ForMAX - a beamline for multiscale and multimodal structural characterization of hierarchical materials.

The ForMAX beamline at the MAX IV Laboratory provides multiscale and multimodal structural characterization of hierarchical materials in the nanometre to millimetre range by combining small- and wide-angle X-ray scattering with full-field microtomography. The modular design of the beamline is optimized for easy switching between different experimental modalities. The beamline has a special focus on the development of novel fibrous materials from forest resources, but it is also well suited for studies within, for example, food science and biomedical research.

Increasing drug-related mortality rates over the last decade in Scotland are not just due to an ageing cohort: A retrospective longitudinal cohort study.

BACKGROUND: In Europe, North America, and Australia, mortality due to drug-related (DR) causes amongst people who inject drugs (PWID) is a major issue. Our objective was to characterise temporal trends in DR mortality rates in a large cohort of PWID in Scotland over the past decade, all of whom had been diagnosed with hepatitis C virus (HCV) infection, and to investigate factors associated with DR mortality. METHODS: Retrospective longitudinal cohort study linking Scotland's national HCV Diagnosis Database and deaths registry. The study cohort consisted of all individuals with likely injection drug use-related route of HCV acquisition, who had been diagnosed with HCV between 1991 and 2018, and were alive and aged under 65 years on 1 January 2009. We used Lexis expansion to adjust for ageing cohort effects and calculated the mortality rate from an underlying/contributing DR cause over the period 2009-2018. We fitted Poisson regression models to estimate the temporal trend adjusting for attained age, sex, referral setting, region, and viraemic status at baseline. RESULTS: Amongst the study population (n = 35,065; 236,914 person-years), a total of 1900 DR deaths occurred; the DR mortality rate increased from 5.6/1000 [101 deaths] in 2009 to 12.4/1000 [342] person-years in 2018. Increasing trends were observed for all age-groups except 55-64 years. The overall DR mortality rate was highest for referrals for HCV testing from prison (11.0/1000) and hospital settings (10.0/1000). Mortality increased with calendar time period, with significantly raised adjusted rate ratios (RRs) from 2015 (RR=1.40, 95% CI:1.16-1.69) to 2018 (RR=2.23, 95% CI:1.88-2.64), compared with 2011-2012, for older age (35-44: RR=1.37, 95% CI:1.20-1.56; 45-54: RR=1.32, CI:1.14-1.53) compared with <35 years, for persons diagnosed with HCV since 2009 (RR=1.34, 95% CI:1.21-1.49), and for prison and hospital referrals (RRs of 1.30, 1.37) compared with GP referrals. CONCLUSION: Increasing DR mortality rates in Scotland over the past decade are not just due to an ageing cohort. Harm reduction services will likely need to expand and adapt to reverse the recent upward trends in DR mortality in PWID.

Tracking capsule activation and crack healing in a microcapsule-based self-healing polymer.

Structural polymeric materials incorporating a microencapsulated liquid healing agent demonstrate the ability to autonomously heal cracks. Understanding how an advancing crack interacts with the microcapsules is critical to optimizing performance through tailoring the size, distribution and density of these capsules. For the first time, time-lapse synchrotron X-ray phase contrast computed tomography (CT) has been used to observe in three-dimensions (3D) the dynamic process of crack growth, microcapsule rupture and progressive release of solvent into a crack as it propagates and widens, providing unique insights into the activation and repair process. In this epoxy self-healing material, 150 µm diameter microcapsules within 400 µm of the crack plane are found to rupture and contribute to the healing process, their discharge quantified as a function of crack propagation and distance from the crack plane. Significantly, continued release of solvent takes place to repair the crack as it grows and progressively widens.

The incidence of symptomatic infection with influenza virus in the Netherlands 2011/2012 through 2016/2017, estimated using Bayesian evidence synthesis.

Due to differences in the circulation of influenza viruses, distribution and antigenic drift of A subtypes and B lineages, and susceptibility to infection in the population, the incidence of symptomatic influenza infection can vary widely between seasons and age-groups. Our goal was to estimate the symptomatic infection incidence in the Netherlands for the six seasons 2011/2012 through 2016/2017, using Bayesian evidence synthesis methodology to combine season-specific sentinel surveillance data on influenza-like illness (ILI), virus detections in sampled ILI cases and data on healthcare-seeking behaviour. Estimated age-aggregated incidence was 6.5 per 1000 persons (95% uncertainty interval (UI): 4.7-9.0) for season 2011/2012, 36.7 (95% UI: 31.2-42.8) for 2012/2013, 9.1 (95% UI: 6.3-12.9) for 2013/2014, 41.1 (95% UI: 35.0-47.7) for 2014/2015, 39.4 (95% UI: 33.4-46.1) for 2015/2016 and 27.8 (95% UI: 22.7-33.7) for season 2016/2017. Incidence varied substantially between age-groups (highest for the age-group <5 years: 23 to 47/1000, but relatively low for 65+ years: 2 to 34/1000 over the six seasons). Integration of all relevant data sources within an evidence synthesis framework has allowed the estimation - with appropriately quantified uncertainty - of the incidence of symptomatic influenza virus infection. These estimates provide valuable insight into the variation in influenza epidemics across seasons, by virus subtype and lineage, and between age-groups.

Quantifying the impact of mass vaccination programmes on notified cases in the Netherlands.

Vaccination programmes are considered a main contributor to the decline of infectious diseases over the 20th century. In recent years, the national vaccination coverage in the Netherlands has been declining, highlighting the need for continuous monitoring and evaluation of vaccination programmes. Our aim was to quantify the impact of long-standing vaccination programmes on notified cases in the Netherlands. We collected and digitised previously unavailable monthly case notifications of diphtheria, poliomyelitis, mumps and rubella in the Netherlands over the period 1919-2015. Poisson regression models accounting for seasonality, multi-year cycles, secular trends and auto-correlation were fit to pre-vaccination periods. Cases averted were calculated as the difference between observed and expected cases based on model projections. In the first 13 years of mass vaccinations, case notifications declined rapidly with 82.4% (95% credible interval (CI): 74.9-87.6) of notified cases of diphtheria averted, 92.9% (95% CI 85.0-97.2) cases of poliomyelitis, and 79.1% (95% CI 67.1-87.4) cases of mumps. Vaccination of 11-year-old girls against rubella averted 49.9% (95% CI 9.3-73.5) of cases, while universal vaccination averted 68.1% (95% CI 19.4-87.3) of cases. These findings show that vaccination programmes have contributed substantially to the reduction of infectious diseases in the Netherlands.

Estimated incidence and number of outpatient visits for seasonal influenza in 2015-2016 in Beijing, China.

Information on morbidity burden of seasonal influenza in China is limited. A multiplier model was used to estimate the incidence and number of outpatient visits for seasonal influenza by age group for the 2015-2016 season in Beijing, the capital of China, based on reported numbers of influenza-like illness consultations and proportions of positive cases from influenza surveillance systems in Beijing, general consultation rates and other parameters from previous studies, surveys and surveillance systems. An estimated total of 1 190 200 (95% confidence interval (CI) 830 400-1 549 900) cases of influenza virus infections occurred in Beijing, 2015-2016 season, with an attack rate of 5·5% (95% CI 3·9-7·2%). These infections resulted in an estimated 468 280 (95% CI 70 700-606 800) outpatient visits, with an attack rate of 2·2% (95% CI 0·3-2·8%). The attack rate of influenza virus infections was highest among children aged 0-4 years (31·9% (95% CI 21·9-41·9%)), followed by children aged 5-14 years (18·7% (95% CI 12·9-24·5%)). Our study demonstrated a substantial influenza-related morbidity in Beijing, China, especially among the preschool- and school-aged children. This suggests that development or modification of seasonal influenza targeted vaccination strategies need to recognize that incidence is highest in children.

Microstructural evolution during sintering of copper particles studied by laboratory diffraction contrast tomography (LabDCT).

Pressureless sintering of loose or compacted granular bodies at elevated temperature occurs by a combination of particle rearrangement, rotation, local deformation and diffusion, and grain growth. Understanding of how each of these processes contributes to the densification of a powder body is still immature. Here we report a fundamental study coupling the crystallographic imaging capability of laboratory diffraction contrast tomography (LabDCT) with conventional computed tomography (CT) in a time-lapse study. We are able to follow and differentiate these processes non-destructively and in three-dimensions during the sintering of a simple copper powder sample at 1050 °C. LabDCT quantifies particle rotation (to <0.05° accuracy) and grain growth while absorption CT simultaneously records the diffusion and deformation-related morphological changes of the sintering particles. We find that the rate of particle rotation is lowest for the more highly coordinated particles and decreases during sintering. Consequently, rotations are greater for surface breaking particles than for more highly coordinated interior ones. Both rolling (cooperative) and sliding particle rotations are observed. By tracking individual grains the grain growth/shrinkage kinetics during sintering are quantified grain by grain for the first time. Rapid, abnormal grain growth is observed for one grain while others either grow or are consumed more gradually.

On compression and damage evolution in two thermoplastics.

The well-known Taylor cylinder impact test, which follows the impact of a flat-ended cylindrical rod onto a rigid stationary anvil, is conducted over a range of impact speeds for two polymers, polytetrafluoroethylene (PTFE) and polyetheretherketone (PEEK). In previous work, experiments and a model were developed to capture the deformation behaviour of the cylinder after impact. These works showed a region in which spatial and temporal variation of both longitudinal and radial deformation provided evidence of changes in phase within the material. In this further series of experiments, this region is imaged in a range of impacted targets at the Diamond synchrotron. Further techniques were fielded to resolve compressed regions within the recovered polymer cylinders that showed a fracture zone in the impact region. The combination of macroscopic high-speed photography and three-dimensional X-ray imaging has identified the development of failure with these polymers and shown that there is no abrupt transition in behaviours but rather a continuous range of responses to competing operating mechanisms. The behaviours noted in PEEK in these polymers show critical gaps in understanding of polymer high strain-rate response.

Prognosis of 1169 hepatitis C chronically infected patients with decompensated cirrhosis in the predirect-acting antiviral era.

At a population level, little is known regarding the risk of liver- and nonliver-related mortality and hospitalization and the development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients with decompensated cirrhosis (DC). This large-scale national record-linkage study estimates these outcomes following first hospital admission for DC. Record-linkages between national HCV diagnosis and clinical databases and the national inpatient hospital episode database and mortality register were conducted to follow-up the disease course of all identified HCV-diagnosed and chronically infected persons. The study population consisted of 1169 HCV chronically infected persons who had a first hospital admission for DC within the period 1994-2013. We observed an overall average annual percentage change of 12.6% in new DC patients (from 63 in 1994-1999 to 541 in 2009-2013), with no evidence for any improvement in the relative risks of liver-related or all-cause death over time. Between 1 January 1994 and 31 May 2014, 722 and 95 DC patients had died of a liver- and a nonliver-related cause, respectively, and 106 patients had a subsequent first admission for HCC. The 5-year cumulative incidence of liver-related mortality, nonliver-related mortality and first subsequent HCC admission was 61.3%, 8.2% and 8.8%, respectively. The health burden in HCV-infected patients associated with development of decompensated cirrhosis has increased dramatically over the last 20 years. Our findings establish the baseline mortality and HCC progression rates in DC patients against which the impact of new antiviral therapies can be measured.

Non-destructive mapping of grain orientations in 3D by laboratory X-ray microscopy.

The ability to characterise crystallographic microstructure, non-destructively and in three-dimensions, is a powerful tool for understanding many aspects related to damage and deformation mechanisms in polycrystalline materials. To this end, the technique of X-ray diffraction contrast tomography (DCT) using monochromatic synchrotron and polychromatic laboratory X-ray sources has been shown to be capable of mapping crystal grains and their orientations non-destructively in 3D. Here we describe a novel laboratory-based X-ray DCT modality (LabDCT), enabling the wider accessibility of the DCT technique for routine use and in-depth studies of, for example, temporal changes in crystallographic grain structure non-destructively over time through '4D' in situ time-lapse studies. The capability of the technique is demonstrated by studying a titanium alloy (Ti-ß21S) sample. In the current implementation the smallest grains that can be reliably detected are around 40 µm. The individual grain locations and orientations are reconstructed using the LabDCT method and the results are validated against independent measurements from phase contrast tomography and electron backscatter diffraction respectively. Application of the technique promises to provide important insights related to the roles of recrystallization and grain growth on materials properties as well as supporting 3D polycrystalline modelling of materials performance.

Employing temporal self-similarity across the entire time domain in computed tomography reconstruction.

There are many cases where one needs to limit the X-ray dose, or the number of projections, or both, for high frame rate (fast) imaging. Normally, it improves temporal resolution but reduces the spatial resolution of the reconstructed data. Fortunately, the redundancy of information in the temporal domain can be employed to improve spatial resolution. In this paper, we propose a novel regularizer for iterative reconstruction of time-lapse computed tomography. The non-local penalty term is driven by the available prior information and employs all available temporal data to improve the spatial resolution of each individual time frame. A high-resolution prior image from the same or a different imaging modality is used to enhance edges which remain stationary throughout the acquisition time while dynamic features tend to be regularized spatially. Effective computational performance together with robust improvement in spatial and temporal resolution makes the proposed method a competitive tool to state-of-the-art techniques.

Correlative tomography.

Increasingly researchers are looking to bring together perspectives across multiple scales, or to combine insights from different techniques, for the same region of interest. To this end, correlative microscopy has already yielded substantial new insights in two dimensions (2D). Here we develop correlative tomography where the correlative task is somewhat more challenging because the volume of interest is typically hidden beneath the sample surface. We have threaded together x-ray computed tomography, serial section FIB-SEM tomography, electron backscatter diffraction and finally TEM elemental analysis all for the same 3D region. This has allowed observation of the competition between pitting corrosion and intergranular corrosion at multiple scales revealing the structural hierarchy, crystallography and chemistry of veiled corrosion pits in stainless steel. With automated correlative workflows and co-visualization of the multi-scale or multi-modal datasets the technique promises to provide insights across biological, geological and materials science that are impossible using either individual or multiple uncorrelated techniques.

Attendance at specialist hepatitis clinics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland's Hepatitis C Action Plan.

Primary goals of the Hepatitis C Action Plan for Scotland Phase II (May 2008-March 2011) were to increase, among persons chronically infected with the hepatitis C (HCV) virus, attendance at specialist outpatient clinics and initiation on antiviral therapy. We evaluated progress towards these goals by comparing the odds, across time, of (a) first clinic attendance within 12 months of HCV diagnosis (n = 9747) and (b) initiation on antiviral treatment within 12 months of first attendance (n = 5736). Record linkage between the national HCV diagnosis (1996-2009) and HCV clinical (1996-2010) databases and logistic regression analyses were conducted for both outcomes. For outcome (a), 32% and 45% in the respective pre-Phase II (before 1 May 2008) and Phase II periods attended a specialist clinic within 12 months of diagnosis; the odds of attendance within 12 months increased over time (OR = 1.05 per year, 95% CI: 1.04-1.07), but was not significantly greater for persons diagnosed with HCV in the Phase II era, compared with the pre-Phase II era (OR = 1.1, 95% CI: 0.9-1.3), after adjustment for temporal trend. For outcome (b), 13% and 28% were initiated on treatment within 12 months of their first clinic attendance in the pre-Phase II and Phase II periods, respectively. Higher odds of treatment initiation were associated with first clinic attendance in the Phase II (OR = 1.9, 95% CI: 1.5-2.4), compared with the pre-Phase II era. Results were consistent with a positive impact of the Hepatitis C Action Plan on the treatment of chronically infected individuals, but further monitoring is required to confirm a sustained effect.

Impact of measles national vaccination coverage on burden of measles across 29 Member States of the European Union and European Economic Area, 2006-2011.

BACKGROUND: Challenges in reaching good vaccination coverage against measles emerged in several European Union/European Economic Area Member States (EU/EEA MS) leading to progressive accumulation of susceptible individuals and outbreaks. The Burden of Communicable Diseases in Europe (BCoDE) project developed a methodology for measuring the burden of communicable diseases expressed in Disability-Adjusted Life Years (DALYs) in the EU/EEA MS. The aim of this study was to compare national vaccination coverage and burden of measles across EU/EEA MS. METHODS: Country-specific data on measles national vaccination coverage 2006-2011 from 29 EU/EEA MS (MCV1) were retrieved from Centralized Information System for Infectious Diseases (CISID). DALYs were calculated for each country separately using a disease progression model with a single input parameter (annual measles incidence, adjusted for under-estimation). A software application was used to compute estimated DALYs according to country-specific and year-specific population age-distributions (data retrieved from Eurostat). Log-linear mixed-effect regression modeling approach was used to investigate a linear relation between natural logarithm-transformed DALYs and coverage. RESULTS: The reported annual vaccination coverage ranged from 72.6% to 100%. The estimated national annual burden ranged from 0 to 30.6 DALYs/100,000. Adjusting for year, there was a significant negative relationship between coverage and burden. For a given country there was a decrease in log-transformed DALYs/100,000 of 0.025 (95% confidence interval: -0.047 to -0.003) for every percentage increase in vaccination coverage. The largest effect of calendar time on estimated burden of measles was observed for the year 2011, the smallest was for the year 2007. CONCLUSIONS: This study shows that the degree of success of national measles vaccination programs, when measured by the coverage obtained, is significantly associated with overall impact of measles across EU/EEA MS. In EU/EEA MS each percentage point increase in national vaccination coverage seems to lead to early significant reduction of overall burden of measles.

The disease burden of hepatitis B, influenza, measles and salmonellosis in Germany: first results of the burden of communicable diseases in Europe study.

Setting priorities in the field of infectious diseases requires evidence-based and robust baseline estimates of disease burden. Therefore, the European Centre for Disease Prevention and Control initiated the Burden of Communicable Diseases in Europe (BCoDE) project. The project uses an incidence- and pathogen-based approach to measure the impact of both acute illness and sequelae of infectious diseases expressed in disability-adjusted life years (DALYs). This study presents first estimates of disease burden for four pathogens in Germany. The number of reported incident cases adjusted for underestimation served as model input. For the study period 2005-2007, the average disease burden was estimated at 33 116 DALYs/year for influenza virus, 19 115 DALYs/year for Salmonella spp., 8708 DALYs/year for hepatitis B virus and 740 DALYs/year for measles virus. This methodology highlights the importance of sequelae, particularly for hepatitis B and salmonellosis, because if omitted, the burden would have been underestimated by 98% and 56%, respectively.

Estimating the number of injecting drug users in Scotland's HCV-diagnosed population using capture-recapture methods.

In countries maintaining national hepatitis C virus (HCV) surveillance systems, a substantial proportion of individuals report no risk factors for infection. Our goal was to estimate the proportion of diagnosed HCV antibody-positive persons in Scotland (1991-2010) who probably acquired infection through injecting drug use (IDU), by combining data on IDU risk from four linked data sources using log-linear capture-recapture methods. Of 25,521 HCV-diagnosed individuals, 14,836 (58%) reported IDU risk with their HCV diagnosis. Log-linear modelling estimated a further 2484 HCV-diagnosed individuals with IDU risk, giving an estimated prevalence of 83. Stratified analyses indicated variation across birth cohort, with estimated prevalence as low as 49% in persons born before 1960 and greater than 90% for those born since 1960. These findings provide public-health professionals with a more complete profile of Scotland's HCV-infected population in terms of transmission route, which is essential for targeting educational, prevention and treatment interventions.

Survival and re-admission of patients admitted with alcoholic liver disease to a West of Scotland hospital.

Alcoholic liver disease including cirrhosis is a major health burden with huge cost to the National Health Service due to frequent hospital admissions of patients with alcoholic liver disease. The highest morbidity and mortality from alcoholic liver disease in Western Europe is in the West of Scotland. This study analyses the mortality and re-admission rates of patients admitted with alcoholic liver disease to a Glasgow hospital and compares the outcome with a Scotland wide historic control. Mortality in the study of 124 patients admitted to the hospital with alcoholic liver disease was 18% during index admission, and was 40% when including follow-up of one year after discharge. Re-admissions were high in this population. Seventy-five per cent of patients had at least one re-admission within one year, and patients spent an average of over one month in hospital during the study period. Survival rates in the Glasgow hospital were comparable to survival in the Scottish cohort. However, re-admission rates were significantly higher in the Glasgow hospital. In conclusion, patients with alcoholic liver disease requiring hospitalisation have very high mortality and frequent re-admissions.

Excess mortality among the elderly in 12 European countries, February and March 2012.

In February and March 2012, excess deaths among the elderly have been observed in 12 European countries that carry out weekly monitoring of all-cause mortality. These preliminary data indicate that the impact of influenza in Europe differs from the recent pandemic and post-pandemic seasons. The current excess mortality among the elderly may be related to the return of influenza A(H3N2) virus, potentially with added effects of a cold snap.

Imaging brain amyloid deposition using grating-based differential phase contrast tomography.

One of the core pathological features of Alzheimer's disease (AD) is the accumulation of amyloid plaques in the brain. Current efforts of medical imaging research aim at visualizing amyloid plaques in living patients in order to evaluate the progression of the pathology, but also to facilitate the diagnosis of AD at the prodromal stage. In this study, we evaluated the capabilities of a new experimental imaging setup to image amyloid plaques in the brain of a transgenic mouse model of Alzheimer's disease. This imaging setup relies on a grating interferometer at a synchrotron X-ray source to measure the differential phase contrast between brain tissue and amyloid plaques. It provides high-resolution images with a large field of view, making it possible to scan an entire mouse brain. Here, we showed that this setup yields sufficient contrast to detect amyloid plaques and to quantify automatically several important structural parameters, such as their size and their regional density in 3D, on the scale of a whole mouse brain. Whilst future developments are required to apply this technique in vivo, this grating-based setup already gives the possibility to perform powerful studies aiming at quantifying the amyloid pathology in mouse models of AD and might accelerate the evaluation of anti-amyloid compounds. In addition, this technique may also facilitate the development of other amyloid imaging methods such as positron emission tomography (PET) by providing convenient high-resolution 3D data of the plaque distribution for multimodal comparison.

Estimating the variability in the risk of infection for hepatitis C in the Glasgow injecting drug user population.

Glasgow (Scotland's largest city) has a high prevalence of injecting drug use and has one of the highest prevalences of hepatitis C virus (HCV) infection in injecting drug users (IDUs) in Western Europe. HCV prevalence data from surveys of Glasgow's IDUs from 1990 to 2007 were utilized and a model was applied that described the prevalence of HCV as a function of the rate (force) of infection. Force-of-infection estimates for HCV that may vary over time and injecting career length over a range of variables were investigated. New initiates to injecting were found to be at increased risk of HCV infection, with being recruited from a street location and reporting injecting in prison leading to a significant increase in the risk of infection in new initiates. These results indicate areas of importance for the planning of public health measures that target the IDU population.