Quasi-qualitative evaluation of Progressive Counting in secure accommodation in Scotland:An exploratory cluster case study

This was the first study to introduce a brief exposure therapy, within a trauma-informed phase approach, into a secure facility in Scotland. An exploratory cluster case study was used to identify the perceptions of the first three youth who completed Progressive Counting (PC), a novel approach to brief exposure, within the Fairy Tale Model. The youth and their newly trained therapist received a semi-structured interview at 3 months following the completion of therapy. In-depth interviews involving rating scales and open-ended questions were conducted by telephone and digitally recorded. A quasi-qualitative approach was used to analyze data. Independent ratings by two researchers checked for inter-rater reliability. A retrospective expert rating was provided for treatment fidelity. Youth reported a range of gains in relation to program objectives including reduced distress and putting trauma into the past. Challenges of implementation are discussed. More rigorous evaluation of PC, including randomized control trials, is needed before PC can be recommended as a treatment of choice

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Patient-reported outcome measures of the impact of cancer on patient’s everyday lives: a systematic review

Purpose: Patients with advanced disease are living longer and commonly used patient-reported outcome measures (PROMs) may miss relevant elements of the quality of extended survival. This systematic review examines the measures used to capture aspects of the quality of survival including impact on patients’ everyday lives such as finances, work and family roles. Methods: Searches were conducted in MEDLINE, EMBASE, CINAHL and PsycINFO restricted to English language articles. Information on study characteristics, instruments and outcomes was systematically extracted and synthesised. A predefined set of criteria was used to rate the quality of studies. Results: From 2761 potentially relevant articles, 22 met all inclusion criteria, including 10 concerning financial distress, 3 on roles and responsibilities and 9 on multiple aspects of social well-being. Generally, studies were not of high quality; many lacked bias free participant selection, had confounding factors and had not accounted for all participants. High levels of financial distress were reported and were associated with multiple demographic factors such as age and income. There were few reports concerned with impacts on patients’ roles/responsibilities in everyday life although practical and emotional struggles with parenting were identified. Social difficulties were common and associated with multiple factors including being a caregiver. Many studies were single time-point surveys and used non-validated measures. Exceptions were employment of the COST and Social Difficulties Inventory (SDI), validated measures of financial and social distress respectively. Conclusions: Impact on some important parts of patients’ everyday lives is insufficiently and inconsistently captured. Further PROM development focussing on roles and responsibilities, including work and caring for dependents, is warranted. Implications for Cancer Survivors: Factors such as finances, employment and responsibility for caring for dependents (e.g. children and elderly relatives) can affect the well-being of cancer survivors. There is a need to ensure that any instruments used to assess patients’ social well-being are broad enough to include these areas so that any difficulties arising can be better understood and appropriately supported

Uniaxial Stress Effects on the Low-Field Magnetoacoustic Interactions in Low and Medium Carbon Steels

In the past, we have shown that the low-field magnetoacoustic technique is capable of detecting uniaxial compression in steel components without necessiating a calibration standard [1,2]. This is because the initial slope of the AF(B)/F curve (fractional frequency change of phase-locked acoustic waves as a function of net magnetic induction) is negative only under compression and positive otherwise, when the specimens are magnetized along the static unaxial stress axis.</p

Epistatic Relationships between sarA and agr in Staphylococcus aureus Biofilm Formation

Background: The accessory gene regulator (agr) and staphylococcal accessory regulator (sarA) play opposing roles in Staphylococcus aureus biofilm formation. There is mounting evidence to suggest that these opposing roles are therapeutically relevant in that mutation of agr results in increased biofilm formation and decreased antibiotic susceptibility while mutation of sarA has the opposite effect. To the extent that induction of agr or inhibition of sarA could potentially be used to limit biofilm formation, this makes it important to understand the epistatic relationships between these two loci. Methodology/Principal Findings: We generated isogenic sarA and agr mutants in clinical isolates of S. aureus and assessed the relative impact on biofilm formation. Mutation of agr resulted in an increased capacity to forma biofilmin the 8325-4 laboratory strain RN6390 but had little impact in clinical isolates S. aureus. In contrast, mutation of sarA resulted in a reduced capacity to form a biofilm in all clinical isolates irrespective of the functional status of agr. This suggests that the regulatory role of sarA in biofilm formation is independent of the interaction between sarA and agr and that sarA is epistatic to agr in this context. This was confirmed by demonstrating that restoration of sarA function restored the ability to form a biofilm even in the corresponding agr mutants. Mutation of sarA in clinical isolates also resulted in increased production of extracellular proteases and extracellular nucleases, both of which contributed to the biofilm-deficient phenotype of sarA mutants. However, studies comparing different strains with and without proteases inhibitors and/or mutation of the nuclease genes demonstrated that the agr-independent, sarA-mediated repression of extracellular proteases plays a primary role in this regard. Conclusions and Significance: The results we report suggest that inhibitors of sarA-mediated regulation could be used to limit biofilm formation in S. aureus and that the efficacy of such inhibitors would not be limited by spontaneous mutation of agr in the human host

A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model

Alzheimer disease models and human neuropathology: similarities and differences

Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Aβ peptide and the intracellular accumulation of tau protein. Mutated human APP transgenes result in the deposition of Aβ peptide, similar but not identical to the Aβ peptide of human senile plaque. Amyloid angiopathy is common. Besides the deposition of Aβ, axon dystrophy and alteration of dendrites have been observed. All of the mutations cause an increase in Aβ 42 levels, except for the Arctic mutation, which alters the Aβ sequence itself. Overexpressing wild-type APP alone (as in the murine models of human trisomy 21) causes no Aβ deposition in most mouse lines. Doubly (APP × mutated PS1) transgenic mice develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out or overexpressed have been produced, as well as lines with altered expression of neprilysin, the main degrading enzyme of Aβ. The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Aβ in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations. They have allowed some insight to be gained into the kinetics of the changes. The connection between the symptoms, the lesions and the increase in Aβ oligomers has been found to be difficult to unravel. Neurofibrillary tangles are only found in mouse lines that overexpress mutated tau or human tau on a murine tau −/− background. A triply transgenic model (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its physiological relevance may be discussed. A number of modulators of Aβ or of tau accumulation have been tested. A transgenic model may be analyzed at three levels at least (symptoms, lesions, cause of the disease), and a reading key is proposed to summarize this analysis

Age and hippocampal volume predict distinct parts of default mode network activity

Group comparison studies have established that activity in the posterior part of the default-mode network (DMN) is down-regulated by both normal ageing and Alzheimer’s disease (AD). In this study linear regression models were used to disentangle distinctive DMN activity patterns that are more profoundly associated with either normal ageing or a structural marker of neurodegeneration. 312 datasets inclusive of healthy adults and patients were analysed. Days of life at scan (DOL) and hippocampal volume were used as predictors. Group comparisons confirmed a significant association between functional connectivity in the posterior cingulate/retrosplenial cortex and precuneus and both ageing and AD. Fully-corrected regression models revealed that DOL significantly predicted DMN strength in these regions. No such effect, however, was predicted by hippocampal volume. A significant positive association was found between hippocampal volumes and DMN connectivity in the right temporo-parietal junction (TPJ). These results indicate that postero-medial DMN down-regulation may not be specific to neurodegenerative processes but may be more an indication of brain vulnerability to degeneration. The DMN-TPJ disconnection is instead linked to the volumetric properties of the hippocampus, may reflect early-stage regional accumulation of pathology and might be of aid in the clinical detection of abnormal ageing