Altered nociceptive, endocrine, and dorsal horn neuron responses in rats following a neonatal immune challenge

Summary The neonatal period is characterized by significant plasticity where the immune, endocrine, and nociceptive systems undergo fine-tuning and maturation. Painful experiences during this period can result in long-term alterations in the neurocircuitry underlying nociception, including increased sensitivity to mechanical or thermal stimuli. Less is known about the impact of neonatal exposure to mild inflammatory stimuli, such as lipopolysaccharide (LPS), on subsequent inflammatory pain responses. Here we examine the impact of neonatal LPS exposure on inflammatory pain sensitivity and HPA axis activity during the first three postnatal weeks. Wistar rats were injected with LPS (0.05 mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 7, 13, and 22. One hour after formalin injection, blood was collected to assess corticosterone responses. Transverse spinal cord slices were also prepared for whole-cell patch clamp recording from lumbar superficial dorsal horn neurons (SDH). Brains were obtained at PND 22 and the hypothalamus was isolated to measure glucocorticoid (GR) and mineralocorticoid receptor (MR) transcript expression using qRT-PCR. Behavioural analyses indicate that at PND 7, no significant differences were observed between saline- or LPS-challenged rats. At PND 13, LPS-challenged rats exhibited enhanced licking (p < .01), and at PND 22, increased flinching in response to formalin injection (p < .05). LPS-challenged rats also displayed increased plasma corticosterone at PND 7 and PND 22 (p < .001) but not at PND 13 following formalin administration. Furthermore, at PND 22 neonatal LPS exposure induced decreased levels of GR mRNA and increased levels of MR mRNA in the hypothalamus. The intrinsic properties of SDH neurons were similar at PND 7 and PND 13. However, at PND 22, ipsilateral SDH neurons in LPS-challenged rats had a lower input resistance compared to their saline-challenged counterparts (p < .05). These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, corticosterone levels, and dorsal horn neuron properties following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping pain sensitivity later in life. This programming involves both spinal cord neurons and the HPA axis.

Do motor vehicle crashes arise from single or multiple unique risk processes? An inquiry into crash causes and modelling

Crashes at any particular transport network location consist of a chain of events arising from a multitude of potential causes and/or contributing factors whose nature is likely to reflect geometric characteristics of the road, spatial effects of the surrounding environment, and human behavioural factors. It is postulated that these potential contributing factors do not arise from the same underlying risk process, and thus should be explicitly modelled and understood. The state of the practice in road safety network management applies a safety performance function that represents a single risk process to explain crash variability across network sites. This study aims to elucidate the importance of differentiating among various underlying risk processes contributing to the observed crash count at any particular network location. To demonstrate the principle of this theoretical and corresponding methodological approach, the study explores engineering (e.g. segment length, speed limit) and unobserved spatial factors (e.g. climatic factors, presence of schools) as two explicit sources of crash contributing factors. A Bayesian Latent Class (BLC) analysis is used to explore these two sources and to incorporate prior information about their contribution to crash occurrence. The methodology is applied to the state controlled roads in Queensland, Australia and the results are compared with the traditional Negative Binomial (NB) model. A comparison of goodness of fit measures indicates that the model with a double risk process outperforms the single risk process NB model, and thus indicating the need for further research to capture all the three crash generation processes into the SPFs.

Association between glaucoma and at–fault motor vehicle collision involvement among older drivers

Objective To examine the association between glaucoma and motor vehicle collision (MVC) involvement among older drivers, including the role of visual field impairment that may underlie any association found. Design A retrospective population-based study Participants A sample of 2,000 licensed drivers aged 70 years and older who reside in north central Alabama. Methods At-fault MVC involvement for five years prior to enrollment was obtained from state records. Three aspects of visual function were measured: habitual binocular distance visual acuity, binocular contrast sensitivity and the binocular driving visual field constructed from combining the monocular visual fields of each eye. Poisson regression was used to calculate crude and adjusted rate ratios (RR) and 95% confidence intervals (CI). Main Outcomes Measures At-fault MVC involvement for five years prior to enrollment. Results Drivers with glaucoma (n = 206) had a 1.65 (95% confidence interval [CI] 1.20-2.28, p = 0.002) times higher MVC rate compared to those without glaucoma after adjusting for age, gender and mental status. Among those with glaucoma, drivers with severe visual field loss had higher MVC rates (RR = 2.11, 95% CI 1.09-4.09, p = 0.027), whereas no significant association was found among those with impaired visual acuity and contrast sensitivity. When the visual field was sub-divided into six regions (upper, lower, left, and right visual fields; horizontal and vertical meridians), we found that impairment in the left, upper or lower visual field was associated with higher MVC rates, and an impaired left visual field showed the highest RR (RR = 3.16, p = 0.001) compared to other regions. However, no significant association was found in deficits in the right side or along the horizontal or vertical meridian. Conclusions A population-based study suggests that older drivers with glaucoma are more likely to have a history of at-fault MVC involvement than those without glaucoma. Impairment in the driving visual field in drivers with glaucoma appears to have an independent association with at-fault MVC involvement, whereas visual acuity and contrast sensitivity impairments do not.

‘Lemon Laws’: an inquiry into consumer protections and remedies for buyers of new motor vehicles

1. Under the Terms of Reference for the Committee’s Inquiry, ‘lemons’ are defined as ‘new motor vehicles with numerous, severe defects that re-occur despite multiple repair attempts or where defects have caused a new motor vehicle to be out of service for a prolonged period of time’. Consumers are currently protected in relation to lemon purchases by the Australian Consumer Law (ACL) located in Schedule 2 of the Competition and Consumer Act 2010 (Cth) (CCA). The ACL applies as a law of Queensland pursuant to the Fair Trading Act 1989 (Qld). The voluntary recall and consumer guarantees law took effect on 1 January 2011. 2. In 2006, the Government of Victoria made a commitment to introduce a lemon law into the provisions of the then Fair Trading Act 1999 (Vic). The public consultation process on the proposal to introduce a lemon law for motor vehicle purchases in Victoria was conducted by Ms Janice Munt MP, with the assistance of Consumer Affairs Victoria (CAV). CAV released an Issues Paper to canvas with industry and the community options for the development and introduction of a motor vehicle lemon law.(Consumer Affairs Victoria, Introducing Victorian motor vehicle lemon laws, Issues Paper, (September, 2007). 3. A CAV report prepared by Janice Munt MP was released in July, 2008 (Consumer Affairs Victoria, Motor Cars: A report on the motor vehicle lemon law consultations (July 2008) (Victorian Lemon Law Report). However, the Victorian proposal was overtaken by events leading to the adoption of a uniform consumer protection law in all Australian jurisdictions, the ACL. 4. The structure of this submission is to consider first the three different bases upon which consumers can obtain relief for economic loss arising from defects in motor vehicles. The second part of the submission considers the difficulties encountered by consumers in litigating motor vehicle disputes in the courts and tribunals. The third part of the submission examines the approach taken in other jurisdictions to resolving motor vehicle disputes. The final part of the submission considers a number of possible reforms that could be made to the existing law and its enforcement to reduce consumer detriment arising from the purchase of ‘lemon’ motor vehicles. 5. There are three principal bases upon which a consumer can obtain redress for defects in new motor vehicles under the ACL. The first is where the manufacturer admits liability and initiates the voluntary recall procedure provided for in s 128 of the ACL. Under this basis the manufacturer generally repairs or replaces the part subject to the recall free of charge. The second basis is where the manufacturer or dealer denies liability and the consumer is initiates proceedings in the court or tribunal seeking a statutory remedy under the ACL, the nature of which will depend on whether the failure to comply with the consumer guarantee was major or not. The third basis upon which a consumer can obtain redress is pursuant to public enforcement by the ACCC. Each basis will be considered in this part. What all three bases have in common is the need to conduct an investigation to identify the nature of the defect and how it arose.

The lived experience of diagnosis delivery in motor neurone disease: A sociological-phenomenological study

Relatively few previous studies of individuals receiving a diagnosis of Motor Neurone Disease within the UK health care system have employed qualitative approaches to examine the diagnostic journey from a patient perspective. A qualitative sociological study was undertaken, involving interviews with 42 participants diagnosed with MND, to provide insight into their experiences of undergoing testing and receiving a diagnosis. Adopting a sociological-phenomenological perspective, this article examines key themes that emerged from participant accounts surrounding the lived experience of the diagnostic journey. The key themes that emerged were: The diagnostic quest; living with uncertainty; hearing bad news; communication difficulties; and a reified body of medical interest. In general, doctor-patient communication both at pre and post diagnosis was experienced as highly stressful, distressing and profoundly upsetting. Participants reported such distress as being due to the mode of delivery and communication strategies used by health professionals. We therefore suggest that professional training needs to emphasize the importance to health professionals of fostering greater levels of tact, sensitivity and empathy towards patients diagnosed with devastating, life-limiting illnesses such as MND.

A Bayesian latent class safety performance function for identifying motor vehicle crash blackspots

The current state of the practice in Blackspot Identification (BSI) utilizes safety performance functions based on total crash counts to identify transport system sites with potentially high crash risk. This paper postulates that total crash count variation over a transport network is a result of multiple distinct crash generating processes including geometric characteristics of the road, spatial features of the surrounding environment, and driver behaviour factors. However, these multiple sources are ignored in current modelling methodologies in both trying to explain or predict crash frequencies across sites. Instead, current practice employs models that imply that a single underlying crash generating process exists. The model mis-specification may lead to correlating crashes with the incorrect sources of contributing factors (e.g. concluding a crash is predominately caused by a geometric feature when it is a behavioural issue), which may ultimately lead to inefficient use of public funds and misidentification of true blackspots. This study aims to propose a latent class model consistent with a multiple crash process theory, and to investigate the influence this model has on correctly identifying crash blackspots. We first present the theoretical and corresponding methodological approach in which a Bayesian Latent Class (BLC) model is estimated assuming that crashes arise from two distinct risk generating processes including engineering and unobserved spatial factors. The Bayesian model is used to incorporate prior information about the contribution of each underlying process to the total crash count. The methodology is applied to the state-controlled roads in Queensland, Australia and the results are compared to an Empirical Bayesian Negative Binomial (EB-NB) model. A comparison of goodness of fit measures illustrates significantly improved performance of the proposed model compared to the NB model. The detection of blackspots was also improved when compared to the EB-NB model. In addition, modelling crashes as the result of two fundamentally separate underlying processes reveals more detailed information about unobserved crash causes.