Projecting the clinical burden of chronic kidney disease at the patient level (Inside CKD): a microsimulation modelling study.

Background: Chronic kidney disease (CKD) is a global concern that presents significant challenges for disease management. Several factors drive CKD prevalence, including primary risk factors, such as type 2 diabetes and hypertension, and an ageing population. Inside CKD is an international initiative that aims to raise awareness of the substantial burden incurred by CKD. Methods: Using a peer-reviewed microsimulation method, the clinical burden of CKD was estimated from 2022 to 2027. Demographic data from the Americas, Europe, and Asia-Pacific/Middle East were used to generate virtual populations and to project the prevalence of CKD, kidney replacement therapy, associated cardiovascular complications, comorbid conditions, and all-cause mortality in the CKD population over the modelled time frame. Findings: Across the 31 participating countries/regions, the total prevalence of CKD was projected to rise to 436.6 million cases by 2027 (an increase of 5.8% from 2022), with most cases (∼80%) undiagnosed. Inside CKD projected a mean of 8859 cases of heart failure, 10,244 of myocardial infarction, and 7797 of stroke per 100,000 patients with CKD by 2027. Interpretation: The clinical impact of CKD is substantial and likely to increase; the high prevalence of undiagnosed cases and associated complications may benefit from the implementation of health policy interventions that promote screening, earlier diagnosis, and interventions to improve outcomes. Funding: AstraZeneca.

The bearing capacity of asteroid (65803) Didymos estimated from boulder tracks.

The bearing capacity - the ability of a surface to support applied loads - is an important parameter for understanding and predicting the response of a surface. Previous work has inferred the bearing capacity and trafficability of specific regions of the Moon using orbital imagery and measurements of the boulder tracks visible on its surface. Here, we estimate the bearing capacity of the surface of an asteroid for the first time using DART/DRACO images of suspected boulder tracks on the surface of asteroid (65803) Didymos. Given the extremely low surface gravity environment, special attention is paid to the underlying assumptions of the geotechnical approach. The detailed analysis of the boulder tracks indicates that the boulders move from high to low gravitational potential, and provides constraints on whether the boulders may have ended their surface motion by entering a ballistic phase. From the 9 tracks identified with sufficient resolution to estimate their dimensions, we find an average boulder track width and length of 8.9 ± 1.5 m and 51.6 ± 13.3 m, respectively. From the track widths, the mean bearing capacity of Didymos is estimated to be 70 N/m2, implying that every 1 m2 of Didymos' surface at the track location can support only ~70 N of force before experiencing general shear failure. This value is at least 3 orders of magnitude less than the bearing capacity of dry sand on Earth, or lunar regolith.

Evidence for multi-fragmentation and mass shedding of boulders on rubble-pile binary asteroid system (65803) Didymos.

Asteroids smaller than 10 km are thought to be rubble piles formed from the reaccumulation of fragments produced in the catastrophic disruption of parent bodies. Ground-based observations reveal that some of these asteroids are today binary systems, in which a smaller secondary orbits a larger primary asteroid. However, how these asteroids became binary systems remains unclear. Here, we report the analysis of boulders on the surface of the stony asteroid (65803) Didymos and its moonlet, Dimorphos, from data collected by the NASA DART mission. The size-frequency distribution of boulders larger than 5 m on Dimorphos and larger than 22.8 m on Didymos confirms that both asteroids are piles of fragments produced in the catastrophic disruption of their progenitors. Dimorphos boulders smaller than 5 m have size best-fit by a Weibull distribution, which we attribute to a multi-phase fragmentation process either occurring during coalescence or during surface evolution. The density per km2 of Dimorphos boulders ≥1 m is 2.3x with respect to the one obtained for (101955) Bennu, while it is 3.0x with respect to (162173) Ryugu. Such values increase once Dimorphos boulders ≥5 m are compared with Bennu (3.5x), Ryugu (3.9x) and (25143) Itokawa (5.1x). This is of interest in the context of asteroid studies because it means that contrarily to the single bodies visited so far, binary systems might be affected by subsequential fragmentation processes that largely increase their block density per km2. Direct comparison between the surface distribution and shapes of the boulders on Didymos and Dimorphos suggest that the latter inherited its material from the former. This finding supports the hypothesis that some asteroid binary systems form through the spin up and mass shedding of a fraction of the primary asteroid.

Fast boulder fracturing by thermal fatigue detected on stony asteroids.

Spacecraft observations revealed that rocks on carbonaceous asteroids, which constitute the most numerous class by composition, can develop millimeter-to-meter-scale fractures due to thermal stresses. However, signatures of this process on the second-most populous group of asteroids, the S-complex, have been poorly constrained. Here, we report observations of boulders' fractures on Dimorphos, which is the moonlet of the S-complex asteroid (65803) Didymos, the target of NASA's Double Asteroid Redirection Test (DART) planetary defense mission. We show that the size-frequency distribution and orientation of the mapped fractures are consistent with formation through thermal fatigue. The fractures' preferential orientation supports that these have originated in situ on Dimorphos boulders and not on Didymos boulders later transferred to Dimorphos. Based on our model of the fracture propagation, we propose that thermal fatigue on rocks exposed on the surface of S-type asteroids can form shallow, horizontally propagating fractures in much shorter timescales (100 kyr) than in the direction normal to the boulder surface (order of Myrs). The presence of boulder fields affected by thermal fracturing on near-Earth asteroid surfaces may contribute to an enhancement in the ejected mass and momentum from kinetic impactors when deflecting asteroids.

First experience using a novel microsurgical robotic device for free flap surgery in cranio- and maxillofacial surgery.

Many surgical fields profit from robotic support devices. After the first case reports about the use of a special microsurgical roboter (Symani Sugrical System, Medical Microinstruments, Pisa, Italy) we evaluated the potential of such a device in cranio- and maxillofacial surgery in a world's first single-center case series. This novel piece of equipment is meant to assist the surgeon anastomosing small vessels, nerves and lymphatic vessels. In total 30 free flaps were performed and compared to another 30 conventionally anastomosed free flaps. In total 127 anastomoses were surveyed. We encountered a lot of potential for robotic supported operations in the field of cranio- and maxillofacial surgery. However, the surgery time for robotic supported anastomosis with an average time of 32.5 min to perform arterial anastomosis was significant longer than the conventional ones, which needed 11.8 min on average. Tremor Filter and Motion Scaling are promising features for future microsurgery but the grip of the microinstruments has to be improved. It remains to be seen if the potential will be validated after the upcoming learning period and if robotic support devices will prevail in cranio- and maxillofacial surgery.

Nodal Heterogeneity can Induce Ghost Triadic Effects in Relational Event Models.

Temporal network data is often encoded as time-stamped interaction events between senders and receivers, such as co-authoring scientific articles or communication via email. A number of relational event frameworks have been proposed to address specific issues raised by complex temporal dependencies. These models attempt to quantify how individual behaviour, endogenous and exogenous factors, as well as interactions with other individuals modify the network dynamics over time. It is often of interest to determine whether changes in the network can be attributed to endogenous mechanisms reflecting natural relational tendencies, such as reciprocity or triadic effects. The propensity to form or receive ties can also, at least partially, be related to actor attributes. Nodal heterogeneity in the network is often modelled by including actor-specific or dyadic covariates. However, comprehensively capturing all personality traits is difficult in practice, if not impossible. A failure to account for heterogeneity may confound the substantive effect of key variables of interest. This work shows that failing to account for node level sender and receiver effects can induce ghost triadic effects. We propose a random-effect extension of the relational event model to deal with these problems. We show that it is often effective over more traditional approaches, such as in-degree and out-degree statistics. These results that the violation of the hierarchy principle due to insufficient information about nodal heterogeneity can be resolved by including random effects in the relational event model as a standard.

Scalable inference of cell differentiation networks in gene therapy clonal tracking studies of haematopoiesis.

MOTIVATION: Investigating cell differentiation under a genetic disorder offers the potential for improving current gene therapy strategies. Clonal tracking provides a basis for mathematical modelling of population stem cell dynamics that sustain the blood cell formation, a process known as haematopoiesis. However, many clonal tracking protocols rely on a subset of cell types for the characterization of the stem cell output, and the data generated are subject to measurement errors and noise. RESULTS: We propose a stochastic framework to infer dynamic models of cell differentiation from clonal tracking data. A state-space formulation combines a stochastic quasi-reaction network, describing cell differentiation, with a Gaussian measurement model accounting for data errors and noise. We developed an inference algorithm based on an extended Kalman filter, a nonlinear optimization, and a Rauch-Tung-Striebel smoother. Simulations show that our proposed method outperforms the state-of-the-art and scales to complex structures of cell differentiations in terms of nodes size and network depth. The application of our method to five in vivo gene therapy studies reveals different dynamics of cell differentiation. Our tool can provide statistical support to biologists and clinicians to better understand cell differentiation and haematopoietic reconstitution after a gene therapy treatment. The equations of the state-space model can be modified to infer other dynamics besides cell differentiation. AVAILABILITY AND IMPLEMENTATION: The stochastic framework is implemented in the R package Karen which is available for download at https://cran.r-project.org/package=Karen. The code that supports the findings of this study is openly available at https://github.com/delcore-luca/CellDifferentiationNetworks.

Spermatogenesis after gonadotoxic childhood treatment: follow-up of 12 patients.

STUDY QUESTION: What is the long-term impact of presumed gonadotoxic treatment during childhood on the patient's testicular function at adulthood? SUMMARY ANSWER: Although most patients showed low testicular volumes and some degree of reproductive hormone disruption 12.3 (2.3-21.0) years after gonadotoxic childhood therapy, active spermatogenesis was demonstrated in the semen sample of 8 out of the 12 patients. WHAT IS KNOWN ALREADY: In recent decades, experimental testicular tissue banking programmes have been set up to safeguard the future fertility of young boys requiring chemo- and/or radiotherapy with significant gonadotoxicity. Although the risk of azoospermia following such therapies is estimated to be high, only limited long-term data are available on the reproductive potential at adulthood. STUDY DESIGN SIZE DURATION: This single-centre prospective cohort study was conducted between September 2020 and February 2023 and involved 12 adult patients. PARTICIPANTS/MATERIALS SETTING METHODS: This study was carried out in a tertiary care centre and included 12 young adults (18.1-28.3 years old) who had been offered testicular tissue banking prior to gonadotoxic treatment during childhood. All patients had a consultation and physical examination with a fertility specialist, a scrotal ultrasound to measure the testicular volumes and evaluate the testicular parenchyma, a blood test for assessment of reproductive hormones, and a semen analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Testicular tissue was banked prior to the gonadotoxic treatment for 10 out of the 12 included patients. Testicular volumes were low for 9 patients, and 10 patients showed some degree of reproductive hormone disruption. Remarkably, ongoing spermatogenesis was demonstrated in 8 patients at a median 12.3 (range 2.3-21.0) years post-treatment. LIMITATIONS REASONS FOR CAUTION: This study had a limited sample size, making additional research with a larger study population necessary to verify these preliminary findings. WIDER IMPLICATIONS OF THE FINDINGS: These findings highlight the need for multicentric research with a larger study population to establish universal inclusion criteria for immature testicular tissue banking. STUDY FUNDING/COMPETING INTERESTS: This study was conducted with financial support from the Research Programme of the Research Foundation-Flanders (G010918N), Kom Op Tegen Kanker, and Scientific Fund Willy Gepts (WFWG19-03). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: NCT04202094; https://clinicaltrials.gov/ct2/show/NCT04202094?id=NCT04202094&draw=2&rank=1 This study was registered on 6 December 2019, and the first patient was enrolled on 8 September 2020.

A mixed-effects stochastic model reveals clonal dominance in gene therapy safety studies.

BACKGROUND: Mathematical models of haematopoiesis can provide insights on abnormal cell expansions (clonal dominance), and in turn can guide safety monitoring in gene therapy clinical applications. Clonal tracking is a recent high-throughput technology that can be used to quantify cells arising from a single haematopoietic stem cell ancestor after a gene therapy treatment. Thus, clonal tracking data can be used to calibrate the stochastic differential equations describing clonal population dynamics and hierarchical relationships in vivo. RESULTS: In this work we propose a random-effects stochastic framework that allows to investigate the presence of events of clonal dominance from high-dimensional clonal tracking data. Our framework is based on the combination between stochastic reaction networks and mixed-effects generalized linear models. Starting from the Kramers-Moyal approximated Master equation, the dynamics of cells duplication, death and differentiation at clonal level, can be described by a local linear approximation. The parameters of this formulation, which are inferred using a maximum likelihood approach, are assumed to be shared across the clones and are not sufficient to describe situation in which clones exhibit heterogeneity in their fitness that can lead to clonal dominance. In order to overcome this limitation, we extend the base model by introducing random-effects for the clonal parameters. This extended formulation is calibrated to the clonal data using a tailor-made expectation-maximization algorithm. We also provide the companion  package RestoreNet, publicly available for download at https://cran.r-project.org/package=RestoreNet . CONCLUSIONS: Simulation studies show that our proposed method outperforms the state-of-the-art. The application of our method in two in-vivo studies unveils the dynamics of clonal dominance. Our tool can provide statistical support to biologists in gene therapy safety analyses.

Pig fetal skeletal muscle development is associated with genome-wide DNA hypomethylation and corresponding alterations in transcript and microRNA expression.

Fetal myogenesis represents a critical period of porcine skeletal muscle development and requires coordinated expression of thousands of genes. Epigenetic mechanisms, including DNA methylation, drive transcriptional regulation during development; however, these processes are understudied in developing porcine tissues. We performed bisulfite sequencing to assess DNA methylation in pig longissimus dorsi muscle at 41- and 70-days gestation (dg), as well as RNA- and small RNA-sequencing to identify coordinated changes in methylation and expression between myogenic stages. We identified 45 739 differentially methylated regions (DMRs) between stages, and the majority (N = 34 232) were hypomethylated at 70 versus 41 dg. Integration of methylation and transcriptomic data revealed strong associations between differential gene methylation and expression. Differential miRNA methylation was significantly negatively correlated with abundance, and dynamic expression of assayed miRNAs persisted postnatally. Motif analysis revealed significant enrichment of myogenic regulatory factor motifs among hypomethylated regions, suggesting that DNA hypomethylation may function to increase accessibility of muscle-specific transcription factors. We show that developmental DMRs are enriched for GWAS SNPs for muscle- and meat-related traits, demonstrating the potential for epigenetic processes to influence phenotypic diversity. Our results enhance understanding of DNA methylation dynamics of porcine myogenesis and reveal putative cis-regulatory elements governed by epigenetic processes.

Drivers of the decrease of patent similarities from 1976 to 2021.

The citation network of patents citing prior art arises from the legal obligation of patent applicants to properly disclose their invention. One way to study the relationship between current patents and their antecedents is by analyzing the similarity between the textual elements of patents. Many patent similarity indicators have shown a constant decrease since the mid-70s. Although several explanations have been proposed, more comprehensive analyses of this phenomenon have been rare. In this paper, we use a computationally efficient measure of patent similarity scores that leverages state-of-the-art Natural Language Processing tools, to investigate potential drivers of this apparent similarity decrease. This is achieved by modeling patent similarity scores by means of generalized additive models. We found that non-linear modeling specifications are able to distinguish between distinct, temporally varying drivers of the patent similarity levels that explain more variation in the data (R2 ∼ 18%) compared to previous methods. Moreover, the model reveals an underlying trend in similarity scores that is fundamentally different from the one presented previously.

Increased microchimerism in peripheral blood of women with systemic lupus erythematosus: relation with pregnancy.

OBJECTIVES: We aimed to determine the presence, amount and origin of microchimerism in peripheral blood of pregnant and non-pregnant parous women with systemic lupus erythematosus (SLE) as compared to control subjects. METHODS: We performed a comparative study in which peripheral blood was drawn from eleven female non-pregnant SLE-patients and 22 control subjects, and from six pregnant SLE-patients and eleven control subjects during gestation and up to six months postpartum. Quantitative PCR for insertion-deletion polymorphisms and null alleles was used to detect microchimerism in peripheral blood mononuclear cells and granulocytes. RESULTS: Microchimerism was detected more often in non-pregnant SLE-patients than control subjects (54.4% vs. 13.6%, respectively; p=0.03). When present, the median total number of foetal chimeric cells was 5 gEq/106 in patients and 2.5gEq/106 in control subjects (p=0.048). Microchimerism was mostly foetal in origin; maternal microchimerism was detected in one patient and one control subject. In control subjects, microchimerism was always derived from only one source whereas in 50% of patients it originated from multiple sources. The pregnant patients had a significantly higher median number of foetal chimeric cells in the granulocyte fraction just after delivery than control subjects (7.5 gEq/106 vs. 0 gEq/106, respectively; p=0.02). CONCLUSIONS: Just after delivery, SLE-patients had more microchimerism than control subjects. Three months post-partum, microchimerism was no longer detectable, only to reappear many years after the last pregnancy, more often and at higher levels in SLE-patients than in control subjects. This suggests that these chimeric cells may originate from non-circulating foetal chimeric stem cells.

Dynamic symptom networks across different at-risk stages for psychosis: An individual and transdiagnostic perspective.

The clinical staging model distinguishes different stages of mental illness. Early stages, are suggested to be more mild, diffuse and volatile in terms of expression of psychopathology than later stages. This study aimed to compare individual transdiagnostic symptom networks based on intensive longitudinal data between individuals in different early clinical stages for psychosis. It was hypothesized that with increasing clinical stage (i) density of symptom networks would increase and (ii) psychotic experiences would be more central in the symptom networks. Data came from a 90-day diary study, resulting in 8640 observations within N = 96 individuals, divided over four subgroups representing different early clinical stages (n1 = 25, n2 = 27, n3 = 24, n4 = 20). Sparse Time Series Chain Graphical Models were used to create individual contemporaneous and temporal symptom networks based on 10 items concerning symptoms of depression, anxiety, psychosis, non-specific and vulnerability domains. Network density and symptom centrality (strength) were calculated individually and compared between and within the four subgroups. Level of psychopathology increased with clinical stage. The symptom networks showed large between-individual variation, but neither network density not psychotic symptom strength differed between the subgroups in the contemporaneous (pdensity = 0.59, pstrength > 0.51) and temporal (pdensity = 0.75, pstrength > 0.35) networks. No support was found for our hypothesis that higher clinical stage comes with higher symptom network density or a more central role for psychotic symptoms. Based on the high inter-individual variability, our results highlight the importance of individualized assessment of symptom networks.

Was R < 1 before the English lockdowns? On modelling mechanistic detail, causality and inference about Covid-19.

Detail is a double edged sword in epidemiological modelling. The inclusion of mechanistic detail in models of highly complex systems has the potential to increase realism, but it also increases the number of modelling assumptions, which become harder to check as their possible interactions multiply. In a major study of the Covid-19 epidemic in England, Knock et al. (2020) fit an age structured SEIR model with added health service compartments to data on deaths, hospitalization and test results from Covid-19 in seven English regions for the period March to December 2020. The simplest version of the model has 684 states per region. One main conclusion is that only full lockdowns brought the pathogen reproduction number, R, below one, with R ≫ 1 in all regions on the eve of March 2020 lockdown. We critically evaluate the Knock et al. epidemiological model, and the semi-causal conclusions made using it, based on an independent reimplementation of the model designed to allow relaxation of some of its strong assumptions. In particular, Knock et al. model the effect on transmission of both non-pharmaceutical interventions and other effects, such as weather, using a piecewise linear function, b(t), with 12 breakpoints at selected government announcement or intervention dates. We replace this representation by a smoothing spline with time varying smoothness, thereby allowing the form of b(t) to be substantially more data driven, and we check that the corresponding smoothness assumption is not driving our results. We also reset the mean incubation time and time from first symptoms to hospitalisation, used in the model, to values implied by the papers cited by Knock et al. as the source of these quantities. We conclude that there is no sound basis for using the Knock et al. model and their analysis to make counterfactual statements about the number of deaths that would have occurred with different lockdown timings. However, if fits of this epidemiological model structure are viewed as a reasonable basis for inference about the time course of incidence and R, then without very strong modelling assumptions, the pathogen reproduction number was probably below one, and incidence in substantial decline, some days before either of the first two English national lockdowns. This result coincides with that obtained by more direct attempts to reconstruct incidence. Of course it does not imply that lockdowns had no effect, but it does suggest that other non-pharmaceutical interventions (NPIs) may have been much more effective than Knock et al. imply, and that full lockdowns were probably not the cause of R dropping below one.

Bistability in fatty-acid oxidation resulting from substrate inhibition.

In this study we demonstrated through analytic considerations and numerical studies that the mitochondrial fatty-acid ß-oxidation can exhibit bistable-hysteresis behavior. In an experimentally validated computational model we identified a specific region in the parameter space in which two distinct stable and one unstable steady state could be attained with different fluxes. The two stable states were referred to as low-flux (disease) and high-flux (healthy) state. By a modular kinetic approach we traced the origin and causes of the bistability back to the distributive kinetics and the conservation of CoA, in particular in the last rounds of the ß-oxidation. We then extended the model to investigate various interventions that may confer health benefits by activating the pathway, including (i) activation of the last enzyme MCKAT via its endogenous regulator p46-SHC protein, (ii) addition of a thioesterase (an acyl-CoA hydrolysing enzyme) as a safety valve, and (iii) concomitant activation of a number of upstream and downstream enzymes by short-chain fatty-acids (SCFA), metabolites that are produced from nutritional fibers in the gut. A high concentration of SCFAs, thioesterase activity, and inhibition of the p46Shc protein led to a disappearance of the bistability, leaving only the high-flux state. A better understanding of the switch behavior of the mitochondrial fatty-acid oxidation process between a low- and a high-flux state may lead to dietary and pharmacological intervention in the treatment or prevention of obesity and or non-alcoholic fatty-liver disease.

[Current developments on digitalization : Analysis of quality and economics in healthcare]. / Aktuelle Entwicklungen zur Digitalisierung : Eine Analyse zu Qualität und Ökonomie in der Gesundheitsversorgung.

BACKGROUND: In the German healthcare system and thus also in the field of urology, economic conditions are becoming increasingly relevant and, in addition, digital applications are becoming more widely used. OBJECTIVES: Health economic analysis of the framework of digitalization in the German healthcare system and selected areas of application in urology. METHODS: Analysis of the report of the German Advisory Council for the development of healthcare. Conduction of a systematic literature analysis on the use of structured reporting and analysis of selected literature on telemedical applications in urology from a health economic point of view. RESULTS: The German Advisory Council for the development of healthcare identifies the regulation and complexity of the German healthcare system as well as the handling of data protection and data security as key obstacles to digitalization. The use of structured reporting can increase the quality, effectiveness, and efficiency of reporting in urology. In terms of costs, significant savings can be realized with increasing digitalization in medicine. CONCLUSIONS: From a medical and health economic perspective, there is a need for further development in the framework for digital applications in the German healthcare system with regard to information security and data protection. With the appropriate use of digital applications such as structured reporting and telemedicine, optimal conditions can be established for the increasing use of artificial intelligence in the field of urology.

Was R<1 before the English lockdowns? On modelling mechanistic detail, causality and inference about Covid-19

Detail is a double edged sword in epidemiological modelling. The inclusion of mechanistic detail in models of highly complex systems has the potential to increase realism, but it also increases the number of modelling assumptions, which become harder to check as their possible interactions multiply. In a major study of the Covid-19 epidemic in England, Knock et al. (2020) fit an age structured SEIR model with added health service compartments to data on deaths, hospitalization and test results from Covid-19 in seven English regions for the period March to December 2020. The simplest version of the model has 684 states per region. One main conclusion is that only full lockdowns brought the pathogen reproduction number, R, below one, with R >> 1 in all regions on the eve of March 2020 lockdown. We critically evaluate the Knock et al. epidemiological model, and the semi-causal conclusions made using it, based on an independent reimplementation of the model designed to allow relaxation of some of its strong assumptions. In particular, Knock et al. model the effect on transmission of both non-pharmaceutical interventions and other effects, such as weather, using a piecewise linear function, b(t), with 12 breakpoints at selected government announcement or intervention dates. We replace this representation by a smoothing spline with time varying smoothness, thereby allowing the form of b(t) to be substantially more data driven, and we check that the corresponding smoothness assumption is not driving our results. We also reset the mean incubation time and time from first symptoms to hospitalisation, used in the model, to values implied by the papers cited by Knock et al. as the source of these quantities. We conclude that there is no sound basis for using the Knock et al. model and their analysis to make counterfactual statements about the number of deaths that would have occurred with different lockdown timings. However, if fits of this epidemiological model structure are viewed as a reasonable basis for inference about the time course of incidence and R, then without very strong modelling assumptions, the pathogen reproduction number was probably below one, and incidence in substantial decline, some days before either of the first two English national lockdowns. This result coincides with that obtained by more direct attempts to reconstruct incidence. Of course it does not imply that lockdowns had no effect, but it does suggest that other non-pharmaceutical interventions (NPIs) may have been more effective than Knock et al. imply, and that full lockdowns were probably not the cause of R dropping below one.

Sample collection from asteroid (162173) Ryugu by Hayabusa2: Implications for surface evolution.

The near-Earth asteroid (162173) Ryugu is thought to be a primitive carbonaceous object that contains hydrated minerals and organic molecules. We report sample collection from Ryugu's surface by the Hayabusa2 spacecraft on 21 February 2019. Touchdown images and global observations of surface colors are used to investigate the stratigraphy of the surface around the sample location and across Ryugu. Latitudinal color variations suggest the reddening of exposed surface material by solar heating and/or space weathering. Immediately after touchdown, Hayabusa2's thrusters disturbed dark, fine grains that originate from the redder materials. The stratigraphic relationship between identified craters and the redder material indicates that surface reddening occurred over a short period of time. We suggest that Ryugu previously experienced an orbital excursion near the Sun.

Scapular free flap as a good choice for mandibular reconstruction: 119 out of 280 cases after resection of oral squamous cell carcinoma in a single institution.

Microsurgical procedures for reconstruction after resection of head and neck tumours have become standardised and reliable. Among them, the scapular free flap is used less often, mostly to avoid excessive operating times. We hypothesise that complex reconstructions after resection of oral squamous cell carcinoma (OSCC) are successful even with time-consuming free flaps such as the scapular free flap. In this retrospective, single-centre study, we used the evaluation of medical records to investigate the postoperative outcome of microvascular reconstruction after ablative surgery of OSCC. Associations among the categorical variables were analysed using Pearson's chi squared test or Fisher's exact test. Among the continuous variables, the t test or Mann-Whitney U test were used as appropriate. For multivariate analysis, the logistic regression model was calculated. In the sample of 280 free flap reconstructions, we performed 142 radial forearm and 119 scapular free flaps. The American Society of Anesthesiology (ASA) score (p=0.006) and the duration of the operation (p=0.010) are independent factors which influence the need for operative revisions. The type of free flap is irrelevant for that. With 4.2% flap losses, scapular free flaps were successful; even in patients ≥ 70 years old (0 flap losses). Complex reconstructions after surgical resection of OSCC are successful even in aged patients. The scapular free flap is a good choice for mandibular reconstruction despite the time-consuming intraoperative repositioning of the patient. In an increasingly ageing group of patients, who have more vascular diseases, scapular free flaps could be a very successful alternative after ablative surgery of oral squamous cell carcinoma.