A socio-spatial analysis of pedestrian falls in Aotearoa New Zealand.

Falls are a leading cause of injury and accidental death, particularly amongst older people. Evidence of environmental risk factors for pedestrian falls among older adults could support age-friendly urban design and contribute to efforts to reduce the incidence of pedestrian falls and support outdoor mobility among older adults. Yet investigation of the environment in which pedestrian falls occur is often hampered by its reliance on participant recall and self-report information. We identified the point locations of falls occurring on the road or street among adults that were attended by an ambulance in New Zealand over a two-year period (2016-2018) and connected these to a range of social (e.g. deprivation) and environmental (e.g. slope, greenspace) risk factors. Three types of analysis were used: a descriptive analysis of fall rates, logistic regression assessing whether a patient was transported to hospital following a fall, and a negative binomial regression analysis of the pedestrian falls by small area. We found a number of differences in the built environment surrounding fall locations between age groups. Compared with younger age groups, older adults showed high fall rates closer to home, and higher fall rates in areas with many types of destinations nearby. Additionally, our results showed a higher rate of pedestrian falls in more deprived areas. People who live in more deprived areas also fell over more frequently, but the pattern is stronger based on deprivation at the fall location, rather than home location. Residents of more deprived areas were less likely to be transported to hospital following a fall. Thus, our findings have equity implications for both environments and patient experience. These patterns could not have been identified without the novel use of spatially specific fall data.

Quantitative comparison of expression with adeno-associated virus (AAV-2) brain-specific gene cassettes.

This study compared a range of mammalian CNS expression cassettes in recombinant adeno-associated virus (AAV-2) vectors using strong endogenous promoter sequences, with or without a strong post-regulatory element and polyadenylation signal. Changes in these elements led to transgene expression varying by over three orders of magnitude. In experiments conducted in primary cell culture and in >100 stereotactically injected rats, we observed highly efficient and stable (>15 months) gene expression in neurons and limited expression in glia; the highest expression occurred with endogenous, nonviral promoters such as neuron-specific enolase and beta-actin. The packaging size of AAV-2 was maximized at 5.7 kb without impairing gene expression, as judged by direct comparison with a number of smaller AAV-2 constructs. The genomic insert size and titer were confirmed by Southern blot and quantitative PCR, and infectivity was tested by particle titer using ELISA with a conformation-dependent epitope that requires the full intact capsid. A packaging and purification protocol we describe allows for high-titer, high-capacity AAV-2 vectors that can transduce over 2 x 10(5) neurons in vivo per microliter of vector, using the strongest expression cassette.

Mycobacterium bovis-infected cervine alveolar macrophages secrete lymphoreactive lipid antigens.

Tuberculosis is caused by intracellular bacteria belonging to the genus Mycobacterium, including M. tuberculosis and M. bovis. Alveolar macrophages (AMs) are the primary host cell for inhaled mycobacteria. However, little is known about the mechanisms by which infected AMs can process and present mycobacterial antigens to primed lymphocytes and how these responses may affect ensuing protection in the host. In the present study, we sought to determine whether AMs from a naturally susceptible host for Mycobacterium bovis (red deer) could produce and secrete soluble immunoreactive antigens following mycobacterial infection in vitro. Confluent monolayers of deer AMs were infected with either heat-killed or live virulent M. bovis or M. bovis BCG at a multiplicity of infection of 5:1 and cultured for 48 h. Culture supernatants were collected, concentrated, and tested for the presence of mycobacterial antigens in a lymphocyte proliferation assay by using peripheral blood mononuclear cells from M. bovis-sensitized or naive deer. Supernatants derived from macrophages which had been infected with live bacilli stimulated the proliferation of antigen-sensitized, but not naive, lymphocytes. Supernatants derived from uninoculated AMs or AMs inoculated with heat-killed bacilli failed to stimulate lymphocyte proliferation. The lymphoproliferative activity was retained following lipid extraction of the supernatants, which were free of amino groups as determined by thin-layer chromatography. These results demonstrate that mycobacteria which are actively growing within AMs produce lipids which are secreted into the extracellular milieu and that these lipids are recognized by lymphocytes from mycobacterium-primed hosts. We suggest that mycobacterial lipids are released from AMs following aerosol infection in vivo and that they play an important role in the early immune response to tuberculosis.

An oral vaccine against NMDAR1 with efficacy in experimental stroke and epilepsy.

The brain is generally considered immunoprivileged, although increasing examples of immunological responses to brain antigens, neuronal expression of major histocompatibility class I genes, and neurological autoimmunity have been recognized. An adeno-associated virus (AAV) vaccine generated autoantibodies that targeted a specific brain protein, the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor. After peroral administration of the AAV vaccine, transgene expression persisted for at least 5 months and was associated with a robust humoral response in the absence of a significant cell-mediated response. This single-dose vaccine was associated with strong anti-epileptic and neuroprotective activity in rats for both a kainate-induced seizure model and also a middle cerebral artery occlusion stroke model at 1 to 5 months following vaccination. Thus, a vaccination strategy targeting brain proteins is feasible and may have therapeutic potential for neurological disorders.

Preventing adolescent drug abuse and high school dropout through an intensive school-based social network development program.

Purpose. The hypothesis tested was that experimental subjects, relative to controls, would demonstrate significant increases in school performance and decreases in drug involvement at program exit (5 months) and at follow-up (10 months). Design. A two-group, repeated-measures, intervention trial was the design used. Setting. The study involved four urban Northwest high schools. Subjects. Participants included 259 youth at high risk of potential school dropout, 101 in the experimental group and 158 in the control group. Intervention. The Personal Growth Class experimental condition was a one-semester, five-month elective course taken as one of five or six regular classes. It had a 1:12 teacher-student ratio, and integrated group support and life-skills training interventions. The control condition included a regular school schedule. Measures. School performance measures (semester GPA, class absences) came from school records. Drug use progression, drug control, and adverse consequences were measured by the Drug Involvement Scale for Adolescents. Self-esteem, school bonding, and deviant peer bonding were measured using the High School Questionnaire: Inventory of Experiences. All multi-item scales had acceptable reliability and validity. Results. As predicted, trend analyses revealed significantly different patterns of change over time between groups in drug control problems and consequences; in GPA (but not attendance); and in self-esteem, deviant peer bonding, and school bonding. The program appeared to stem the progression of drug use, but group differences only approached significance. Conclusion. Program efficacy was demonstrated particularly for decreasing drug control problems and consequences; increasing GPA and school bonding; and desired changes in self-esteem and deviant peer bonding. Program effects on progression of drug use were less definitive.

Physician consent and researchers' access to patients.

Institutional review boards may require that researchers obtain permission from a patient's physician before initiating patient contact. We describe how this requirement affected a study of head injuries. Physicians denied study participation to 8% of 243 subjects; 9% of 126 physicians denied contact with at least one subject. Most physicians responded within ten days, although seven required more than a month to respond. Delays in reaching potential subjects compromise some clinical research protocols. Physicians may refuse permission for some patients, introducing selection biases. Our study did not detect such an effect, but investigators should be alert to such problems in their own research.

Evaluation of potentially preventable deaths among pedestrian and bicyclist fatalities.

The prehospital, emergency department, and in-hospital care of 84 patients who died following a pedestrian- or bicycle-motor vehicle collision in a four-county area was retrospectively reviewed using a systematic, detailed scoring system. The purpose of the study was to examine the effectiveness of an advanced paramedic-regionalized trauma care system and to examine the usefulness of a systematic evaluation tool in identifying preventable and possibly preventable deaths. Among the 84 deaths, one was judged to be preventable and 18 possibly preventable. The one preventable death occurred in the emergency department, while the possibly preventable deaths more commonly occurred after 48 hours and were due to central nervous system injury, sepsis, and multiple organ failure. Prolonged prehospital and emergency department time and failure to establish an airway were the most common problems identified as contributing to fatal outcome. The use of explicit criteria was demonstrated to be an effective addition to the analysis of trauma care systems.

The public cost of motorcycle trauma.

Despite the effectiveness of motorcycle helmet legislation, many states have repealed these laws during the last decade. Aspects often neglected by policymakers are who pays for the care of these victims and how much of this cost is subsidized by public funds. To determine the extent of this subsidy, we studied the cost of care of 105 motorcyclists hospitalized at a major trauma center during a 12-month period. Total direct costs for these 105 patients, followed up for a mean of 20 months, were more than $2.7 million, with an average of $25,764 per patient. Only 60% of the direct costs were accounted for by the initial hospital care; 23% of costs were for rehabilitation care or readmission for treatment of acute problems. The majority (63.4%) of care was paid for by public funds, with Medicaid accounting for more than half of all charges.