1,163 research outputs found
Fiber-Flux Diffusion Density for White Matter Tracts Analysis: Application to Mild Anomalies Localization in Contact Sports Players
We present the concept of fiber-flux density for locally quantifying white
matter (WM) fiber bundles. By combining scalar diffusivity measures (e.g.,
fractional anisotropy) with fiber-flux measurements, we define new local
descriptors called Fiber-Flux Diffusion Density (FFDD) vectors. Applying each
descriptor throughout fiber bundles allows along-tract coupling of a specific
diffusion measure with geometrical properties, such as fiber orientation and
coherence. A key step in the proposed framework is the construction of an FFDD
dissimilarity measure for sub-voxel alignment of fiber bundles, based on the
fast marching method (FMM). The obtained aligned WM tract-profiles enable
meaningful inter-subject comparisons and group-wise statistical analysis. We
demonstrate our method using two different datasets of contact sports players.
Along-tract pairwise comparison as well as group-wise analysis, with respect to
non-player healthy controls, reveal significant and spatially-consistent FFDD
anomalies. Comparing our method with along-tract FA analysis shows improved
sensitivity to subtle structural anomalies in football players over standard FA
measurements
Halo score (temporal artery, its branches and axillary artery) as a diagnostic, prognostic and disease monitoring tool for Giant Cell Arteritis (GCA)
Background
Giant cell arteritis (GCA) is a common large vessel vasculitis of the elderly, often associated with sight loss. Glucocorticoids (GC remain the mainstay of treatment, although biologic treatments have been approved. Biomarkers predicting disease severity, relapse rates and damage are lacking in GCA.
EULAR recommends ultrasound (US) as the first investigation for suspected GCA. The cardinal US finding, a non-compressible halo, is currently categorised as either negative or positive. However, the extent and severity of this finding may vary.
In this study, we hypothesise whether the extent and severity of the halo sign [calculated as a single composite Halo score (HS)] of temporal and axillary arteries may be of diagnostic, prognostic and monitoring importance; whether baseline HS is linked to disease outcomes, relapses and damage; whether HS can stratify GCA patients for individual treatment needs; whether HS can function as an objective monitoring tool during follow up.
Methods
This is a prospective, observational study. Suspected GCA Participants will be selected from the GCA FTC at the participating centres in the UK. Informed consent will be obtained, and patients managed as part of standard care. Patients with GCA will have HS (temporal and axillary arteries) measured at baseline and months 1,3,6 and 12 long with routine clinical assessments, blood sampling and patient-reported outcomes (EQ5D). Non-GCA patients will be discharged back to the referral team and will have a telephone interview in 6 months.
We aim to recruit 272 suspected GCA referrals which should yield 68 patients (25% of referrals) with confirmed GCA. The recruitment will be completed in 1 year with an estimated total study period of 24 months.
Discussion
The identification of prognostic factors in GCA is both timely and needed. A prognostic marker, such as the HS, could help to stratify GCA patients for an appropriate treatment regimen. Tocilizumab, an IL-6R blocking agent, switches off the acute phase response (C-Reactive Protein), making it difficult to measure the disease activity. Therefore, an independent HS, and changes in that score during treatment and follow-up, maybe a more objective measure of response compare to patient-reported symptoms and clinical assessment alone
HL-1 cells express an inwardly rectifying K+ current activated via muscarinic receptors comparable to that in mouse atrial myocytes
An inwardly rectifying K^+ current is present in atrial cardiac myocytes that is activated by acetylcholine (I_{KACh}). Physiologically, activation of the current in the SA node is important in slowing the heart rate with increased parasympathetic tone. It is a paradigm for the direct regulation of signaling effectors by the Gβγ G-protein subunit. Many questions have been addressed in heterologous expression systems with less focus on the behaviour in native myocytes partly because of the technical difficulties in undertaking comparable studies in native cells. In this study, we characterise a potassium current in the atrial-derived cell line HL-1. Using an electrophysiological approach, we compare the characteristics of the potassium current with those in native atrial cells and in a HEK cell line expressing the cloned Kir3.1/3.4 channel. The potassium current recorded in HL-1 is inwardly rectifying and activated by the muscarinic agonist carbachol. Carbachol-activated currents were inhibited by pertussis toxin and tertiapin-Q. The basal current was time-dependently increased when GTP was substituted in the patch-clamp pipette by the non-hydrolysable analogue GTPγS. We compared the kinetics of current modulation in HL-1 with those of freshly isolated atrial mouse cardiomyocytes. The current activation and deactivation kinetics in HL-1 cells are comparable to those measured in atrial cardiomyocytes. Using immunofluorescence, we found GIRK4 at the membrane in HL-1 cells. Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch
A perspective on using experiment and theory to identify design principles in dye-sensitized solar cells
Dye-sensitized solar cells (DSCs) have been the subject of wide-ranging studies for many
years because of their potential for large-scale manufacturing using roll-to-roll processing
allied to their use of earth abundant raw materials. Two main challenges exist for DSC
devices to achieve this goal; uplifting device efficiency from the 12 to 14% currently
achieved for laboratory-scale ‘hero’ cells and replacement of the widely-used liquid
electrolytes which can limit device lifetimes. To increase device efficiency requires optimized
dye injection and regeneration, most likely from multiple dyes while replacement
of liquid electrolytes requires solid charge transporters (most likely hole transport materials
– HTMs). While theoretical and experimental work have both been widely applied to
different aspects of DSC research, these approaches are most effective when working in
tandem. In this context, this perspective paper considers the key parameters which
influence electron transfer processes in DSC devices using one or more dye molecules
and how modelling and experimental approaches can work together to optimize electron
injection and dye regeneration.
This paper provides a perspective that theory and experiment are best used in tandem to study
DSC device
The role of magnetic anisotropy in the Kondo effect
In the Kondo effect, a localized magnetic moment is screened by forming a
correlated electron system with the surrounding conduction electrons of a
non-magnetic host. Spin S=1/2 Kondo systems have been investigated extensively
in theory and experiments, but magnetic atoms often have a larger spin. Larger
spins are subject to the influence of magnetocrystalline anisotropy, which
describes the dependence of the magnetic moment's energy on the orientation of
the spin relative to its surrounding atomic environment. Here we demonstrate
the decisive role of magnetic anisotropy in the physics of Kondo screening. A
scanning tunnelling microscope is used to simultaneously determine the
magnitude of the spin, the magnetic anisotropy and the Kondo properties of
individual magnetic atoms on a surface. We find that a Kondo resonance emerges
for large-spin atoms only when the magnetic anisotropy creates degenerate
ground-state levels that are connected by the spin flip of a screening
electron. The magnetic anisotropy also determines how the Kondo resonance
evolves in a magnetic field: the resonance peak splits at rates that are
strongly direction dependent. These rates are well described by the energies of
the underlying unscreened spin states.Comment: 14 pages, 4 figures, published in Nature Physic
The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation
Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters
Role of the halo sign in the assessment of giant cell arteritis: a systematic review and meta-analysis
Objectives This systematic review and meta-analysis aimed to evaluate the diagnostic value of the halo sign in the assessment of GCA.
Methods A systematic literature review was performed using MEDLINE, EMBASE and Cochrane central register databases up to August 2020. Studies informing on the sensitivity and specificity of the US halo sign for GCA (index test) were selected. Studies with a minimum of five participants were included. Study articles using clinical criteria, imaging such as PET-CT and/or temporal artery biopsy (TAB) as the reference standards were selected. Meta-analysis was conducted with a bivariate model.
Results The initial search yielded 4023 studies. Twenty-three studies (patients n = 2711) met the inclusion criteria. Prospective (11 studies) and retrospective (12 studies) studies in academic and non-academic centres were included. Using clinical diagnosis as the standard (18 studies) yielded a pooled sensitivity of 67% (95% CI: 51, 80) and a specificity of 95% (95% CI: 89, 98%). This gave a positive and negative likelihood ratio for the diagnosis of GCA of 14.2 (95% CI: 5.7, 35.5) and 0.375 (95% CI: 0.22, 0.54), respectively. Using TAB as the standard (15 studies) yielded a pooled sensitivity of 63% (95% CI: 50, 75) and a specificity of 90% (95% CI: 81, 95).
Conclusion The US halo sign is a sensitive and specific approach for GCA assessment and plays a pivotal role in diagnosis of GCA in routine clinical practice
Оценивание финансово-экономической безопасности предприятий молокоперерабатывающей отрасли
The essence of the concept “financial and economic security of the enterprise” is
covered. Methodological approaches to the enterprise financial and economic security evaluation
are considered, enabling the method of index numberrating score of the enterprise financial and
economic security to be found. Dynamics of milk anddairy production in Ukraine has been studied.
Ukrainian regions leading in liquid processed milk production have been identified. Dynamics of
milk and dairy production per man has been analyzed which allowed to find out the annual
increase in demand per man. Integrated index of the dairy enterprise financial and economic
security has been evaluated. As a result, the ways to increase the managerial efficiency of financial
and economic security of the following enterprises:PJSC "Dubnomoloko", PJSC "Kupyans'ki milk
canning plant", PJSC the "Yagotyns'ki creamery", PJSC the "Pervomais'ki milk canning plant" are
offered.У статті розкрито сутність поняття фінансово-економічної безпеки
підприємства. Розглянуто методичні підходи щодо оцінювання фінансово-економічної
безпеки підприємства, що дозволило виявити підхід рейтингової оцінки показника
фінансово-економічної безпеки підприємства. Досліджено динаміку виробництва молока та
молочних продуктів України. Виявити області України, які є лідерами з виробництва молока
рідкого обробленого. Проаналізовано динаміку виробництва молока та молочних продуктів
на одну особу, що дозволило встановити щорічне зростання попиту на одну особу.
Визначено підприємства молокопереробної галузі. Проведено оцінку інтегрального
показника фінансово-економічної безпеки підприємств молокопереробної галузі. За
результатами оцінки запропоновано шляхи підвищення ефективності управління фінансово-економічної безпеки таких підприємств, як: ПАТ «Дубномолоко», ПАТ «Куп’янський
молочноконсервний комбінат», ПАТ «Яготинський маслозавод», ПАТ «Первомайський
молочноконсервний комбінат».В статье раскрыто сущность понятия финансово-экономическая
безопасность предприятия. Рассмотрено методические подходы относительно оценивания
финансово-экономической безопасности предприятия, что позволило выявить поход
рейтинговой оценки показателя финансово-экономической безопасности предприятия.
Исследовано динамику производства молока и молочных продуктов Украины. Выявлены
области Украины, которые являются лидерами по производству молока жидкого
обработанного. Проанализировано динамику производства молока и молочных продуктов на
одного человека, что позволило установить ежегодный рост спроса на одного человека.
Определены предприятия молокоперерабатывающей отрасли. Проведена оценка
интегрального показателя финансово-экономической безопасности предприятий
молокоперерабатывающей отрасли. По результатам оценки предложены пути повышения
эффективности управления финансово-экономической безопасности таких предприятий,
как: ПАО «Дубномолоко», ПАО «Купянский молочноконсервный комбинат», ПАО
«Яготинский маслозавод», ПАО «Первомайский молочноконсервный комбинат»
Flavor Physics in an SO(10) Grand Unified Model
In supersymmetric grand-unified models, the lepton mixing matrix can possibly
affect flavor-changing transitions in the quark sector. We present a detailed
analysis of a model proposed by Chang, Masiero and Murayama, in which the
near-maximal atmospheric neutrino mixing angle governs large new b -> s
transitions. Relating the supersymmetric low-energy parameters to seven new
parameters of this SO(10) GUT model, we perform a correlated study of several
flavor-changing neutral current (FCNC) processes. We find the current bound on
B(tau -> mu gamma) more constraining than B(B -> X_s gamma). The LEP limit on
the lightest Higgs boson mass implies an important lower bound on tan beta,
which in turn limits the size of the new FCNC transitions. Remarkably, the
combined analysis does not rule out large effects in B_s-B_s-bar mixing and we
can easily accomodate the large CP phase in the B_s-B_s-bar system which has
recently been inferred from a global analysis of CDF and DO data. The model
predicts a particle spectrum which is different from the popular Constrained
Minimal Supersymmetric Standard Model (CMSSM). B(tau -> mu gamma) enforces
heavy masses, typically above 1 TeV, for the sfermions of the degenerate first
two generations. However, the ratio of the third-generation and
first-generation sfermion masses is smaller than in the CMSSM and a (dominantly
right-handed) stop with mass below 500 GeV is possible.Comment: 44 pages, 5 figures. Footnote and references added, minor changes,
Fig. 2 corrected; journal versio
Genetics of callous-unemotional behavior in children
Callous-unemotional behavior (CU) is currently under consideration as a subtyping index for conduct disorder diagnosis. Twin studies routinely estimate the heritability of CU as greater than 50%. It is now possible to estimate genetic influence using DNA alone from samples of unrelated individuals, not relying on the assumptions of the twin method. Here we use this new DNA method (implemented in a software package called Genome-wide Complex Trait Analysis, GCTA) for the first time to estimate genetic influence on CU. We also report the first genome-wide association (GWA) study of CU as a quantitative trait. We compare these DNA results to those from twin analyses using the same measure and the same community sample of 2,930 children rated by their teachers at ages 7, 9 and 12. GCTA estimates of heritability were near zero, even though twin analysis of CU in this sample confirmed the high heritability of CU reported in the literature, and even though GCTA estimates of heritability were substantial for cognitive and anthropological traits in this sample. No significant associations were found in GWA analysis, which, like GCTA, only detects additive effects of common DNA variants. The phrase ‘missing heritability’ was coined to refer to the gap between variance associated with DNA variants identified in GWA studies versus twin study heritability. However, GCTA heritability, not twin study heritability, is the ceiling for GWA studies because both GCTA and GWA are limited to the overall additive effects of common DNA variants, whereas twin studies are not. This GCTA ceiling is very low for CU in our study, despite its high twin study heritability estimate. The gap between GCTA and twin study heritabilities will make it challenging to identify genes responsible for the heritability of CU
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