A preliminary assessment of age at death determination using the nuclear weapons testing 14C activity of dentine and enamel

Calibration (using CALIBomb) of radiocarbon measurements made on the enamel of human teeth from people born during the nuclear era typically produce 2 possible age ranges that potentially reflect the period of tooth formation. These ranges correspond to periods before and after the 1963 atmospheric 14C maximum. Further measurements made on the collagen component of the combined dentine and cementum from the roots of the same teeth enable the appropriate age range to be selected. Using this range and the formation times for individual teeth, we estimated the year of birth of the individuals and compared these to the known dates of birth. The results were relatively accurate and confirmed those of a previous study by another research group. The present study demonstrates that it is possible to produce a good estimate of the year of birth from a single tooth

The role of the practice educator in supporting nursing and midwifery students’ clinical practice learning: An appreciative inquiry

High quality, supportive practice learning experiences are crucial for ensuring that student nurses and midwives develop into competent practitioners who are fit for practice. The practice educator role is one model of practice learning support but the role is relatively new and has been little investigated. This paper reports on an appreciative inquiry that explored the current practice educator role at one university in England, with the aim of reaching a consensus for how the role could be enhanced. The first phase involved in-depth interviews with 18 participants: practice educators (n = 10); student nurse representatives (n= 5) and practice based education leads (n = 3). The interviews were analysed thematically. Three themes related to social processes involved in the role: being a bridge, being there, and social identity. The other themes described contributions to the practice learning environment: safeguarding, support, critical thinking. The second phase used a modified Delphi technique. Participants ranked trigger statements, related to the themes, in order of importance. Two consensus workshops were held where the statements were reviewed by practice educators, students and learning environment leads, following which principles and practices of the practice educator role were agreed. In conclusion, the strength of the practice educator role is that it bridges the worlds of university and practice. This bridging resulted from social processes that required a sustained presence in practice to engage in the reality of everyday practice and gain the shared social identity of a practitioner

Investigation of the pathological mechanisms in canine degenerative myelopathy and the potential involvement of extracellular vesicles in disease progression

Canine degenerative myelopathy (DM) is a progressive and lethal adult-onset neurodegenerative disease with nonspecific clinical signs that can end in tetraplegia and respiratory dysfunction. It is frequently identified in German shepherd dogs (GSD) but has been described in other breeds. A definitive diagnosis is reached after histopathological examination of the spinal cord where axon degeneration and demyelination are characterised. Mutations in the gene encoding superoxide dismutase 1 (SOD1) are thought to have a pathological role in the disease and genotyping of the Sod1 gene can be used with clinical signs and histology to diagnose DM. The genetics, clinical signs and histology of DM suggests it may be a good naturally occurring large animal model for some forms of the human motor neurone disease, amyotrophic lateral sclerosis (ALS). This study aimed to 1) establish if defective cellular clearance pathways play a role in the aggregation of SOD1 and 2) if these defects contribute to the secretion of SOD1 positive extracellular vesicles (EVs) that 3) can spread mutant protein in a prion-like manner. Finally, 4) was to validate these findings with spinal cord tissue from DM cases using proteomics and biochemistry. In vitro studies using a neuroblastoma derived cell line (SK-N-SH) were conducted to assess the effect of disrupting various cell clearance and toxicity pathways on wildtype (WT) and mutant SOD1 aggregation and EV production. The reducing agent dithiothreitol increased the propensity of WT- and DM-SOD1 to aggregate (p ≤ 0.01) but did not have a statistically significant impact on the production of SOD1 positive EVs from cells. The autophagy inhibitor chloroquine increased the percentage of cells with DM-SOD1 aggregates (p ≤ 0.01), but not WT-SOD1 aggregates. EV secretion was not statistically significantly affected by chloroquine treatment in cells with DM-SOD1, but there was a significant increase in the EV marker flotillin-1 from cells containing WT-SOD1 (p ≤ 0.01). The proteasome inhibitor MG312 significantly increased the number of cells with WT- and DM-SOD1 aggregates (p < 0.0001), but they were higher in DM-SOD1 transfected cells (p ≤ 0.05). Flotillin-1 showed a downward trend from treated cells however this was only statistically supported with EVs from WT-SOD1 containing cells (p ≤ 0.01). WT- and DM-SOD1 showed an upwards trend in the EV fraction, but only reached significance in EVs from the cells containing DM-SOD1 (p ≤ 0.01). Overall, disruption to the main protein processing pathways caused the induction of nontypical clearance pathways and some of these appear to be less effective in the presence of the DM associated Sod1 mutation. Further, mutant SOD1 may have an impact on the stabilisation of the cell membrane as indicated by changes to associated proteins and this could have subsequent effects on protein clearance, particularly at the level of the endosome pathway and EVs. Further studies indicated there is a potential for EVs to spread WT- and DM-SOD1 to other cells in culture which suggests EVs could be recruited in DM for the spread of mutant SOD1 to other cells and may contribute to the progression of DM throughout the thoracic spinal cord and to the cervical and lumbar regions. Biochemical and proteomics analysis of spinal cords from control and DM dogs suggested axon and myelin integrity was disrupted and astrocytes were activated at early stages of DM. Evidence suggested these changes were the consequence of altered cellular metabolism, intracellular structure and protein processing. The Sod1 mutation caused an apparent reduction in SOD1 enzyme activity further suggesting the mutation is a contributor to the pathogenesis and progression of DM. Changes to plasma membrane organisation were also highlighted in the ex vivo study and may indicate perturbations to protein and lipid turnover. Ultimately the findings presented in this thesis contribute to the understanding of DM pathogenesis and will aid the search for DM biomarkers to enable earlier diagnosis, monitor disease progression and identify treatment targets

An improved process for the fabrication and surface treatment of custom-made titanium cranioplasty implants informed by surface analysis

Cranioplasty implants are routinely fabricated from commercially pure titanium plates by maxillofacial prosthetists. The differing fabrication protocols adopted by prosthetists working at different hospital sites gives rise to considerable variations in surface topography and composition of cranioplasty implants, with residues from the fabrication processes having been found to become incorporated into the surface of the implant. There is a growing recognition among maxillofacial prosthetists of the need to standardise these protocols to ensure quality and consistency of practice within the profession. In an effort to identify and eliminate the source of the inclusions associated with one such fabrication protocol, the present study examined the surfaces of samples subjected to each of the manufacturing steps involved. Surface and elemental analysis techniques identified the main constituent of the surface inclusions to be silicon from the glass beads used to texture the surface of the implant during fabrication. Subsequent analysis of samples prepared according to a revised protocol resulted in a more homogeneous titanium dioxide surface as evidenced by the reduction in area occupied by surface inclusions (from 8.51% ± 2.60% to 0.93% ± 0.62%). These findings may inform the development of improved protocols for the fabrication of titanium cranioplasty plates

Supporting information for National, regional, and worldwide estimates of low birthweight rates in 2015, with trends from 2000: a systematic analysis

Data produced by the World Health Organization, UNICEF, LSHTM and Johns Hopkins University to estimate national low birthweight (LBW) and numbers for 195 countries. LBW data was collated through a systematic review of national routine/registration systems, nationally representative surveys, and other data sources, and subsequently modelled using restricted maximum likelihood estimation with country-level random effects. Data includes a list of 1447 rate data points used as an input to the modelled estimates, yearly national-level covariates for each of the 195 countries studied from 2000 to 2015, and information on estimated low birthweight rates from 2000 to 2015 for 148 countries with data. Stata code used to generate these estimates is provided

Barriers and facilitators to healthcare practitioners providing care for pregnant women with epilepsy:A systematic review and narrative synthesis

Purpose: Despite published guidelines for managing pregnant women with epilepsy, their care is sub-optimal. We undertook a review to establish the barriers and facilitators to healthcare practitioners providing optimal care. Methods: A systematic search of ASSIA, CINAHL complete, MEDLINE, SCOPUS, and the Cochrane database of systematic reviews between 2013 and 2023 and narrative synthesis. Results: From 580 potential papers, we included 16 studies. There were a total of 2045 participants across all studies, who consisted mostly of obstetricians/gynaecologists (n=447) and neurologists (n=765) but also included midwives/nurses (n=70), general practitioners (n=107) and pharmacists (n=156) with the others being mixed groups of physicians, advanced practitioners or unspecified. Thirteen studies were questionnaire surveys and three used qualitative methods. Nine tested or asked about practitioners’ knowledge. Although knowledge was generally adequate, practitioners found it difficult to apply in challenging or complex cases. Other barriers included challenges to joint working (between primary and secondary care and between different specialist groups), communication with women and environmental factors such as lack of time and guideline availability. Practitioners expressed the importance of providing good care for pregnant women with epilepsy. Conclusion: More qualitative studies are needed to understand the challenges and needs of practitioners caring for pregnant women with epilepsy. To address this, based on studies available we suggest joint (neurology and obstetrics) clinics, the availability and dissemination of guidelines, a risk evaluation tool and guidelines in the content and nature of communication with women

Barriers and facilitators to healthcare practitioners providing care for pregnant women with epilepsy : A systematic review and narrative synthesis

We acknowledge the contribution of Helen Ryba, subject specialist librarian who contributed to our search strategy and Joy Orpin, research fellow, who contributed to the extraction of survey data. Registration of the review Prospero CRD42023450252Peer reviewe

Inequalities in children’s mental health prescribing and referrals for specialist mental health services

Peer reviewe