Alexander disease is a rare disorder of the central nervous system of unknown
etiology. Infants with Alexander disease develop a leukoencephalopathy
with macrocephaly, seizures and psychomotor ...retardation, leading to death
usually within the first decade; patients with juvenile or adult forms typically
experience ataxia, bulbar signs and spasticity, and a more slowly progressive
course. The pathological hallmark of all forms of Alexander disease is the
presence of Rosenthal fibers, cytoplasmic inclusions in astrocytes that contain
the intermediate filament protein GFAP in association with small heat-shock
proteins. We previously found that overexpression of human
GFAP in astrocytes of transgenic mice is fatal and accompanied by the presence
of inclusion bodies indistinguishable from human Rosenthal fibers.
These results suggested that a primary alteration in GFAP may be responsible
for Alexander disease. Sequence analysis of DNA samples from patients representing
different Alexander disease phenotypes revealed that most cases are associated
with non-conservative mutations in the coding region of GFAP. Alexander
disease therefore represents the first example of a primary genetic disorder
of astrocytes, one of the major cell types in the vertebrate CNS.
Summary Background Lowering of blood pressure prevents stroke but optimum target levels to prevent recurrent stroke are unknown. We investigated the effects of different blood-pressure targets on the ...rate of recurrent stroke in patients with recent lacunar stroke. Methods In this randomised open-label trial, eligible patients lived in North America, Latin America, and Spain and had recent, MRI-defined symptomatic lacunar infarctions. Patients were recruited between March, 2003, and April, 2011, and randomly assigned, according to a two-by-two multifactorial design, to a systolic-blood-pressure target of 130–149 mm Hg or less than 130 mm Hg. The primary endpoint was reduction in all stroke (including ischaemic strokes and intracranial haemorrhages). Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov , number NCT 00059306. Findings 3020 enrolled patients, 1519 in the higher-target group and 1501 in the lower-target group, were followed up for a mean of 3·7 (SD 2·0) years. Mean age was 63 (SD 11) years. After 1 year, mean systolic blood pressure was 138 mm Hg (95% CI 137–139) in the higher-target group and 127 mm Hg (95% CI 126–128) in the lower-target group. Non-significant rate reductions were seen for all stroke (hazard ratio 0·81, 95% CI 0·64–1·03, p=0·08), disabling or fatal stroke (0·81, 0·53–1·23, p=0·32), and the composite outcome of myocardial infarction or vascular death (0·84, 0·68–1·04, p=0·32) with the lower target. The rate of intracerebral haemorrhage was reduced significantly (0·37, 0·15–0·95, p=0·03). Treatment-related serious adverse events were infrequent. Interpretation Although the reduction in stroke was not significant, our results support that in patients with recent lacunar stroke, the use of a systolic-blood-pressure target of less than 130 mm Hg is likely to be beneficial. Funding National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS)
Headspace solid-phase microextraction (HS-SPME) was studied for the high-resolution gas chromatographic (HRGC) analysis of esters in wines. Five different SPME fibers were tested and the influence of ...different factors such as temperature and time of desorption, extraction time, extraction technique, stirring, sample and vial volume, sugar and ethanol content were studied and optimised using model solutions. The proposed HS-SPME–GC method is an appropriate technique for the quantitative analysis of esters in dry and sweet white wines.
The mass-spring-damper system has the minimum complexity scenario which characterizes almost all the mechanical vibration phenomena. Also it is well known that a second-order differential equation ...can model its dynamics. However, if the damper has a magnetorheological fluid, then it shows viscoelastic properties in the presence of a magnetic field. Hence the mathematical model that best reflects the dynamics of this system is a fractional order differential equation. Naturally, here the Mittag–Leffler function appears in the analytical solution. Mathematical modeling of the mass-spring-magnetorheological damper mechanical system has been presented here. The main focus of the investigation is to show how the fractional order
γ
changes by varying the viscosity damping coefficient
β
. These observations have been made by varying current intensity in the range of 0.2–2 A. A Helmholtz coil has been used to produce the magnetic field. It is worth mentioning that, this work has a high pedagogical value in the connection of fractional calculus to mechanical vibrations as well as it can be used as a starting point for a more advanced treatment of fractional mechanical oscillations.
The effect of isothermal pre-oxidation treatments on the β-(Ni,Pt)Al + IDZ + René N5 system degradation is reported here. The pre-oxidation treatments were carried out from 900 °C (mostly θ-Al2O3 ...growing conditions) to 1200 °C (mainly α-Al2O3 growing conditions) for 5 h, under an Ar-stream with pO2 = 1 × 10−5 atm. The correlation between the structural, microstructural, and chemical properties of the β-(Ni,Pt)Al BC show that pre-oxidation parameters have an important effect on the multi-elemental counter diffusion phenomena along the BC. Heat treatments performed above 1100 °C resulted in loss of stability of the BC, partially disordering of the β phase promoting the β → β + L10 and β → β + L12 transformations. A significant BC + IDZ thickness increase of 55% at 1200 °C was observed with respect to the as-received specimen resulting in a severe BC degradation. Multi-elemental inward diffusion is the main mechanism responsible for BC degradation at high temperatures.
•BC microstructural degradation is highly dependent on the pre-oxidation temperature.•An unbalanced diffusivity due to TGO formation promotes an excessively TGO/BC-interfacial voids and a BC Pt-enrichment.•The two-sublattice model adequately describes the elemental distribution within the β phase.•A partially disordering and phase transformations β → β + L10 and β → β + L12 take place for pre-oxidation above 1100 °C.
LEMVIDA is a real-world prospective study of 3-year follow-up on quality of life of patients with multiple sclerosis (MS) receiving alemtuzumab in Spain.
This is an interim analysis evaluating the ...baseline characteristics of patients who started alemtuzumab between October 2016-September 2018. For 3 additional subanalysis patients were categorised by baseline EDSS score; time of alemtuzumab initiation during the recruitment period (cohort 1: October 2016-March 2017, cohort 2: April-September 2017, cohort 3: October 2017-March 2018 and cohort 4: April-September 2018); and the presence of highly active MS criteria.
161 patients were analysed: 67.1% female, age 38.7 ± 9.4 years, MS duration 8.5 ± 6.0 years, EDSS 3.3 ± 1.7 and number of relapses in the previous 2 years 1.8 ± 1.3. 48.3% of patients presented gadolinium-enhanced (Gd+) lesions (mean: 5.2 ± 6.9) and 63.1% had received prior treatment with fingolimod or natalizumab. Baseline EDSS scores and number of Gd+ lesions were higher in cohort 1 than in cohort 4 (4.1 ± 1.8 vs 3.2 ± 1.7; P = .040 and 10.9 ± 11.9 vs 4.5 ± 5.7; P = .020). The frequency of prior treatment with fingolimod and natalizumab was lower in cohort 4 (60.6%) than in cohort 1 (70.6%) (comparison between groups not analysed).
Unlike phase 3 studies of alemtuzumab, the patients included in LEMVIDA are older, have a longer duration of MS, higher disability and have received previous immunosuppressants. However, throughout the recruitment period, there is a tendency towards an early beginning of treatment with alemtuzumab, probably due to the evidence of higher effectiveness in the early stages of MS.
Efficacy and toxicity of anthracycline treatment in acute myeloid leukemia (AML) is mediated by reactive oxygen species (ROS). NADPH oxidase is the major endogenous source of ROS and a key mediator ...of oxidative cardiac damage. The impact of NADPH oxidase polymorphisms (CYBA:rs4673, NCF4:rs1883112, RAC2:rs13058338) was evaluated in 225 adult de novo AML patients. Variant alleles of NCF4 and RAC2 were related to higher complete remission (P=0.035, P=0.016), and CYBA homozygous variant showed lower overall survival with recessive model (P=0.045). Anthracycline-induced cardiotoxicity was associated to NCF4 homozygous variant (P=0.012) and CYBA heterozygous genotype (P=0.027). Novel associations were found between variant allele of CYBA and lower lung and gastrointestinal toxicities, and a protective effect in nephrotoxicity and RAC2 homozygous variant. Moreover, RAC2 homozygous variant was related to delayed thrombocytopenia recovery. This study supports the interest of NADPH oxidase polymorphisms regarding efficacy and toxicity of AML induction therapy, in a coherent integrated manner.
We present an analysis of coronal mass ejections (CMEs) observed by the
Heliospheric Imagers
(HIs) onboard NASA’s
Solar Terrestrial Relations Observatory
(STEREO) spacecraft. Between August 2008 and ...April 2014 we identify 273 CMEs that are observed simultaneously, by the HIs on both spacecraft. For each CME, we track the observed leading edge, as a function of time, from both vantage points, and apply the Stereoscopic Self-Similar Expansion (SSSE) technique to infer their propagation throughout the inner heliosphere. The technique is unable to accurately locate CMEs when their observed leading edge passes between the spacecraft; however, we are able to successfully apply the technique to 151, most of which occur once the spacecraft-separation angle exceeds
180
∘
, during solar maximum. We find that using a small half-width to fit the CME can result in inferred acceleration to unphysically high velocities and that using a larger half-width can fail to accurately locate the CMEs close to the Sun because the method does not account for CME over-expansion in this region. Observed velocities from SSSE are found to agree well with single-spacecraft (SSEF) analysis techniques applied to the same events. CME propagation directions derived from SSSE and SSEF analysis agree poorly because of known limitations present in the latter.
Seismic amplifications from offshore to shore Ávila-Carrera, R.; Flores-Guzmán, N.; Olivera-Villaseñor, E. ...
Applied ocean research,
October 2015, 2015-10-00, 20151001, Letnik:
53
Journal Article
Recenzirano
•Boundary Element Method applied to ocean problems. This leads to systems of integral equations. Seismic amplifications due to seismic motions are obtained. Results in frequency domain are presented.
...The objective of this study is to determine numerical estimations of seismic amplifications of waves traveling from offshore to shore considering the effect of sea floor configurations. According to the Boundary Element Method, boundary elements were used to irradiate waves and density force can be determined for each element. From this hypothesis, Huygens’ Principle is implemented since diffracted waves are constructed at the boundary from which they are radiated and this is equivalent to Somigliana's theorem. Application of boundary conditions leads to determine a system of integral equations of Fredholm type of second kind, which is solved by the Gaussian method. Various numerical models were analyzed, a first one was used to validate the proposed formulation and some other models were used to show various ideal sea floor configurations to estimate seismic amplifications. Once the formulation was validated, basic slope configurations were studied for estimating spectra of seismic amplifications for various sea floor materials. In general terms, compressional waves (P-waves) can produce seismic amplifications of the incident wave in the order of 2–5. On the other hand, distortional waves (S-waves) can produce amplifications up to 5.5 times the incident wave. A relevant finding is that the highest seismic amplifications due to an offshore earthquake are always located near the shore-line and not offshore despite the seafloor configuration.
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