Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis

Common fragile sites (cfs) are specific regions in the human genome that are particularly prone to genomic instability under conditions of replicative stress. Several investigations support the view that common fragile sites play a role in carcinogenesis. We discuss a genome-wide approach based on graph theory and Gene Ontology vocabulary for the functional characterization of common fragile sites and for the identification of genes that contribute to tumour cell biology. CFS were assembled in a network based on a simple measure of correlation among common fragile site patterns of expression. By applying robust measurements to capture in quantitative terms the non triviality of the network, we identified several topological features clearly indicating departure from the Erdos-Renyi random graph model. The most important outcome was the presence of an unexpected large connected component far below the percolation threshold. Most of the best characterized common fragile sites belonged to this connected component. By filtering this connected component with Gene Ontology, statistically significant shared functional features were detected. Common fragile sites were found to be enriched for genes associated to the immune response and to mechanisms involved in tumour progression such as extracellular space remodeling and angiogenesis. Our results support the hypothesis that fragile sites serve a function; we propose that fragility is linked to a coordinated regulation of fragile genes expression.Comment: 18 pages, accepted for publication in BMC Bioinformatic

Overcoming Barriers to Skills Training in Borderline Personality Disorder: A Qualitative Interview Study

Despite evidence suggesting that skills training is an important mechanism of change in dialectical behaviour therapy, little research exploring facilitators and barriers to this process has been conducted. The study aimed to explore clients’ experiences of barriers to dialectical behaviour therapy skills training and how they felt they overcame these barriers, and to compare experiences between treatment completers and dropouts. In-depth qualitative interviews were conducted with 40 clients with borderline personality disorder who had attended a dialectical behaviour therapy programme. A thematic analysis of participants’ reported experiences found that key barriers to learning the skills were anxiety during the skills groups and difficulty understanding the material. Key barriers to using the skills were overwhelming emotions which left participants feeling unable or unwilling to use them. Key ways in which participants reported overcoming barriers to skills training were by sustaining their commitment to attending therapy and practising the skills, personalising the way they used them, and practising them so often that they became an integral part of their behavioural repertoire. Participants also highlighted a number of key ways in which they were supported with their skills training by other skills group members, the group therapists, their individual therapist, friends and family. Treatment dropouts were more likely than completers to describe anxiety during the skills groups as a barrier to learning, and were less likely to report overcoming barriers to skills training via the key processes outlined above. The findings of this qualitative study require replication, but could be used to generate hypotheses for testing in further research on barriers to skills training, how these relate to dropout, and how they can be overcome. The paper outlines several such suggestions for further research

Immunological Sex Differences in Socially Promiscuous African Ground Squirrels

Differences in how males and females respond to foreign antigens are common across taxa. Such sexual differences in the immune system are predicted to be greater in species with high promiscuity and sociality as these factors increase the likelihood of disease transmission. Intense sperm competition is thought to further this sexual dichotomy as increased investment in spermatogenesis likely incurs additional immunological costs. Xerus inauris, a ground squirrel found throughout southern Africa, is extremely social and promiscuous with one of the highest male reproductive investments among rodents. These life-history attributes suggest males and females should demonstrate a large dichotomy in immunity. Contrary to our prediction, we found no difference in spleen mass between the sexes. However, we did find significant biases in leukocyte types and red blood cell counts, possibly reflecting responses to parasite types. Among males, we predicted greater investments in spermatogenesis would result in reduced immunological investments. We found a negative association between testes and spleen size and a positive relationship between testes and number of lice suggesting trade-offs in reproductive investment possibly due to the costs associated with spermatogenesis and immunity. We suggest when measuring sexual differences in immunity it is important to consider the effects of reproductive pressures, parasite types, and life history costs

"What Do They Want Me To Say?" The hidden curriculum at work in the medical school selection process: a qualitative study

<p>Abstract</p> <p>Background</p> <p>There has been little study of the role of the essay question in selection for medical school. The purpose of this study was to obtain a better understanding of how applicants approached the essay questions used in selection at our medical school in 2007.</p> <p>Methods</p> <p>The authors conducted a qualitative analysis of 210 essays written as part of the medical school admissions process, and developed a conceptual framework to describe the relationships, ideas and concepts observed in the data.</p> <p>Results</p> <p>Findings of this analysis were confirmed in interviews with applicants and assessors. Analysis revealed a tension between "genuine" and "expected" responses that we believe applicants experience when choosing how to answer questions in the admissions process. A theory named "What do they want me to say?" was developed to describe the ways in which applicants modulate their responses to conform to their expectations of the selection process; the elements of this theory were confirmed in interviews with applicants and assessors.</p> <p>Conclusions</p> <p>This work suggests the existence of a "hidden curriculum of admissions" and demonstrates that the process of selection has a strong influence on applicant response. This paper suggests ways that selection might be modified to address this effect. Studies such as this can help us to appreciate the unintended consequences of admissions processes and can identify ways to make the selection process more consistent, transparent and fair.</p

Social conditions of becoming homelessness: qualitative analysis of life stories of homeless peoples

Background It is increasingly acknowledged that homelessness is a more complex social and public health phenomenon than the absence of a place to live. This view signifies a paradigm shift, from the definition of homelessness in terms of the absence of permanent accommodation, with its focus on pathways out of homelessness through the acquisition and maintenance of permanent housing, to understanding the social context of homelessness and social interventions to prevent it. However, despite evidence of the association between homelessness and social factors, there is very little research that examines the wider social context within which homelessness occurs from the perspective of homeless people themselves. This study aims to examine the stories of homeless people to gain understanding of the social conditions under which homelessness occurs, in order to propose a theoretical explanation for it. Method Twenty-six semi-structured interviews were conducted with homeless people in three centres for homeless people in Cheshire North West of England. Results The analysis revealed that becoming homeless is a process characterised by a progressive waning of resilience capacity to cope with life challenges created by series of adverse incidents in one’s life. The data show that final stage in the process of becoming homeless is complete collapse of relationships with those close to them. Most prominent pattern of behaviours participants often describe as main causes of breakdown of their relationships are: 1. engaging in maladaptive behavioural lifestyle including taking drugs and/or excessive alcohol drinking 2. Being in trouble with people in authorities. Conclusion Homeless people describe the immediate behavioural causes of homelessness, however, the analysis revealed the social and economic conditions within which homelessness occurred. The participants’ descriptions of the social conditions in which were raised and their references to maladaptive behaviours which led to them becoming homeless, led us to conclude that they believe that their social condition affected their life chances: that these conditions were responsible for their low quality of social connections, poor educational attainment, insecure employment and other reduced life opportunities available to them

A Multi-Center, Qualitative Assessment of Pediatrician and Maternal Perspectives on Rotavirus Vaccines and the Detection of Porcine circovirus

<p>Abstract</p> <p>Background</p> <p>In 2010, researchers using novel laboratory techniques found that US-licensed rotavirus vaccines contain DNA or DNA fragments from <it>Porcine circovirus </it>(PCV), a virus common among pigs but not believed to cause illness in humans. We sought to understand pediatricians' and mothers' perspectives on this finding.</p> <p>Methods</p> <p>We conducted three iterations of focus groups for pediatricians and non-vaccine hesitant mothers in Seattle, WA, Cincinnati, OH, and Rochester, NY. Focus groups explored perceptions of rotavirus disease, rotavirus vaccination, and attitudes about the detection of PCV material in rotavirus vaccines.</p> <p>Results</p> <p>Pediatricians understood firsthand the success of rotavirus vaccines in preventing severe acute gastroenteritis among infants and young children. They measured this benefit against the theoretical risk of DNA material from PCV in rotavirus vaccines, determining overall that the PCV finding was of no clinical significance. Particularly influential was the realization that the large, randomized clinical trials that found both vaccines to be highly effective and safe were conducted with DNA material from PCV already in the vaccines.</p> <p>Most mothers supported the ideal of full disclosure regarding vaccination risks and benefits. However, with a scientific topic of this complexity, simplified information regarding PCV material in rotavirus vaccines seemed frightening and suspicious, and detailed information was frequently overwhelming. Mothers often remarked that if they did not understand a medical or technical topic regarding their child's health, they relied on their pediatrician's guidance.</p> <p>Many mothers and pediatricians were also concerned that persons who abstain from pork consumption for religious or personal reasons may have unsubstantiated fears of the PCV finding.</p> <p>Conclusions</p> <p>Pediatricians considered the detection of DNA material from PCV in rotavirus vaccines a "non-issue" and reported little hesitation in continuing to recommend the vaccines. Mothers desired transparency, but ultimately trusted their pediatrician's recommendation. Both vaccines are currently approved for their intended use, and no risk of human PCV illness has been reported. Communicating this topic to pediatricians and mothers requires sensitivity to a broad range of technical understanding and personal concerns.</p

Code Status Discussions Between Attending Hospitalist Physicians and Medical Patients at Hospital Admission

BackgroundBioethicists and professional associations give specific recommendations for discussing cardiopulmonary resuscitation (CPR).ObjectiveTo determine whether attending hospitalist physicians' discussions meet these recommendations.DesignCross-sectional observational study on the medical services at two hospitals within a university system between August 2008 and March 2009.ParticipantsAttending hospitalist physicians and patients who were able to communicate verbally about their medical care.Main measuresWe identified code status discussions in audio-recorded admission encounters via physician survey and review of encounter transcripts. A quantitative content analysis was performed to determine whether discussions included elements recommended by bioethicists and professional associations. Two coders independently coded all discussions; Cohen's kappa was 0.64-1 for all reported elements.Key resultsAudio-recordings of 80 patients' admission encounters with 27 physicians were obtained. Eleven physicians discussed code status in 19 encounters. Discussions were more frequent in seriously ill patients (OR 4, 95% CI 1.2-14.6), yet 66% of seriously ill patients had no discussion. The median length of the code status discussions was 1 min (range 0.2-8.2). Prognosis was discussed with code status in only one of the encounters. Discussions of patients' preferences focused on the use of life-sustaining interventions as opposed to larger life goals. Descriptions of CPR as an intervention used medical jargon, and the indication for CPR was framed in general, as opposed to patient-specific scenarios. No physician quantitatively estimated the outcome of or provided a recommendation about the use of CPR.ConclusionsCode status was not discussed with many seriously ill patients. Discussions were brief, and did not include elements that bioethicists and professional associations recommend to promote patient autonomy. Local and national guidelines, research, and clinical practice changes are needed to clarify and systematize with whom and how CPR is discussed at hospital admission