Stepfamilies and older people: evaluating the implications of family change for an ageing population

The changing nature of family life has become a major issue in contemporary Britain. Concerns that change will bring moral decline and social fragmentation are countered by a more optimistic view which focuses on a future of more equitable and flexible family ties. Research drawing on area-based data in Luton amongst older, middle-aged and younger people with experience of family change suggests that so far as inter-generational relations, caring, and transfers of family wealth are concerned, traditional attitudes towards blood ties, household independence and care and support survive alongside new step relationships. The research also suggests that although several respondents had more than one generation of experience of family change, the language of step relationships is still one which is not yet completely accepted, or one with which people feel completely at ease

Effective leadership in multi-ethnic schools: school community perspectives and their leadership implications

A project report for the National College for School Leadership, exploring issues of effective leadership in ethnically diverse schools. The paper collates the views of school leaders, staff, students and community representatives

The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections.

Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy-number variants, and single gene mutations. CDH is the most expensive noncardiac congenital defect. Management frequently requires implementation of extracorporeal membrane oxygenation (ECMO), which increases management expenditures 2.4-3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in-hospital survival of 80%-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including postcardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections, and developmental delay. Rapid whole-genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_ 3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day

Potentially Diagnostic Electron Paramagnetic Resonance Spectra Elucidate the Underlying Mechanism of Mitochondrial Dysfunction in the Deoxyguanosine Kinase Deficient Rat Model of a Genetic Mitochondrial DNA Depletion Syndrome

A novel rat model for a well-characterized human mitochondrial disease, mitochondrial DNA depletion syndrome with associated deoxyguanosine kinase (DGUOK) deficiency, is described. The rat model recapitulates the pathologic and biochemical signatures of the human disease. The application of electron paramagnetic (spin) resonance (EPR) spectroscopy to the identification and characterization of respiratory chain abnormalities in the mitochondria from freshly frozen tissue of the mitochondrial disease model rat is introduced. EPR is shown to be a sensitive technique for detecting mitochondrial functional abnormalities in situ and, here, is particularly useful in characterizing the redox state changes and oxidative stress that can result from depressed expression and/or diminished specific activity of the distinct respiratory chain complexes. As EPR requires no sample preparation or non-physiological reagents, it provides information on the status of the mitochondrion as it was in the functioning state. On its own, this information is of use in identifying respiratory chain dysfunction; in conjunction with other techniques, the information from EPR shows how the respiratory chain is affected at the molecular level by the dysfunction. It is proposed that EPR has a role in mechanistic pathophysiological studies of mitochondrial disease and could be used to study the impact of new treatment modalities or as an additional diagnostic tool

The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69185/1/33256_ftp.pd

The humanistic burden of Pompe disease: are there still unmet needs? A systematic review

Background: Humanistic burden considers the impact of an illness on a patient's health-related quality of life (HRQoL), activities of daily living (ADL), caregiver health, and caregiver QoL. Humanistic burden also considers treatment satisfaction and adherence to treatment regimens. Pompe disease is an autosomal recessive, progressive, multisystemic neuromuscular disease. Approval of enzyme-replacement therapy (ERT) markedly improved prognosis for patients, but considerable morbidity and a substantial humanistic burden remain. This article characterizes the humanistic burden of Pompe disease through a systematic literature review. Methods: A systematic search of MEDLINE (R) and Embase (R) with back-referencing and supplementary literature searches was performed to retrieve data from interventional and non- interventional studies on the humanistic burden of Pompe disease. Publications were screened according to predefined criteria, extracted, and assessed for quality. Extracted data were narratively synthesized. Results: No publications on the humanistic burden of infantile-onset Pompe disease (IOPD) were identified. As such, of 17 publications included here, all are in patients with late-onset Pompe disease (LOPD). Thirteen publications were initiated after approval of ERT, two were initiated before, and two overlapped the approval of ERT. The review shows that LOPD patients have a significantly lower HRQoL than the general population, even if treated with ERT. On transitioning to ERT, treatment was associated with improvement in the physical component score of the SF-36 and fatigue, although the SF-36 mental component score remained stable. Physical HRQoL remained below population norms after 4 years of ERT. Significantly more ERT-treated patients reported pain than controls, and bodily pain worsened in later years following ERT initiation. Treatment-naive LOPD patients had significantly poorer ADL functioning compared with the general population, although ERT stabilized deteriorating functioning impairment. ERT studies showed caregivers provide 17.7 h/week informal care on average. Fifty percent, 40% and <20% of caregivers reported mental health, physical health, and financial/relational problems, respectively. In ERT-naive patients, wheelchair use and home ventilatory support was associated with lower physical HRQoL and ADL functioning. In ERT-treated patients, key factors predicting worse HRQoL and ADL functioning were higher respiratory distress, poorer sleep quality, greater pain, and more fatigue. Conclusions: Pompe disease has a substantial humanistic burden, with strong inter-relationships among and between humanistic burden parameters and clinical progression

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes

Implicit versus explicit attitude to doping: which better predicts athletes’ vigilance towards unintentional doping?

Objectives: This preliminary study examined whether implicit doping attitude, explicit doping attitude, or both, predicted athletes’ vigilance towards unintentional doping. Design: A cross-sectional correlational design. Methods: Australian athletes (N = 143; Mage = 18.13, SD = 4.63) completed measures of implicit doping attitude (brief single-category implicit association test), explicit doping attitude (Performance Enhancement Attitude Scale), avoidance of unintentional doping (Self-Reported Treatment Adherence Scale), and behavioural vigilance task of unintentional doping (reading the ingredients of an unfamiliar food product). Results: Positive implicit doping attitude and explicit doping attitude were negatively related to athletes’ likelihood of reading the ingredients table of an unfamiliar food product, and positively related to athletes’ vigilance toward unintentional doping. Neither attitude measures predicted avoidance of unintentional doping. Overall, the magnitude of associations by implicit doping attitude appeared to be stronger than that of explicit doping attitude. Conclusions: Athletes with positive implicit and explicit doping attitudes were less likely to read the ingredients table of an unknown food product, but were more likely to be aware of the possible presence of banned substances in a certain food product. Implicit doping attitude appeared to explain athletes’ behavioural response to the avoidance of unintentional doping beyond variance explained by explicit doping attitude

Relativistic electron beams accelerated by an interplanetary shock

Collisionless shock waves have long been considered amongst the most prolific particle accelerators in the universe. Shocks alter the plasma they propagate through and often exhibit complex evolution across multiple scales. Interplanetary (IP) traveling shocks have been recorded in-situ for over half a century and act as a natural laboratory for experimentally verifying various aspects of large-scale collisionless shocks. A fundamentally interesting problem in both helio and astrophysics is the acceleration of electrons to relativistic energies (more than 300 keV) by traveling shocks. This letter presents first observations of field-aligned beams of relativistic electrons upstream of an IP shock observed thanks to the instrumental capabilities of Solar Orbiter. This study aims to present the characteristics of the electron beams close to the source and contribute towards understanding their acceleration mechanism. On 25 July 2022, Solar Orbiter encountered an IP shock at 0.98 AU. The shock was associated with an energetic storm particle event which also featured upstream field-aligned relativistic electron beams observed 14 minutes prior to the actual shock crossing. The distance of the beam's origin was investigated using a velocity dispersion analysis (VDA). Peak-intensity energy spectra were anaylzed and compared with those obtained from a semi-analytical fast-Fermi acceleration model. By leveraging Solar Orbiter's high-time resolution Energetic Particle Detector (EPD), we have successfully showcased an IP shock's ability to accelerate relativistic electron beams. Our proposed acceleration mechanism offers an explanation for the observed electron beam and its characteristics, while we also explore the potential contributions of more complex mechanisms.Comment: Main text: 6 pages, 2 figures. Supplementary material: 6 pages, 7 figure