Vaccination against COVID-19 reduced the mortality risk of COVID-positive hip fracture patients to baseline levels: the nationwide data-linked IMPACT Protect study.

This nationwide study used data-linked records to assess the effect of COVID-19 vaccination among hip fracture patients. Vaccination was associated with a lower risk of contracting COVID-19 and, among COVID-positive patients, it reduced the mortality risk to that of COVID-negative patients. This provides essential data for future communicable disease outbreaks. PURPOSE: COVID-19 confers a three-fold increased mortality risk among hip fracture patients. The aims were to investigate whether vaccination was associated with: i) lower mortality risk, and ii) lower likelihood of contracting COVID-19 within 30 days of fracture. METHODS: This nationwide cohort study included all patients aged > 50 years that sustained a hip fracture in Scotland between 01/03/20-31/12/21. Data from the Scottish Hip Fracture Audit were collected and included: demographics, injury and management variables, discharge destination, and 30-day mortality status. These variables were linked to government-managed population level records of COVID-19 vaccination and laboratory testing. RESULTS: There were 13,345 patients with a median age of 82.0 years (IQR 74.0-88.0), and 9329/13345 (69.9%) were female. Of 3022/13345 (22.6%) patients diagnosed with COVID-19, 606/13345 (4.5%) were COVID-positive within 30 days of fracture. Multivariable logistic regression demonstrated that vaccinated patients were less likely to be COVID-positive (odds ratio (OR) 0.41, 95% confidence interval (CI) 0.34-0.48, p < 0.001) than unvaccinated patients. 30-day mortality rate was higher for COVID-positive than COVID-negative patients (15.8% vs 7.9%, p < 0.001). Controlling for confounders (age, sex, comorbidity, deprivation, pre-fracture residence), unvaccinated patients with COVID-19 had a greater mortality risk than COVID-negative patients (OR 2.77, CI 2.12-3.62, p < 0.001), but vaccinated COVID19-positive patients were not at increased risk of death (OR 0.93, CI 0.53-1.60, p = 0.783). CONCLUSION: Vaccination was associated with lower COVID-19 infection risk. Vaccinated COVID-positive patients had a similar mortality risk to COVID-negative patients, suggesting a reduced severity of infection. This study demonstrates the efficacy of vaccination in this vulnerable patient group, and presents data that will be valid in the management of future outbreaks.

Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography.

Riboswitches are structural RNA elements that are generally located in the 5' untranslated region of messenger RNA. During regulation of gene expression, ligand binding to the aptamer domain of a riboswitch triggers a signal to the downstream expression platform. A complete understanding of the structural basis of this mechanism requires the ability to study structural changes over time. Here we use femtosecond X-ray free electron laser (XFEL) pulses to obtain structural measurements from crystals so small that diffusion of a ligand can be timed to initiate a reaction before diffraction. We demonstrate this approach by determining four structures of the adenine riboswitch aptamer domain during the course of a reaction, involving two unbound apo structures, one ligand-bound intermediate, and the final ligand-bound conformation. These structures support a reaction mechanism model with at least four states and illustrate the structural basis of signal transmission. The three-way junction and the P1 switch helix of the two apo conformers are notably different from those in the ligand-bound conformation. Our time-resolved crystallographic measurements with a 10-second delay captured the structure of an intermediate with changes in the binding pocket that accommodate the ligand. With at least a 10-minute delay, the RNA molecules were fully converted to the ligand-bound state, in which the substantial conformational changes resulted in conversion of the space group. Such notable changes in crystallo highlight the important opportunities that micro- and nanocrystals may offer in these and similar time-resolved diffraction studies. Together, these results demonstrate the potential of 'mix-and-inject' time-resolved serial crystallography to study biochemically important interactions between biomacromolecules and ligands, including those that involve large conformational changes.

Socioeconomic deprivation status predicts both the incidence and nature of Achilles tendon rupture.

PURPOSE: The aim of this study was to describe the epidemiology of Achilles tendon rupture (ATR) and its relationship with socioeconomic deprivation status (SEDS). The hypothesis was that ATR occurs more frequently in socioeconomically deprived patients. Secondary aims were to determine variations in circumstances of injury between more and less deprived patients. METHODS: A 6-year retrospective review of consecutive patients presenting with ATR was undertaken. The health-board population was defined using governmental population data and SEDS was defined using the Scottish Index of Multiple Deprivation. The primary outcome was an epidemiological description and comparison of incidence in more and less deprived cohorts. Secondary outcomes included reporting of the relationship between SEDS and patient and injury characteristics with univariate and binary logistic regression analyses. RESULTS: There were 783 patients (567 male; 216 female) with ATR. Mean incidence for adults (≥ 18 years) was 18.75/100,000 per year (range 16.56-23.57) and for all ages was 15.26/100,000 per year (range 13.51 to 19.07). Incidence in the least deprived population quintiles (4th and 5th quintiles; 18.07 per 100,000/year) was higher than that in the most deprived quintiles (1st and 2nd; 11.32/100,000 per year; OR 1.60, 95%CI 1.35-1.89; p < 0.001). When adjusting for confounding factors, least deprived patients were more likely to be > 50 years old (OR 1.97; 95%CI 1.24-3.12; p = 0.004), to sustain ATR playing sports (OR 1.72, 95%CI 1.11-2.67; p = 0.02) and in the spring (OR 1.65, 95%CI 1.01-2.70; p = 0.045) and to give a history of preceding tendinitis (OR 4.04, 95%CI 1.49-10.95; p = 0.006). They were less likely to sustain low-energy injuries (OR 0.44, 95%CI 0.23-0.87; p = 0.02) and to be obese (OR 0.25-0.41, 95%CI 0.07-0.90; p ≤ 0.03). CONCLUSIONS: The incidence of ATR was higher in less socioeconomically deprived populations and the hypothesis was therefore rejected. Significant variations in patient and predisposing factors, mechanisms of injury and seasonality were demonstrated between most and least deprived groups, suggesting that circumstances and nature of ATR may vary with SEDS and these are not a homogenous group of injuries. LEVEL OF EVIDENCE: Prognostic Study Level III.

Rate and factors associated with surgical site infection following aseptic revision fixation of orthopaedic trauma injuries.

PURPOSE: The primary aim of this study was to define the rate of infection following revision of fixation for aseptic failure. The secondary aims were to identify factors associated with an infection following revision and patient morbidity following deep infection. METHODS: A retrospective study was undertaken to identify patients who underwent aseptic revision surgery during a 3-year period (2017-2019). Regression analysis was used to identify independent factors associated with SSI. RESULTS: Eighty-six patients were identified that met the inclusion criteria, with a mean age of 53 (range 14-95) years and 48 (55.8%) were female. There were 15 (17%) patients with an SSI post revision surgery (n = 15/86). Ten percent (n = 9) of all revisions acquired a 'deep infection', which carried a high morbidity with a total of 23 operations, including initial revision, being undertaken for these patients as salvage procedures and three progressed to an amputation. Alcohol excess (odds ratio (OR) 1.61, 95% CI 1.01-6.36, p = 0.046) and chronic obstructive pulmonary disease (OR 11.1, 95% CI 1.00-133.3, p = 0.050) were independently associated with an increased risk of SSI. CONCLUSION: Aseptic revision surgery had a high rate of SSI (17%) and deep infection (10%). All deep infections occurred in the lower limb with the majority of these seen in ankle fractures. Alcohol excess and COPD were independent risk factors associated with an SSI and patients with a history of these should be counselled accordingly. LEVEL OF EVIDENCE: Retrospective Case Series, Level IV.

Towards performing high-resolution inelastic X-ray scattering measurements at hard X-ray free-electron lasers coupled with energetic laser drivers.

High-resolution inelastic X-ray scattering is an established technique in the synchrotron community, used to investigate collective low-frequency responses of materials. When fielded at hard X-ray free-electron lasers (XFELs) and combined with high-intensity laser drivers, it becomes a promising technique for investigating matter at high temperatures and high pressures. This technique gives access to important thermodynamic properties of matter at extreme conditions, such as temperature, material sound speed, and viscosity. The successful realization of this method requires the acquisition of many identical laser-pump/X-ray-probe shots, allowing the collection of a sufficient number of photons necessary to perform quantitative analyses. Here, a 2.5-fold improvement in the energy resolution of the instrument relative to previous works at the Matter in Extreme Conditions (MEC) endstation, Linac Coherent Light Source (LCLS), and the High Energy Density (HED) instrument, European XFEL, is presented. Some aspects of the experimental design that are essential for improving the number of photons detected in each X-ray shot, making such measurements feasible, are discussed. A careful choice of the energy resolution, the X-ray beam mode provided by the XFEL, and the position of the analysers used in such experiments can provide a more than ten-fold improvement in the photometrics. The discussion is supported by experimental data on 10 µm-thick iron and 50 nm-thick gold samples collected at the MEC endstation at the LCLS, and by complementary ray-tracing simulations coupled with thermal diffuse scattering calculations.

Digitized adiabatic quantum computing with a superconducting circuit.

Quantum mechanics can help to solve complex problems in physics and chemistry, provided they can be programmed in a physical device. In adiabatic quantum computing, a system is slowly evolved from the ground state of a simple initial Hamiltonian to a final Hamiltonian that encodes a computational problem. The appeal of this approach lies in the combination of simplicity and generality; in principle, any problem can be encoded. In practice, applications are restricted by limited connectivity, available interactions and noise. A complementary approach is digital quantum computing, which enables the construction of arbitrary interactions and is compatible with error correction, but uses quantum circuit algorithms that are problem-specific. Here we combine the advantages of both approaches by implementing digitized adiabatic quantum computing in a superconducting system. We tomographically probe the system during the digitized evolution and explore the scaling of errors with system size. We then let the full system find the solution to random instances of the one-dimensional Ising problem as well as problem Hamiltonians that involve more complex interactions. This digital quantum simulation of the adiabatic algorithm consists of up to nine qubits and up to 1,000 quantum logic gates. The demonstration of digitized adiabatic quantum computing in the solid state opens a path to synthesizing long-range correlations and solving complex computational problems. When combined with fault-tolerance, our approach becomes a general-purpose algorithm that is scalable.

Toward an integrated platform for characterizing laser-driven, isochorically heated plasmas with 1 µm spatial resolution.

Warm dense matter is a region of phase space that is of high interest to multiple scientific communities ranging from astrophysics to inertial confinement fusion. Further understanding of the conditions and properties of this complex state of matter necessitates experimental benchmarking of the current theoretical models. We discuss the development of an x-ray radiography platform designed to measure warm dense matter transport properties at large laser facilities such as the OMEGA Laser Facility. Our platform, Fresnel diffractive radiography, allows for high spatial resolution imaging of isochorically heated targets, resulting in notable diffractive effects at sharp density gradients that are influenced by transport properties such as thermal conductivity. We discuss initial results, highlighting the capabilities of the platform in measuring diffractive features with micrometer-level spatial resolution.

The epidemiology of Achilles tendon re-rupture and associated risk factors: male gender, younger age and traditional immobilising rehabilitation are risk factors.

PURPOSE: The aim of this study was to describe the epidemiology of Achilles tendon re-rupture. Secondary aims were to identify factors predisposing to increased Achilles tendon re-rupture risk, at the time of primary Achilles tendon rupture. METHODS: A retrospective review of all patients with primary Achilles tendon rupture and Achilles tendon re-rupture was undertaken. Two separate databases were compiled: the first included all Achilles tendon re-ruptures presenting during the study period and described epidemiology, mechanisms and nature of the re-rupture; the second was a case-control study analysing differences between patients with primary Achilles tendon rupture during the study period, who did, or did not, go on to develop re-rupture, with minimum review period of 1.5 years. RESULTS: Seven hundred and eighty-three patients (567 males, 216 females) attended with primary Achilles tendon rupture and 48 patients (41 males, 7 females) with Achilles tendon re-rupture. Median time to re-rupture was 98.5 days (IQR 82-122.5), but 8/48 re-ruptures occurred late (range 3 to 50 years) after primary Achilles tendon rupture. Males were affected more commonly (OR = 7.40, 95% CI 0.91-60.15; p = 0.034). Mean Achilles tendon re-rupture incidence was 0.94/100,000/year for all ages and 1.16/100,000/year for adults (≥ 18 years). Age distribution was bimodal for both primary Achilles tendon rupture and re-rupture, peaking in the fifth decade, with secondary peaks in older age. Incidence of re-rupture was higher in less socioeconomically deprived sub-populations (OR = 2.01, 95%CI 1.01-3.97, p = 0.04). The majority of re-ruptures were low-energy injuries. Greater risk of re-rupture was noted for patients with primary rupture aged < 45 years [adjusted odds ratio (aOR) 1.96; p = 0.037] and those treated with traditional cast immobilisation (aOR 2.20; p = 0.050). CONCLUSION: The epidemiology of Achilles tendon re-rupture is described and known trends (e.g. male predilection) are confirmed, while other novel findings are described, including incidence of a small but significant number of late re-ruptures, occurring years after the primary injury and an increased incidence of re-rupture in less socioeconomically deprived patients. Younger age and traditional immobilising cast treatment of primary Achilles tendon rupture were independently associated with Achilles tendon re-rupture. LEVEL OF EVIDENCE: III.

Fetal-placental blood flow and neurodevelopment in childhood: population-based neuroimaging study.

OBJECTIVE: Antenatal Doppler measurements of the fetal umbilical and cerebral circulations can predict perinatal complications; however, it is unclear if subtle variations in antenatal Doppler measurements are associated with long-term neurodevelopmental outcome. In this study, we examined whether antenatal Doppler measurements of the fetal-placental circulation are associated with cognitive and motor abilities and brain morphology in childhood. METHODS: To evaluate differences in long-term sequelae across the continuum of the umbilical and cerebral artery circulations in the general population, we utilized a population-based longitudinal cohort study approach. In women from the Generation R study, we measured second- and third-trimester umbilical artery pulsatility index (UA-PI). Children underwent non-verbal intelligence testing at 4-8 years of age, and at 8-12 years they underwent finger-tapping tests to measure fine motor skills, balance beam tests to measure gross motor skills and brain magnetic resonance imaging. We assessed the relationships between prenatal UA-PI and neurodevelopmental outcome using linear regression. We adjusted for child age and sex, maternal age, education, parity and smoking status. RESULTS: The study sample included 2803 pregnancies. Higher third-trimester UA-PI was associated with poorer fine motor performance (0.41 (95% CI, 0.11-0.70) fewer taps on the finger-tapping test per 1 SD higher UA-PI) and gross motor performance (0.64 (95% CI, 0.20-1.08) fewer steps on the balance beam test per 1 SD higher UA-PI). One SD higher third-trimester UA-PI was also associated with 0.65 (95% CI, 0.04-1.25) points lower intelligence quotient; however, unlike the associations with motor abilities, this finding did not persist after correction for multiple testing. Higher second-trimester UA-PI was associated with smaller brain volume (6.1 (95% CI, 1.0-11.3) cm3 reduction per 1 SD higher UA-PI), but the association did not persist after correction for multiple testing. CONCLUSION: Higher placental vascular resistance may have mild adverse effects on neurodevelopmental outcome at school age. While these effects are subtle at population level, we encourage future research into the role of early circulation in brain development. This information could be used to develop targeted interventions. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

State preservation by repetitive error detection in a superconducting quantum circuit.

Quantum computing becomes viable when a quantum state can be protected from environment-induced error. If quantum bits (qubits) are sufficiently reliable, errors are sparse and quantum error correction (QEC) is capable of identifying and correcting them. Adding more qubits improves the preservation of states by guaranteeing that increasingly larger clusters of errors will not cause logical failure-a key requirement for large-scale systems. Using QEC to extend the qubit lifetime remains one of the outstanding experimental challenges in quantum computing. Here we report the protection of classical states from environmental bit-flip errors and demonstrate the suppression of these errors with increasing system size. We use a linear array of nine qubits, which is a natural step towards the two-dimensional surface code QEC scheme, and track errors as they occur by repeatedly performing projective quantum non-demolition parity measurements. Relative to a single physical qubit, we reduce the failure rate in retrieving an input state by a factor of 2.7 when using five of our nine qubits and by a factor of 8.5 when using all nine qubits after eight cycles. Additionally, we tomographically verify preservation of the non-classical Greenberger-Horne-Zeilinger state. The successful suppression of environment-induced errors will motivate further research into the many challenges associated with building a large-scale superconducting quantum computer.

Mealtime and patient factors associated with meal completion in hospitalised older patients: An exploratory observation study.

AIMS AND OBJECTIVES: To examine mealtime and patient factors associated with meal completion among hospitalised older patients. We also considered contextual factors such as staffing levels and ward communication. BACKGROUND: Sub-optimum nutrition is a modifiable risk factor for hospital associated decline (HAD) in older patients. Yet, the quality of mealtime experiences can be overlooked within ward routinised practice. DESIGN: Cross sectional, descriptive observation study. METHODS: We undertook structured observation of mealtimes examining patient positioning, mealtime set-up and feeding assistance. The outcome was meal completion categorised as 0, 25%, 50%, 75% or 100%. Data were collected on patient characteristics and ward context. We used mixed-effects ordinal regression models to examine patient and mealtime factors associated with higher meal completion producing odds ratios (OR) and 95% confidence intervals (CI). The study was reported as per STROBE guidelines. RESULTS: We included 60 patients with a median age of 82 years (IQR 76-87) and clinical frailty score of 5 IQR (4-6). Of the 279 meals, 51% were eaten completely, 6% three quarters, 15% half, 18% a quarter and 10% were not eaten at all. Mealtime predictors with a weak association with less-meal completion were requiring assistance, special diets, lying in bed, and red tray (indicator of nutrition risk), but were not statistically significant. Significant patient-level factors were higher values for frailty (OR 0.34 [0.11-1.04]) and Malnutrition Universal Screening Tool (OR 0.22 [0.08-0.62]). The average nurse-to-patient ratio was 1:5.5. CONCLUSION: Patient factors were the strongest predictors for meal completion, but mealtime factors had a subtle influence. The nursing teams' capacity to prioritise mealtimes above competing demands is important as part of a comprehensive nutrition strategy. RELEVANCE TO CLINICAL PRACTISE: Nurses are central to optimising nutrition for frail older patients. It requires ward leadership to instil a culture of prioritising assisted mealtimes, improved communication, greater autonomy to tailor nutrition strategies and safe staffing levels.

Observation of topological transitions in interacting quantum circuits.

Topology, with its abstract mathematical constructs, often manifests itself in physics and has a pivotal role in our understanding of natural phenomena. Notably, the discovery of topological phases in condensed-matter systems has changed the modern conception of phases of matter. The global nature of topological ordering, however, makes direct experimental probing an outstanding challenge. Present experimental tools are mainly indirect and, as a result, are inadequate for studying the topology of physical systems at a fundamental level. Here we employ the exquisite control afforded by state-of-the-art superconducting quantum circuits to investigate topological properties of various quantum systems. The essence of our approach is to infer geometric curvature by measuring the deflection of quantum trajectories in the curved space of the Hamiltonian. Topological properties are then revealed by integrating the curvature over closed surfaces, a quantum analogue of the Gauss-Bonnet theorem. We benchmark our technique by investigating basic topological concepts of the historically important Haldane model after mapping the momentum space of this condensed-matter model to the parameter space of a single-qubit Hamiltonian. In addition to constructing the topological phase diagram, we are able to visualize the microscopic spin texture of the associated states and their evolution across a topological phase transition. Going beyond non-interacting systems, we demonstrate the power of our method by studying topology in an interacting quantum system. This required a new qubit architecture that allows for simultaneous control over every term in a two-qubit Hamiltonian. By exploring the parameter space of this Hamiltonian, we discover the emergence of an interaction-induced topological phase. Our work establishes a powerful, generalizable experimental platform to study topological phenomena in quantum systems.

Superconducting quantum circuits at the surface code threshold for fault tolerance.

A quantum computer can solve hard problems, such as prime factoring, database searching and quantum simulation, at the cost of needing to protect fragile quantum states from error. Quantum error correction provides this protection by distributing a logical state among many physical quantum bits (qubits) by means of quantum entanglement. Superconductivity is a useful phenomenon in this regard, because it allows the construction of large quantum circuits and is compatible with microfabrication. For superconducting qubits, the surface code approach to quantum computing is a natural choice for error correction, because it uses only nearest-neighbour coupling and rapidly cycled entangling gates. The gate fidelity requirements are modest: the per-step fidelity threshold is only about 99 per cent. Here we demonstrate a universal set of logic gates in a superconducting multi-qubit processor, achieving an average single-qubit gate fidelity of 99.92 per cent and a two-qubit gate fidelity of up to 99.4 per cent. This places Josephson quantum computing at the fault-tolerance threshold for surface code error correction. Our quantum processor is a first step towards the surface code, using five qubits arranged in a linear array with nearest-neighbour coupling. As a further demonstration, we construct a five-qubit Greenberger-Horne-Zeilinger state using the complete circuit and full set of gates. The results demonstrate that Josephson quantum computing is a high-fidelity technology, with a clear path to scaling up to large-scale, fault-tolerant quantum circuits.

Sustaining global partnerships for simulation integration: lessons from the field.

AIM: A reciprocal partnership between two World Health Organization Collaborating Centers in the Americas region aimed to strengthen nursing and midwifery education through innovative integration of high-fidelity simulation. METHODS/IMPLEMENTATION: Immersion of a visiting scholar in six-week training within a North American nursing school (host) solidified simulation champion designation, upon return at the home institution. Next, two expert nursing faculty implemented a train-the-trainer simulation course on-site. Following evaluation and virtual debriefing, a midwifery faculty visited the host institution for second-round training. CONCLUSION: This ongoing program targets faculty development needs through a strong academic partnership, built upon global awareness and sustainable engagement.

Spectrally tunable chiral Bragg reflectors for on-demand beam generation.

We demonstrate the generation of spectrally tunable phase-dependent wavefronts, using the 2D Airy as the primary test case, via a polymer-stabilized cholesteric liquid crystal (PSCLC) element. Specifically, we use a novel spatial light modulator (SLM) based projection system to photo-align the initial helix angle landscape of the PSCLC so that it imparts the appropriate cubic phase profile to the reflected beam. This element is spectrally selective, with a reflection bandwidth of ≈ 100 nm, and electrically tunable from λ = 530 nm to 760 nm. Under both green and red laser illumination, the element is shown to conditionally form an Airy beam depending on the position of the electrically tailored reflection band. We briefly demonstrate the generality of this approach by producing PSCLC elements which form a computer-generated hologram and a higher-order Mathieu beam.

Diabatic Gates for Frequency-Tunable Superconducting Qubits.

We demonstrate diabatic two-qubit gates with Pauli error rates down to 4.3(2)×10^{-3} in as fast as 18 ns using frequency-tunable superconducting qubits. This is achieved by synchronizing the entangling parameters with minima in the leakage channel. The synchronization shows a landscape in gate parameter space that agrees with model predictions and facilitates robust tune-up. We test both iswap-like and cphase gates with cross-entropy benchmarking. The presented approach can be extended to multibody operations as well.

Fluctuations of Energy-Relaxation Times in Superconducting Qubits.

Superconducting qubits are an attractive platform for quantum computing since they have demonstrated high-fidelity quantum gates and extensibility to modest system sizes. Nonetheless, an outstanding challenge is stabilizing their energy-relaxation times, which can fluctuate unpredictably in frequency and time. Here, we use qubits as spectral and temporal probes of individual two-level-system defects to provide direct evidence that they are responsible for the largest fluctuations. This research lays the foundation for stabilizing qubit performance through calibration, design, and fabrication.

Validation of patient-reported global severity of atopic dermatitis in adults.

BACKGROUND: Atopic dermatitis (AD) is associated with a heterogeneous presentation and clinical course. There is a lack of simple and validated severity assessments that are feasible for clinical practice and epidemiological research. OBJECTIVES: We sought to validate patient-reported global AD severity in adults. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 265). RESULTS: At baseline and follow-up, patient-reported global AD severity significantly correlated with oSCORAD (Spearman ρ = 0.56 and 0.49), SCORAD (0.64 and 0.56), EASI (0.56 and 0.50), BSA (0.52 and 0.45), NRS-itch (0.60 and 0.53), POEM (0.50 and 0.48), and DLQI (0.50 and 0.49) (P < .0001 for all). Patient-reported moderate and severe AD vs mild AD were associated with significantly higher oSCORAD, SCORAD, EASI, BSA, NRS-itch, POEM, and DLQI (P < .0001 for all). There was moderate concordance between patient-reported AD severity (mild, moderate, and severe) and previously developed severity strata for oSCORAD (κ = 0.39), SCORAD (κ = 0.47), EASI (κ = 0.37), NRS-itch (κ = 0.49), POEM (κ = 0.37), and DLQI (κ = 0.40). Among patients with severe disease at baseline, those who reported mild or moderate disease on follow-up had significantly greater absolute reductions of oSCORAD (-23.4/-9.7/-1.8), SCORAD (-33.0/-13.2/-2.3), EASI (-17.1/-9.8/-3.2), BSA (-46%/-15%/-4%), NRS-itch (-5/-2/0), POEM (-5/-2/0), and DLQI (-8/-6/-1) than those who continued to report severe disease (Kruskal-Wallis, P ≤ .0003 for all). CONCLUSIONS: Patient-reported AD severity appears to be sufficiently valid for assessing AD severity in the clinical and epidemiological setting.

Severity strata for five patient-reported outcomes in adults with atopic dermatitis.

BACKGROUND: Several patient-reported outcomes have been used to assess the burden of atopic dermatitis (AD). Some are disease specific, such as the Patient-Oriented Eczema Measure (POEM), while others pertain to itch, for example the numerical rating scale (NRS)-itch, ItchyQoL and 5-D itch, or dermatological disease in general, for example the Dermatology Life Quality Index (DLQI). Development of severity strata is essential for proper interpretability of these assessments. OBJECTIVES: To confirm previously developed strata for POEM, DLQI and raw ItchyQoL, and develop strata for the NRS-itch, mean ItchyQoL and 5-D itch scale for use in adults with AD. METHODS: Self-administered questionnaires were completed by 210 adults with AD in a dermatology practice setting. Strata were selected using an anchoring approach based on patient-reported disease severity. RESULTS: We confirmed the existing strata for POEM (mild 0-7, moderate 8-16, severe 17-28; κ = 0·440), DLQI (mild 0-5, moderate 6-10, severe 11-30; κ = 0·398) and NRS-itch (mild 0-3, moderate 4-6, severe 7-10; κ = 0·499). However, the preferred band for raw ItchyQoL was mild 22-58, moderate 59-74 and severe 75-110 (κ = 0·379) and for mean ItchyQoL, mild 1-2·9, moderate 3·0-3·9, severe 4·0-5·0 (κ = 0·374). The preferred band for 5-D itch scale was mild 0-11, moderate 12-17 and severe 18-25 (κ = 0·331). CONCLUSIONS: Existing strata for POEM and DLQI performed well in adult AD. Previously reported strata for visual analogue scale-itch performed best for NRS-itch. We identified banding for the raw ItchyQoL for our AD population that varies slightly from the banding published for a more heterogeneous population. Finally, we proposed strata for mean ItchyQoL and 5-D itch scale in adult AD.

Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight.

The morphology of micrometre-size particulate matter is of critical importance in fields ranging from toxicology to climate science, yet these properties are surprisingly difficult to measure in the particles' native environment. Electron microscopy requires collection of particles on a substrate; visible light scattering provides insufficient resolution; and X-ray synchrotron studies have been limited to ensembles of particles. Here we demonstrate an in situ method for imaging individual sub-micrometre particles to nanometre resolution in their native environment, using intense, coherent X-ray pulses from the Linac Coherent Light Source free-electron laser. We introduced individual aerosol particles into the pulsed X-ray beam, which is sufficiently intense that diffraction from individual particles can be measured for morphological analysis. At the same time, ion fragments ejected from the beam were analysed using mass spectrometry, to determine the composition of single aerosol particles. Our results show the extent of internal dilation symmetry of individual soot particles subject to non-equilibrium aggregation, and the surprisingly large variability in their fractal dimensions. More broadly, our methods can be extended to resolve both static and dynamic morphology of general ensembles of disordered particles. Such general morphology has implications in topics such as solvent accessibilities in proteins, vibrational energy transfer by the hydrodynamic interaction of amino acids, and large-scale production of nanoscale structures by flame synthesis.