Modeling Maintenance of Long-Term Potentiation in Clustered Synapses, Long-Term Memory Without Bistability

Memories are stored, at least partly, as patterns of strong synapses. Given molecular turnover, how can synapses maintain strong for the years that memories can persist? Some models postulate that biochemical bistability maintains strong synapses. However, bistability should give a bimodal distribution of synaptic strength or weight, whereas current data show unimodal distributions for weights and for a correlated variable, dendritic spine volume. Bistability of single synapses has also never been empirically demonstrated. Thus it is important for models to simulate both unimodal distributions and long-term memory persistence. Here a model is developed that connects ongoing, competing processes of synaptic growth and weakening to stochastic processes of receptor insertion and removal in dendritic spines. The model simulates long-term (in excess of 1 yr) persistence of groups of strong synapses. A unimodal weight distribution results. For stability of this distribution it proved essential to incorporate resource competition between synapses organized into small clusters. With competition, these clusters are stable for years. These simulations concur with recent data to support the clustered plasticity hypothesis, which suggests clusters, rather than single synaptic contacts, may be a fundamental unit for storage of long-term memory. The model makes empirical predictions, and may provide a framework to investigate mechanisms maintaining the balance between synaptic plasticity and stability of memory.Comment: 17 pages, 5 figure

Rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory joint disease, which can cause cartilage and bone damage as well as disability. Early diagnosis is key to optimal therapeutic success, particularly in patients with well-characterised risk factors for poor outcomes such as high disease activity, presence of autoantibodies, and early joint damage. Treatment algorithms involve measuring disease activity with composite indices, applying a treatment-to-target strategy, and use of conventional, biological, and newz non-biological disease-modifying antirheumatic drugs. After the treatment target of stringent remission (or at least low disease activity) is maintained, dose reduction should be attempted. Although the prospects for most patients are now favourable, many still do not respond to current therapies. Accordingly, new therapies are urgently required. In this Seminar, we describe current insights into genetics and aetiology, pathophysiology, epidemiology, assessment, therapeutic agents, and treatment strategies together with unmet needs of patients with rheumatoid arthritis

A Phase III Study Evaluating Continuation, Tapering, and Withdrawal of Certolizumab Pegol After One Year of Therapy in Patients With Early Rheumatoid Arthritis

Objective: For DMARD-naïve, early rheumatoid arthritis patients who achieved sustained low disease activity (sLDA; DAS28[ESR]≤3.2 at both Weeks 40 and 52) after 1 year of treatment with certolizumab pegol (CZP 200mg Q2W+optimized MTX), we evaluated whether continuation of CZP as a standard (200mg Q2W+MTX) or reduced-frequency (200mg Q4W+MTX) dose was superior to stopping CZP (placebo+MTX) in maintaining LDA for 1 additional year. Methods: 293 patients from C-EARLY Period 1 were re-randomized 2:3:2 in Period 2 to CZP standard (n=84), reduced-frequency (n=127), CZP stopped (n=82). The primary endpoint was the percentage of patients who maintained LDA throughout Weeks 52-104 without flares. Hierarchical testing scheme: CZP standard versus CZP stopped, if p<0.05 achieved, then CZP reduced-frequency versus CZP stopped (non-responder imputation). Results: 36% fewer patients than projected achieved sLDA in Period 1 and were eligible for enrollment in Period 2. A higher proportion of CZP standard and reduced-frequency patients maintained LDA versus CZP stopped (48.8% [p=0.112], 53.2% [p=0.041; nominal p value, first hierarchical test not significant] versus 39.2%). Similar trends were observed for radiographic non-progression (change from baseline mTSS≤0.5; 79.2%, 77.9% versus 70.3%) and normative physical function (HAQ-DI≤0.5; 71.4%, 70.6% versus 57.0%). Safety profiles were similar between all groups, with no new safety signals identified for continuing CZP to Week 104. No deaths were reported. Conclusion: The study failed to meet its primary endpoint. However, there were no clinically meaningful differences between the standard or reduced-frequency doses of CZP+MTX; both more effectively controlled rheumatoid arthritis in comparison to CZP withdrawal

Designing a Self-Powered Device to Aid in Fencing Training and Scoring

The purpose of this project is to redesign a currently available electric training tool for the sport of fencing in order to fix several existing faults such as cost and power use. The second stage of this project uses this new low-power design to explore small-scale energy harvesting by integrating a charging mechanism into the device to generate power from the movements of the fencer. This goal of this project is to research and explore modern low-power device design, at both the hardware and software levels, and then to apply those techniques to improve a real-world product. The final result of this product is an improved and affordable fencing training tool, as well as an alternative power supply design for the device that uses energy harvesting to charge and power the device and remove the need for batteries or an external charger. The first step of this project was to implement the core functions with low power requirements. The microcontroller I selected was the PIC12F1840, an 8-bit, low-power microcontroller. The power consumption was minimized in both hardware and software designs. The base device has low enough power consumption that replacing the battery with an energy-harvesting power supply is possible. The energy harvester uses a piezoelectric element for power generation and a super capacitor for storage in place of a battery

The Perceived Impacts Of Therapy Dogs On Students As Viewed Through The Human-Animal Interaction Framework

This study employed a qualitative case study approach to explore the perceptions of teachers/staff members directly associated with the therapy dog (TD) program in their school. These perceptions were regarding the TD program’s effectiveness in (a) student social interaction, (b) stress coping and self-regulation, (c) engagement and/or attention, and (d) motivation and/or self-efficacy. The human-animal interaction (HAI) theoretical framework (Gee et al., 2017) served as a focal lens in this study. Data was collected from a middle school in the midwestern United States and through social media. Thirteen participants were from middle school and eight were obtained via social media. Further, interviews were conducted with five individuals representing both sites. Interpretation of the data and themes developed revealed that the majority of participants found perceived impacts from therapy dogs on: (a) student social interaction, (b) stress coping, (c) self-regulation, (d) engagement and/or attention, (e) motivation, and (f) social-emotional development. The study’s conclusions aligned with its research questions involving the impact of therapy dogs. The findings led to recommendations for the development of a tool to assess therapy dogs’ well-being. Designation of key canine demographic information is needed in the field as well as a centralized database to warehouse information collected. This study’s recommendations include additional research on the impacts of the COVID-19 pandemic on therapy dog programs, the therapy dogs themselves, and teachers/staff members’ needs and benefits from therapy dogs during the pandemic. Finally, this study recommends examination of a student’s perspective of the therapy dog’s role and how that perspective affects the efficacy of the intervention