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<p dir="ltr">Individuals with typical audiometric sensitivity exhibit varying speech perception abilities in noisy environments, which may decline with age. Temporal processing plays a pivotal role in speech perception, especially in challenging listening conditions. Auditory decline due to aging involves both peripheral pathology and central auditory system changes, impacting temporal processing. To delineate the contributions of these changes, measurements of within- and across-channel temporal processing were conducted in a wide age range of normal-hearing individuals. Robust perception of within-channel temporal cues requires precise coding at both peripheral and central auditory pathway levels, while cross-channel processing relies on central mechanisms. Comprehensive data collection involved behavioral and electrophysiological measures, revealing age-related increases in behavioral thresholds, less robust cortical responses to gaps and temporal-coherence changes, and declining SPIN performance. Cross-channel measures proved to be more predictive of speech perception outcomes, emphasizing the significance of central auditory changes in age-related perceptual deficits.</p><p dir="ltr">A mini-EEG cap to record cortical EEG auditory responses to gaps in chinchillas using a new sedation protocol was validated. This advancement enhances translational potential and paves the way for exploring cortical auditory processing using complex stimuli in animal models. By facilitating simultaneous exploration of both subcortical and cortical consequences of auditory system pathologies, this development contributes to a more comprehensive understanding of auditory processes across species.</p>

Human temporal bone specimens are used in experiments measuring the sound transfer of the middle ear, which is the standard method used in the development of active and passive middle ear implants. Statistical analyses of these experiments usually require that the TB samples are representative of the population of non-pathological middle ears. Specifically, this means that the specimens must be mechanically well-characterized. We present an in-depth statistical analysis of 478 data sets of middle ear transfer functions (METFs) from different laboratories. The data sets are preprocessed and various contributions to the variance of the data are evaluated. We then derive a statistical range as a reference against which individual METF measurements may be validated. The range is calculated as the two-sided 95% tolerance interval at audiological frequencies. In addition, the mean and 95% confidence interval of the mean are given as references for assessing the validity of a sample group. Finally, we provide a suggested procedure for measuring METFs using the methods described herein.

Detection of alloreactive anti-HLA antibodies is a frequent and mandatory test before and after organ transplantation to determine the antigenic targets of the antibodies. Nowadays, this test involves the measurement of fluorescent signals generated through antibody–antigen reactions on multi-beads flow cytometers. In this study, in a cohort of 1,066 patients from one country, anti-HLA class I responses were analyzed on a panel of 98 different antigens. Knowing that the immune system responds typically to “shared” antigenic targets, we studied the clustering patterns of antibody responses against HLA class I antigens without any a priori hypothesis, applying two unsupervised machine learning approaches. At first, the principal component analysis (PCA) projections of intralocus specific responses showed that anti-HLA-A and anti-HLA-C were the most distantly projected responses in the population with the anti-HLA-B responses to be projected between them. When PCA was applied on the responses against antigens belonging to a single locus, some already known groupings were confirmed while several new crossreactive patterns of alloreactivity were detected. Anti-HLA-A responses projected through PCA suggested that three cross-reactive groups accounted for about 70% of the variance observed in the population, while anti-HLA-B responses were mainly characterized by a distinction between previously described Bw4 and Bw6 cross-reactive groups followed by several yet undocumented or poorly described ones. Furthermore, anti-HLA-C responses could be explained by two major cross-reactive groups completely overlapping with previously described C1 and C2 allelic groups. A second featurebased analysis of all antigenic specificities, projected as a dendrogram, generated a robust measure of allelic antigenic distances depicting bead-array defined cross reactive groups. Finally, amino acid combinations explaining major population specific crossreactive groups were described. The interpretation of the results was based on the current knowledge of the antigenic targets of the antibodies as they have been characterized either experimentally or computationally and appear at the HLA epitope registry.

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Traumatic brain injury (TBI) has a dramatic impact on our society in terms of mortality, morbidity, and inherently high financial costs. Formidable research efforts are being addressed to the identification of neuroprotective agents capable of ameliorating the neurological outcome after TBI. Preclinical studies have recently demonstrated lithium to be a promising neuroprotective agent for both acute ischemic brain injury and chronic neurodegenerative disease. In light of these encouraging data, we designed a lateral fluid-percussion injury (FPI) study aimed at investigating the role of early post-traumatic administration of lithium as a strategy for reducing TBI-induced motor and cognitive deficits. The optimal dose of this agent and the time window for its administration have been determined on the basis of data derived from the assessment of motor and cognitive functioning in experimental animals, as well as from the stereological quantification of neuronal survival (PID 7) within the CA3 and hilar regions of the hippocampus ipsilateral to the FPI. In addition, we attempted to elucidate the mechanisms underlying the neuroprotective properties of this drug via western blot analysis of levels of the pro-apoptotic marker caspase-3 (PID 1, 7) and two neuroplasticity markers, growth associated protein-43 (GAP-43) and brain-derived neurotrophic factor (BDNF) (PID 1, 7, 21). Our findings indicate that low-dose lithium chloride (0.125 or 0.25 mmol/kg), given either 30 min or 8 hr after lateral FPI significantly ameliorates injury-induced cognitive and motor impairment. Specifically, cell survival in the CA3 region of the hippocampus of the injured lithium-treated animals (but not in the hilus) was significantly increased compared to injured vehicle-treated animals. Western blot analyses revealed a significant increase in GAP-43 levels on PID 7 in injured animals when treated with lithium, indicating a possible mechanism for lithium-induced neuroprotection. In contrast, BDNF levels were relatively unchanged until PID 21, and caspase-3 activation was not observed at all, suggesting that these proteins play less significant roles in the observed neuroprotective effects of lithium treatment after lateral FPI. Early administration of lithium, within 8 hours after TBI, holds promise as an effective therapy to ameliorate postinjury neurobehavioral deficits and warrants further investigation in clinical TBI studies.

Using an emergent design, this study developed a program approach for young people in the child headed households of Zambia. Phase I dealt with prior ethnography, Phase II focused on independent living services, and Phase III concerned translation to Zambia. A total of 36 participants from Richmond, consisting of 20 Richmond Department of Social Services workers and youth and 16 Africans, were recruited. Three major themes emerged: feasibility, content, and quality. Lessons learned about translational research highlight the need for uniformity in a cultural screen’s composition. This might enhance the richness of perspectives on young people. Lessons for the Department of Social Services include a need to focus on tracking young people exiting services. This might involve exit interviews with young people and guidance with life decisions. There were lessons about decisions regarding local and expert knowledge in the translation process. This often becomes difficult when there are no assurances of participant uniformity. Paying attention to issues of local and expert knowledge would eliminate decision barriers that might arise during the translational process. Implications for social work education suggest that an emphasis on cultural competency might help students at the BSW and MSW levels to become better managers of adolescents. Implications for practice and policy include enhancing access to education and health for all young people. This process might be facilitated by the enactment of polices that highlight education and health for all young people at national and state levels. The following are crucial considerations for practice with young people: recruiting and training appropriate staff, promoting civic education, collaborating with young people, strengthening community involvement, strengthening agency collaboration, and developing targeted services. Implications for further research include: exploring what areas to consider when making a paradigm jump, considering cultural principles as bridges for making that jump, examining the implications for translational research as opposed to diffusion of innovation, determining what types of research samples would eliminate some of the gender issues that emerge with focus groups, recruiting more young people as participants, and conducting a study that focuses on lived experiences of young people.

The thesis aims to present a case for a rethinking of the paradigmatic frames underpinning food marketing control policy and research. In support of its contention, it reports on the methodological strategies, evidence outcomes and knowledge translation contributions of a series of research projects. The projects were commissioned by national and international policy makers during the period 2009-2015 in support of responsible food marketing policy development. They were conceptualised, developed and interpreted through participatory and iterative research planning processes. The research drew on theories and constructs from multiple disciplines. Public health, marketing and policy science contributed most, but information economics and management theories also informed research design and analysis and interpretation of findings. Its key generalizable findings can be summarised as follows: • The identification of a fragmented but convergent pool of evidence indicating contemporary food and beverage marketing is an interactive, dynamic phenomenon. • The identification of a fragmented but convergent pool of evidence demonstrating it significantly impacts sociocultural determinants of food behaviours. • The generation of evidence demonstrating a gap between the strategic aims of responsible marketing policy regimes and the inherent capacity of implemented interventions to constrain marketing’s food environment impacts. • The generation of evidence demonstrating that critical re-appraisal of food marketing policy research assumptions and preconceptions is a strategy supportive of policy innovation. • The generation of evidence that research intended to support real world multi-stakeholder policy development processes requires additional skills to those established and recognised as central to high quality research. These include the ability to engage with dynamic and politicised policy processes and their public communications challenges. • The generation of evidence that can inform future independent benchmark standard for responsible marketing development initiatives. • The generation of evidence that can inform future research on designing and developing policy that is ‘future proof’ and targets marketing’s sociocultural food environment impacts. Its most significant knowledge translation contributions have been: • Support for the WHO Set of Recommendations on the Marketing of Foods and Non-alcoholic Beverages to Children (subsequently endorsed at the 2010 World Health Assembly and the 2011 United Nations General Assembly). • Participatory research contributions to the Scottish Government’s responsible marketing standard development initiative (PAS2500). • Supporting the planning and development of the Scottish Government’s Supporting Healthy Choices Policy initiative. • Knowledge exchange with policy makers and stakeholders engaged in a scoping and prioritisation initiative commissioned by the United Kingdom’s Department of Health (An analysis of the regulatory and voluntary landscape concerning the marketing and promotion of food and drink to children). • Supporting responsible marketing policy agendas targeted to the engagement of a broad mix of stakeholders in innovative policy development processes. • Supporting policy makers’ efforts to increase popular support for stronger, more effective responsible marketing policy controls. The thesis therefore aims to present evidence that the programme of research presented here has made useful and original contributions to evidence and knowledge on contemporary food marketing and its impacts on food behaviours and the food environment. It aims to build on this by demonstrating how this evidence informed and supported policy development. Through this the thesis aims to support its case that a rethinking of food marketing policy research assumptions and conceptions can expand and enrich the evidence base as well as real world policy innovation.