Developing an unguided internet-delivered Intervention for emotional distress in primary care patients: Applying common factor and person-based approaches.

Background Developing effective, unguided Internet interventions for mental health represents a challenge. Without structured human guidance, engagement with these interventions is often limited and the effectiveness reduced. If their effectiveness can be increased, they have great potential for broad, low-cost dissemination. Improving unguided Internet interventions for mental health requires a renewed focus on the proposed underlying mechanisms of symptom improvement and the involvement of target users from the outset. Objective The aim of our study was to develop an unguided e-mental health intervention for distress in primary care patients, drawing on meta-theory of psychotherapeutic change and utilizing the person-based approach (PBA) to guide iterative qualitative piloting with patients. Methods Common factors meta-theory informed the selection and structure of therapeutic content, enabling flexibility whilst retaining the proposed necessary ingredients for effectiveness. A logic model was designed outlining intervention components and proposed mechanisms underlying improvement. The PBA provided a framework for systematically incorporating target-user perspective into the intervention development. Primary care patients (N=20) who had consulted with emotional distress in the last 12 months took part in exploratory qualitative interviews, and a subsample (n=13) undertook think-aloud interviews with a prototype of the intervention. Results A flexible intervention was developed, to be used as and when patients need, diverting from a more traditional, linear approach. Based on the in-depth qualitative findings, disorder terms such as “depression” were avoided, and discussions of psychological symptoms were placed in the context of stressful life events. Think-aloud interviews showed that patients were positive about the design and structure of the intervention. On the basis of patient feedback, modifications were made to increase immediate access to all therapeutic techniques. Conclusions Detailing theoretical assumptions underlying Internet interventions for mental health, and integrating this approach with systematic in-depth qualitative research with target patients is important. These strategies may provide novel ways for addressing the challenges of unguided delivery. The resulting intervention, Healthy Paths, will be evaluated in primary care-based randomized controlled trials, and deployed as a massive open online intervention (MOOI)

Factors associated with completion of bowel cancer screening and the potential effects of simplifying the screening test algorithm

BACKGROUND: The primary colorectal cancer screening test in England is a guaiac faecal occult blood test (gFOBt). The NHS Bowel Cancer Screening Programme (BCSP) interprets tests on six samples on up to three test kits to determine a definitive positive or negative result. However, the test algorithm fails to achieve a definitive result for a significant number of participants because they do not comply with the programme requirements. This study identifies factors associated with failed compliance and modifications to the screening algorithm that will improve the clinical effectiveness of the screening programme. METHODS: The BCSP Southern Hub data for screening episodes started in 2006–2012 were analysed for participants aged 60–69 years. The variables included age, sex, level of deprivation, gFOBt results and clinical outcome. RESULTS: The data set included 1 409 335 screening episodes; 95.08% of participants had a definitively normal result on kit 1 (no positive spots). Among participants asked to complete a second or third gFOBt, 5.10% and 4.65%, respectively, failed to return a valid kit. Among participants referred for follow up, 13.80% did not comply. Older age was associated with compliance at repeat testing, but non-compliance at follow up. Increasing levels of deprivation were associated with non-compliance at repeat testing and follow up. Modelling a reduction in the threshold for immediate referral led to a small increase in completion of the screening pathway. CONCLUSIONS: Reducing the number of positive spots required on the first gFOBt kit for referral for follow-up and targeted measures to improve compliance with follow-up may improve completion of the screening pathway

Pig α₁-Acid Glycoprotein: Characterization and First Description in Any Species as a Negative Acute Phase Protein.

The serum protein α1-acid glycoprotein (AGP), also known as orosomucoid, is generally described as an archetypical positive acute phase protein. Here, porcine AGP was identified, purified and characterized from pooled pig serum. It was found to circulate as a single chain glycoprotein having an apparent molecular weight of 43 kDa by SDS-PAGE under reducing conditions, of which approximately 17 kDa were accounted for by N-bound oligosaccharides. Those data correspond well with the properties of the protein predicted from the single porcine AGP gene (ORM1, Q29014 (UniProt)), containing 5 putative glycosylation sites. A monoclonal antibody (MAb) was produced and shown to quantitatively and specifically react with all microheterogenous forms of pig AGP as analyzed by 2-D electrophoresis. This MAb was used to develop an immunoassay (ELISA) for quantification of AGP in pig serum samples. The adult serum concentrations of pig AGP were in the range of 1-3 mg/ml in a number of conventional pig breeds while it was lower in Göttingen and Ossabaw minipigs (in the 0.3 to 0.6 mg/ml range) and higher in young (2-5 days old) conventional pigs (mean: 6.6 mg/ml). Surprisingly, pig AGP was found to behave as a negative acute phase protein during a range of experimental infections and aseptic inflammation with significant decreases in serum concentration and in hepatic ORM1 expression during the acute phase response. To our knowledge this is the first description in any species of AGP being a negative acute phase protein

Screening a Peptide Library by DSC and SAXD: Comparison with the Biological Function of the Parent Proteins

We have recently identified the membranotropic regions of the hepatitis C virus proteins E1, E2, core and p7 proteins by observing the effect of protein-derived peptide libraries on model membrane integrity. We have studied in this work the ability of selected sequences of these proteins to modulate the Lβ-Lα and Lα-HII phospholipid phase transitions as well as check the viability of using both DSC and SAXD to screen a protein-derived peptide library. We demonstrate that it is feasible to screen a library of peptides corresponding to one or several proteins by both SAXD and DSC. This methodological combination should allow the identification of essential regions of membrane-interacting proteins which might be implicated in the molecular mechanism of membrane fusion and/or budding

Developing an unguided internet-delivered Intervention for emotional distress in primary care patients: Applying common factor and person-based approaches.

Background Developing effective, unguided Internet interventions for mental health represents a challenge. Without structured human guidance, engagement with these interventions is often limited and the effectiveness reduced. If their effectiveness can be increased, they have great potential for broad, low-cost dissemination. Improving unguided Internet interventions for mental health requires a renewed focus on the proposed underlying mechanisms of symptom improvement and the involvement of target users from the outset. Objective The aim of our study was to develop an unguided e-mental health intervention for distress in primary care patients, drawing on meta-theory of psychotherapeutic change and utilizing the person-based approach (PBA) to guide iterative qualitative piloting with patients. Methods Common factors meta-theory informed the selection and structure of therapeutic content, enabling flexibility whilst retaining the proposed necessary ingredients for effectiveness. A logic model was designed outlining intervention components and proposed mechanisms underlying improvement. The PBA provided a framework for systematically incorporating target-user perspective into the intervention development. Primary care patients (N=20) who had consulted with emotional distress in the last 12 months took part in exploratory qualitative interviews, and a subsample (n=13) undertook think-aloud interviews with a prototype of the intervention. Results A flexible intervention was developed, to be used as and when patients need, diverting from a more traditional, linear approach. Based on the in-depth qualitative findings, disorder terms such as “depression” were avoided, and discussions of psychological symptoms were placed in the context of stressful life events. Think-aloud interviews showed that patients were positive about the design and structure of the intervention. On the basis of patient feedback, modifications were made to increase immediate access to all therapeutic techniques. Conclusions Detailing theoretical assumptions underlying Internet interventions for mental health, and integrating this approach with systematic in-depth qualitative research with target patients is important. These strategies may provide novel ways for addressing the challenges of unguided delivery. The resulting intervention, Healthy Paths, will be evaluated in primary care-based randomized controlled trials, and deployed as a massive open online intervention (MOOI).</p

Identification of a yeast artificial chromosome (YAC) spanning the synovial sarcoma-specific t(X;18)(p11.2;q11.2) breakpoint.

A somatic cell hybrid containing the synovial sarcoma-associated t(X;18)(p11.2;q11.2) derivative (der(X)) chromosome was used to characterize the translocation breakpoint region on the X chromosome. By using Southern hybridization of DNA from this der(X) hybrid in conjunction with Xp-region specific radiation reduced cell hybrids and probes, it was found that this breakpoint maps within the ornithine aminotransferase (OAT) L1 cluster. A yeast artificial chromosome (YAC) clone (OAT YAC2) which hybridizes to a human OAT cDNA probe and is known to contain part of the OATL1 cluster was selected and used to confirm these results both by fluorescence in situ hybridization on synovial sarcoma patient material and by hybridization of its end-clones to the der(X) containing hybrid cells. It was found that indeed the human Xp sequences contained within this YAC are split as a consequence of the (X;18) translocation. Therefore, we conclude that OAT YAC2 spans the synovial sarcoma-specific translocation breakpoint and, as such, may serve as an ideal starting point from which the gene(s) involved in the development of this soft tissue tumor can be isolated