Historic Churches and Their Hygrothermal Environment: A Review of Criteria Related to Building Fabric, Artefacts, Artwork and Occupants

Regarded as important cultural heritage, historic churches have been utilised over hundreds of years for worship and community benefit. Simple on/off space heating systems are installed in many churches to increase human comfort. However, the conservation of the important historic artefacts and artwork contained within may not have been fully considered. This review attempts to appraise the standards in place for artefacts and artwork. A consensus of 15–25 °C and 40–65% relative humidity is established as safe from the standards reviewed. Consideration is given to the environment within the church to understand if such exacting conditions can be met. The review finds that the conservation and preservation of artefacts and buildings are aligned goals, although striving to meet specified target ranges for artefact types is not fully compatible with historic churches. The stability of the internal environment is clearly an important factor in conservation and benefits human comfort expectations. Churches may contain microclimates throughout the building, complicating the use of target ranges for artefacts, artwork and comfort. The findings of this study can assist historic churches in managing the change, alteration or installation of heating systems

Avatar therapy for persecutory auditory hallucinations: What is it and how does it work?

We have developed a novel therapy based on a computer program, which enables the patient to create an avatar of the entity, human or non-human, which they believe is persecuting them. The therapist encourages the patient to enter into a dialogue with their avatar, and is able to use the program to change the avatar so that it comes under the patient's control over the course of six 30-min sessions and alters from being abusive to becoming friendly and supportive. The therapy was evaluated in a randomised controlled trial with a partial crossover design. One group went straight into the therapy arm: "immediate therapy". The other continued with standard clinical care for 7 weeks then crossed over into Avatar therapy: "delayed therapy". There was a significant reduction in the frequency and intensity of the voices and in their omnipotence and malevolence. Several individuals had a dramatic response, their voices ceasing completely after a few sessions of the therapy. The average effect size of the therapy was 0.8. We discuss the possible psychological mechanisms for the success of Avatar therapy and the implications for the origins of persecutory voices. © 2013 Copyright Taylor and Francis Group, LLC

Gene and cell therapy in South Africa: Current status and future prospects

South Africa has a high disease burden resulting from communicable and non-communicable diseases. Current therapeutic interventions rarely result in a cure and the associated lifelong treatment places a considerable strain on an overburdened health sector. Gene and cell therapies present novel alternatives to disease management, offering the promise of a single treatment and a lifelong cure. Although challenges remain, investment in the field has started to bear fruit, with a number of gene and cell therapeutics reaching the market in the past decade. To take full advantage of these developments, it is important that a proactive approach to nurturing appropriate human and material resources is adopted in the country

Randomised controlled trial to improve health and reduce substance use in established psychosis (IMPaCT): cost-effectiveness of integrated psychosocial health promotion

Background: There is mounting evidence that people with severe mental illness have unhealthy lifestyles, high rates of cardiovascular and metabolic diseases, and greater risk of early mortality. This study aimed to assess the cost-effectiveness of a health promotion intervention seeking to improve physical health and reduce substance use in people with psychosis. Methods: Participants with a psychotic disorder, aged 18-65 years old and registered on an enhanced care approach programme or equivalent were recruited from community mental health teams in six mental health trusts in England. Participants were randomisation to either standard community mental health team care (treatment as usual) or treatment as usual with an integrated health promotion intervention (IMPaCT). Cost-effectiveness and cost-utility analyses from health and social care and societal perspectives were conducted alongside a cluster randomised controlled trial. Total health and social care costs and total societal costs at 12 and 15 months were calculated as well as cost-effectiveness (incremental cost-effectiveness ratios and cost-effectiveness acceptability curves) at 15 months based on quality of life (SF-36 mental and physical health components, primary outcome measures) and quality adjusted life years (QALYs) using two measures, EQ-5D-3 L and SF-36. Data were analysed using bootstrapped regressions with covariates for relevant baseline variables. Results: At 12-15 months 301 participants had full data needed to be included in the economic evaluation. There were no differences in adjusted health and social care costs (£95, 95% CI -£1410 to £1599) or societal costs (£675, 95% CI -£1039 to £2388) between the intervention and control arms. Similarly, there were no differences between the groups in the SF-36 mental component (−0.80, 95% CI -3.66 to 2.06), SF-36 physical component (−0.68, 95% CI -3.01 to 1.65), QALYs estimated from the SF-36 (−0.00, −0.01 to 0.00) or QALYs estimated from the EQ-5D-3 L (0.00, 95% CI -0.01 to 0.02). Cost-effectiveness acceptability curves for all four outcomes and from both cost perspectives indicate that the probability of the health promotion intervention being cost-effective does not exceed 0.4 for willingness to pay thresholds ranging from £0-£50,000. Conclusions: Alongside no evidence of additional quality of life/clinical benefit, there is also no evidence of cost-effectiveness

Invasive Plants in U. S. National Wildlife Refuges: A Coordinated Research Project Using Undergraduate Ecology Students

Answering large-scale questions in ecology can involve time-consuming data compilation. We show how networks of undergraduate classes can make these projects more manageable and provide an authentic research experience for students. With this approach, we examined the factors associated with plant species richness in US national wildlife refuges. We found that the richness of harmful invasive plants and the richness of native plants were positively correlated in mainland refuges but negatively correlated in island refuges. Nonnative richness and invasive richness were also positively correlated with colonization pressure as indicated by nonnative richness around each refuge. Associations between refuge characteristics and invasive plants varied substantially among regions, with refuge area and habitat diversity important predictors of invasion in some regions but not in others. Our results serve to identify the refuges that are most susceptible to plant invasion and demonstrate the potential value of a new model for education and research integration

Domesticated Dogs’ (Canis familiaris) Response to Dishonest Human Points

We would like to thank Sherry McClurkin, Robin Reutten, and Chelsea Taglang for their assistance in data collection and participant recruitment for this study. Correspondence concerning this article should be addressed to Shannon M.A. Kundey at Hood College, Department of Psychology, 401 Rosemont Avenue, Room ROS 27, Frederick, MD 21701, U.S.A. ([email protected]).Pointing is a conventional communicative gesture used by humans to direct others’ attention to an environmental feature. Several researchers have argued that pointing becomes so ingrained for humans from a young age that children often have difficulty interpreting the gesture in a novel way. Recent research suggests domestic dogs are also sensitive to human gestures (including points) and proficient in recognizing and acting on humans’ visual attention. We explored the role of pointing in dogs’ choice behavior and whether dogs, like human children, have difficulty interpreting the gesture novelly. In Experiment 1, we explored whether dogs would differentially follow a static human point when it was administered by a familiar or unfamiliar individual and that individual indicated or failed to indicate the correct location of a food reward. The results indicated dogs chose the container specified by the demonstrators’ point in the honest and dishonest condition. Demonstrator familiarity did not alter performance. In Experiment 2, we compared dogs’ propensity to follow a static point versus other cues (momentary point, standing location) when the cue never indicated the correct location of a food reward, which was either visible or hidden during choice. The results suggested dogs did not inhibit their approach to a location indicated by a deceptive static point even when the location of a reward was visibly available during choice. However, dogs used a deceptive momentary point or standing location to locate food in both visible and hidden trials. In Experiment 3, we explored if dogs could overcome their tendency to follow a deceptive static point. These results indicated dogs learned to inhibit their approach to a deceptive static point when the reward was visible during choice. However, when information about the reward’s location was later hidden, dogs reverted to following the demonstrator’s static point

The Efficacy of Generating Three Independent Anti-HIV-1 siRNAs from a Single U6 RNA Pol III-Expressed Long Hairpin RNA

RNA Interference (RNAi) effectors have been used to inhibit rogue RNAs in mammalian cells. However, rapidly evolving sequences such as the human immunodeficiency virus type 1 (HIV-1) require multiple targeting approaches to prevent the emergence of escape variants. Expressed long hairpin RNAs (lhRNAs) have recently been used as a strategy to produce multiple short interfering RNAs (siRNAs) targeted to highly variant sequences. We aimed to characterize the ability of expressed lhRNAs to generate independent siRNAs that silence three non-contiguous HIV-1 sites by designing lhRNAs comprising different combinations of siRNA-encoding sequences. All lhRNAs were capable of silencing individual target sequences. However, silencing efficiency together with concentrations of individual lhRNA-derived siRNAs diminished from the stem base (first position) towards the loop side of the hairpin. Silencing efficacy against HIV-1 was primarily mediated by siRNA sequences located at the base of the stem. Improvements could be made to first and second position siRNAs by adjusting spacing arrangements at their junction, but silencing of third position siRNAs remained largely ineffective. Although lhRNAs offer advantages for combinatorial RNAi, we show that good silencing efficacy across the span of the lhRNA duplex is difficult to achieve with sequences that encode more than two adjacent independent siRNAs

Design of RNAi Hairpins for Mutation-Specific Silencing of Ataxin-7 and Correction of a SCA7 Phenotype

Spinocerebellar ataxia type 7 is a polyglutamine disorder caused by an expanded CAG repeat mutation that results in neurodegeneration. Since no treatment exists for this chronic disease, novel therapies such post-transcriptional RNA interference-based gene silencing are under investigation, in particular those that might enable constitutive and tissue-specific silencing, such as expressed hairpins. Given that this method of silencing can be abolished by the presence of nucleotide mismatches against the target RNA, we sought to identify expressed RNA hairpins selective for silencing the mutant ataxin-7 transcript using a linked SNP. By targeting both short and full-length tagged ataxin-7 sequences, we show that mutation-specific selectivity can be obtained with single nucleotide mismatches to the wild-type RNA target incorporated 3′ to the centre of the active strand of short hairpin RNAs. The activity of the most effective short hairpin RNA incorporating the nucleotide mismatch at position 16 was further studied in a heterozygous ataxin-7 disease model, demonstrating significantly reduced levels of toxic mutant ataxin-7 protein with decreased mutant protein aggregation and retention of normal wild-type protein in a non-aggregated diffuse cellular distribution. Allele-specific mutant ataxin7 silencing was also obtained with the use of primary microRNA mimics, the most highly effective construct also harbouring the single nucleotide mismatch at position 16, corroborating our earlier findings. Our data provide understanding of RNA interference guide strand anatomy optimised for the allele-specific silencing of a polyglutamine mutation linked SNP and give a basis for the use of allele-specific RNA interference as a viable therapeutic approach for spinocerebellar ataxia 7

Randomised control trial of the effectiveness of an integrated psychosocial health promotion intervention aimed at improving health and reducing substance use in established psychosis (IMPaCT)

© 2017 The Author(s). Background: People with psychosis have a reduced life expectancy of 10-20years, largely due to cardiovascular disease. This trial aimed to determine the effectiveness of a modular health promotion intervention (IMPaCT Therapy) in improving health and reducing cardiovascular risk in psychosis. Methods: A multicentre, two arm, parallel cluster RCT was conducted across five UK mental health NHS trusts. Community care coordinators (CC) were randomly assigned to training and supervision in delivering IMPaCT Therapy or treatment as usual (TAU) to current patients with psychosis (cluster). The primary outcome was the physical and mental health subscales of the Short form-36 (SF-36) questionnaire. Results: Of 104 care coordinators recruited, 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) randomised to TAU. Of 406 patients, 318 (78%) and 301 (74%) attended 12- and 15-month follow-up respectively. IMPaCT therapy showed no significant effect on the physical or mental health component SF-36 scores versus TAU at 12 or 15months. No effect was observed for cardiovascular risk indicators, except for HDL cholesterol, which improved more with IMPACT therapy than TAU (Treatment effect (95% CI); 0.085 (0.007 to 0.16); p= 0.034). The 22% of patients who received > 180min of IMPACT Therapy in addition to usual care achieved a greater reduction in waist circumference than did controls, which was clinically significant. Conclusion: Training and supervising community care coordinators to use IMPaCT therapy in patients with psychosis is insufficient to significantly improve physical or mental health quality of life. The search for effective, pragmatic interventions deliverable in health care services continues. Trial registration: The trial was retrospectively registered with ISRCTN registry on 23/4/2010 at ISRCTN58667926 ; recruitment started on 01/03/2010 with first randomization on 09.08.2010 ISRCTN58667926