Atomic clocks are vital in a wide array of technologies and experiments, including tests of fundamental physics
. Clocks operating at optical frequencies have now demonstrated fractional stability ...and reproducibility at the 10
level, two orders of magnitude beyond their microwave predecessors
. Frequency ratio measurements between optical clocks are the basis for many of the applications that take advantage of this remarkable precision. However, the highest reported accuracy for frequency ratio measurements has remained largely unchanged for more than a decade
. Here we operate a network of optical clocks based on
Al
(ref.
),
Sr (ref.
) and
Yb (ref.
), and measure their frequency ratios with fractional uncertainties at or below 8 × 10
. Exploiting this precision, we derive improved constraints on the potential coupling of ultralight bosonic dark matter to standard model fields
. Our optical clock network utilizes not just optical fibre
, but also a 1.5-kilometre free-space link
. This advance in frequency ratio measurements lays the groundwork for future networks of mobile, airborne and remote optical clocks that will be used to test physical laws
, perform relativistic geodesy
and substantially improve international timekeeping
.
Unusual tremor syndromes: know in order to recognise Ure, Robert J; Dhanju, Sanveer; Lang, Anthony E ...
Journal of Neurology, Neurosurgery and Psychiatry,
11/2016, Volume:
87, Issue:
11
Journal Article, Book Review
Peer reviewed
Tremor is a common neurological condition in clinical practice; yet, few syndromes are widely recognised and discussed in the literature. As a result, there is an overdiagnosis of well-known causes, ...such as essential tremor. Many important unusual syndromes should be considered in the differential diagnosis of patients with tremor. The objective of this review is to provide broad clinical information to aid in the recognition and treatment of various unusual tremor syndromes in the adult and paediatric populations. The review comprised of a comprehensive online search using PubMed, Ovid database and Google Scholar to identify the available literature for each unusual tremor syndrome. The review includes fragile X-associated tremor/ataxia syndrome, spinocerebellar ataxia type 12, tremors caused by autosomal recessive cerebellar ataxias, myorhythmia, isolated tongue tremor, Wilson's disease, slow orthostatic tremor, peripheral trauma-induced tremor, tardive tremor and rabbit syndrome, paroxysmal tremors (hereditary chin tremor, bilateral high-frequency synchronous discharges, head tremor, limb-shaking transient ischaemic attack), bobble-head doll syndrome, spasmus nutans and shuddering attacks. Rare tremors generally present with an action tremor and a variable combination of postural and kinetic components with resting tremors less frequently seen. The phenomenology of myorhythmia is still vague and a clinical definition is proposed. The recognition of these entities should facilitate the correct diagnosis and guide the physician to a prompt intervention.
Grating magneto-optical traps are an enabling quantum technology for portable metrological devices with ultracold atoms. However, beam diffraction efficiency and angle are affected by wavelength, ...creating a single-optic design challenge for laser cooling in two stages at two distinct wavelengths – as commonly used for loading, e.g., Sr or Yb atoms into optical lattice or tweezer clocks. Here, we optically characterize a wide variety of binary gratings at different wavelengths to find a simple empirical fit to experimental grating diffraction efficiency data in terms of dimensionless etch depth and period for various duty cycles. The model avoids complex 3D light-grating surface calculations, yet still yields results accurate to a few percent across a broad range of parameters. Gratings optimized for two (or more) wavelengths can now be designed in an informed manner suitable for a wide class of atomic species enabling advanced quantum technologies.
ABSTRACT
Objective:
Enteric bacterial pathogens cause diarrheal disease and mortality at significant rates throughout the world, particularly in children younger than 5 years. Our ability to combat ...bacterial pathogens has been hindered by antibiotic resistance, a lack of effective vaccines, and accurate models of infection. With the renewed interest in bacteriophage therapy, we sought to use a novel human intestinal model to investigate the efficacy of a newly isolated bacteriophage against Shigella flexneri.
Methods:
An S. flexneri 2457T‐specific bacteriophage was isolated and assessed through kill curve experiments and infection assays with colorectal adenocarcinoma HT‐29 cells and a novel human intestinal organoid‐derived epithelial monolayer model. In our treatment protocol, organoids were generated from intestinal crypt stem cells, expanded in culture, and seeded onto transwells to establish 2‐dimensional monolayers that differentiate into intestinal cells.
Results:
The isolated bacteriophage efficiently killed S. flexneri 2457T, other S. flexneri strains, and a strain of 2457T harboring an antibiotic resistance cassette. Analyses with laboratory and commensal Escherichia coli strains demonstrated that the bacteriophage was specific to S. flexneri, as observed under co‐culture conditions. Importantly, the bacteriophage prevented both S. flexneri 2457T epithelial cell adherence and invasion in both infection models.
Conclusions:
Bacteriophages offer feasible alternatives to antibiotics for eliminating enteric pathogens, confirmed here by the bacteriophage‐targeted killing of S. flexneri. Furthermore, application of the organoid model has provided important insight into Shigella pathogenesis and bacteriophage‐dependent intervention strategies. The screening platform described herein provides proof‐of‐concept analysis for the development of novel bacteriophage therapies to target antibiotic‐resistant pathogens.
BackgroundHepatocellular carcinoma (HCC) risk-scores may predict HCC in Asian entecavir (ETV)-treated patients. We aimed to study risk factors and performance of risk scores during ETV treatment in ...an ethnically diverse Western population.MethodsWe studied all HBV monoinfected patients treated with ETV from 11 European referral centres within the VIRGIL Network.ResultsA total of 744 patients were included; 42% Caucasian, 29% Asian, 19% other, 10% unknown. At baseline, 164 patients (22%) had cirrhosis. During a median follow-up of 167 (IQR 82–212) weeks, 14 patients developed HCC of whom nine (64%) had cirrhosis at baseline. The 5-year cumulative incidence rate of HCC was 2.1% for non-cirrhotic and 10.9% for cirrhotic patients (p<0.001). HCC incidence was higher in older patients (p<0.001) and patients with lower baseline platelet counts (p=0.02). Twelve patients who developed HCC achieved virologic response (HBV DNA <80 IU/mL) before HCC. At baseline, higher CU-HCC and GAG-HCC, but not REACH-B scores were associated with development of HCC. Discriminatory performance of HCC risk scores was low, with sensitivity ranging from 18% to 73%, and c-statistics from 0.71 to 0.85. Performance was further reduced in Caucasians with c-statistics from 0.54 to 0.74. Predicted risk of HCC based on risk-scores declined during ETV therapy (all p<0.001), but predictive performances after 1 year were comparable to those at baseline.ConclusionsCumulative incidence of HCC is low in patients treated with ETV, but ETV does not eliminate the risk of HCC. Discriminatory performance of HCC risk scores was limited, particularly in Caucasians, at baseline and during therapy.
Background and Aim
The incidence and consequences of flares during first‐line nucleos(t)ide analogue therapy are largely unknown. We aimed to investigate the incidence and outcome of alanine ...aminotransferase (ALT) flares during long‐term entecavir (ETV) in chronic hepatitis B (CHB).
Methods
CHB patients treated with ETV monotherapy from 11 European centers were studied. Flare was defined as > 3× increase in ALT compared with baseline or lowest on‐treatment level and an absolute ALT > 3× ULN. Flares were designated as host‐induced (preceded by hepatitis B virus (HBV)‐DNA decline), virus‐induced (HBV‐DNA increase), or indeterminate (stable HBV‐DNA).
Results
Seven hundred and twenty‐nine patients were treated with ETV for median of 3.5 years. Thirty patients developed a flare with cumulative incidence of 6.3% at year 5. Baseline hepatitis B e antigen (HBeAg)‐positivity (HR 2.84; P = 0.005) and high HBV‐DNA (Hazard ratio (HR) 1.30; P = 0.003) predicted flares. There were 12 (40%) host‐induced, 7 (23%) virus‐induced, and 11 (37%) indeterminate flares. Host‐induced flares occurred earlier than virus‐induced (median: 15 vs 83 weeks; P = 0.027) or indeterminate flares (15 vs 109 weeks; P = 0.011). Host‐induced flares were associated with biochemical remission, and HBeAg (n = 3) and hepatitis B surface antigen (n = 2) seroconversions were exclusively observed among patients with these flares. Virus‐induced flares were associated with ETV resistance (n = 2) and non‐compliance (n = 1).
Conclusion
The incidence of ALT flares during ETV was low in this real‐life cohort. ETV can be safely continued in patients with host‐induced flares. Treatment adherence and drug resistance must be assessed in patients with virus‐induced flares.
Manual materials handling occupations often involve repetitive lifting, lowering, and carrying motions, which can lead to muscular fatigue and/or injury. The risk increases when loads must be worn on ...the body for the entirety of a job shift. Exoskeletons have been developed to assist these types of motions, but require the user to bear the weight of a load through their body. Load carriage exoskeletons have been developed to offload worn mass from the user to the ground through the device structure, but they have had limited success and have not been well studied in manual materials handling tasks. In this paper, we introduce a hip-knee-ankle exoskeleton and two control methods: virtual model control and gravity compensation. We compared the ability of each controller to reduce lower-limb muscle activity during squatting. Because the virtual model controller is tailored to squatting, we hypothesized that it would outperform gravity compensation. Both controllers were able to reduce the activity of major lower-limb muscle groups during squatting when compared to squatting with the exoskeleton turned off. Contrary to our original hypothesis, the gravity compensation controller generally outperformed the virtual model controller, which may have been caused by the gravity compensation controller having more consistent knee torque application and the virtual model controller requiring better per-user tuning and familiarization. These results indicate the efficacy of both controllers in reducing injury risk in the lower limbs during squatting.
We use frequency-comb-based optical two-way time-frequency transfer (O-TWTFT) to measure the optical frequency ratio of state-of-the-art ytterbium and strontium optical atomic clocks separated by a ...1.5-km open-air link. Our free-space measurement is compared to a simultaneous measurement acquired via a noise-cancelled fiber link. Despite nonstationary, ps-level time-of-flight variations in the free-space link, ratio measurements obtained from the two links, averaged over 30.5 hours across six days, agree to 6×10^{−19}, showing that O-TWTFT can support free-space atomic clock comparisons below the 10^{−18} level.
Full text
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CMK, CTK, FMFMET, NUK, UL
The IBM Research Division has developed the Resource Capacity Planning (RCP) Optimizer to support the Workforce Management Initiative (WMI) of IBM. RCP applies supply chain management techniques to ...the problem of planning the needs of IBM for skilled labor in order to satisfy service engagements, such as consulting, application development, or customer support. This paper describes two RCP models and presents two approaches to solving each of them. We also describe the motivation for using one approach over another. The models are built using the Watson Implosion Technology toolkit, which consists of a supply chain model, solvers for analysis and optimization, and an Application Programming Interface (API) for developing a solution. The models that we built solve two core resource planning problems, gap/glut analysis and resource action planning. The gap/glut analysis is similar to material requirements planning (MRP), in which shortages (gaps) and excesses (gluts) of resources are determined on the basis of expected demand. The goal of the resource action planning problem is to determine what resource actions to take in order to fill the gaps and reduce the gluts. The gap/glut analysis engine is currently deployed within the IBM service organization to report gaps and gluts in personnel. PUBLICATION ABSTRACT
Abstract
Commonly used for Parkinson’s disease (PD), deep brain stimulation (DBS) produces marked clinical benefits when optimized. However, assessing the large number of possible stimulation ...settings (i.e., programming) requires numerous clinic visits. Here, we examine whether functional magnetic resonance imaging (fMRI) can be used to predict optimal stimulation settings for individual patients. We analyze 3 T fMRI data prospectively acquired as part of an observational trial in 67 PD patients using optimal and non-optimal stimulation settings. Clinically optimal stimulation produces a characteristic fMRI brain response pattern marked by preferential engagement of the motor circuit. Then, we build a machine learning model predicting optimal vs. non-optimal settings using the fMRI patterns of 39 PD patients with a priori clinically optimized DBS (88% accuracy). The model predicts optimal stimulation settings in unseen datasets: a priori clinically optimized and stimulation-naïve PD patients. We propose that fMRI brain responses to DBS stimulation in PD patients could represent an objective biomarker of clinical response. Upon further validation with additional studies, these findings may open the door to functional imaging-assisted DBS programming.
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