Clinical and genetic analysis of 29 Brazilian patients with Huntington’s disease-like phenotype

Huntington’s disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington’s disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and choreaacanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype. Key words: Huntington’s disease, Huntington’s disease-like, chorea-acanthocytosis, Huntington’s disease-like 2

Observations of the 2019 April 4 Solar Energetic Particle Event at the Parker Solar Probe

A solar energetic particle event was detected by the Integrated Science Investigation of the Sun (IS⊙IS) instrument suite on Parker Solar Probe (PSP) on 2019 April 4 when the spacecraft was inside of 0.17 au and less than 1 day before its second perihelion, providing an opportunity to study solar particle acceleration and transport unprecedentedly close to the source. The event was very small, with peak 1 MeV proton intensities of ~0.3 particles (cm² sr s MeV)⁻¹, and was undetectable above background levels at energies above 10 MeV or in particle detectors at 1 au. It was strongly anisotropic, with intensities flowing outward from the Sun up to 30 times greater than those flowing inward persisting throughout the event. Temporal association between particle increases and small brightness surges in the extreme-ultraviolet observed by the Solar TErrestrial RElations Observatory, which were also accompanied by type III radio emission seen by the Electromagnetic Fields Investigation on PSP, indicates that the source of this event was an active region nearly 80° east of the nominal PSP magnetic footpoint. This suggests that the field lines expanded over a wide longitudinal range between the active region in the photosphere and the corona

Energetic Particle Increases Associated with Stream Interaction Regions

The Parker Solar Probe was launched on 2018 August 12 and completed its second orbit on 2019 June 19 with perihelion of 35.7 solar radii. During this time, the Energetic Particle Instrument-Hi (EPI-Hi, one of the two energetic particle instruments comprising the Integrated Science Investigation of the Sun, IS⊙IS) measured seven proton intensity increases associated with stream interaction regions (SIRs), two of which appear to be occurring in the same region corotating with the Sun. The events are relatively weak, with observed proton spectra extending to only a few MeV and lasting for a few days. The proton spectra are best characterized by power laws with indices ranging from −4.3 to −6.5, generally softer than events associated with SIRs observed at 1 au and beyond. Helium spectra were also obtained with similar indices, allowing He/H abundance ratios to be calculated for each event. We find values of 0.016–0.031, which are consistent with ratios obtained previously for corotating interaction region events with fast solar wind ≤ 600 km s⁻¹. Using the observed solar wind data combined with solar wind simulations, we study the solar wind structures associated with these events and identify additional spacecraft near 1 au appropriately positioned to observe the same structures after some corotation. Examination of the energetic particle observations from these spacecraft yields two events that may correspond to the energetic particle increases seen by EPI-Hi earlier

Free Energy of an Inhomogeneous Superconductor: a Wave Function Approach

A new method for calculating the free energy of an inhomogeneous superconductor is presented. This method is based on the quasiclassical limit (or Andreev approximation) of the Bogoliubov-de Gennes (or wave function) formulation of the theory of weakly coupled superconductors. The method is applicable to any pure bulk superconductor described by a pair potential with arbitrary spatial dependence, in the presence of supercurrents and external magnetic field. We find that both the local density of states and the free energy density of an inhomogeneous superconductor can be expressed in terms of the diagonal resolvent of the corresponding Andreev Hamiltonian, resolvent which obeys the so-called Gelfand-Dikii equation. Also, the connection between the well known Eilenberger equation for the quasiclassical Green's function and the less known Gelfand-Dikii equation for the diagonal resolvent of the Andreev Hamiltonian is established. These results are used to construct a general algorithm for calculating the (gauge invariant) gradient expansion of the free energy density of an inhomogeneous superconductor at arbitrary temperatures.Comment: REVTeX, 28 page

Boundary degrees of freedom in fractional quantum Hall effect: Excitations on common boundary of two samples

Using the Carlip's method we have derived the boundary action for the fermion Chern-Simons theory of quantum Hall effects on a planar region with a boundary. We have computed both the bulk and edge responses of currents to the external electric field. From this we obtain the well-known anomaly relation and the boundary Hall current without introducing any ad hoc assumptions such as the chirality condition. In addition, the edge current on the common boundary of two samples is found to be proportional to the difference between Chern-Simons coupling strengths.Comment: 20 pages, uses revte

Insights from Amphioxus into the Evolution of Vertebrate Cartilage

Central to the story of vertebrate evolution is the origin of the vertebrate head, a problem difficult to approach using paleontology and comparative morphology due to a lack of unambiguous intermediate forms. Embryologically, much of the vertebrate head is derived from two ectodermal tissues, the neural crest and cranial placodes. Recent work in protochordates suggests the first chordates possessed migratory neural tube cells with some features of neural crest cells. However, it is unclear how and when these cells acquired the ability to form cellular cartilage, a cell type unique to vertebrates. It has been variously proposed that the neural crest acquired chondrogenic ability by recruiting proto-chondrogenic gene programs deployed in the neural tube, pharynx, and notochord. To test these hypotheses we examined the expression of 11 amphioxus orthologs of genes involved in neural crest chondrogenesis. Consistent with cellular cartilage as a vertebrate novelty, we find that no single amphioxus tissue co-expresses all or most of these genes. However, most are variously co-expressed in mesodermal derivatives. Our results suggest that neural crest-derived cartilage evolved by serial cooption of genes which functioned primitively in mesoderm

Spin-accumulation and Andreev-reflection in a mesoscopic ferromagnetic wire

The electron transport though ferromagnetic metal-superconducting hybrid devices is considered in the non-equilibrium Green's function formalism in the quasiclassical approximation. Attention if focused on the limit in which the exchange splitting in the ferromagnet is much larger than the superconducting energy gap. Transport properties are then governed by an interplay between spin-accumulation close to the interface and Andreev reflection at the interface. We find that the resistance can either be enhanced or lowered in comparison to the normal case and can have a non-monotonic temperature and voltage dependence. In the non-linear voltage regime electron heating effects may govern the transport properties, leading to qualitative different behaviour than in the absence of heating effects. Recent experimental results on the effect of the superconductor on the conductance of the ferromagnet can be understood by our results for the energy-dependent interface resistance together with effects of spin- accumulation without invoking long range pairing correlations in the ferromagnet.Comment: 15 pages, 12 figures included, submitted to PR

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) less than 100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is less than 100 mg/dL, but when risk is very high, an LDL-C goal of less than 70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C less than 100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is less than 130 mg/dL, but an LDL-C goal less than 100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy

Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines.

"The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) less than 100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is less than 100 mg/dL, but when risk is very high, an LDL-C goal of less than 70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C less than 100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is less than 130 mg/dL, but an LDL-C goal less than 100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.

Energetic Particle Observations from the Parker Solar Probe Using Combined Energy Spectra from the IS⊙IS Instrument Suite

The Integrated Science Investigations of the Sun (IS⊙IS) instrument suite includes two Energetic Particle instruments: EPI-Hi, designed to measure ions from ~1 to 200 MeV nuc⁻¹, and EPI-Lo, designed to measure ions from ~20 to ~15 MeV nuc⁻¹. We present an analysis of eight energetic proton events observed across the energy range of both instruments during Parker Solar Probe's (PSP) first two orbits in order to examine their combined energy spectra. Background corrections are applied to help resolve spectral breaks between the two instruments and are shown to be effective. In doing so we demonstrate that even in the early stages of calibration, IS⊙IS is capable of producing reliable spectral observations across broad energy ranges. In addition to making groundbreaking measurements very near the Sun, IS⊙IS also characterizes energetic particle populations over a range of heliocentric distances inside 1 au. During the first two orbits, IS⊙IS observed energetic particle events from a single corotating interaction region (CIR) at three different distances from the Sun. The events are separated by two Carrington rotations and just 0.11 au in distance; however, the relationship shown between proton intensities and proximity of the spacecraft to the source region shows evidence of the importance of transport effects on observations of energetic particles from CIRs. Future IS⊙IS observations of similar events over larger distances will help disentangle the effects of CIR-related acceleration and transport. We apply similar spectral analyses to the remaining five events, including four that are likely related to stream interaction regions (SIRs) and one solar energetic particle (SEP) event