Developing a System to Investigate Age-Related Differences in the Real-Time Utilization of Dynamically Changing External Cues during Navigation

Successful navigation depends critically upon two broad categories of sensory information, environmental (allothetic) and self-motion (idiothetic). Both the hippocampus and the medial portion of the entorhinal cortex (MEC) are critical for spatial navigation and contain functionally distinct sub-networks of spatially-modulated cells. These cells are characterized by their tuning to different spatial sensory-perceptual features of the environment and all utilize both allothetic and idiothetic cues to anchor and update their spatial firing to generate a comprehensive and dynamic representation of space. As with older adults, aged rats show pronounced impairments on a number of different spatial navigation tasks and these impairments are accompanied by a bias toward relying on egocentric over allocentric navigation strategies. Similarly, the hippocampus and MEC are also highly susceptible to age-associated changes. The influence visual allothetic cues exert on hippocampal place cell spatial tuning is diminished and delayed in aged animals. Two plausible and non-exclusive explanations that could account for these age-related alterations in allothetic processing are 1) circuit disruptions caused by known age-related functional and anatomical changes in the entorhinal-hippocampal processing pathway or 2) degraded sensory-perceptual information resulting from well-established age-related deficits across multiple sensory domains. Either of these possibilities could have the effect of either slowing allothetic cue processing or weakening the ability of these cues to influence firing field alignment. Within this context, this thesis was conceived with the aim of investigating the degree and timing with which young and aged animals utilize allothetic and idiothetic feedback to update their internal representation of space and calibrate their behavioral output. A large focus of this thesis is given to the incremental design and piloting of a number of novel technologies. Foremost among the methodological contributions of this study is the development of an augmented reality behavioral apparatus, termed the Instantaneous Cue Rotation (ICR) arena, which utilizes projected visual cues to allow for rapid remote control of all symmetry breaking visual features in the environment as rats actively engage in a visual-cue based goal navigation task. The results of extensive behavioral piloting of old and young rats validate both the ICR rotation manipulation as well as the mobile reward delivery system. This system traverses the track in tandem with the rat, enabling food based spatial reinforcement while preventing food-related olfactory cues from becoming associated with any specific location. In parallel with this work, microdrive technology was developed to enable simultaneous recording from both MEC and CA1 which is discussed along with results from single-region hippocampal and MEC implanted rats assessed in the context of a cue rotation manipulation conceptually similar to the that of the ICR. Finally, the results of the behavioral study suggest that in young rats the cue rotation exerts reliable but incomplete control over running behavior. In aged rats, by comparison, the cues exert an overall less pronounced influence on running behavior, consistent with known age-related deficits in allothetic processing. When assessed on a lap-by-lap basis, it was found that the behavior of both young and aged rats became progressively more aligned with the cues over the first few laps following cue rotation. These findings suggest a progressive realignment of behavior from an egocentric to an allocentric reference frame which is reminiscent of the reported progressive realignment of place field firing in response to conflicting spatial feedback

What do we know about preventing school violence? A systematic review of systematic reviews

Many children across the world are exposed to school violence, which undermines their right to education and adversely affects their development. Studies of interventions for school violence suggest that it can be prevented. However, this evidence base is challenging to navigate. We completed a systematic review of interventions to reduce four types of school violence: (a) peer violence; (b) corporal punishment; (c) student-on-teacher violence and (d) teacher-on-student violence. Reviewers independently searched databases and journals. Included studies were published between 2005 and 2015; in English; considered school-based interventions for children and measured violence as an outcome. Many systematic reviews were found, thus we completed a systematic review of systematic reviews. Only systematic reviews on interventions for intimate partner violence (IPV) and peer aggression were found. These reviews were generally of moderate quality. Research on both types of violence was largely completed in North America. Only a handful of programmes demonstrate promise in preventing IPV. Cognitive behavioral, social-emotional and peer mentoring/mediation programmes showed promise in reducing the levels of perpetration of peer aggression. Further research needs to determine the long-term effects of interventions, potential moderators and mediators of program effects, program effects across different contexts and key intervention components

Engagement in parenting programmes: exploring facilitators of and barriers to participation

The large-scale delivery of evidence-based parenting programmes is key to nation building in South Africa. In order to achieve change, parents must participate in these programmes. This policy brief aims to contribute to an understanding of participation by exploring the barriers and facilitators encountered by a sample of parents who were invited to take part in one of two local parenting programmes. Recommendations to improve recruitment and retention strategies are provided

Lorentz- and permutation-invariants of particles

Abstract: Two theorems of Weyl tell us that the algebra of Lorentz- (and parity-) invariant polynomials in the momenta of n particles are generated by the dot products and that the redundancies which arise when n exceeds the spacetime dimension d are generated by the (d + 1)-minors of the n × n matrix of dot products. We extend the first theorem to include the action of an arbitrary permutation group P ⊂ S n on the particles, to take account of the quantum-field-theoretic fact that particles can be indistinguishable. Doing so provides a convenient set of variables for describing scattering processes involving identical particles, such as pp → jjj, for which we provide an explicit minimal set of Lorentz- and permutation-invariant generators. Additionally, we use the Cohen–Macaulay structure of the Lorentz-invariant algebra to provide a more direct characterisation in terms of a Hironaka decomposition. Among the benefits of this approach is that it can be generalized straightforwardly to when parity is not a symmetry and to cases where a permutation group acts on the particles. In the first non-trivial case, n = d + 1, we give a homogeneous system of parameters that is valid for the action of an arbitrary permutation symmetry and make a conjecture for the full Hironaka decomposition in the case without permutation symmetry. An appendix gives formulæ for the computation of the relevant Hilbert series for d ⩽ 4

Email for clinical communication between healthcare professionals

Email is one of the most widely used methods of communication, but its use in healthcare is still uncommon. Where email communication has been utilised in health care, its purposes have included clinical communication between healthcare professionals, but the effects of using email in this way are not well known. We updated a 2012 review of the use of email for two-way clinical communication between healthcare professionals

Heat Shock Protein 70 Prevents both Tau Aggregation and the Inhibitory Effects of Preexisting Tau Aggregates on Fast Axonal Transport

Aggregation and accumulation of the microtubule-associated protein tau are associated with cognitive decline and neuronal degeneration in Alzheimer's disease and other tauopathies. Thus, preventing the transition of tau from a soluble state to insoluble aggregates and/or reversing the toxicity of existing aggregates would represent a reasonable therapeutic strategy for treating these neurodegenerative diseases. Here we demonstrate that molecular chaperones of the heat shock protein 70 (Hsp70) family are potent inhibitors of tau aggregation in vitro, preventing the formation of both mature fibrils and oligomeric intermediates. Remarkably, addition of Hsp70 to a mixture of oligomeric and fibrillar tau aggregates prevents the toxic effect of these tau species on fast axonal transport, a critical process for neuronal function. When incubated with preformed tau aggregates, Hsp70 preferentially associated with oligomeric over fibrillar tau, suggesting that prefibrillar oligomeric tau aggregates play a prominent role in tau toxicity. Taken together, our data provide a novel molecular basis for the protective effect of Hsp70 in tauopathies

SMS for Life: a pilot project to improve anti-malarial drug supply management in rural Tanzania using standard technology

Background: Maintaining adequate supplies of anti-malarial medicines at the health facility level in rural sub-Saharan Africa is a major barrier to effective management of the disease. Lack of visibility of anti-malarial stock levels at the health facility level is an important contributor to this problem. Methods: A 21-week pilot study, 'SMS for Life', was undertaken during 2009-2010 in three districts of rural Tanzania, involving 129 health facilities. Undertaken through a collaborative partnership of public and private institutions, SMS for Life used mobile telephones, SMS messages and electronic mapping technology to facilitate provision of comprehensive and accurate stock counts from all health facilities to each district management team on a weekly basis. The system covered stocks of the four different dosage packs of artemether-lumefantrine (AL) and quinine injectable. Results: Stock count data was provided in 95% of cases, on average. A high response rate (≥ 93%) was maintained throughout the pilot. The error rate for composition of SMS responses averaged 7.5% throughout the study; almost all errors were corrected and messages re-sent. Data accuracy, based on surveillance visits to health facilities, was 94%. District stock reports were accessed on average once a day. The proportion of health facilities with no stock of one or more anti-malarial medicine (i.e. any of the four dosages of AL or quinine injectable) fell from 78% at week 1 to 26% at week 21. In Lindi Rural district, stock-outs were eliminated by week 8 with virtually no stock-outs thereafter. During the study, AL stocks increased by 64% and quinine stock increased 36% across the three districts. Conclusions: The SMS for Life pilot provided visibility of anti-malarial stock levels to support more efficient stock management using simple and widely available SMS technology, via a public-private partnership model that worked highly effectively. The SMS for Life system has the potential to alleviate restricted availability of anti-malarial drugs or other medicines in rural or under-resourced areas

Spectrophotometric Distances to Galactic H\,{\sc{ii}} Regions

We present a near infrared study of the stellar content of 35 H\,{\sc{ii}} regions in the Galactic plane. In this work, we have used the near infrared domain $J-$, $H-$ and $K_{s}-$ band color images to visually inspect the sample. Also, color-color and color-magnitude diagrams were used to indicate ionizing star candidates, as well as, the presence of young stellar objects such as classical TTauri Stars (CTTS) and massive young stellar objects (MYSOs). We have obtained {\it Spitzer} IRAC images for each region to help further characterize them. {\it Spitzer} and near infrared morphology to place each cluster in an evolutionary phase of development. {\it Spitzer} photometry was also used to classify the MYSOs. Comparison of the main sequence in color-magnitude diagrams to each observed cluster was used to infer whether or not the cluster kinematic distance is consistent with brightnesses of the stellar sources. We find qualitative agreement for a dozen of the regions, but about half the regions have near infrared photometry that suggests they may be closer than the kinematic distance. A significant fraction of these already have spectrophotometric parallaxes which support smaller distances. These discrepancies between kinematic and spectrophotometric distances are not due to the spectrophotometric methodologies, since independent non-kinematic measurements are in agreement with the spectrophotometric results. For instance, trigonometric parallaxes of star-forming regions were collected from the literature and show the same effect of smaller distances when compared to the kinematic results. In our sample of H\,{\sc{ii}} regions, most of the clusters are evident in the near infrared images. Finally, it is possible to distinguish among qualitative evolutionary stages for these objects.Comment: 59 pages, 146 figures and 4 tables. MNRAS accepte