First Workshop on Regional Approaches to Stockpile Reduction in Southeast Europe

Faced with the significant security and humanitarian impacts of stockpiled weapons and munitions, countries and organizations in Southeast Europe met in May to discuss strategies for stockpile reduction. The workshop, held in Croatia, focused on regional approaches to this problem, emphasizing information-sharing and coordination across borders

Passive immunotherapy against Aβ in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage

BACKGROUND: Anti-Aβ immunotherapy in transgenic mice reduces both diffuse and compact amyloid deposits, improves memory function and clears early-stage phospho-tau aggregates. As most Alzheimer disease cases occur well past midlife, the current study examined adoptive transfer of anti-Aβ antibodies to 19- and 23-month old APP-transgenic mice. METHODS: We investigated the effects of weekly anti-Aβ antibody treatment on radial-arm water-maze performance, parenchymal and vascular amyloid loads, and the presence of microhemorrhage in the brain. 19-month-old mice were treated for 1, 2 or 3 months while 23-month-old mice were treated for 5 months. Only the 23-month-old mice were subject to radial-arm water-maze testing. RESULTS: After 3 months of weekly injections, this passive immunization protocol completely reversed learning and memory deficits in these mice, a benefit that was undiminished after 5 months of treatment. Dramatic reductions of diffuse Aβ immunostaining and parenchymal Congophilic amyloid deposits were observed after five months, indicating that even well-established amyloid deposits are susceptible to immunotherapy. However, cerebral amyloid angiopathy increased substantially with immunotherapy, and some deposits were associated with microhemorrhage. Reanalysis of results collected from an earlier time-course study demonstrated that these increases in vascular deposits were dependent on the duration of immunotherapy. CONCLUSIONS: The cognitive benefits of passive immunotherapy persist in spite of the presence of vascular amyloid and small hemorrhages. These data suggest that clinical trials evaluating such treatments will require precautions to minimize potential adverse events associated with microhemorrhage

Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice

BACKGROUND: The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss. RESULTS: We report that in addition to decreased mRNA expression, there was decreased overall Na+/K+ ATPase enzyme activity in the amyloid-containing hippocampi of the APP+PS1 mice (although not in the amyloid-free cerebellum). In addition, dual immunolabeling revealed an absence of Na+/K+ ATPase staining in a zone surrounding congophilic plaques that was occupied by dystrophic neurites. We also demonstrate that cerebral Na+/K+ ATPase activity can be directly inhibited by high concentrations of soluble Aβ. CONCLUSIONS: The data suggest that the reductions in Na+/K+ ATPase activity in Alzheimer tissue may not be purely secondary to neuronal loss, but may results from direct effects of amyloid on this enzyme. This disruption of ion homeostasis and osmotic balance may interfere with normal electrotonic properties of dendrites, blocking intraneuronal signal processing, and contribute to neuritic dystrophia. These results suggest that therapies aimed at enhancing Na+/K+ ATPase activity in AD may improve symptoms and/or delay disease progression

Ariel - Volume 11 Number 2

Executive Editors Ellen Feldman Leonardo S. Nasca, Jr. Business .Managers Barbara L. Davies Martin B. Getzow News Editor Aaron D. Bleznak Features Editor Hugh A. Gelabert CAHS Editor Joan M. Greco Editorial Page Editor Samuel Markind Photography Editor Leonardo S. Nasca, Jr. Sports Editor Paul F. Mansfiel

Dynamic Fuzzy c-Means (dFCM) Clustering and its Application to Calorimetric Data Reconstruction in High Energy Physics

In high energy physics experiments, calorimetric data reconstruction requires a suitable clustering technique in order to obtain accurate information about the shower characteristics such as position of the shower and energy deposition. Fuzzy clustering techniques have high potential in this regard, as they assign data points to more than one cluster,thereby acting as a tool to distinguish between overlapping clusters. Fuzzy c-means (FCM) is one such clustering technique that can be applied to calorimetric data reconstruction. However, it has a drawback: it cannot easily identify and distinguish clusters that are not uniformly spread. A version of the FCM algorithm called dynamic fuzzy c-means (dFCM) allows clusters to be generated and eliminated as required, with the ability to resolve non-uniformly distributed clusters. Both the FCM and dFCM algorithms have been studied and successfully applied to simulated data of a sampling tungsten-silicon calorimeter. It is seen that the FCM technique works reasonably well, and at the same time, the use of the dFCM technique improves the performance.Comment: 15 pages, 10 figures. It is accepted for publication in NIM

Severe symptomatic aortic stenosis: medical therapy and transcatheter aortic valve implantation (TAVI)—a real-world retrospective cohort analysis of outcomes and cost-effectiveness using national data

Objectives: Determine the real-world difference between 2 groups of patients with severe aortic stenosis and similar baseline comorbidities: surgical turn down (STD) patients, who were managed medically prior to the availability of transcatheter aortic valve implantation (TAVI) following formal surgical outpatient assessment, and patients managed with a TAVI implant. Design: Retrospective cohort study from real-world data. Setting: Electronic patient letters were searched for patients with a diagnosis of severe aortic stenosis and a formal outpatient STD prior to the availability of TAVI (1999–2009). The second group comprised the first 90 cases of TAVI in South Wales (2009 onwards). 2 years prior to and 5 years following TAVI/STD were assessed. Patient data were pseudoanonymised, using the Secure Anonymized Information Linkage (SAIL) databank, and extracted from Office National Statistics (ONS), PatientEpisode Database for Wales (PEDW) and general practitioner databases. Population: 90 patients who had undergone TAVI in South Wales, and 65 STD patients who were medically managed. Main outcome measures: Survival, hospital admission frequency and length of stay, primary care visits, and cost-effectiveness. Results: TAVI patients were significantly older (81.8 vs 79.2), more likely to be male (59.1% vs 49.3%), baseline comorbidities were balanced. Mortality in TAVI versus STD was 28% vs 70% at 1000 days follow-up. There were significantly more hospital admissions per year in the TAVI group prior to TAVI/STD (1.5 (IQR 1.0– 2.4) vs 1.0 IQR (0.5–1.5)). Post TAVI/STD, the TAVI group had significantly lower hospital admissions (0.3 (IQR 0.0–1.0) vs 1.2 (IQR 0.7–3.0)) and lengths of stay (0.4 (IQR 0.0–13.8) vs 11.0 (IQR 2.5–28.5), p<0.05). The incremental cost-effectiveness ratio (ICER) for TAVI was £10 533 per quality-adjusted life year (QALY). Conclusions: TAVI patients were more likely to survive and avoid hospital admissions compared with the medically managed STD group. The ICER for TAVI was £10 533 per QALY, making it a cost-effective procedure

The potential for leguminous crops in Scotland

The Scottish Government is committed to reducing greenhouse gas (GHG) emissions from agriculture as part of its pledge to achieve net-zero emissions in Scotland by 2045. In 2018, agriculture accounted for 18% of Scotland’s total GHG emissions, with a significant share coming from nitrogen fertilisers (1.4% of Scotland’s total GHG emissions are from soil as a consequence of applying nitrogen fertilisers). Scotland’s Climate Change Plan update1 envisages that nitrogen emissions, including from nitrogen fertiliser, will have fallen through a combination of improved understanding, efficiencies and improved soil condition. One policy approach identified as having potential to deliver this outcome is through the use of leguminous crops to fix atmospheric nitrogen, potentially reducing the need for synthetic fertiliser. Increasing legume production could also help build protein self-sufficiency in Scotland. This study assesses the opportunities, challenges and barriers influencing potential production of grain and forage legumes in Scotland. Grain legumes are crops such as beans and peas which are cultivated for their seeds and used for both human and animal consumption. Forage legumes include lucerne (also known as alfalfa), clover and vetch which are sown in pasture and grazed by livestock or used for cutting for hay or silage

90.6% efficient 11MHz 22W LED driver using GaN FETs and burst-mode controller with 0.96 power factor

With the advent of reliable, high brightness and high efficacy LEDs, the lighting industry is expected to see a significant growth in the near future. However, for LEDs to completely replace the traditional incandescent and CFL bulbs, the power converters within the LED drivers need to be miniaturized. Superior figure of merit (R[subscript ds,ON]xQ[subscript g]) of Gallium Nitride (GaN) FETs over Silicon FETs [1] can enable both high efficiency and high frequency operation, thereby making power converters smaller, more efficient and reliable. By using integrated controllers and drivers, the number of components on the driver PCB can be reduced, further miniaturizing the driver. This work focuses on demonstrating a small form factor, high efficiency offline LED driver using GaN FETs with an integrated gate driver and controller circuit implemented on a 0.35μm CMOS process with [3.3V over 15V] voltage handling capability.MIT Energy Initiativ

Ariel - Volume 11 Number 1

Executive Editors Ellen Feldman Leonardo S. Nasca, Jr. Business Managers Barbara L. Davies Martin B. Getzow News Editor Aaron D. Bleznak Features Editor Dave Van Wagoner CAHS Editor Joan M. Greco Editorial Page Editor Samuel Markind Photography Editor Leonardo S. Nasca, Jr. Sports Editor Paul F. Mansfiel