Vehicle crashworthiness and the older motorist

This study examines the relationship between age and the injury outcomes for belted drivers in road vehicle crashes in the United Kingdom. The sample of 1,541 drivers was divided into three age groups: 889 drivers were aged 17–39 years (young drivers) ; 515 were 40–64 years (middle-aged), and 137 aged 65–84 years (older drivers). Both frontal and side impact crashes in which the vehicles sustained sufficient damage to be towed away from the scene are considered. Indepth information obtained from examinations of the crashed vehicles was combined with clinical data obtained from hospitals to throw light on the mechanisms that led to the injuries. Results show that in crashes of approximately equal severity, older drivers were significantly more likely than middle-aged and young drivers to be fatally injured in both frontal ( p<0.001) and side ( p<0.05) impact crashes. The results also show that older drivers sustained more injuries to the chest ( p<0.0001) and that this body region is particularly problematic. The main sources of the chest injuries were found to be the seat belt in frontal crashes and the door in side impact crashes. As the number of older car users will increase rapidly in most OECD countries in the coming decades, the results suggest that vehicle re-designs are required, including in-vehicle crashworthiness systems, to take into account older people’s relatively low tolerance of crash impacts

An overview of requirements for the crash protection of older drivers

For some time now, it has been recognised that a major shift is occurring in the population age distributions of most motorised countries resulting in a growing number of older persons with an increasing need for mobility. It is expected that the mobility of older persons will become even more reliant on the motor vehicle as European countries in particular undergo transitions towards decentralisation and suburbanisation and because of the well-established longevity factor. As a group, older drivers do not currently represent a major road safety problem in most Western societies when compared with other age groups such as the young. However, they are involved in significantly more serious injury and casualty crashes per head of population. Furthermore, as older drivers are likely to become a more significant problem in the years ahead, it is now necessary to examine some vehicle design factors that affect the safety of the older driver in a crash

Crash characteristics and injury outcomes for older passenger car occupants

For some time now, it has been recognised that a major shift is occurring in the population age distributions of most motorised countries resulting in a growing number of older persons with an increasing need for mobility. It is expected that the mobility of older persons will become even more reliant on the motor vehicle as European countries in particular undergo transitions towards decentralisation and suburbanisation and because of the well-established longevity factor. This study compares injury outcomes in passenger car crashes for belted occupants of different ages. The study considers drivers and front seat passengers. National accident data in the UK show that whilst older car occupants are less likely to be involved in a car accident than younger occupants, in the event of a crash, older occupants are more likely to be killed or to sustain serious injury. This, in conjunction with the increasing numbers of older licence holder and car users implies that the protection of the inherently frail elderly should become a priority for the future. Analysis of the UK in-depth accident data revealed that the older car occupants were significantly more prone to serious chest injury than their younger counterparts and that these injuries were predominantly due to forces exerted by the restraint system, particularly in frontal impacts. Since by the year 2030 one in four persons will be aged over 65 in most Organisation for Economic Cooperation and Development (OECD) countries, the results suggest a need for intervention through vehicle design including in-vehicle crashworthiness systems that take into account the reduced tolerance to impact that occurs with ageing

Mutation screening of retinal dystrophy patients by targeted capture from tagged pooled DNAs and next generation sequencing.

Purpose: Retinal dystrophies are genetically heterogeneous, resulting from mutations in over 200 genes. Prior to the development of massively parallel sequencing, comprehensive genetic screening was unobtainable for most patients. Identifying the causative genetic mutation facilitates genetic counselling, carrier testing and prenatal/pre-implantation diagnosis, and often leads to a clearer prognosis. In addition, in a proportion of cases, when the mutation is known treatment can be optimised and patients are eligible for enrolment into clinical trials for gene-specific therapies. Methods: Patient genomic DNA was sheared, tagged and pooled in batches of four samples, prior to targeted capture and next generation sequencing. The enrichment reagent was designed against genes listed on the RetNet database (July 2010). Sequence data were aligned to the human genome and variants were filtered to identify potential pathogenic mutations. These were confirmed by Sanger sequencing. Results: Molecular analysis of 20 DNAs from retinal dystrophy patients identified likely pathogenic mutations in 12 cases, many of them known and/or confirmed by segregation. These included previously described mutations in ABCA4 (c.6088C>T,p.R2030*; c.5882G>A,p.G1961E), BBS2 (c.1895G>C,p.R632P), GUCY2D (c.2512C>T,p.R838C), PROM1 (c.1117C>T,p.R373C), RDH12 (c.601T>C,p.C201R; c.506G>A,p.R169Q), RPGRIP1 (c.3565C>T,p.R1189*) and SPATA7 (c.253C>T,p.R85*) and new mutations in ABCA4 (c.3328+1G>C), CRB1 (c.2832_2842+23del), RP2 (c.884-1G>T) and USH2A (c.12874A>G,p.N4292D). Conclusions: Tagging and pooling DNA prior to targeted capture of known retinal dystrophy genes identified mutations in 60% of cases. This relatively high success rate may reflect enrichment for consanguineous cases in the local Yorkshire population, and the use of multiplex families. Nevertheless this is a promising high throughput approach to retinal dystrophy diagnostics

Characterization and genomic localization of a SMAD4 processed pseudogene

Like many clinical diagnostic laboratories, the Yorkshire Regional Genetics Service undertakes routine investigation of cancer-predisposed individuals by high-throughput sequencing of patient DNA that has been target-enriched for genes associated with hereditary cancer. Accurate diagnosis using such reagents requires alertness regarding rare nonpathogenic variants that may interfere with variant calling. In a cohort of 2042 such cases, we identified 5 that initially appeared to be carriers of a 95-bp deletion of SMAD4 intron 6. More detailed analysis indicated that these individuals all carried one copy of a SMAD4 processed gene. Because of its interference with diagnostic analysis, we characterized this processed gene in detail. Whole-genome sequencing and confirmatory Sanger sequencing of junction PCR products were used to show that in each of the 5 cases, the SMAD4 processed gene was integrated at the same position on chromosome 9, located within the last intron of the SCAI gene. This rare polymorphic processed gene therefore reflects the occurrence of a single ancestral retrotransposition event. Compared to the reference SMAD4 mRNA sequence NM_005359.5 (https://www.ncbi.nlm.nih.gov/nucleotide), the 5' and 3' untranslated regions of the processed gene are both truncated, but its open reading frame is unaltered. Our experience leads us to advocate the use of an RNA-seq aligner as part of diagnostic assay quality assurance, since this allows recognition of processed pseudogenes in a comparatively facile automated fashion

Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation.

Combined radiochemotherapy is the currently used therapy for locally advanced pancreatic ductal adenocarcinoma (PDAC), but normal tissue toxicity limits its application. Here we test the hypothesis that inhibition of ATR (ATM-Rad3-related) could increase the sensitivity of the cancer cells to radiation or chemotherapy without affecting normal cells. We tested VE-822, an ATR inhibitor, for in vitro and in vivo radiosensitization. Chk1 phosphorylation was used to indicate ATR activity, γH2AX and 53BP1 foci as evidence of DNA damage and Rad51 foci for homologous recombination activity. Sensitivity to radiation (XRT) and gemcitabine was measured with clonogenic assays in vitro and tumor growth delay in vivo. Murine intestinal damage was evaluated after abdominal XRT. VE-822 inhibited ATR in vitro and in vivo. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. VE-822 decreased survival of pancreatic cancer cells but not normal cells in response to XRT or gemcitabine. VE-822 markedly prolonged growth delay of pancreatic cancer xenografts after XRT and gemcitabine-based chemoradiation without augmenting normal cell or tissue toxicity. These findings support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC

Robotics use in the care and management of people living with Diabetes Mellitus in the community – a scoping review protocol

The aim of the review is to identify and map the range of available evidence on the types of robotic devices and their impact on people living with Diabetes Mellitus in the community. The outcome of this scoping review will inform the development and testing of a future robotic intervention