The acceptability and feasibility of using the Adult Social Care Outcomes Toolkit (ASCOT) to inform practice in care homes

Background: The Adult Social Care Outcomes Toolkit (ASCOT) measures social care related quality of life (SCRQoL) and can be used to measure outcomes and demonstrate impact across different social care settings. This exploratory study built on previous work by collecting new inter-rater reliability data on the mixed-methods version of the toolkit and exploring how it might be used to inform practice in four case study homes. Method: We worked with two care home providers to agree an in-depth study collecting SCRQoL data in four case-study homes. Data was collected about residents’ age, ethnicity, cognitive impairment, ability to perform activities of daily living and SCRQoL in the four homes. Feedback sessions with staff and managers were held in the homes two weeks after baseline and follow-up data collected three months later. Interviews with managers explored their views of the feedback and recorded any changes that had been made because of it. Results: Participant recruitment was challenging, despite working in partnership with the homes. Resident response rates ranged from 23 to 54 % with 58 residents from four care homes taking part in the research. 53 % lacked capacity to consent. Inter-rater reliability for the ASCOT ratings of SCRQoL were good at time one (IRR = 0.72) and excellent at time two (IRR = 0.76). During the study, residents’ ability to perform activities of daily living declined significantly (z = -2.67, p < .01), as did their expected needs in the absence of services (z = -2.41, p < .05). Despite these rapid declines in functionings, residents’ current SCRQoL declined slightly but not significantly (Z = -1.49, p = .14). Staff responded positively to the feedback given and managers reported implementing changes in practice because of it. Conclusion: This exploratory study faced many challenges in the recruitment of residents, many of whom were cognitively impaired. Nevertheless, without a mixed-methods approach many of the residents living in the care homes would have been excluded from the research altogether or had their views represented only by a representative or proxy. The value of the mixed-methods toolkit and its potential for use by providers is discussed

Metarhizium brunneum Blastospore Pathogenesis in Aedes aegypti Larvae: Attack on Several Fronts Accelerates Mortality

Aedes aegypti is the vector of a wide range of diseases (e.g. yellow fever, dengue, Chikungunya and Zika) which impact on over half the world's population. Entomopathogenic fungi such as Metarhizium anisopliae and Beauveria bassiana have been found to be highly efficacious in killing mosquito larvae but only now are the underlying mechanisms for pathogenesis being elucidated. Recently it was shown that conidia of M. anisopliae caused stress induced mortality in Ae. aegypti larvae, a different mode of pathogenicity to that normally seen in terrestrial hosts. Blastospores constitute a different form of inoculum produced by this fungus when cultured in liquid media and although blastospores are generally considered to be more virulent than conidia no evidence has been presented to explain why. In our study, using a range of biochemical, molecular and microscopy methods, the infection process of Metarhizium brunneum (formerly M. anisopliae) ARSEF 4556 blastospores was investigated. It appears that the blastospores, unlike conidia, readily adhere to and penetrate mosquito larval cuticle. The blastospores are readily ingested by the larvae but unlike the conidia are able infect the insect through the gut and rapidly invade the haemocoel. The fact that pathogenicity related genes were upregulated in blastospores exposed to larvae prior to invasion, suggests the fungus was detecting host derived cues. Similarly, immune and defence genes were upregulated in the host prior to infection suggesting mosquitoes were also able to detect pathogen-derived cues. The hydrophilic blastospores produce copious mucilage, which probably facilitates adhesion to the host but do not appear to depend on production of Pr1, a cuticle degrading subtilisin protease, for penetration since protease inhibitors did not significantly alter blastospore virulence. The fact the blastospores have multiple routes of entry (cuticle and gut) may explain why this form of the inoculum killed Ae. aegypti larvae in a relatively short time (12-24hrs), significantly quicker than when larvae were exposed to conidia. This study shows that selecting the appropriate form of inoculum is important for efficacious control of disease vectors such as Ae. aegypti

Effect of repeat human blood feeding on Wolbachia density and dengue virus infection in Aedes aegypti

BACKGROUND: The introduction of the endosymbiotic bacterium, Wolbachia into Aedes aegypti populations is a novel approach to reduce disease transmission. The presence of Wolbachia limits the ability of the mosquito to transmit dengue virus (DENV) and the strength of this effect appears to correlate with Wolbachia densities in the mosquito. There is also some evidence that Wolbachia densities may increase following the consumption of a bloodmeal. Here we have examined whether multiple blood feeds lead to increases in density or associated changes in Wolbachia-mediated blocking of DENV. METHODS: The Wolbachia infected Aedes aegypti mosquito line was used for the study. There were three treatment groups; a non-blood fed control, a second group fed once and a third group fed twice on human blood. All groups were orally infected with DENV-2 and then their midguts and salivary glands were dissected 10–11 days post infection. RNA/DNA was simultaneously extracted from each tissue and subsequently used for DENV RNA copies and Wolbachia density quantification, respectively. RESULTS: We found variation between replicate vector competence experiments and no clear evidence that Wolbachia numbers increased in either the salivary glands or remainder of the body with feeding and hence saw no corresponding improvements in DENV blocking. CONCLUSIONS: Aedes aegypti are “sip” feeders returning often to obtain bloodmeals and hence it is important to assess whether repeat blood feeding improved the efficacy of Wolbachia-based DENV blocking. Our work suggests in the laboratory context when Wolbachia densities are high that repeat feeding does not improve blocking and hence this ability should likely be stable with respect to feeding cycle in the field

Effect of repeat human blood feeding on Wolbachia density and dengue virus infection in Aedes aegypti

BACKGROUND: The introduction of the endosymbiotic bacterium, Wolbachia into Aedes aegypti populations is a novel approach to reduce disease transmission. The presence of Wolbachia limits the ability of the mosquito to transmit dengue virus (DENV) and the strength of this effect appears to correlate with Wolbachia densities in the mosquito. There is also some evidence that Wolbachia densities may increase following the consumption of a bloodmeal. Here we have examined whether multiple blood feeds lead to increases in density or associated changes in Wolbachia-mediated blocking of DENV. METHODS: The Wolbachia infected Aedes aegypti mosquito line was used for the study. There were three treatment groups; a non-blood fed control, a second group fed once and a third group fed twice on human blood. All groups were orally infected with DENV-2 and then their midguts and salivary glands were dissected 10–11 days post infection. RNA/DNA was simultaneously extracted from each tissue and subsequently used for DENV RNA copies and Wolbachia density quantification, respectively. RESULTS: We found variation between replicate vector competence experiments and no clear evidence that Wolbachia numbers increased in either the salivary glands or remainder of the body with feeding and hence saw no corresponding improvements in DENV blocking. CONCLUSIONS: Aedes aegypti are “sip” feeders returning often to obtain bloodmeals and hence it is important to assess whether repeat blood feeding improved the efficacy of Wolbachia-based DENV blocking. Our work suggests in the laboratory context when Wolbachia densities are high that repeat feeding does not improve blocking and hence this ability should likely be stable with respect to feeding cycle in the field

RIL RTPCR and CHC data

qRT-PCR data for three genes (AmyPres CL481res NinaDres) and cuticular hydrocarbons (lc1 lc2 lc3 lc5 lc6 lc7 lc8 lc9) for 430 individuals from 41 RILs and 2 parental lines (EUNGC and FORS4). Canonical variates for genes (V1, V2, V3) and CHCs (W1, W2, W3) are also given

15 RIL CHC and gene factor means

RIL line means for 12 genetic factors and 9 cuticular hydrocarbons for the line-mean analysis presented in Table 2

Whole-Exome-Sequencing Identifies Mutations in Histone Acetyltransferase Gene KAT6B in Individuals with the Say-Barber-Biesecker Variant of Ohdo Syndrome

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS or Ohdo syndrome) is a multiple anomaly syndrome characterized by severe intellectual disability, blepharophimosis, and a mask-like facial appearance. A number of individuals with SBBYSS also have thyroid abnormalities and cleft palate. The condition usually occurs sporadically and is therefore presumed to be due in most cases to new dominant mutations. In individuals with SBBYSS, a whole-exome sequencing approach was used to demonstrate de novo protein-truncating mutations in the highly conserved histone acetyltransferase gene KAT6B (MYST4/MORF)) in three out of four individuals sequenced. Sanger sequencing was used to confirm truncating mutations of KAT6B, clustering in the final exon of the gene in all four individuals and in a further nine persons with typical SBBYSS. Where parental samples were available, the mutations were shown to have occurred de novo. During mammalian development KAT6B is upregulated specifically in the developing central nervous system, facial structures, and limb buds. The phenotypic features seen in the Qkf mouse, a hypomorphic Kat6b mutant, include small eyes, ventrally placed ears and long first digits that mirror the human phenotype. This is a further example of how perturbation of a protein involved in chromatin modification might give rise to a multisystem developmental disorder