Quantitative methods for the analysis of CFTR transcripts/splicing variants

AbstractIn cystic fibrosis (CF), transcript analysis and quantification are important for diagnosis, prognosis and also as surrogate markers for some therapies including gene therapy. Classical RNA-based methods require significant expression levels in target samples for appropriate analysis, thus PCR-based methods are evolving towards reliable quantification. Various protocols for the quantitative analysis of CFTR transcripts (including those resulting from splicing variants) are described and discussed here

Understanding potential career changers’ experience of career confidence following a positive psychology based coaching programme

Changes in the labour market over the last decades have led to an increase in the number of career and job changes individuals are likely to face in their working lives. Previous research indicates that a high level of confidence can help individuals to make positive career changes, yet an agreed definition of confidence is not widely accepted, and the literature provides a limited evidence base for practice. This research involved five female participants who were contemplating a career change. They took part in a coaching programme which consisted of four positive psychology interventions based on a proposal of core confidence as a higher order construct composed of self-efficacy, hope, optimism and resilience. Data were gathered through semi-structured interviews and written reflections and an interpretative phenomenological analysis showed that participants perceived their career confidence before the programme as low, incorporating negative affect and self-doubt. After the programme, participants demonstrated increased career engagement, self-awareness and a positive and optimistic outlook. The analysis revealed that change was effected through the development of hope, change in cognitive processes and coaching as a catalyst. Implications for the definition of career confidence, and for positive psychology and career coaching practice are considered

Streptococcus pneumoniae Serotype-2 Childhood Meningitis in Bangladesh: A Newly Recognized Pneumococcal Infection Threat

BACKGROUND: Streptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV) targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD) caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention. METHODS AND FINDINGS: Cases with suspected IPD had blood or cerebrospinal fluid (CSF) collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal meningitis, accounting for 20.4% (45/221; 95% CI 15%-26%) of cases. Ninety eight percent (45/46) of these serotype-2 strains were isolated from meningitis cases, yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI 3.4-256.3). The serotype-2 strains had three closely related pulsed field gel electrophoresis types. CONCLUSIONS: S. pneumoniae serotype-2 was found to possess an unusually high potential for causing meningitis and was the leading serotype-specific cause of childhood meningitis in Bangladesh over the past decade. Persisting disease occurrence or progressive spread would represent a major potential infection threat since serotype-2 is not included in PCVs currently licensed or under development

Higher quality of life and lower depression for people on art in Uganda as compared to a community control group

Provision of antiretroviral treatment (ART) to people living with HIV (PLWH) has increased globally. Research measuring whether ART restores subjective well-being to "normal" levels is lacking, particularly in resource limited settings. The study objectives are to compare quality of life and depression symptoms for PLWH on ART to a general community population and to explore factors to explain these differences, including socio-economic status and the impact of urban or rural residence. PLWH on ART (n = 263) were recruited from ART delivery sites and participants not on ART (n = 160) were recruited from communities in Wakiso District, Uganda. Participants were interviewed using the translated World Health Organisation Quality of Life brief measure, the Hopkins Symptom Checklist depression section, and questions about socioeconomic status, residence as urban or rural and, for PLWH on ART, self-reported adherence and use of HIV counselling. Compared to the community sample and controlling for location of residence, PLWH on ART had significantly higher quality of life (QOL) for physical, psychological and environment domains, but not the social domain. These differences were not due to socio-economic status alone. Depression scores were significantly lower for PLWH on ART. Both comparisons controlled for the effect of location of residence. People on ART self-reported high adherence and the majority had used HIV counselling services. Our findings show better QOL amongst PLWH on ART compared to a general community sample, which cannot be explained solely by differences in socio-economic status nor location of residence. The general community sample results point towards the challenges of life in this setting. Access to health services may underpin this difference and further research should explore this finding, in addition to identification of psychological mechanisms that relate to better QOL. ART provision infrastructure has clear benefits. Further work should consider sustainability and replication for other health conditions. © 2014 Martin et al

The “Tango Argentino”: a metaphor for understanding effectuation processes

The authors use the analogy of the Argentine Tango to illuminate entrepreneurial effectuation as a process of becoming. Drawing on the metaphor of dance, the authors highlight seven areas for theory development that could further a performative theory of effectuation. These include the study of the micro-level movement and flow in the dance as “intimate steps,” and understanding the interplay between entrepreneur and ecosystem as “contextual rhythms.” They further propose that the study of changing leadership in the dance could illuminate how causal processes “become” effectual and suggest a concept of “attunement” to consider how inexperienced entrepreneurs learn contextual rhythms and, therefore, benefit for effectuation processes. Finally, they posit that the intimate steps leading to creativity in the dance relative to different levels of proximity and distance between the dancers should be understood alongside the movements and flows through which dancers maintain their individuality during such intimate movements and flows

Plant-made vaccines in support of the Millennium Development Goals

Vaccines are one of the most successful public health achievements of the last century. Systematic immunisation programs have reduced the burden of infectious diseases on a global scale. However, there are limitations to the current technology, which often requires costly infrastructure and long lead times for production. Furthermore, the requirement to keep vaccines within the cold-chain throughout manufacture, transport and storage is often impractical and prohibitively expensive in developing countries—the very regions where vaccines are most needed. In contrast, plant-made vaccines (PMVs) can be produced at a lower cost using basic greenhouse agricultural methods, and do not need to be kept within such narrow temperature ranges. This increases the feasibility of developing countries producing vaccines locally at a small-scale to target the specific needs of the region. Additionally, the ability of plant-production technologies to rapidly produce large quantities of strain-specific vaccine demonstrates their potential use in combating pandemics. PMVs are a proven technology that has the potential to play an important role in increasing global health, both in the context of the 2015 Millennium Development Goals and beyond

The third international hackathon for applying insights into large-scale genomic composition to use cases in a wide range of organisms

publishedVersio

Modelling Everyday Understandings of Mortality: A Qualitative Enquiry

With few exceptions, much of the literature on mortality awareness (MA; the realization of one’s own and other’s mortality), though based on quantitative research, is focused on its negative effects and processes associated with fearing its occurrence. However, recent studies have demonstrated that MA is multifaceted and can be associated with positive processes and outcomes. Here, everyday understandings of MA were investigated using grounded theory. Ten participants engaged in one-off semistructured interviews about their everyday experiences of MA. Grounded theory analysis revealed four main themes: (a) Moments of MA, (b) Functionality of MA, (c) Coping strategies for MA, and (d) Inability to cope with MA. Each of these themes is composed of two to five subthemes. The results supported the notion that MA is experienced in a multidimensional manner, which appears to align with elements of the Multidimensional Mortality Awareness Measure and Model. Furthermore, positive and/or negative outcomes appeared to depend on the function attributed to MA by the individual. Therefore, the ability to attribute such function to MA appears to be important in our understanding of this key existential issue