Insertion/deletion-related polymorphisms in the human T cell receptor beta gene complex.

Insertion/deletion related polymorphisms (IDRP) involving stretches of 15-30 kb within the human TCR-beta gene complex were revealed by pulse-field gel electrophoresis. Two independent IDRP systems were detected by analysis of Sfi I- and Sal I-digested human DNA samples using probes for TCR C and V region gene segments. The allelic nature of these systems was verified in family studies, and mapping data allowed localization of one area of insertion/deletion among the V gene segments and the other near the C region genes. All but one of 50 individuals tested could be typed for the two allelic systems, and gene frequencies for the two allelic forms were 0.37/0.61 and 0.46/0.54, indicating that these polymorphisms are widespread

Characterisation of variant alleles at the HUMD21S11 locus

University of Technology, Sydney. Faculty of Science.Significant genetic substructure within a population can affect the evidential weight of a DNA profile to the detriment of a defendant. To prevent this from occurring, forensic examiners continually look to understand more about the degree and structure of genetic variation within a population. A part of this involves the characterisation of the microsatellite loci applied in forensic testing. The HUMD21S11 microsatellite is commonly used in forensic examinations in conjunction with a suite of other microsatellite loci in order to identify individuals who may have been present at a crime scene, or who cannot be identified through more traditional non-genetic means (such as visual, dental or medical records) . This research confirmed the existence of an ancestral relationship between the indigenous populations of Australia and Papua N ew Gu1nea as well as the presence of regional differentiation within the Australian Aboriginal population. The sequence variation present at the HUMD21S11 microsatellite locus makes it a suitable candidate to further understand and describe the regional differentiation within the Australian Aboriginal population. This study also confirmed that microsateliites are able to retain their variability after structural change (Moller et al. 1994, Brinkmann et al. 1996, Griffiths et al. 1998, Walsh et al. 2003), and that a single mutation event can involve single repeat units or multiple repeat units. The structural complexity of microsatellites like HUMD21S11 could be used to further develop mutation models as well as investigate the proposal that the mutation rate of microsatellite loci is be dependent on the DNA sequence present. The sequence variation at the HUMD21S11 microsatellite is prevalent enough in the Australian Aboriginal population, to warrant a more complete investigation of the genetic variation at this locus. However, in order to better understand the genetic diversity present in the Australian Aboriginal populations, examination of the population based on traditional tribal boundaries (rather than judicial boundaries) is recommended. Additional population studies at the sequence level will increase our level of understanding about the genetic relationships of the Australian Aboriginal population on a local and global level. The sequence data obtained will also assist in the understanding of the mutation process and aid in the development of statistical models

Age related deviation of gait from normality in alkaptonuria.

Alkaptonuria is a rare metabolic disease leading to systemic changes including early and severe arthropathy which affects mobility. Due to unknown reasons, the onset of degenerative changes is delayed to around 30 years of age when both objective and subjective symptoms develop. In order to complement describing the structural changes in alkaptonuria with measures of movement function, clinical gait analysis was added to the list of assessments in 2013. The aim of this study was to describe the deviation of gait from normality as a function of age in patients with alkaptonuria. Three-dimensional movement of reflective markers attached to joints were captured during walking in 39 patients and 10 controls. Subsequent to processing the data to emphasise the shape of marker trajectories, the mean Movement Deviation Profile was generated for all participants. This single number measure gives the deviation of a patient’s gait from a distributed definition of gait normality. Results showed that gait deviation roughly follows a sigmoid profile with minimal increase of gait deviations in a younger patient group and an abrupt large increase around the second half of the 4th decade of life. Larger variations of gait deviations were found in the older group than in the younger group suggesting a complex interaction of multiple factors which determine gait function after symptoms manifest. Continued gait analysis of adults with AKU, extended to younger adults and children with AKU, is expected to complete understanding of both the natural history of alkaptonuria and how interventions can affect movement function

The holistic phase model of early adult crisis

The objective of the current study was to explore the structural, temporal and experiential manifestations of crisis episodes in early adulthood, using a holistic-systemic theoretical framework. Based on an analysis of 50 interviews with individuals about a crisis episode between the ages of 25 and 35, a holistic model was developed. The model comprises four phases: (1) Locked-in, (2) Separation/Time-out, (3) Exploration and (4) Rebuilding, which in turn have characteristic features at four levels—person-in-environment, identity, motivation and affect-cognition. A crisis starts out with a commitment at work or home that has been made but is no longer desired, and this is followed by an emotionally volatile period of change as that commitment is terminated. The positive trajectory of crisis involves movement through an exploratory period towards active rebuilding of a new commitment, but ‘fast-forward’ and ‘relapse’ loops can interrupt Phases 3 and 4 and make a positive resolution of the episode less likely. The model shows conceptual links with life stage theories of emerging adulthood and early adulthood, and it extends current understandings of the transitional developmental challenges that young adults encounter

Trends in the availability and usage of electrophysical agents in physiotherapy practices from 1990 to 2010: A review

This is the Pre-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 Maney PublishingBackground: The use of electrophysical agents has a historically important role in physiotherapy practice. There are anecdotal reports that the availability and usage of electrotherapy modalities are declining, which may have implications for physiotherapy practice. The aim of this literature review was to provide scientific evidence on electrotherapy usage in the last 20 years by identifying trends in availability, use, and non-use of nine electrotherapeutic modalities in physiotherapy practices during 1990s and 2000s. Methods: Review of empirical studies published in the English language from 1990 to 2010 and identified through searching online bibliographic databases, which included: Medline/OvidSP, PubMed Central, CINAHL/EBSCOhost, ScienceDirect, Scopus, ISI Web of Science, and Google Scholar. Findings: In the last 20 years, ultrasound availability and usage show increasing trends in several countries. The availability and use of pulsed shortwave diathermy and laser have shown steady trends. Transcutaneous electrical nerve stimulation, interferential, and biofeedback availability and usage have shown increasing trends in the UK and decreasing trends in Australia and the Republic of Ireland. Trends of continuous shortwave diathermy availability and use are declining irrespective of the country of the study. The availability and usage of microwave diathermy and H-wave show steeply declining trends, while there is a sharp rise in their non-availability over the last several years. Conclusions: The availability and use of electrophysical agents have greatly changed in the last 20 years. Declining trends in the availability and usage along with increasing trend of non-availability of electrotherapy modalities may have implications for electrotherapy education, training, and practice in the coming years.This study was funded by Health & Safety Executive, UK (grant no. 4371/R47.022)

The dynamics of apparent horizons in Robinson-Trautman spacetimes

We present an alternative scheme of finding apparent horizons based on spectral methods applied to Robinson-Trautman spacetimes. We have considered distinct initial data such as representing the spheroids of matter and the head-on collision of two non-rotating black holes. The evolution of the apparent horizon is presented. We have obtained in some cases a mass gap between the final Bondi and apparent horizon masses, whose implications were briefly commented in the light of the thermodynamics of black holes.Comment: 9 pages, 7 figure

Giant Cell Arteritis and COVID-19: Similarities and Discriminators. A Systematic Literature Review

OBJECTIVE: To identify shared and distinct features of giant cell arteritis (GCA) and Coronavirus disease 2019 (COVID-19) to reduce diagnostic error that could cause delays in correct treatment. METHODS: Two systematic literature reviews determined the frequency of clinical features of GCA and COVID-19 in published reports. Frequencies in each disease were summarised using median and range. RESULTS: Headache was common in GCA but was also observed in COVID-19 (66% for GCA, 10% for COVID-19). Jaw claudication or visual loss (43% and 26% in GCA, respectively) were not reported in COVID-19. Both diseases featured fatigue (38% for GCA, 43% for COVID-19) and elevated inflammatory markers (CRP elevated in 100% of GCA, 66% of COVID-19), but platelet count was elevated in 47% of GCA but 4% of COVID-19. Cough and fever were commonly reported in COVID-19 and less frequently in GCA (cough, 63% for COVID-19 versus 12% for GCA; fever, 83% for COVID-19 versus 27% for GCA). Gastrointestinal upset was occasionally reported in COVID-19 (8%), rarely in GCA (4%). Lymphopenia was more common in COVID-19 than GCA (53% in COVID-19, 2% in GCA). Alteration of smell and taste been described in GCA but their frequency is unclear. CONCLUSION: Overlapping features of GCA and COVID-19 include headache, fever, elevated CRP and cough. Jaw claudication, visual loss, platelet count and lymphocyte count may be more discriminatory. Physicians should be aware of the possibility of diagnostic confusion. We have designed a simple checklist to aid evidence-based evaluation of patients with suspected GCA

The moderating role of overcommitment in the relationship between psychological contract breach and employee mental health

Reimann M. The moderating role of overcommitment in the relationship between psychological contract breach and employee mental health. JOURNAL OF OCCUPATIONAL HEALTH. 2016;58(4-5):425-433.Objectives: This study investigated whether the association between perceived psychological contract breach (PCB) and employee mental health is moderated by the cognitive-motivational pattern of overcommitment (OC). Linking the psychological contract approach to the effort-reward imbalance model, this study examines PCB as an imbalance in employment relationships that acts as a psychosocial stressor in the work environment and is associated with stress reactions that in turn negatively affect mental health. Methods: The analyses were based on a sample of 3,667 employees who participated in a longitudinal linked employer employee survey representative of large organizations (with at least 500 employees who are subject so social security contributions) in Germany. Fixed-effects regression models, including PCB and OC, were estimated for employee mental health, and interaction effects between PCB and OC were assessed. Results: The multivariate fixed-effects regression analyses showed a significant negative association between PCB and employee mental health. The results also confirmed that OC does indeed significantly increase the negative effect of PCB on mental health and that OC itself has a significant and negative effect on mental health. Conclusions: The results suggest that employees characterized by the cognitive-motivational pattern of OC are at an increased risk of developing poor mental health if they experience PCB compared with employees who are not overly committed to their work. The results of this study support the assumption that psychosocial work stressors play an important role in employee mental health

Clinical pathways for patients with giant cell arteritis during the COVID-19 pandemic: an international perspective

Giant cell arteritis, a common primary systemic vasculitis affecting older people, presents acutely as a medical emergency and requires rapid specialist assessment and treatment to prevent irreversible vision loss. Disruption of the health-care system caused by the COVID-19 pandemic exposed weak points in clinical pathways for diagnosis and treatment of giant cell arteritis, but has also permitted innovative solutions. The essential roles played by all professionals, including general practitioners and surgeons, in treating these patients have become evident. Patients must also be involved in the reshaping of clinical services. As an international group of authors involved in the care of patients with giant cell arteritis, we reflect in this Viewpoint on rapid service adaptations during the first peak of COVID-19, evaluate challenges, and consider implications for the future

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity