Mindfulness based cognitive therapy for young people and their carers: A mixed-methods feasibility study

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.We aimed to evaluate whether Mindfulness Based Cognitive Therapy (MBCT) was feasible and acceptable for young people, their parents and the clinicians working with them; whether a parallel course for parents was a useful addition; and whether attendance at MBCT was associated with improved outcomes. The design was a mixed methods service evaluation of an eight session MBCT programme for young people who were recovering from depression. The course was a manualised eight session group intervention. Both young people (n=18) and parents (n=21) completed validated measures before and after the course. Semi-structured interviews were completed with some group participants and clinical staff working in the service. Care records were searched for additional contact following the intervention. Qualitative data from young people, parents and clinicians suggested that MBCT was acceptable and feasible, and provided strategies to cope. The parent course was reported to provide personal support to parents and helped them cope with their child’s depression while also impacting the family, promoted shared understanding of depression and strategies to combat it, and addressed intergenerational aspects of depression. 84% of participants attended at least 6/8 sessions and 48% required no further intervention within the following year. Young people had statistically significant improvements across all outcome measures, while parents had statistically significant improvements in rumination, self-compassion and decentering.Daniel Racey completed this work whilst supported by an NIHR Academic Clinical Fellowship while Kelly Blockley and Vashti Berry are supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula

Biological effects of rinsing morsellised bone grafts before and after impaction

Rinsing bone grafts before or both before and after impaction might have different effects on the incorporation of the graft. Rinsing again after impaction might negatively influence bone induction if growth factors released by impaction are washed away. We studied if transforming growth factor-βs (TGF-βs) and bone morphogenetic proteins (BMPs) are released from the mineralised matrix by impaction and if these released growth factors induce osteogenic differentiation in human mesenchymal stem cells (hMSCs). Rinsed morsellised bone allografts were impacted in a cylinder and the escaping fluid was collected. The fluid was analysed for the presence of TGF-βs and BMPs, and the osteoinductive capacity was tested on hMSCs. Abundant TGF-β was present in the fluid. No BMPs could be detected. Osteogenic differentiation of hMSCs was inhibited by the fluid. Results from our study leave us only able to speculate whether rinsing grafts again after impaction has a beneficial effect on the incorporation process or not

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

"I really should've gone to the doctor": older adults and family caregivers describe their experiences with community-acquired pneumonia

BACKGROUND: Responding to acute illness symptoms can often be challenging for older adults. The primary objective of this study was to describe how community-dwelling older adults and their family members responded to symptoms of community-acquired pneumonia (CAP). METHODS: A qualitative study that used face-to-face semi-structured interviews to collect data from a purposeful sample of seniors aged 60+ and their family members living in a mid-sized Canadian city. Data analysis began with descriptive and interpretive coding, then advanced as the research team repeatedly compared emerging thematic categories to the raw data. Searches for disconfirming evidence and member checking through focus groups provided additional data and helped ensure rigour. RESULTS: Community-acquired pneumonia symptoms varied greatly among older adults, making decisions to seek care difficult for them and their family members. Both groups took varying amounts of time as they attempted to sort out what was wrong and then determine how best to respond. Even after they concluded something was wrong, older adults with confirmed pneumonia continued to wait for days, to over a week, before seeking medical care. Participants provided diverse reasons for this delay, including fear, social obligations (work, family, leisure), and accessibility barriers (time, place, systemic). Several older adults and family members regretted their delays in seeking help. CONCLUSION: Treatment-seeking delay is a variable, multi-phased decision-making process that incorporates symptom assessment plus psychosocial and situational factors. Public health and health care professionals need to educate older adults about the potential causes and consequences of unnecessary waits. Such efforts may reduce the severity of community-acquired pneumonia upon presentation at clinics and hospitals, and that, in turn, could potentially improve health outcomes

Changes in immunocompetent cells after interstitial laser thermotherapy of breast cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Local tumour destruction has been shown to give rise to changes in immunocompetent cells. The aim of this study was to describe the effect of interstitial laser thermotherapy (ILT) of breast carcinoma in the tumour and in regional lymph nodes. METHODS: Seventeen women that underwent radical surgical excision after non-radical ILT were studied. ILT was performed at a steady-state temperature of 48°C for 30 min. Surgical excision was performed 12 (6-23) days after ILT. Six patients with breast cancer not treated with ILT before surgery served as controls. Immunohistological reactions were performed on core needle biopsies prior to treatment and on the excised specimens. RESULTS: ILT resulted in more CD8 lymphocytes and CD68 macrophages within the tumour (P < 0.05 and P < 0.01, respectively) and higher counts of CD20 (P < 0.05), CD68 (P < 0.001) and CD83 (P < 0.01) at the tumour border, when compared to pre-treatment values. In the control patients not receiving ILT, CD8 cells increased within the tumour after resection (P < 0.05). With the probable exception of CD25 Foxp3 cells, the presence of cancer in a lymph node influenced the findings in lymph nodes (examined for CD1a, CD25, Foxp3 CD25, CD83 cells). Thus, comparisons between ILT and control patients were restricted to patients without lymph node metastases. In these patients, ILT and resection were followed by a decrease in CD25 Foxp3 lymphocytes (P < 0.05), when compared to surgical resection alone. CONCLUSIONS: ILT induced changes in immunocompetent cells in patients with breast cancer. The stimulation of the immune system is an added feature of ILT in treatment of patients with breast cancer

Dual-functioning transcription factors in the developmental gene network of Drosophila melanogaster

Quantitative models for transcriptional regulation have shown great promise for advancing our understanding of the biological mechanisms underlying gene regulation. However, all of the models to date assume a transcription factor (TF) to have either activating or repressing function towards all the genes it is regulating.In this paper we demonstrate, on the example of the developmental gene network in D. melanogaster, that the data-fit can be improved by up to 40% if the model is allowing certain TFs to have dual function, that is, acting as activator for some genes and as repressor for others. We demonstrate that the improvement is not due to additional flexibility in the model but rather derived from the data itself. We also found no evidence for the involvement of other known site-specific TFs in regulating this network. Finally, we propose SUMOylation as a candidate biological mechanism allowing TFs to switch their role when a small ubiquitin-like modifier (SUMO) is covalently attached to the TF. We strengthen this hypothesis by demonstrating that the TFs predicted to have dual function also contain the known SUMO consensus motif, while TFs predicted to have only one role lack this motif.We argue that a SUMOylation-dependent mechanism allowing TFs to have dual function represents a promising area for further research and might be another step towards uncovering the biological mechanisms underlying transcriptional regulation

Cardiac Complications in Patients with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Observational Studies

Vicente Corrales-Medina and colleagues report estimates of the risk of cardiac complications among patients with community-acquired pneumonia from a systematic review and meta-analysis

Fire performance of phase change material enhanced plasterboard

Sustainable construction materials are increasingly being used to reduce the carbon footprint of modern buildings. These materials have the potential to change the fire dynamics of compartments by altering the compartment energy balance however there is little quantitative understanding of how these materials behave in the event of a real fire. The changes in fire dynamics may be due to increased fuel load in a compartment, reduced time to failure or promotion of flame spread. The objective of this research is to quantify how Phase Change Materials (PCMs) perform in realistic fire scenarios. It was found that a plasterboard product containing microencapsulated PCMs will behave similarly to a charring solid and have the potential to contribute significant fuel to a compartment fire but that they maintain integrity for the duration of flaming period. The critical heat flux for this product was determined in the cone calorimeter to be 17.5 ± 2.5 kW m−2, the peak heat release rate and mass loss rate ranged from 60.2 kW m−2 to 107 kW m−2 and 1.88 g s−1 m−2 to 8.47 g s−1 m−2 respectively for exposures between 20 kW m−2 and 70 kW m−2. Sample orientation was found to increase the peak heat release rate by up to 25%, whilst having little to no effect on the mass loss rate. These parameters, in addition to the in-depth temperature evolution and ignition properties, can be used as design criteria for balancing energy savings with quantified fire performance

HIV-1 subtype and viral tropism determination for evaluating antiretroviral therapy options: an analysis of archived Kenyan blood samples

<p>Abstract</p> <p>Background</p> <p>Infection with HIV-1 is characterized by genetic diversity such that specific viral subtypes are predominant in specific geographical areas. The genetic variation in HIV-1 <it>pol </it>and <it>env </it>genes is responsible for rapid development of resistance to current drugs. This variation has influenced disease progression among the infected and necessitated the search for alternative drugs with novel targets. Though successfully used in developed countries, these novel drugs are still limited in resource-poor countries. The aim of this study was to determine HIV-1 subtypes, recombination, dual infections and viral tropism of HIV-1 among Kenyan patients prior to widespread use of antiretroviral drugs.</p> <p>Methods</p> <p>Remnant blood samples from consenting sexually transmitted infection (STI) patients in Nairobi were collected between February and May 2001 and stored. Polymerase chain reaction and cloning of portions of HIV-1 <it>gag</it>, <it>pol </it>and <it>env </it>genes was carried out followed by automated DNA sequencing.</p> <p>Results</p> <p>Twenty HIV-1 positive samples (from 11 females and 9 males) were analyzed. The average age of males (32.5 years) and females (26.5 years) was significantly different (p value < 0.0001). Phylogenetic analysis revealed that 90% (18/20) were concordant HIV-1 subtypes: 12 were subtype A1; 2, A2; 3, D and 1, C. Two samples (10%) were discordant showing different subtypes in the three regions. Of 19 samples checked for co-receptor usage, 14 (73.7%) were chemokine co-receptor 5 (CCR5) variants while three (15.8%) were CXCR4 variants. Two had dual/mixed co-receptor use with X4 variants being minor population.</p> <p>Conclusion</p> <p>HIV-1 subtype A accounted for majority of the infections. Though perceived to be a high risk population, the prevalence of recombination in this sample was low with no dual infections detected. Genotypic co-receptor analysis showed that most patients harbored viruses that are predicted to use CCR5.</p