Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency

In-Home Training for Fathers of Children with Autism: A Follow up Study and Evaluation of Four Individual Training Components

Literature regarding fathers of children with autism remains sparse, and because mothers are the more common intervening parent, few training methods have focused on fathers. Thus, we sought to evaluate effects of in-home training directed at fathers and their ability to train mothers in the same manner in which they were trained. Fathers were taught four skills commonly associated with in-home training interventions for parents of children with autism: following the child’s lead, imitation with animation, commenting on the child, and expectant waiting. Father skills were evaluated twice a week for 12 weeks during videotaped in-home father–child play sessions. Analyses included visual inspection of graphed data and statistical analyses of father skill acquisition, mother skill acquisition, and child behaviors with both parents. A multivariate repeated measures analysis of 18 dyads revealed significant increases in frequencies of fathers’ imitation with animation, expectant waiting, and commenting on the child. Child initiating rates increased significantly as did frequencies of child non-speech vocalizations. Analysis of mothers revealed significant increases in frequencies of imitation with animation, expectant waiting, and following the child’s lead. Child behaviors had similar results for father and mother sessions. Findings are consistent with those from our first study indicating that fathers can effectively implement skills that promote father–child social interactions and that children respond positively to this approach

Personality trait development in midlife: exploring the impact of psychological turning points

This study examined long-term personality trait development in midlife and explored the impact of psychological turning points on personality change. Selfdefined psychological turning points reflect major changes in the ways people think or feel about an important part of their life, such as work, family, and beliefs about themselves and about the world. This study used longitudinal data from the Midlife in the US survey to examine personality trait development in adults aged 40–60 years. The Big Five traits were assessed in 1995 and 2005 by means of self-descriptive adjectives. Seven types of self-identified psychological turning points were obtained in 1995. Results indicated relatively high stability with respect to rankorders and mean-levels of personality traits, and at the same time reliable individual differences in change. This implies that despite the relative stability of personality traits in the overall sample, some individuals show systematic deviations from the sample mean-levels. Psychological turning points in general showed very little influence on personality trait change, although some effects were found for specific types of turning points that warrant further research, such as discovering that a close friend or relative was a much better person than one thought they were

Association of MC1R Variants and host phenotypes with melanoma risk in CDKN2A mutation carriers: a GenoMEL study

<p><b>Background</b> Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited.</p> <p><b>Methods</b> We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided.</p> <p><b>Results</b> Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10−6 ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; Ptrend = 1.86 × 10−8). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10−6 ≤ P ≤ .02).</p> <p><b>Conclusion</b> Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.</p&gt

The role of informal dimensions of safety in high-volume organisational routines:an ethnographic study of test results handling in UK general practice

Abstract Background The handling of laboratory, imaging and other test results in UK general practice is a high-volume organisational routine that is both complex and high risk. Previous research in this area has focused on errors and harm, but a complementary approach is to better understand how safety is achieved in everyday practice. This paper ethnographically examines the role of informal dimensions of test results handling routines in the achievement of safety in UK general practice and how these findings can best be developed for wider application by policymakers and practitioners. Methods Non-participant observation was conducted of high-volume organisational routines across eight UK general practices with diverse organisational characteristics. Sixty-two semi-structured interviews were also conducted with the key practice staff alongside the analysis of relevant documents. Results While formal results handling routines were described similarly across the eight study practices, the everyday structure of how the routine should be enacted in practice was informally understood. Results handling safety took a range of local forms depending on how different aspects of safety were prioritised, with practices varying in terms of how they balanced thoroughness (i.e. ensuring the high-quality management of results by the most appropriate clinician) and efficiency (i.e. timely management of results) depending on a range of factors (e.g. practice history, team composition). Each approach adopted created its own potential risks, with demands for thoroughness reducing productivity and demands for efficiency reducing handling quality. Irrespective of the practice-level approach adopted, staff also regularly varied what they did for individual patients depending on the specific context (e.g. type of result, patient circumstances). Conclusions General practices variably prioritised a legitimate range of results handling safety processes and outcomes, each with differing strengths and trade-offs. Future safety improvement interventions should focus on how to maximise practice-level knowledge and understanding of the range of context-specific approaches available and the safeties and risks inherent in each within the context of wider complex system conditions and interactions. This in turn has the potential to inform new kinds of proactive, contextually appropriate approaches to intervention development and implementation focusing on the enhanced deliberation of the safety of existing high-volume routines

Seasonal influenza risk in hospital healthcare workers is more strongly associated with household than occupational exposures: results from a prospective cohort study in Berlin, Germany, 2006/07

Background: Influenza immunisation for healthcare workers is encouraged to protect their often vulnerable patients but also due to a perceived higher risk for influenza. We aimed to compare the risk of influenza infection in healthcare workers in acute hospital care with that in non-healthcare workers over the same season. Methods: We conducted a prospective, multicentre cohort study during the 2006/07 influenza season in Berlin, Germany. Recruited participants gave serum samples before and after the season, and completed questionnaires to determine their relevant exposures and possible confounding factors. The main outcome measure was serologically confirmed influenza infection (SCII), defined as a fourfold or greater rise in haemagglutination inhibition antibody titres to a circulating strain of influenza (with post-season titre at least 1:40). Weekly mobile phone text messages were used to prompt participants to report respiratory illnesses during the influenza season. A logistic regression model was used to assess the influence of potential risk factors. Results: We recruited 250 hospital healthcare workers (mean age 35.7 years) and 486 non-healthcare workers (mean age 39.2 years) from administrative centres, blood donors and colleges. Overall SCII attack rate was 10.6%. Being a healthcare worker was not a risk factor for SCII (relative risk 1.1, p=0.70). The final multivariate model had three significant factors: living with children (odds ratio [OR] 3.7, p=0.005), immunization (OR 0.50, p=0.02), and - among persons living in households without children - ownership of a car (OR 3.0, p=0.02). Living with three or more children (OR 13.8,

Entrepreneurs' exit and paths to retirement : theoretical and empirical considerations

The number of ageing entrepreneurs in micro- and small-sized companies is rapidly increasing in Finland and other European Union countries. Over half a million jobs, in over one hundred thousand companies within the EU, are lost annually due to unsuccessful, predominantly retirement-related transfers of businesses. This challenge coincides with EU Grand Challenges and has been highlighted in the Entrepreneurship 2020 Action Plan (European Commission 2013). It has been estimated that in Finland, some 8000 jobs are lost yearly due to the ageing of entrepreneurs. Therefore, entrepreneur ageing has implications not only for the ageing individual but also for the company and the society at large. As entrepreneurs age it becomes more essential for them to start planning when and how they transition into retirement. While they may experience several exits and subsequent re-entries into working life via buying or starting new companies, exiting ones entrepreneurial career due to old age retirement differs from exits that occur earlier during the career. In this chapter, we provide a short overview of the entrepreneur retirement and exit literature from an age perspective. Furthermore, we present a theoretical conceptualization which combines entrepreneur retirement process with exit theories. This will enable scholars to better understand the retirement process, including decision-making, transitioning, and adjustment to retirement. We also provide empirical evidence using data collected among Finnish entrepreneurs in 2012 and 2015, where we outline the types of exits and assess several factors, including age, in association with exit intentions.fi=vertaisarvioitu|en=peerReviewed

Co-morbidity and polypharmacy in Parkinson's Disease:insights from a large Scottish primary care database

Background: Parkinson’s disease is complicated by comorbidity and polypharmacy, but the extent and patterns of these are unclear. We describe comorbidity and polypharmacy in patients with and without Parkinson’s disease across 31 other physical, and seven mental health conditions. Methods: We analysed primary health-care data on 510,502 adults aged 55 and over. We generated standardised prevalence rates by age-groups, gender, and neighbourhood deprivation, then calculated age, sex and deprivation adjusted odds ratios (OR) and 95% confidence intervals (95% CI) for those with PD compared to those without, for the prevalence, and number of conditions. Results: Two thousand six hundred forty (0.5%) had Parkinson’s disease, of whom only 7.4% had no other conditions compared with 22.9% of controls (adjusted OR [aOR] 0.43, 95% 0.38–0.49). The Parkinson’s group had more conditions, with the biggest difference found for seven or more conditions (PD 12.1% vs. controls 3.9%; aOR 2.08 95% CI 1.84–2.35). 12 of the 31 physical conditions and five of the seven mental health conditions were significantly more prevalent in the PD group. 44.5% with Parkinson’s disease were on five to nine repeat prescriptions compared to 24.5% of controls (aOR 1.40; 95% CI 1.28 to 1.53) and 19.2% on ten or more compared to 6.2% of controls (aOR 1.90; 95% CI 1.68 to 2.15). Conclusions: Parkinson’s disease is associated with substantial physical and mental co-morbidity. Polypharmacy is also a significant issue due to the complex nature of the disease and associated treatments

Localized practices and globalized futures: challenges for Alaska coastal community youth

An article from Maritime Studies (2015) 14: