The Effects of BACE and Its Targets on Age-related Seizures in \u3cem\u3eDrosophila\u3c/em\u3e

The presence of Beta-Amyloid (Aβ) containing plaques in the brain is one of the histological hallmarks of Alzheimer’s Disease. β-secretase (BACE) is the enzyme responsible for producing this Aβ cleavage product and has also been shown to affect myelination and general neuronal activity. Observations from geriatric medicine suggest that there may be an increase in seizure activity associated with Alzheimer’s Disease. Preliminary data suggests that both over- and under-expression of BACE contributes to mechanically stimulated seizures in Drosophila. In vertebrates, seizure activity has been correlated with many factors including Neuregulin production and Na+ Pump activity. Both of these proteins have also been shown to require BACE activity for proper function. However, their roles in BACE related seizures remains unknown. Here we are following up on this preliminary study and exploring the roles of Vein (the Drosophila homolog of Neuregulin) and Numb (a negative regulator of the Notch Pathway). We have confirmed that any perturbation in dBACE (Drosophila BACE) levels causes a significant increase in age related seizures, suggesting that that BACE levels must be tightly regulated. In addition an increase of Vein levels also cause a dramatic increase in seizure amounts and duration suggesting that BACE, at least in part, is acting through this signaling pathway. Understanding which BACE related signaling pathways are responsible for age related seizure activity can lead to new treatments which will hopefully slow the progression of Alzheimer’s and other related neurodegenerative diseases

Outcomes of ventriculoperitoneal shunt insertion in the management of idiopathic intracranial hypertension in children

Purpose The ventriculoperitoneal (VP) shunt has become the procedure of choice for treatment of idiopathic intracranial hypertension (IIH). We aimed to assess the efficacy of frameless stereotactic placement of VP shunts for the management of medically resistant IIH in children and to assess the role of gender and obesity in the aetiology of the condition. Methods This is a retrospective analysis of the case notes of 10 patients treated surgically at the University Hospital of Wales in Cardiff, from May 2006 to September 2012. Results VP shunts were successful in relieving headache, papilloedema and stabilising vision. No sex predilection was identified, and increased BMI was a feature throughout the population, regardless of age. Conclusions Neuronavigated VP shunt insertion is an effective mode of treatment for medically resistant IIH in children. The aetiological picture in children does not seem to be dominated by obesity, as in adults. Literature on childhood IIH is sparse, and larger scale, comparative studies would be of benefit to treating clinicians

Unilateral, trifocal, diaphyseal fracture of the radius with ipsilateral mid-shaft ulna fracture in an adult: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, a trifocal, diaphyseal fracture of the radius associated with ipsilateral mid-shaft fracture of the ulna in an adult has not been reported in the literature to date. The AO classification system does not include such a fracture configuration.</p> <p>Case presentation</p> <p>We report a case of trifocal, diaphyseal fracture of the radius with a mid-diaphyseal fracture of the ulna in a 53-year-old Caucasian, British, right-hand dominant woman involved in a head-on collision with another vehicle. The management of this rare fracture configuration is described and alternative treatment options discussed.</p> <p>Conclusions</p> <p>We describe an unusual, complex fracture, which with prompt surgical treatment resulted in a rapid, full and satisfactory functional recovery for our patient.</p

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Value-added measures for schools in England: looking inside the ‘black box’ of complex metrics

Value-added measures can be used to allocate funding to schools, to identify those institutions in need of special attention and to underpin government guidance on targets. In England, there has been a tendency to include in these measures an ever-greater number of contextualising variables and to develop ever-more complex models that encourage (or ‘impose’) in schools a single uniform method of analysing data, but whose intricacies are not fully understood by practitioners. The competing claims of robustness, usability and accessibility remain unresolved because it is unclear whether the purpose of the measurement is teacher accountability, pupil predictability or school improvement. This paper discusses the provenance and shortcomings of value-added measurement in England (and the Pupil Level Annual Schools Census that informs it) including the fact that although the metrics are essential for School Effectiveness Research, they fail to capture in its entirety the differential effectiveness of schools across the prior attainment range and across sub-groups of students and subjects

Ectopic lens material in an otherwise healthy 5-week-old infant.

To report the unusual finding of ectopic lens material in an otherwise healthy 5-week-old infant

Rapid Acquisition in Concurrent Chains: Evidence for a Decision Model

Pigeons' choice in concurrent chains can adapt to rapidly changing contingencies. Grace, Bragason, and McLean (2003) found that relative initial-link response rate was sensitive to the immediacy ratio in the current session when one of the terminal-link fixed-interval schedules was changed daily according to a pseudorandom binary sequence (e.g., Schofield & Davison, 1997). The present experiment tested whether the degree of variation in delays across sessions had any effect on acquisition rate in Grace et al.'s (2003) rapid-acquisition procedure. In one condition (“minimal variation”), the left terminal link was always fixed-interval 8 s and the right terminal link was either fixed-interval 4 s or fixed-interval 16 s. In the other condition (“maximal variation”), a unique pair of fixed-interval values was used in each session. Responding was sensitive to the current-session immediacy ratio in both conditions, but across subjects there was no systematic difference in sensitivity. These results challenge the view that initial-link responding in the rapid-acquisition procedure is determined by changes in the learned value of the terminal-link stimuli, and suggests instead that a process resembling categorical discrimination may control performance. A decision model based on the assumption that delays are categorized as short or long relative to the history of delays provided a good account of the data and shows promise in being able to explain other choice phenomena