes are differentially expressed in the small intestines of W/W(V )mice. Differential gene comparison might contribute to our understanding of motility disorders associated with the loss of the interstitial cells of Cajal

Implementation of Triple P-Positive Parenting Program in Hong Kong: Predictors of programme completion and clinical outcomes

This study examined the effectiveness of the Triple P-Positive Parenting Program in a government child health service delivery context with Chinese parents in Hong Kong. Specifically, the study sought to identify pre-intervention variables that might predict programme outcomes such as, level of clinical improvement and programme completion. Participants were 661 parents of pre-school and primary aged children participating in a group version of the Triple P-Positive Parenting Program. There were significant decreases in disruptive child behaviours, levels of parenting stress, general stress and anxiety and an increase in parenting sense of competence. Greater change in reports of child behaviour problems was related to lower levels of family income, new immigrant family status, and higher pre-intervention levels of parenting stress. The present study provides a profile of parents who are most likely to benefit from parent training programmes

Off-shell superconformal nonlinear sigma-models in three dimensions

We develop superspace techniques to construct general off-shell N=1,2,3,4 superconformal sigma-models in three space-time dimensions. The most general N=3 and N=4 superconformal sigma-models are constructed in terms of N=2 chiral superfields. Several superspace proofs of the folklore statement that N=3 supersymmetry implies N=4 are presented both in the on-shell and off-shell settings. We also elaborate on (super)twistor realisations for (super)manifolds on which the three-dimensional N-extended superconformal groups act transitively and which include Minkowski space as a subspace.Comment: 67 pages; V2: typos corrected, one reference added, version to appear on JHE

CJCheck Stage 1: development and testing of a checklist for reporting community juries – Delphi process and analysis of studies published in 1996–2015

Background Opportunities for community members to actively participate in policy development are increasing. Community/citizen's juries (CJs) are a deliberative democratic process aimed to illicit informed community perspectives on difficult topics. But how comprehensive these processes are reported in peer-reviewed literature is unknown. Adequate reporting of methodology enables others to judge process quality, compare outcomes, facilitate critical reflection and potentially repeat a process. We aimed to identify important elements for reporting CJs, to develop an initial checklist and to review published health and health policy CJs to examine reporting standards. Design Using the literature and expertise from CJ researchers and policy advisors, a list of important CJ reporting items was suggested and further refined. We then reviewed published CJs within the health literature and used the checklist to assess the comprehensiveness of reporting. Results CJCheck was developed and examined reporting of CJ planning, juror information, procedures and scheduling. We screened 1711 studies and extracted data from 38. No studies fully reported the checklist items. The item most consistently reported was juror numbers (92%, 35/38), while least reported was the availability of expert presentations (5%, 2/38). Recruitment strategies were described in 66% of studies (25/38); however, the frequency and timing of deliberations was inadequately described (29%, 11/38). Conclusions Currently CJ publications in health and health policy literature are inadequately reported, hampering their use in policy making. We propose broadening the CJCheck by creating a reporting standards template in collaboration with international CJ researchers, policy advisors and consumer representatives to ensure standardized, systematic and transparent reporting.RT was supported by a NHMRC Screening and Test Evaluation Program (STEP) Grant (#633033). RS was supported by a Bond University Vice Chancellor’s Research Grant Scheme. CD, SMC and LR received funding support from NHMRC Project Grant (#1023197). CD received funding support from a NHMRC Project Grant (#1083079). SMC is funded through NHMRC Career Development Fellowship (#1032963). JMS was funded by an Australian National Preventive Health Agency Fellowship (20STR2013F) and an NHMRC Capacity Building Grant (565501)