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A worldwide vaccination programme is the chosen strategy against the COVID-19 pandemic. Vaccine hesitancy, however, forms a threat to achieving a high degree of vaccination. Healthcare workers (HCWs) are exposed to greater risks, in addition to HCWs who care for people with intellectual disabilities (ID). However, little is still known about these groups’ vaccine hesitancy. This review aims to provide insight into the intentions and attitudes of HCWs on COVID-19 vaccination, including those who care for people with ID. The search included both types and was conducted in nine databases. A total of 26 papers were identified concerning the vaccine intentions of 43,199 HCWs worldwide. The data were gathered both quantitively and qualitatively. The papers were analysed for all of the themes regarding vaccine intentions, which were: (1) percentages of vaccine willingness; (2) predictors of willingness; (3) attitudes of willingness and hesitancy; (4) sources of vaccination information; (5) contextual factors and changes in COVID-19 vaccine acceptance over time; and (6) future strategies for interventions. Concerns about vaccine safety, efficacy and short- and long-term side effects were the most prominent in HCWs and, therefore, should be addressed in future intervention strategies. Furthermore, interactive interventions are recommended to facilitate exchange, and accurate information should be accessible to target groups on social media platforms.

Traditionally, cryocooler life time and reliability have been a limiting factor for infrared systems, with significant advances having been made over the last two decades. This has culminated in the development, qualification, and production of high-availability cryocoolers, enabling multi-year 24/7 operation of infrared sensors with a vanishingly small failure probability. We will discuss high-availability solutions based on Stirling technology for applications where the intrinsic drawbacks of pulse-tube technology – such as lower efficiency and a high sensitivity to orientation and ambient temperature – restrict the possibilities to use pulse tubes. In addition, we will discuss the applicability of pulse-tube technology to infrared applications.

Summary A novel cost-effectiveness model framework was developed to incorporate the elevated fracture risk associated with a recent fracture and to allow sequential osteoporosis therapies to be evaluated. Treating patients with severe osteoporosis after a recent fracture with a bone-forming agent followed by antiresorptive therapy can be cost-effective compared with antiresorptive therapy alone. Incorporating these novel technical attributes in economic evaluations can support appropriate policy and reimbursement decision-making. Purpose To develop a cost-effectiveness model accommodating increased fracture risk after a recent fracture and treatment sequencing. Methods A micro-simulation cost-utility model was developed to accommodate both treatment sequencing and increased risk with recent fracture. The risk of fracture was estimated and simulated using the FRAX® algorithms combined with Swedish registry data on imminent fracture relative risk. In the base-case cost-effectiveness analysis, a sequential treatment starting with a bone-forming agent for 12 months followed by an antiresorptive agent for 48 months initiated immediately after a major osteoporotic fracture (MOF) in a 70-year-old woman with a T-score of 2.5 or less was compared to an antiresorptive treatment alone for 60 months. The model was populated with data relevant for a UK population reflecting a personal social service perspective. Results The cost per additional quality-adjusted life year (QALY) gained in the base-case setting was estimated at £34,584. Sensitivity analyses revealed the sequential treatment to be cost-saving compared with administering a bone-forming treatment alone. Without simulating an elevated fracture risk immediately after a recent fracture, the cost per QALY changed from £34,584 to £62,184. Conclusion Incorporating imminent fracture risk in economic evaluations has a significant impact on the cost-effectiveness when evaluating fracture prevention treatments in patients with osteoporosis who sustained a recent fracture. Bone-forming treatment followed by antiresorptive therapy can be cost-effective compared to antiresorptive therapy alone depending on treatment acquisition costs. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-020-05765-7.

Summary Romosozumab is a novel bone-building drug that reduces fracture risk. This health economic analysis indicates that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture. Purpose To estimate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate (“romosozumab-to-alendronate”) compared with alendronate alone in patients with severe osteoporosis at high risk of fracture in Sweden. Methods A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), for women treated with romosozumab-to-alendronate or alendronate alone. Patients aged 74 years with a recent major osteoporotic fracture (MOF) were followed from the start of treatment until the age of 100 years or death. Treatment with romosozumab for 12 months was followed by alendronate for up to 48 months or alendronate alone with a maximum treatment duration of 60 months. The analysis had a societal perspective. Efficacy of romosozumab and alendronate were derived from phase III randomized controlled trials. Resource use and unit costs were collected from the literature. Cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) with QALYs as effectiveness measures. Results The base case analysis showed that sequential romosozumab-to-alendronate treatment was associated with 0.089 additional QALYs at an additional cost of €3002 compared to alendronate alone, resulting in an ICER of €33,732. At a Swedish reference willingness-to-pay per QALY of €60,000, romosozumab-to-alendronate had a 97.9% probability of being cost-effective against alendronate alone. The results were most sensitive to time horizon, persistence assumptions, patient age, and treatment efficacy. Conclusion The results of this study indicate that sequential romosozumab-to-alendronate can be a cost-effective treatment option for postmenopausal women with severe osteoporosis at high risk of fracture. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-020-05780-8.

With miniature high operating temperature cryocoolers becoming commonplace, there is an increasing importance of accurate determination of the thermal properties of infrared dewars such as heat load and thermal mass, as well as an increasing challenge to obtaining these properties. Especially in the case where operating temperature in the application is far from liquid nitrogen temperature, such as with HOT detectors, the use of the various known methods should be carefully evaluated. Inconsistencies in results between the various available methods, such as nitrogen boil-off, multi-slope warm-up calorimetry, and theoretical thermal modelling will be discussed, and the work being done at Thales Cryogenics to resolve these inconsistencies is presented.

Additional file 1. Final list of Delphi questionnaire items with mean scores and percentages. The Delphi questionnaire was established by translating the content of a pilot self-assessment instrument for diversity responsiveness in palliative care projects into a questionnaire. The questionnaire consisted of 33 items, subdivided into four sections. One section with three items on the groups included in the instrument’s focus and three sections with items on the measures from the pilot instrument according to the project stages: set-up; execution, and follow-up. The questionnaire was sent to a panel of experts who were asked to score the questionnaire items’ relevance and feasibility on a 5-point scale (1:not relevant/feasible; 5:entirely relevant/feasible). A priori set consensus rate of 75% were used, where at least 75% of the scores given by the experts should be 4 ≤ (relevance), or 3 ≤ (feasibility) in order to uphold the item in the instrument. Listed here are the final items, after revisions suggested by experts, the mean scores and consensus rate percentages.

Recent developments at Thales Cryogenics have been aimed at improving the performances of 100 W and 200 W input power class flexure bearing Stirling coolers. The aim of these developments has been twofold: To enable multi-year operation with a vanishingly small failure probability (high availability) and to extend the usable range down to below 42 K (low temperature). As the starting point for development, the LSF9589 and LSF9340/LSF9350 cooler ranges were selected. By performing these upgrades, the usability range of the cryocoolers is extended. Multiple upgrades will be shown such as tuning for low-temperature operations and material upgrades. Test results will be presented and potential future improvements will be discussed. The work performed was done for a variety of customers, with applications including nitrogen recondensers for zero boil-off dewars, high temperature superconducting filters, and low temperature longwave infrared detectors.

With the achievements made in the last decade with respect to reliability and cryogenic performance, the use of Stirling and Pulse Tube cryocoolers for new application areas has become viable. Thales Cryogenics has been challenged by its customers to deliver robust and compact solutions for a variety of applications. The test approaches within the Thales Environmental Test Lab – a center of excellence within the Netherlands – have been refined significantly, departing from the classical robustness testing principles, which typically consist of submitting the product to an environment with a compressed energy allocation - shorter time duration and higher PSD levels. An overview is given of recent activities at Thales Cryogenics regarding the development and testing of linear Stirling cryocoolers for extreme environmental conditions. A novel cooler will be presented that has been developed specifically for operation in high ambient temperature conditions. In addition, an overview will be given of ongoing test and development activities regarding coolers for operation under severe mechanical loads. Design aspects, margin philosophy, test plans (including robustness testing) and test results will be presented.

Background and Purpose— Stroke is a relatively common and challenging condition in hospitalized patients. Previous studies have shown delays in recognition and assessment of inpatient strokes leading to poor outcomes. The goal of this quality improvement initiative was to evaluate an in-hospital code stroke algorithm and educational program aimed at reducing the response times for inpatient stroke. Methods— An inpatient code stroke algorithm was developed, and an educational intervention was implemented over 5 months. Data were recorded and compared between the 36-month period before and the 15-month period after the intervention was implemented. Outcome measures included time from last seen normal to initial assessment and from last seen normal to brain imaging. Results— During the study period, there were 218 inpatient strokes (131 before the intervention and 87 after the intervention). Inpatient strokes were more common on cardiovascular wards (45% of cases) and occurred mainly during the perioperative period (60% of cases). After implementation of an inpatient code stroke intervention and educational initiative, there were consistent reductions in all timed outcome measures (median time to initial assessment fell from 600 [109–1460] to 160 [35–630] minutes and time to computed tomographic scan fell from 925 [213–1965] to 348.5 [128–1587] minutes). Conclusions— Our study reveals the efficacy of an inpatient code stroke algorithm and educational intervention directed at nurses and allied health personnel to optimize the prompt management of inpatient strokes. Prompt assessment may lead to faster stroke interventions, which are associated with better outcomes.

The low-frequency pulse-tube cryocooler has been a workhorse for large heat lift applications. However, the highfrequency pulse tube has to date not seen the widespread use in tactical infrared applications that Stirling cryocoolers have had, despite significant advantages in terms of exported vibrations and lifetime. Thales Cryogenics has produced large series of high-frequency pulse-tube cryocoolers for non-infrared applications since 2005. However, the use of Thales pulse-tube cryocoolers for infrared sensing has to date largely been limited to high-end space applications. In this paper, the performances of existing available off-the-shelf pulse-tube cryocoolers are examined versus typical tactical infrared requirements. A comparison is made on efficiency, power density, reliability, and cost. An outlook is given on future developments that could bring the pulse-tube into the mainstream for tactical infrared applications.

During the 2015 SPIE-DSS conference, Thales Cryogenics presented new miniature cryocoolers for high operating temperatures. In this paper, an update is given regarding the qualification programme performed on these new products. Integration aspects are discussed, including an in-depth examination of the influence of the dewar cold finger on sizing and performance of the cryocooler. The UP8197 will be placed in the reference frame of the Thales product range of high-reliability linear cryocoolers, while the rotary solution will be considered as the most compact solution in the Thales portfolio. Compatibility of the cryocoolers design with new and existing 1/4” dewar designs is examined, and potential future developments are presented.

Background: Intradermal immunization is gaining increased attention due to multiple factors: (1) intradermal (ID) vaccination has been shown to induce improved immunogenicity compared to intramuscular (IM) vaccination; (2) ID vaccination has been shown to have a dose-sparing potential over IM leading to a reduced vaccine cost and an increased availability of vaccines worldwide. However, the currently used Mantoux technique for ID injection is difficult to standardize and requires training. The aim of the study was (1) to assess the epidermal and dermal thickness at the proximal ventral and dorsal forearm (PVF & PDF) and deltoid in adults aged 18-65 years (2) to determine the maximum penetration depth and needle characteristics for the development of a platform of medical devices suited for intradermal injection, VAX-ID (TM). Materials and methods: Mean thickness of the PVF, PDF and deltoid were measured using high-frequency ultrasound of healthy adults aged 18-65 years. Correlation with gender, age and BMI was assessed using Mann -Whitney U Test, Spearman correlation and Wilcoxon Signed Ranks Test, respectively. Results: Results showed an overall mean skin thickness of 1.19 mm (0.65-1.55 mm) at the PVF, 1.44 mm (0.78-1.84 mm) at the PDF, and 2.12 mm (1,16-3.19 mm) at the deltoid. Thickness of PVF & PDF and deltoid were significantly different for men vs women (p(mean) < 0.001

The influence of boundary conditions (BC) of the structure in a complex FSI experiment are investigated and different simple models for the BC are presented to accurately capture the behavior of the experiment. The interaction of a shock wave with a supersonic boundary layer on an elastic panel was investigated experimentally in order to validate the numerical tools developed within the SFB/TRR 40. During numerical analysis of the fluid-structure interaction (FSI), the support of the panel was assumed to be fully fixed which turned out to be inappropriate. As the focus of the investigations is on the FSI, it is not desirable to consider the panel clamping region with its rivets where a complex contact and prestressing scenario occurs. Hence, an elegant modeling approach is developed which accounts for the relevant aspects of the clamping while reducing its complexity by far. Translational and rotational springs are included to surrogate the “soft” behavior observed in both in static and dynamic experiments. Additionally, the compressibility of the air enclosed in the cavity below the panel turned out to influence the eigenfrequency of the panel yielding a Robin-type boundary condition. Besides the modeling of boundary conditions, a second aspect in this work is the improvement of the linear solver for monolithic coupled multi-field problems as they occur in thermo-structure interaction. Different preconditioning strategies for the linear systems are applied to the test case which consists of the temperature dependent deformation of a rocket nozzle. Good scalability can be achieved using the developed preconditioning strategies.

In recent years there has been a drive towards miniaturized cooled IDCA solutions for low-power, low-mass, low-size products (SWaP). To support this drive, coolers are developed optimized for high-temperature, low heat load dewar-detector assemblies. In this paper, Thales Cryogenics development activities supporting SWaP are presented. Design choices are discussed and compared to various key requirements. Trade-off analysis results are presented on drive voltage, cold finger definition (length, material, diameter and sealing concept), and other interface considerations, including cold finger definition. In parallel with linear and rotary cooler options, designs for small-size high-efficiency drive electronics based on state-of-the-art architectures are presented.

In a Stirling-type pulse-tube cooler with a dual-opposed piston compressor, the residual vibration exported by the cooler is primarily a result of residual imbalances between compressor motors. Using an electronic feedback loop [1] and driving compressor motors in a master-slave configuration, the exported force from the compressor can be regulated to negligible levels. This has been demonstrated in a multitude of commercial applications [2] as well as in space applications. In a novel application of the same electronic feedback technology, the residual exported forces resulting from the motion of the free moving displacer of a Stirling cold finger are compensated, by using the linear dual-opposed piston compressor as an active balancer. Theoretical analysis of this is provided, measurements are presented on different cooler types, and the effect of integration aspects - hard mount versus suspended – is discussed. The effect on exported vibration as well as power efficiency is discussed and compared between Stirling and pulse-tube type coolers. Currently available off-the-shelf hardware, the CDE7232, is presented and future developments are discussed.

In multipass rendering, care has to be taken to include all light transport only once in the final solution. Therefore the different methods in current multipass configurations handle a perfectly disjunct part of the light transport. In this paper a Monte Carlo variance reduction technique is presented that probabilistically weights overlapping transport between different methods. A good heuristic for the weights is derived so that strengths of the respective methods are retained. The technique is applied to a combination of radiosity and bidirectional path tracing and significant improvement is obtained over the non-weighted combination. This method promises to be a very useful extension to other multipass algorithms as well.

It has been shown that lens regeneration from outer cornea of larval Xenopus laevisis dependent on neural retina both in vivo and in tissue culture. The isolated outer cornea cultured in the presence of bovine brain-derived acidic Fibroblast Growth Factor (aFGF) is able to reprogram the differentiation into lens fibers, although this transdifferentiative process is not coupled with the formation of a normally organized lens. The capacity of aFGF to promote lens differentiation from cornea is not linked to its mitogenic activity. The cultured corneal cells can transdifferentiate into lens fibers in the presence of aFGF when DNA replication and cell proliferation are prevented by addition of aphidicolin, a specific inhibitor of DNA polymerase in eukaryotes, to the culture medium.

Lipoproteins, high-sensitivity C-reactive protein (hs-CRP) and adiponectin have been studied as risk factors for cardiovascular disease (CVD). The aim of this study was to measure and analyze those risk markers in young type 1 diabetic patients and to evaluate the association between adiponectin and different parameters.This cross-sectional study analyzed body mass index, subscapular skinfold thickness, physical activity, nutrition, glycated haemoglobin (HbA1c), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, hs-CRP and adiponectin in 148 young type 1 diabetic patients [age--median (interquartile range)--13.5 (10.3-16.0) yr]. Linear and multiple regression analysis were used.Median HbA1c was 7.5 (7.0-8.1)%. Median cholesterol and hs-CRP levels were normal. Adiponectin was 14.9 (10.8-19.0) microg/ml. There was no correlation between adiponectin and age, diabetes duration, body mass index, physical activity, protein, fat or carbohydrate intake, HbA1c, serum lipids or hs-CRP. But there was a negative correlation between serum adiponectin and skinfold thickness and a positive correlation between adiponectin and daily energy intake. Multiple linear regression analysis showed an independent positive correlation with daily energy intake, saturated fat intake and apolipoprotein B levels.In children and adolescents with relatively well controlled glycaemia, there are no abnormalities of risk markers for cardiovascular disease: lipoproteins, hs-CRP and adiponectin. Adiponectin levels are associated with daily energy intake, saturated fat intake and apolipoprotein B levels suggesting that increased levels of adiponectin could protect patients at increased risk of CVD. A longitudinal analysis is needed to follow up these factors and any occurrence of cardiovascular disease.