Breaking the Entangling Gate Speed Limit for Trapped-Ion Qubits Using a Phase-Stable Standing Wave.

All laser-driven entangling operations for trapped-ion qubits have hitherto been performed without control of the optical phase of the light field, which precludes independent tuning of the carrier and motional coupling. By placing ^{88}Sr^{+} ions in a λ=674 nm standing wave, whose relative position is controlled to ≈λ/100, we suppress the carrier coupling by a factor of 18, while coherently enhancing the spin-motion coupling. We experimentally demonstrate that the off-resonant carrier coupling imposes a speed limit for conventional traveling-wave Mølmer-Sørensen gates; we use the standing wave to surpass this limit and achieve a gate duration of 15 µs, restricted by the available laser power.

Long-period gratings for monitoring the resin transfer molding of fiber-reinforced polymer composites.

The spectral characteristics of long-period gratings (LPGs) have been researched over the last two decades, and many sensing applications of LPGs have been proposed due to their spectral sensitivity to many surrounding environmental parameters such as the temperature, pressure, and refractive index. However, this sensitivity to many parameters can also be a curse due to cross-sensitivity and the inability to distinguish which environmental parameter is responsible for the LPG's spectral behavior. For the application proposed here-monitoring the progress of a resin flow front, its velocity, and the permeability of the reinforcement mats during the infusion stage of resin transfer molding-the multi-sensitivity of LPGs is a distinct advantage, as it provides the ability to monitor the mold environment at various stages of manufacturing.

Ultraviolet A radiation and COVID-19 deaths in the USA with replication studies in England and Italy.

BACKGROUND: Understanding factors impacting deaths from COVID-19 is of the highest priority. Seasonal variation in environmental meteorological conditions affects the incidence of many infectious diseases and may also affect COVID-19. Ultraviolet (UV) A (UVA) radiation induces release of cutaneous photolabile nitric oxide (NO) impacting the cardiovascular system and metabolic syndrome, both COVID-19 risk factors. NO also inhibits the replication of SARS-CoV2. OBJECTIVES: To investigate the relationship between ambient UVA radiation and COVID-19 deaths. METHODS: COVID-19 deaths at the county level, across the USA, were modelled in a zero-inflated negative-binomial model with a random effect for states adjusting for confounding by demographic, socioeconomic and long-term environmental variables. Only those areas where UVB was too low to induce significant cutaneous vitamin D3 synthesis were modelled. We used satellite-derived estimates of UVA, UVB and temperature and relative humidity. Replication models were undertaken using comparable data for England and Italy. RESULTS: The mortality rate ratio (MRR) in the USA falls by 29% [95% confidence interval (CI) 40% to 15%) per 100 kJ m-2 increase in mean daily UVA. We replicated this in independent studies in Italy and England and estimate a pooled decline in MRR of 32% (95% CI 48% to 12%) per 100 kJ m-2 across the three studies. CONCLUSIONS: Our analysis suggests that higher ambient UVA exposure is associated with lower COVID-19-specific mortality. Further research on the mechanism may indicate novel treatments. Optimized UVA exposure may have population health benefits.

Low-dimensional nano-patterned surface fabricated by direct-write UV-chemically induced geometric inscription technique.

We investigate a nano-patterning process which creates reproducible periodic surface topological features that range in size from ∼100 µm to ∼20 µm. Specifically, we have fabricated multi-layered thin films consisting of germanium/silicon strata on a planar substrate, with each layer having nanometers thickness. The material processing exploits focused 244 nm ultra-violet laser light and an opto-mechanical setup typically applied to the inscription of fiber gratings, and is based upon the well-known material compaction interaction of ultra-violet light with germanium oxides. We show this process can be extended to create arrays of metal nano-antennas by adding a metal overlay to the thin film. This results in arrays with dimensions that span nanometer- to centimeter-length scales. Also, each nano-antenna consists of "nano-blocks." Experimental data are presented that show the UV irradiance dosage used to create these metal nanostructures on D-shaped optical fibers has a direct relationship to their transmission spectral characteristics as plasmonic devices.

Attending a social event and consuming alcohol is associated with changes in serum microRNA: a before and after study in healthy adults.

PURPOSE: Circulating microRNAs represent a reservoir for biomarker discovery. Our objective was to profile the change in human circulating microRNA associated with recreational use of alcohol at a social event. MATERIAL AND METHODS: Blood was collected from healthy volunteers (N = 16) before and after recreational consumption of alcohol (ethanol). Biochemistry, hematology and ethanol measurements were performed. The change in the serum small RNA fraction was quantified by RNA sequencing. RESULTS: Blood ethanol was undetectable at study entry in all subjects [<10 mg/dL]. After consuming alcohol the median concentration was 89 mg/dL [IQR: 71-138. Min-max 20-175]. There were no changes in biochemistry and hematology parameters. Serum RNA sequencing identified 1371 small RNA species (1305 microRNAs). There were significant increases [adjusted p-value <0.05, fold increase 2 or more] in 265 microRNAs, around a fifth of the total [median fold increase 2.3 [IQR: 2.1-2.5; Max: 3.7]]. miR-185-5p decreased following alcohol exposure [adjusted p-value <0.05, fold decrease 2 or more]. CONCLUSIONS: The microRNA composition of human serum is dynamic and environmental factors may have a significant impact. Within its context of use the fold change 'signal' of a microRNA must be large enough to negate the risk of false results due to background 'noise'.

Long-term adverse effects of paracetamol - a review.

Paracetamol (acetaminophen) is the most commonly used drug in the world, with a long record of use in acute and chronic pain. In recent years, the benefits of paracetamol use in chronic conditions has been questioned, notably in the areas of osteoarthritis and lower back pain. Over the same period, concerns over the long-term adverse effects of paracetamol use have increased, initially in the field of hypertension, but more recently in other areas as well. The evidence base for the adverse effects of chronic paracetamol use consists of many cohort and observational studies, with few randomized controlled trials, many of which contradict each other, so these studies must be interpreted with caution. Nevertheless, there are some areas where the evidence for harm is more robust, and if a clinician is starting paracetamol with the expectation of chronic use it might be advisable to discuss these side effects with patients beforehand. In particular, an increased risk of gastrointestinal bleeding and a small (~4 mmHg) increase in systolic blood pressure are adverse effects for which the evidence is particularly strong, and which show a degree of dose dependence. As our estimation of the benefits decreases, an accurate assessment of the harms is ever more important. The present review summarizes the current evidence on the harms associated with chronic paracetamol use, focusing on cardiovascular disease, asthma and renal injury, and the effects of in utero exposure.

Real-time chest-wall-motion tracking by a single optical fibre grating: a prospective method for ventilator triggering.

OBJECTIVE: The ventilators involved in non-invasive mechanical ventilation commonly provide ventilator support via a facemask. The interface of the mask with a patient promotes air leaks that cause errors in the feedback information provided by a pneumatic sensor and hence patient-ventilator asynchrony with multiple negative consequences. Our objective is to test the possibility of using chest-wall motion measured by an optical fibre-grating sensor as a more accurate non-invasive ventilator triggering mechanism. APPROACH: The basic premise of our approach is that the measurement accuracy can be improved by using a triggering signal that precedes pneumatic triggering in the neuro-ventilatory coupling sequence. We propose a technique that uses the measurement of chest-wall curvature by a long-period fibre-grating sensor. The sensor was applied externally to the rib-cage and interrogated in the lateral (edge) filtering scheme. The study was performed on 34 healthy volunteers. Statistical data analysis of the time lag between the fibre-grating sensor and the reference pneumotachograph was preceded by the removal of the unwanted heartbeat signal by wavelet transform processing. MAIN RESULTS: The results show a consistent fibre-grating signal advance with respect to the standard pneumatic signal by (230 ± 100) ms in both the inspiratory and expiratory phases. We further show that heart activity removal yields a tremendous improvement in sensor accuracy by reducing it from 60 ml to 0.3 ml. SIGNIFICANCE: The results indicate that the proposed measurement technique may lead to a more reliable triggering decision. Its imperviousness to air leaks, non-invasiveness, low-cost and ease of implementation offer good prospects for applications in both clinical and homecare ventilation.

Novel thermal annealing methodology for permanent tuning polymer optical fiber Bragg gratings to longer wavelengths.

The Bragg wavelength of a polymer optical fiber Bragg grating can be permanently shifted by utilizing the thermal annealing method. In all the reported fiber annealing cases, the authors were able to tune the Bragg wavelength only to shorter wavelengths, since the polymer fiber shrinks in length during the annealing process. This article demonstrates a novel thermal annealing methodology for permanently tuning polymer optical fiber Bragg gratings to any desirable spectral position, including longer wavelengths. Stretching the polymer optical fiber during the annealing process, the period of Bragg grating, which is directly related with the Bragg wavelength, can become permanently longer. The methodology presented in this article can be used to multiplex polymer optical fiber Bragg gratings at any desirable spectral position utilizing only one phase-mask for their photo-inscription, reducing thus their fabrication cost in an industrial setting.

Carbodiimides as catalysts for the reduction of a cadmium hydride complex.

A rare terminal cadmium hydride complex [(BDI)CdH] (BDI = [{N(2,6-iPr2C6H3)C(Me)}2CH]) has been synthesised from [(BDI)CdCl] and LiEt3BH. The hydride can be reduced to the cadmium(i) dimer, [(BDI)CdCd(BDI)] upon treatment with a catalytic amount of diisopropyl- or dicyclohexylcarbodiimide.

Polymer optical fiber Bragg grating inscription with a single UV laser pulse.

We experimentally demonstrate the first polymer optical fiber Bragg grating inscribed with only one krypton fluoride laser pulse. The device has been recorded in a single-mode poly(methyl methacrylate) optical fiber, with a core doped with benzyl dimethyl ketal for photosensitivity enhancement. One laser pulse with a duration of 15 ns, which provide energy density of 974 mJ/cm2, is adequate to introduce a refractive index change of 0.74×10-4 in the fiber core. After the exposure, the reflectivity of the grating increases for a few minutes following a second order exponential saturation. The produced Bragg grating structure rejects 17.9 dB transmitted power, thus providing 98.4% reflectivity, which is well suited for sensing applications. In addition, we report the importance of the fiber thermal treatment before or after the inscription, showing its effects on the lifetime and quality of the grating structures. Optimizing the irradiation conditions and the material chemical composition, a higher refractive index change in the fiber core is feasible. This demonstration significantly improves the potential for commercial exploitation of the technology.

Real-time kinetic binding studies at attomolar concentrations in solution phase using a single-stage opto-biosensing platform based upon infrared surface plasmons.

Here we present a new generic opto-bio-sensing platform combining immobilised aptamers on an infrared plasmonic sensing device generated by nano-structured thin film that demonstrates amongst the highest index spectral sensitivities of any optical fibre sensor yielding on average 3.4 × 104 nm/RIU in the aqueous index regime (with a figure of merit of 330) This offers a single stage, solution phase, atto-molar detection capability, whilst delivering real-time data for kinetic studies in water-based chemistry. The sensing platform is based upon optical fibre and has the potential to be multiplexed and used in remote sensing applications. As an example of the highly versatile capabilities of aptamer based detection using our platform, purified thrombin is detected down to 50 attomolar concentration using a volume of 1mm3 of solution without the use of any form of enhancement technique. Moreover, the device can detect nanomolar levels of thrombin in a flow cell, in the presence of 4.5% w/v albumin solution. These results are important, covering all concentrations in the human thrombin generation curve, including the problematic initial phase. Finally, selectivity is confirmed using complementary and non-complementary DNA sequences that yield performances similar to those obtained with thrombin.

Gabapentin and pregabalin: do the benefits outweigh the harms?

Gabapentin and pregabalin prescribing in Scotland has increased substantially over recent years. Evidence suggests that prescribers may be advocating the use of these medicines off-label to avoid prescribing opioid analgesics. The evidence to support gabapentin and pregabalin use in non-neuropathic pain disorders indicates they are less effective than several other licensed non-opioid analgesics. Notably, patients may not benefit from gabapentin and pregabalin but remain at risk of adverse drug reactions. Furthermore, greater availability has resulted in increased diversion of gabapentin and pregabalin; creating problems within the opioid misuse population and prison service. As a consequence, both gabapentin and pregabalin may soon be controlled under the Misuse of Drugs Act 1971. Prescribers should be aware of the very limited clinical evidence for use of gabapentin and pregabalin outside their licensed indications, as well as their capacity to do harm.

Hand eczema and steroid-refractory chronic hand eczema in general practice: prevalence and initial treatment.

BACKGROUND: The self-reported annual prevalence of hand eczema (HE) in adults is about 10%. Incidence and prevalence data for HE, chronic HE (CHE) and steroid-refractory CHE (SR-CHE) in physician-attended populations are lacking. OBJECTIVES: To estimate the prevalences of HE, CHE and SR-CHE in a primary-care population using a cross-sectional design; and to estimate the incidence of each and describe initial therapy using a cohort approach. METHODS: The population was all patients in the Clinical Practice Research Datalink for 2000-10, 2005-10 and 2010-11. HE was defined as any of 12 diagnoses (six specific to the hand, six for contact dermatitis). HE became CHE if any of these 12, or three additional diagnoses, occurred 90-365 days after the first HE, and if the patient was prescribed at least one course of potent topical steroids. A patient with CHE was classified as having SR-CHE if they were (i) referred to a dermatologist and/or (ii) prescribed phototherapy, systemic immunomodulators, oral corticosteroids, alitretinoin or acitretin. RESULTS: The 1-year adult prevalence of HE was 0·4%. The period prevalences of SR-CHE for 1, 5 and 10 years in adults were 0·008%, 0·036% and 0·072%, respectively; lifetime estimates were 0·071%, 0·080%, 0·098%. About one-half of cases of CHE were steroid refractory. All conditions were more common in female than in male patients. One-third of HE diagnoses were specific for the hand, the remainder were for contact dermatitis. The majority (62%) of newly diagnosed patients with HE were not prescribed treatment in the 12 months after diagnosis. CONCLUSIONS: Although the prevalence of HE could be 2-3 times higher than reported herein, the proportion of adults seeking medical care for HE is a fraction of those who self-report HE. SR-CHE is rare.

Circulating acetaminophen metabolites are toxicokinetic biomarkers of acute liver injury.

Acetaminophen (paracetamol-APAP) is the most common cause of drug-induced liver injury in the Western world. Reactive metabolite production by cytochrome P450 enzymes (CYP-metabolites) causes hepatotoxicity. We explored the toxicokinetics of human circulating APAP metabolites following overdose. Plasma from patients treated with acetylcysteine (NAC) for a single APAP overdose was analyzed from discovery (n = 116) and validation (n = 150) patient cohorts. In the discovery cohort, patients who developed acute liver injury (ALI) had higher CYP-metabolites than those without ALI. Receiver operator curve (ROC) analysis demonstrated that at hospital presentation CYP-metabolites were more sensitive/specific for ALI than alanine aminotransferase (ALT) activity and APAP concentration (optimal CYP-metabolite receiver operating characteristic area under the curve (ROC-AUC): 0.91 (95% confidence interval (CI) 0.83-0.98); ALT ROC-AUC: 0.67 (0.50-0.84); APAP ROC-AUC: 0.50 (0.33-0.67)). This enhanced sensitivity/specificity was replicated in the validation cohort. Circulating CYP-metabolites stratify patients by risk of liver injury prior to starting NAC. With development, APAP metabolites have potential utility in stratified trials and for refinement of clinical decision-making.

Influenza-attributable burden in United Kingdom primary care.

Influenza is rarely laboratory-confirmed and the outpatient influenza burden is rarely studied due to a lack of suitable data. We used the Clinical Practice Research Datalink (CPRD) and surveillance data from Public Health England in a linear regression model to assess the number of persons consulting UK general practitioners (GP episodes) for respiratory illness, otitis media and antibiotic prescriptions attributable to influenza during 14 seasons, 1995-2009. In CPRD we ascertained influenza vaccination status in each season and risk status (conditions associated with severe influenza outcomes). Seasonal mean estimates of influenza-attributable GP episodes in the UK were 857 996 for respiratory disease including 68 777 for otitis media, with wide inter-seasonal variability. In an average season, 2·4%/0·5% of children aged <5 years and 1·3%/0·1% of seniors aged ⩾75 years had a GP episode for respiratory illness attributed to influenza A/B. Two-thirds of influenza-attributable GP episodes were estimated to result in prescription of antibiotics. These estimates are substantially greater than those derived from clinically reported influenza-like illness in surveillance programmes. Because health service costs of influenza are largely borne in general practice, these are important findings for cost-benefit assessment of influenza vaccination programmes.

Comprehensive microRNA profiling in acetaminophen toxicity identifies novel circulating biomarkers for human liver and kidney injury.

Our objective was to identify microRNA (miRNA) biomarkers of drug-induced liver and kidney injury by profiling the circulating miRNome in patients with acetaminophen overdose. Plasma miRNAs were quantified in age- and sex-matched overdose patients with (N = 27) and without (N = 27) organ injury (APAP-TOX and APAP-no TOX, respectively). Classifier miRNAs were tested in a separate cohort (N = 81). miRNA specificity was determined in non-acetaminophen liver injury and murine models. Sensitivity was tested by stratification of patients at hospital presentation (N = 67). From 1809 miRNAs, 75 were 3-fold or more increased and 46 were 3-fold or more decreased with APAP-TOX. A 16 miRNA classifier model accurately diagnosed APAP-TOX in the test cohort. In humans, the miRNAs with the largest increase (miR-122-5p, miR-885-5p, miR-151a-3p) and the highest rank in the classifier model (miR-382-5p) accurately reported non-acetaminophen liver injury and were unaffected by kidney injury. miR-122-5p was more sensitive than ALT for reporting liver injury at hospital presentation, especially combined with miR-483-3p. A miRNA panel was associated with human kidney dysfunction. In mice, miR-122-5p, miR-151a-3p and miR-382-5p specifically reported APAP toxicity - being unaffected by drug-induced kidney injury. Profiling of acetaminophen toxicity identified multiple miRNAs that report acute liver injury and potential biomarkers of drug-induced kidney injury.

Imaging of cardiovascular risk in patients with Turner's syndrome.

Turner's syndrome is a disorder defined by an absent or structurally abnormal second X chromosome and affects around 1 in 2000 newborn females. The standardised mortality ratio in Turner's syndrome is around three-times higher than in the general female population, mainly as a result of cardiovascular disorders. Most striking is the early age at which Turner's syndrome patients develop the life-threatening complications of cardiovascular disorders compared to the general population. The cardiovascular risk stratification in Turner's syndrome is challenging and imaging is not systematically used. The aim of this article is to review cardiovascular risks in this group of patients and discuss a systematic imaging approach for early identification of cardiovascular disorders in these patients.

Time-dependent variation of fiber Bragg grating reflectivity in PMMA-based polymer optical fibers.

In this Letter, we investigate the effects of viscoelasticity on both the strength and resonance wavelength of two fiber Bragg gratings (FBGs) inscribed in microstructured polymer optical fiber (mPOF) made of undoped PMMA. Both FBGs were inscribed under a strain of 1% in order to increase the material photosensitivity. After the inscription, the strain was released, and the FBGs spectra were monitored. We initially observed a decrease of the reflection down to zero after which it began to increase. After that, strain tests were carried out to confirm the results, and finally the gratings were monitored for a further 120 days, with a stable reflection response being observed beyond 50 days.

Aortic dissection in children and adolescents with Turner syndrome: risk factors and management recommendations.

There is a general lack of awareness of the risk of aortic dissection in Turner syndrome (TS) from both patients with TS and their physicians. Patients often ignore symptoms for up to 24 h before seeking medical advice, significantly increasing their risk of death. A clinical profile of those at risk of dissection is emerging and includes the presence of congenital heart defects, aortic dilatation and hypertension. MRI has revolutionised the visualisation of cardiovascular anatomy in TS but remains underutilised, especially in children and adolescents, and there is currently little guidance on blood pressure (BP) assessment or hypertension management. Children and adolescents with TS at risk of dissection could be easily identified by timely imaging and BP assessment. This would allow medical management or surgical intervention to be put in place to reduce the risk of this major, and often fatal, complication. Since guidance is lacking, we have reviewed the literature on the risk factors for dissection in TS during childhood and adolescence, and make recommendations on the assessment and management of these patients.