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Key Issues in Essential Tremor Genetics Research: Where Are We Now and How Can We Move Forward?
Background: Genetics research is an avenue towards understanding essential tremor (ET). Advances have been made in genetic linkage and association: there are three reported ET susceptibility loci, and mixed but growing data on risk associations. However, causal mutations have not been forthcoming. This disappointing lack of progress has opened productive discussions on challenges in ET and specifically ET genetics research, including fundamental assumptions in the field. Methods: This article reviews the ET genetics literature, results to date, the open questions in ET genetics and the current challenges in addressing them. Results: Several inherent ET features complicate genetic linkage and association studies: high potential phenocopy rates, inaccurate tremor self-reporting, and ET misdiagnoses are examples. Increasing use of direct examination data for subjects, family members, and controls is one current response. Smaller moves towards expanding ET phenotype research concepts into non-tremor features, clinically disputed ET subsets, and testing phenotype features instead of clinical diagnosis against genetic data are gradually occurring. The field has already moved to considering complex trait mechanisms requiring detection of combinations of rare genetic variants. Hypotheses may move further to consider novel mechanisms of inheritance, such as epigenetics. Discussion: It is an exciting time in ET genetics as investigators start moving past assumptions underlying both phenotype and genetics experimental contributions, overcoming challenges to collaboration, and engaging the ET community. Multicenter collaborative efforts comprising rich longitudinal prospective phenotype data and neuropathologic analysis combined with the latest in genetics experimental design and technology will be the next wave in the field
Study of an emergency situation using 2D and 3D simulation models
Safety in motorway tunnels has become a critical issue in the last years, especially after the accident happened in 1999 inside the Mont Blanc tunnel, causing 39 deaths and several dozens of intoxications and wounded people. After this tragic event, the European Union imposed stricter regulations and procedures for
emergency situations inside road tunnels longer than 1000 m. According to this situation, the authors propose the use of M&S (Modeling and Simulation) in order to manage a tunnel evacuation after a fire exploding in consequence to an accident, taking into account a series of significant factors like the road signs position (new criteria have been introduced with new regulation), but also human factors which significantly affect the procedure outcome. First a 2-D simulation model has been developed using Java™ Software, in which the user can analyze the behavior of the people escaping and the dynamics of the fire exploded and, consequently, assess the effectiveness of all the emergency procedures and infrastructures. In particular, regarding the state
variables related to the human behavior, the model takes into account the main aspects of PECS (Physical Emotional Cognitive Social) reference models, in which physical, emotional, cognitive and social factors have to be studied. The model presented in this work is in fact quite similar to the one described by (Schmidt, 2000), called “Adam’s World” where Adam, a primitive man, lives in an environment having food sources where he can replenish his energy level, but also traps and danger points to be avoided in order not to consume his energy faster. The aim of the two models is the same: first of all preserve life and health, but the great difference between Schmidt’s model and the authors’ one is that in Adam’s World the social aspect is missing (Adam live alone in his world), while in the evacuation model social aspects can significantly affect the individual’s decisions. Upstream of the evacuation model, a weighted analysis needs to be considered, in fact the individual has to operate different choices considering several aspects, like health or goods preservation,
familiar aspects, panic and so on. For this reason a suitable methodology has been detected: the Analytic
Hierarchic Process (AHP), implemented by the American mathematician Thomas Saaty, which introduced this
technique for Multi-Criteria Analysis. After the considerations on the individuals behavior based on the results
of the analysis, the evacuation model and its results are described and analyzed in the following sections and, in
the final part of the paper, a description of a 3-D tunnel model devoted to study in particular smoke dynamics is
provided, thus it is possible to evaluate the impact of the smoke on the flow of the people escaping from the tunnel
One VCU Art
Art and creativity are at the core of VCU’s identity and culture. ONE VCU Art envisions a vibrant and diverse public art landscape on the VCU campuses that equals VCU’s national reputation and enhances connections with our urban home of Richmond. VCU’s nationally ranked arts programs as well as its relationship with the city of Richmond allow for opportunity to revive efforts to enhance current and future public art on the two Richmond campuses. This is in conjunction with the goals and priorities set out by the VCU strategic plan, Quest 2025: Together We Transform
Effectiveness of citrate buffer-fluoride mixture in Terumo tubes as an inhibitor of in vitro glycolysis
Introduction: Glycolysis affects glucose determination in vitro. The placement of sample tubes in ice-water slurry with plasma separation within 30 minutes is recommended, or alternatively the use of a glycolysis inhibitor. The aim of our two-steps study was to evaluate which Terumo tube is best for glucose determination in routine clinical setting.
Materials and methods: In the first study, blood from 100 volunteers was collected into lithium heparin (LH), NaF/Na heparin (FH) and NaF/citrate buffer/Na2EDTA (FC-Mixture) tubes. LH sample was treated as recommended and considered as reference, while FH and FC-Mixture samples were aliquoted, maintained at room temperature (RT) for 1, 2 and 4 hours; centrifuged and plasma analysed in triplicate. In the second study, samples from 375 volunteers were collected in LH, FH and FC-Mixture tubes and held at RT before centrifugation from 10 to 340 minutes, depending on each laboratory practice. Samples were analysed in one analytical run.
Results: In the first study, FH glucose concentrations were 5.15 ± 0.66 mmol/L, 5.05 ± 0.65 mmol/L and 5.00 ± 0.65 mmol/L (P < 0.001) in tubes stored at RT for 1, 2 and 4 hours, respectively. Mean biases in all time points exceeded the analytical goal for desirable bias based on biological variation criteria. FC-Mixture glucose concentrations were 5.48 ± 0.65 mmol/L, 5.46 ± 0.6 mmol/L and 5.46 ± 0.64 mmol/L in tubes stored at RT for 1, 2 and 4 hours, respectively. Mean biases for FC-Mixture glucose in all time points reached optimal analytical goals. In the second study, the biases for LH and FH glucose compared to reference FC-Mixture glucose exceeded the preset analytical goals, regardless of the blood collection to centrifugation time interval.
Conclusions: FC-mixture tubes glucose concentrations were preserved up to 4h storage at RT. We confirmed that NaF alone does not allow immediate glycolysis inhibition in real life pre-centrifugation storage conditions (up to 340 minutes). FC-Mixture should be used exclusively for glucose determination in laboratories unable to implement the recommended blood samples’ treatment
Facial paralysis associated with acute otitis media
Acute otitis media with facial paralysis is not a very frequent association. AIM: the goal of the present investigation was to asses the evolution of facial paralysis caused by acute otitis media. STUDY FORMAT: clinical-retrospective. MATERIALS AND METHODS: we studied 40 patients with this association, from a total of 2758 cases of facial paralysis seen during this time in the department of facial nerve disorders. All the patients were clinically assessed and had epidemiological data, prognostics and evolution. RESULTS AND CONCLUSION: the paralysis was of sudden onset in 95% of the cases. Recovery was of 85% for grade I (House-Brackman) and 15% for grade II (House-Brackman). Treatment was clinical, with antibiotics and steroids - yielding good results. In those patients with electrical bad prognosis, facial nerve decompression turned their evolution into a favorable one.A otite média aguda com paralisia facial não é uma associação muito freqüente. OBJETIVO: O objetivo deste trabalho foi avaliar a evolução da paralisia facial decorrente de otite média aguda. FORMA DE ESTUDO: Clínico retrospectivo. MATERIAL E MÉTODO: Foram estudados 40 pacientes com esta associação de patologias, num total de 2758 casos de paralisa facial atendidos neste período no setor de distúrbios do nervo facial. Todos os pacientes foram avaliados clinicamente com dados epidemiológicos, prognósticos e evolutivos. RESULTADOS E CONCLUSÃO: A paralisia foi súbita em 95% dos casos. A recuperação foi de 85% para o grau I (House-Brackman) e 15% para o grau II (House-Brackman). O tratamento foi clínico com antibiótico e corticoterapia com bons resultados. Nos pacientes com mau prognóstico elétrico a descompressão do nervo facial fez com que a evolução fosse favorável.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoUNIFESP, EPM, Depto. de Otorrinolaringologia e Cirurgia de Cabeça e PescoçoSciEL
Ultra-deep Large Binocular Camera U-band Imaging of the GOODS-North Field: Depth vs. Resolution
We present a study of the trade-off between depth and resolution using a
large number of U-band imaging observations in the GOODS-North field
(Giavalisco et al. 2004) from the Large Binocular Camera (LBC) on the Large
Binocular Telescope (LBT). Having acquired over 30 hours of data (315 images
with 5-6 mins exposures), we generated multiple image mosaics, starting with
the best atmospheric seeing images (FWHM 0.8"), which constitute
10% of the total data set. For subsequent mosaics, we added in data with
larger seeing values until the final, deepest mosaic included all images with
FWHM 1.8" (94% of the total data set). From the mosaics, we
made object catalogs to compare the optimal-resolution, yet shallower image to
the lower-resolution but deeper image. We show that the number counts for both
images are 90% complete to . Fainter than
27, the object counts from the optimal-resolution image start to
drop-off dramatically (90% between = 27 and 28 mag), while the deepest
image with better surface-brightness sensitivity ( 32
mag arcsec) show a more gradual drop (10% between 27
and 28 mag). For the brightest galaxies within the GOODS-N field, structure and
clumpy features within the galaxies are more prominent in the
optimal-resolution image compared to the deeper mosaics. Finally, we find - for
220 brighter galaxies with 24 mag - only marginal
differences in total flux between the optimal-resolution and lower-resolution
light-profiles to 32 mag arcsec. In only 10% of
the cases are the total-flux differences larger than 0.5 mag. This helps
constrain how much flux can be missed from galaxy outskirts, which is important
for studies of the Extragalactic Background Light.Comment: 24 pages, 14 figures, submitted to PASP, comments welcom
Red Giant stars in the Large Magellanic Cloud clusters
We present deep J,H,Ks photometry and accurate Color Magnitude Diagrams down
to K ~18.5, for a sample of 13 globular clusters in the Large Magellanic Cloud.
This data set combined with the previous sample of 6 clusters published by our
group gives the opportunity to study the properties of giant stars in clusters
with different ages (ranging from ~80 Myr up to ~3.5 Gyr). Quantitative
estimates of star population ratios (by number and luminosity) in the
Asymptotic Giant Branch, the Red Giant Branch and the He-clump, have been
obtained and compared with theoretical models in the framework of probing the
so-called phase transitions. The AGB contribution to the total luminosity
starts to be significant at ~200 Myr and reaches its maximum at ~5-600 Myr,
when the RGB Phase Transition is starting. At ~900 Myr the full developing of
an extended and well populated RGB has been completed. Both the occurrence of
the AGB and RGB Phase Transitions are sharp events, lasting a few hundreds Myr
only. These empirical results agree very well with the theoretical predictions
of simple stellar population models based on canonical tracks and the
fuel-consumption approach.Comment: 32 pages, 11 figures, accepted to Ap
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