Evaluation of a novel assay for detection of the fetal marker RASSF1A: facilitating improved diagnostic reliability of noninvasive prenatal diagnosis

BackgroundAnalysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders. True positive results rely on detection of the fetal target being analysed. No amplification of the target may be interpreted either as a true negative result or a false negative result due to the absence or very low levels of cffDNA. The hypermethylated RASSF1A promoter has been reported as a universal fetal marker to confirm the presence of cffDNA. Using methylation-sensitive restriction enzymes hypomethylated maternal sequences are digested leaving hypermethylated fetal sequences detectable. Complete digestion of maternal sequences is required to eliminate false positive results.MethodscfDNA was extracted from maternal plasma (n = 90) and digested with methylation-sensitive and insensitive restriction enzymes. Analysis of RASSF1A, SRY and DYS14 was performed by real-time PCR.ResultsHypermethylated RASSF1A was amplified for 79 samples (88%) indicating the presence of cffDNA. SRY real time PCR results and fetal sex at delivery were 100% accurate. Eleven samples (12%) had no detectable hypermethylated RASSF1A and 10 of these (91%) had gestational ages less than 7 weeks 2 days. Six of these samples were male at delivery, five had inconclusive results for SRY analysis and one sample had no amplifiable SRY.ConclusionUse of this assay for the detection of hypermethylated RASSF1A as a universal fetal marker has the potential to improve the diagnostic reliability of NIPD for fetal sex determination and single gene disorders

Neuropsychological and functional outcomes in recent-onset major depression, bipolar disorder and schizophrenia-spectrum disorders: a longitudinal cohort study

Functional disability is the lead contributor to burden of mental illness. Cognitive deficits frequently limit functional recovery, although whether changes in cognition and disability are longitudinally associated in recent-onset individuals remains unclear. Using a prospective, cohort design, 311 patients were recruited and assessed at baseline. One hundred and sixty-seven patients met eligibility criteria (M = 21.5 years old, s.d. = 4.8) and returned for follow-up (M = 20.6 months later, s.d. = 7.8). Two-hundred and thirty participants were included in the final analysis, comprising clinically stable patients with major depression (n = 71), bipolar disorder (BD; n = 61), schizophrenia-spectrum disorders (n = 35) and 63 healthy controls. Neuropsychological functioning and self-rated functional disability were examined using mixed-design, repeated-measures analysis, across diagnoses and cognitive clusters, covarying for relevant confounds. Clinical, neuropsychological and functional changes did not differ between diagnoses (all P40.05). Three reliable neuropsychological subgroups emerged through cluster analysis, characterized by psychomotor slowing, improved sustained attention, and improved verbal memory. Controlling for diagnosis and changes in residual symptoms, clusters with improved neuropsychological functioning observed greater reductions in functional disability than the psychomotor slowing cluster, which instead demonstrated a worsening in disability (Po0.01). Improved sustained attention was independently associated with greater likelihood of follow-up employment (Po0.01). Diagnosis of BD uniquely predicted both follow-up employment and independent living. Neuropsychological course appears to be independently predictive of subjective and objective functional outcomes. Importantly, cognitive phenotypes may reflect distinct pathophysiologies shared across major psychiatric conditions, and be ideal targets for personalized early intervention

Engineering handbook

2005 handbook for the faculty of Engineerin

The Impact of Developmental and Humanitarian Aid in the Nation of Haiti

Short term aid has numerous benefits and limitations in contrast with sustainable development. For this project sustainable development is defined as: utilizing the resources in communities and encouraging indigenous leadership to promote well being for future generations. The impact of short term relief is determined by various factors. The focus of this research will be the impact of humanitarian emergency assistance and developmental assistance in the nation of Haiti. The research findings obtained through literature review educates the local community on how to effectively assist developing communities both domestically and abroad to become self-sustaining

The Black River: a comprehensive study of physical and chemical characteristics and their potential management implications.

An analysis of the Black River's biological and physicochemical characteristics was conducted for comparison to the model proposed by the river continuum theory. The theory specifies that the biological fauna, physical characteristics and chemical composition observed, are reflected in river order changes in terms of the presence, absence, or density of producer and consumer communities. The study reflected consistencies between the model and observed physical parameters and chemical attributes, but biological indicators were less corroborating. Physical characteristics such as temperature, depth, width, velocity, discharge, and suspended sediments increased with river mile and trends in the data became apparent. Chemical factors such as nitrates, dissolved oxygen, pH, alkalinity, and hardness, though not as clearly conclusive, show a gradient associated with river order transition. Biological indicators were not as conclusive in supporting the river continuum theory since there was no representation of shredders in the headwaters and predatory species were found at most sites. Management issues of the Black River address the control of soil erosion, species composition, and sedimentation as well as maintaining water temperature.http://deepblue.lib.umich.edu/bitstream/2027.42/54342/1/2778.pd

Young people's understanding, attitudes and involvement in decision-making about genome sequencing for rare diseases: A qualitative study with participants in the UK 100,000 genomes project

Genome sequencing (GS) will have a profound impact on the diagnosis of rare and inherited diseases in children and young people. We conducted 27 semi-structured interviews with young people aged 11-19 having GS through the UK 100,000 Genomes Project. Participants demonstrated an understanding of the role and function of genes and DNA, however the terms 'genome' and 'genome sequencing' were less well understood. Participants were primarily motivated to take part to get a diagnosis or identify the gene causing their condition. The majority of participants understood they might not receive a diagnostic result. Most were unconcerned about data security or access, however anxieties existed around what the results might show and the potential for disappointment if the result was negative. Signing an assent form empowered young people, formalised the process and instilled a sense of responsibility for their choice to participate. Most young people (≥16 years) had consented to receive secondary findings and had come to that decision without parental influence. Our research suggests that at least some young people are capable of making informed decisions about taking part in GS, and that involving them in discussions about testing can empower them to take responsibility over healthcare decisions that affect them

Antimicrobial octapeptin C4 analogues active against Cryptococcus species

Resistance to antimicrobials is a growing problem in both developed and developing countries. In nations where AIDS is most prevalent, the human fungal pathogen Cryptococcus neoformans is a significant contributor to mortality, and its growing resistance to current antifungals an ever-expanding threat. We investigated octapeptin C4, from the cationic cyclic lipopeptide class of antimicrobials, as a potential new antifungal. Octapeptin C4 was a potent, selective inhibitor of this fungal pathogen with minimum inhibitory concentration of 1.56 μg/mL. Further testing of octapeptin C4 against 40 clinical isolates of C. neoformans var. grubii or neoformans showed MIC 1.56-3.13 μg/mL while 20 clinical isolates of C. neoformans var. gattii had MIC 0.78-12.5 μg/mL. In each case MIC values for octapeptin C4 were equivalent to, or better than, current antifungal drugs fluconazole and amphotericin B. The negatively charged polysaccharide capsule of C. neoformans influences the pathogens sensitivity to octapeptin C4 while degree of melanisation had little effect. Testing synthetic octapeptin C4 derivatives provided insight into the structure activity relationships, revealing that the lipophilic amino acid moieties are more important to the activity than the cationic diaminobutyric acid groups. Octapeptins have promising potential for development as anticryptococcal therapeutic agents

Excavations and the afterlife of a professional football stadium, Peel Park, Accrington, Lancashire: towards an archaeology of football

Association football is now a multi-billion dollar global industry whose emergence spans the post-medieval to the modern world. With its professional roots in late 19th-century industrial Lancashire, stadiums built for the professionalization of football first appear in frequency in the North of England. While many historians of sport focus on consumerism and ‘topophilia’ (attachment to place) regarding these local football grounds, archaeological research that has been conducted on the spectator experience suggests status differentiation within them. Our excavations at Peel Park confirm this impression while also showing a significant afterlife to this stadium, particularly through children’s play

Underpinning excellence in higher education – an investigation into the leadership, governance and management behaviours of high-performing academic departments

The changes in government funding alongside external pressures of increased international and national competition have meant that higher education institutions need to excel in a turbulent environment. The leadership, governance and management (LGM) of academic departments are key concerns. This study investigates the correlation between behaviours, attitudes and competencies at a department level and overall departmental performance in terms of hard data measures. The research question this paper seeks to address is: what are the LGM behaviours that are associated with high-performance in academic departments? More than 600 people across 50 academic departments in 5 UK universities were surveyed through the use of three research phases consisting of open-ended questionnaires, critical case sampled semi-structured interviews and a fixed-response survey. Synthesising the data and findings of the study revealed a thematic framework of eight broad themes that contribute to excellence in academic departments. These were in the areas of change management, research and teaching, communication, strategy and shared values, leadership, departmental culture, rewards and staffing. The behaviours associated with each of these themes were used to construct the Underpinning Excellence model

"The communication and support from the health professional is incredibly important": A qualitative study exploring the processes and practices that support parental decision-making about postmortem examination

Background Consent rates for postmortem (PM) examination in the perinatal and paediatric setting have dropped significantly in the United Kingdom, the United States, and the Western Europe. We explored the factors that act as facilitators or barriers to consent and identified processes and practices that support parental decision‐making. Methods A qualitative study conducted with bereaved parents, parent advocates, and health care professionals in the United Kingdom. Analysis was conducted on 439 free‐tect comments within a cross‐sectional survey, interviews with a subset of 20 survey respondents and 25 health professionals, and a focus group with five parent advocates. Results Three broad parental decision‐making groups were identified: 1, “Not open to postmortem examination”; 2, “Consent regardless of concerns”; and 3, “Initially undecided.” Decisional drivers that were particularly important for this “undecided” group were “the initial approach,” “adjustment and deliberation,” “detailed discussion about the procedure,” and “formal consent.” The way in which these were managed by health care staff significantly impacted whether those parents' consented to PM, particularly for those who are ambivalent about the procedure. Conclusions We propose a set of recommendations to improve the way PM counselling and consent is managed. Adopting such measures is likely to lead to improved family experience and more consistent and high‐quality discussion regarding PM