Background
A Task Force was convened by the EFNS/MDS‐ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD.
...Methods
Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations.
Results
For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre‐motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion‐weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of 123IMIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD.
Conclusions
The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role in confirming the diagnosis, and some of them could be possibly used in the near future to identify subjects in a pre‐symptomatic phase of the disease.
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Determining associations between intestinal bacteria and continuously measured physiological outcomes is important for understanding the bacteria-host relationship but is not straightforward since ...abundance data (compositional data) are not normally distributed. To address this issue, we developed a fully Bayesian linear regression model (BRACoD;
B
ayesian
R
egression
A
nalysis of
Co
mpositional
D
ata) with physiological measurements (continuous data) as a function of a matrix of relative bacterial abundances. Bacteria can be classified as operational taxonomic units or by taxonomy (genus, family, etc.). Bacteria associated with the physiological measurement were identified using a Bayesian variable selection method: Stochastic Search Variable Selection. The output is a list of inclusion probabilities (
p
^
) and coefficients that indicate the strength of the association (
β
^
i
n
c
l
u
d
e
d
) for each bacterial taxa. Tests with simulated communities showed that adopting a cut point value of
p
^
≥ 0.3 for identifying included bacteria optimized the true positive rate (TPR) while maintaining a false positive rate (FPR) of ≤ 5%. At this point, the chances of identifying non-contributing bacteria were low and all well-established contributors were included. Comparison with other methods showed that BRACoD (at
p
^
≥ 0.3) had higher precision and a higher TPR than a commonly used center log transformed LASSO procedure (clr-LASSO) as well as higher TPR than an off-the-shelf Spike and Slab method after center log transformation (clr-SS). BRACoD was also less likely to include non-contributing bacteria that merely correlate with contributing bacteria. Analysis of a rat microbiome experiment identified 47 operational taxonomic units that contributed to fecal butyrate levels. Of these, 31 were positively and 16 negatively associated with butyrate. Consistent with their known role in butyrate metabolism, most of these fell within the Lachnospiraceae and Ruminococcaceae. We conclude that BRACoD provides a more precise and accurate method for determining bacteria associated with a continuous physiological outcome compared to clr-LASSO. It is more sensitive than a generalized clr-SS algorithm, although it has a higher FPR. Its ability to distinguish genuine contributors from correlated bacteria makes it better suited to discriminating bacteria that directly contribute to an outcome. The algorithm corrects for the distortions arising from compositional data making it appropriate for analysis of microbiome data.
Dislocation is one of the most common causes of patient and surgeon dissatisfaction following hip replacement and to treat it, the causes must first be understood. Patient factors include age greater ...than 70 years, medical comorbidities, female gender, ligamentous laxity, revision surgery, issues with the abductors, and patient education. Surgeon factors include the annual quantity of procedures and experience, the surgical approach, adequate restoration of femoral offset and leg length, component position, and soft-tissue or bony impingement. Implant factors include the design of the head and neck region, and so-called skirts on longer neck lengths. There should be offset choices available in order to restore soft-tissue tension. Lipped liners aid in gaining stability, yet if improperly placed may result in impingement and dislocation. Late dislocation may result from polyethylene wear, soft-tissue destruction, trochanteric or abductor disruption and weakness, or infection. Understanding the causes of hip dislocation facilitates prevention in a majority of instances. Proper pre-operative planning includes the identification of patients with a high offset in whom inadequate restoration of offset will reduce soft-tissue tension and abductor efficiency. Component position must be accurate to achieve stability without impingement. Finally, patient education cannot be over-emphasised, as most dislocations occur early, and are preventable with proper instructions.
Abstract Cellular microvesicles and nanovesicles (exosomes) are involved in many disease processes and have major potential as biomarkers. However, developments in this area are constrained by ...limitations in the technology available for their measurement. Here we report on the use of fluorescence nanoparticle tracking analysis (NTA) to rapidly size and phenotype cellular vesicles. In this system vesicles are visualized by light scattering using a light microscope. A video is taken, and the NTA software tracks the brownian motion of individual vesicles and calculates their size and total concentration. Using human placental vesicles and plasma, we have demonstrated that NTA can measure cellular vesicles as small as ∼50 nm and is far more sensitive than conventional flow cytometry (lower limit ∼300 nm). By combining NTA with fluorescence measurement we have demonstrated that vesicles can be labeled with specific antibody-conjugated quantum dots, allowing their phenotype to be determined. From the Clinical Editor The authors of this study utilized fluorescence nanoparticle tracking analysis (NTA) to rapidly size and phenotype cellular vesicles, demonstrating that NTA is far more sensitive than conventional flow cytometry.
We have conducted a Galactic plane survey of methanol masers at 6668 MHz using a seven-beam receiver on the Parkes telescope. Here we present results from the first part, which provides sensitive ...unbiased coverage of a large region around the Galactic Centre. Details are given for 183 methanol maser sites in the longitude range 345° through the Galactic Centre to 6°. Within 6° of the Galactic Centre, we found 88 maser sites, of which more than half (48) are new discoveries. The masers are confined to a narrow Galactic latitude range, indicative of many sources at the Galactic Centre distance and beyond, and confined to a thin disc population; there is no high-latitude population that might be ascribed to the Galactic bulge. Within 2° of the Galactic Centre the maser velocities all lie between −60 and +77 km s−1, a range much smaller than the 540 km s−1 range observed in CO. Elsewhere, the maser with highest positive velocity (+107 km s−1) occurs, surprisingly, near longitude 355° and is probably attributable to the Galactic bar. The maser with the most negative velocity (−127 km s−1) is near longitude 346°, within the longitude–velocity locus of the near side of the ‘3-kpc arm’. It has the most extreme velocity of a clear population of masers associated with the near and far sides of the 3-kpc arm. Closer to the Galactic Centre the maser space density is generally low, except within 0.25 kpc of the Galactic Centre itself, the ‘Galactic Centre zone’, where it is 50 times higher, which is hinted at by the longitude distribution, and confirmed by the unusual velocities.
Carotid-artery stenting and carotid endarterectomy are both options for treating carotid-artery stenosis, an important cause of stroke.
We randomly assigned patients with symptomatic or asymptomatic ...carotid stenosis to undergo carotid-artery stenting or carotid endarterectomy. The primary composite end point was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke within 4 years after randomization.
For 2502 patients over a median follow-up period of 2.5 years, there was no significant difference in the estimated 4-year rates of the primary end point between the stenting group and the endarterectomy group (7.2% and 6.8%, respectively; hazard ratio with stenting, 1.11; 95% confidence interval, 0.81 to 1.51; P=0.51). There was no differential treatment effect with regard to the primary end point according to symptomatic status (P=0.84) or sex (P=0.34). The 4-year rate of stroke or death was 6.4% with stenting and 4.7% with endarterectomy (hazard ratio, 1.50; P=0.03); the rates among symptomatic patients were 8.0% and 6.4% (hazard ratio, 1.37; P=0.14), and the rates among asymptomatic patients were 4.5% and 2.7% (hazard ratio, 1.86; P=0.07), respectively. Periprocedural rates of individual components of the end points differed between the stenting group and the endarterectomy group: for death (0.7% vs. 0.3%, P=0.18), for stroke (4.1% vs. 2.3%, P=0.01), and for myocardial infarction (1.1% vs. 2.3%, P=0.03). After this period, the incidences of ipsilateral stroke with stenting and with endarterectomy were similarly low (2.0% and 2.4%, respectively; P=0.85).
Among patients with symptomatic or asymptomatic carotid stenosis, the risk of the composite primary outcome of stroke, myocardial infarction, or death did not differ significantly in the group undergoing carotid-artery stenting and the group undergoing carotid endarterectomy. During the periprocedural period, there was a higher risk of stroke with stenting and a higher risk of myocardial infarction with endarterectomy. (ClinicalTrials.gov number, NCT00004732.)
Cockayne syndrome (CS) is a devastating neurodevelopmental disorder, with growth abnormalities, progeriod features, and sun sensitivity. CS is typically considered to be a DNA repair disorder, since ...cells from CS patients have a defect in transcription-coupled nucleotide excision repair (TC-NER). However, cells from UV-sensitive syndrome patients also lack TC-NER, but these patients do not suffer from the neurologic and other abnormalities that CS patients do. Also, the neurologic abnormalities that affect CS patients (CS neurologic disease) are qualitatively different from those seen in NER-deficient XP patients. Therefore, the TC-NER defect explains the sun sensitive phenotype common to both CS and UVsS, but cannot explain CS neurologic disease. However, as CS neurologic disease is of much greater clinical significance than the sun sensitivity, there is a pressing need to understand its molecular basis. While there is evidence for defective repair of oxidative DNA damage and mitochondrial abnormalities in CS cells, here I propose that the defects in transcription by both RNA polymerases I and II that have been documented in CS cells provide a better explanation for many of the severe growth and neurodevelopmental defects in CS patients than defective DNA repair. The implications of these ideas for interpreting results from mouse models of CS, and for the development of treatments and therapies for CS patients are discussed.
THE DARK ENERGY CAMERA Flaugher, B.; Diehl, H. T.; Honscheid, K. ...
The Astronomical journal,
11/2015, Letnik:
150, Številka:
5
Journal Article
Recenzirano
Odprti dostop
ABSTRACT The Dark Energy Camera is a new imager with a 2 2 diameter field of view mounted at the prime focus of the Victor M. Blanco 4 m telescope on Cerro Tololo near La Serena, Chile. The camera ...was designed and constructed by the Dark Energy Survey Collaboration and meets or exceeds the stringent requirements designed for the wide-field and supernova surveys for which the collaboration uses it. The camera consists of a five-element optical corrector, seven filters, a shutter with a 60 cm aperture, and a charge-coupled device (CCD) focal plane of 250 m thick fully depleted CCDs cooled inside a vacuum Dewar. The 570 megapixel focal plane comprises 62 2k × 4k CCDs for imaging and 12 2k × 2k CCDs for guiding and focus. The CCDs have 15 m × 15 m pixels with a plate scale of 0 263 pixel−1. A hexapod system provides state-of-the-art focus and alignment capability. The camera is read out in 20 s with 6-9 electron readout noise. This paper provides a technical description of the camera's engineering, construction, installation, and current status.
We present a multi-messenger measurement of the Hubble constant H0 using the binary-black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy ...Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in , which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range 20, 140 km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of 10, 220 km s−1 Mpc−1, we find (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H0.
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