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Burn injury induces a complex inflammatory response, both locally and systemically, and is not yet completely unravelled and understood. In order to enable the development of accurate treatment options, it is of paramount importance to fully understand post-burn immunology. Research in the last decades describes insights into the prolonged and excessive inflammatory response that could exist after both severe and milder burn trauma and that this response differs from that of none-burn acute trauma. Persistent activity of complement, acute phase proteins and pro- and anti-inflammatory mediators, changes in lymphocyte activity, activation of the stress response and infiltration of immune cells have all been related to post-burn local and systemic pathology. This “narrative” review explores the current state of knowledge, focusing on both the local and systemic immunology post-burn, and further questions how it is linked to the clinical outcome. Moreover, it illustrates the complexity of post-burn immunology and the existing gaps in knowledge on underlying mechanisms of burn pathology.

In nuclear fuel rod bundles, turbulence-induced pressure fluctuations caused by an axial flow can create small but significant vibrations in the fuel rods, which in turn can cause structural effects such as material fatigue and fretting wear. Fluid-structure interaction simulations can be used to model these vibrations, but for affordable simulations based on the URANS approach, a model for the pressure fluctuations must be utilised. Driven by the goal to improve the current state-of-the-art pressure fluctuation model, AniPFM (Anisotropic Pressure Fluctuation Model) was developed. AniPFM can model velocity fluctuations based on anisotropic Reynolds stress tensors, with temporal correlation through the convection and decorrelation of turbulence. From these velocity fluctuations and the mean flow properties, the pressure fluctuations are calculated. The model was applied to several test cases and shows promising results in terms of reproducing qualitatively similar flow structures, as well as predicting the root-mean-squared pressure fluctuations. While further validation is being performed, the AniPFM has already demonstrated its potential for affordable simulations of turbulence-induced vibrations in industrial nuclear applications.

Objective: Burn injuries are still one of the most common and devastating global health problems worldwide. The vast majority of burns occur in low- and middle-income countries, particularly in sub-Saharan Africa. A certain standard of surgical and anaesthesia care is essential to minimize morbidity and mortality. The aim of this study is to obtain baseline information on surgical burn care in sub-Saharan Africa and to determine how this can be improved. Methods: A systematic review (PRISMA) was conducted. Data was extracted regarding study characteristics, patient and burn characteristics (aetiology of burn, total body surface area (TBSA), depth of burn), wound treatment and surgical care (type of wound dressing, surgery rate, skin graft rate, early vs. delayed) and outcome (mortality, wound infection, take of the grafts, length of stay, contracture formation). Results: Forty-two studies from 12 different countries were included [1–42]. Most studies were case series (37). The mean TBSA was 17.3%. Of the included patients, 44.4% underwent some type of operation. Overall mortality was 13.1%. Only 13 studies reported on the number of patients with deep burn wounds in their population. In this group 89.4% was grafted, of which 25.4% was performed early (

Abstract Burns are a significant cause of trauma, and over the years, the focus of patient care has shifted from just survival to facilitation of improved functional outcomes. Typically, burn treatment, especially in the case of extensive burn injuries, involves surgical excision of injured skin and reconstruction of the burn injury with the aid of skin substitutes. Conventional skin substitutes do not contain all skin cell types and do not facilitate recapitulation of native skin physiology. Three-dimensional (3D) bioprinting for reconstruction of burn injuries involves layer-by-layer deposition of cells along with scaffolding materials over the injured areas. Skin bioprinting can be done either in situ or in vitro. Both these approaches are similar except for the site of printing and tissue maturation. There are technological and regulatory challenges that need to be overcome for clinical translation of bioprinted skin for burn reconstruction. However, the use of bioprinting for skin reconstruction following burns is promising; bioprinting will enable accurate placement of cell types and precise and reproducible fabrication of constructs to replace the injured or damaged sites. Overall, 3D bioprinting is a very transformative technology, and its use for wound reconstruction will lead to a paradigm shift in patient outcomes. In this review, we aim to introduce bioprinting, the different stages involved, in vitro and in vivo skin bioprinting, and the various clinical and regulatory challenges in adoption of this technology.

Severe burn injury causes local and systemic immune responses that can persist up to months, and can lead to systemic inflammatory response syndrome, organ damage and long-term sequalae such as hypertrophic scarring. To prevent these pathological conditions, a better understanding of the underlying mechanisms is essential. In this longitudinal study, we analyzed the temporal peripheral blood immune profile of 20 burn wound patients admitted to the intensive care by flow cytometry and secretome profiling, and compared this to data from 20 healthy subjects. The patient cohort showed signs of systemic inflammation and persistently high levels of pro-inflammatory soluble mediators, such as IL-6, IL-8, MCP-1, MIP-1β, and MIP-3α, were measured. Using both unsupervised and supervised flow cytometry techniques, we observed a continuous release of neutrophils and monocytes into the blood for at least 39 days. Increased numbers of immature neutrophils were present in peripheral blood in the first three weeks after injury (0.1–2.8 × 106/ml after burn vs. 5 × 103/ml in healthy controls). Total lymphocyte numbers did not increase, but numbers of effector T cells as well as regulatory T cells were increased from the second week onward. Within the CD4+ T cell population, elevated numbers of CCR4+CCR6- and CCR4+CCR6+ cells were found. Altogether, these data reveal that severe burn injury induced a persistent innate inflammatory response, including a release of immature neutrophils, and shifts in the T cell composition toward an overall more pro-inflammatory phenotype, thereby continuing systemic inflammation and increasing the risk of secondary complications.

In this paper, we capture and explore the painterly depictions of materials to enable the study of depiction and perception of materials through the artists' eye. We annotated a dataset of 19k paintings with 200k+ bounding boxes from which polygon segments were automatically extracted. Each bounding box was assigned a coarse material label (e.g., fabric) and half was also assigned a fine-grained label (e.g., velvety, silky). The dataset in its entirety is available for browsing and downloading at materialsinpaintings.tudelft.nl. We demonstrate the cross-disciplinary utility of our dataset by presenting novel findings across human perception, art history and, computer vision. Our experiments include a demonstration of how painters create convincing depictions using a stylized approach. We further provide an analysis of the spatial and probabilistic distributions of materials depicted in paintings, in which we for example show that strong patterns exists for material presence and location. Furthermore, we demonstrate how paintings could be used to build more robust computer vision classifiers by learning a more perceptually relevant feature representation. Additionally, we demonstrate that training classifiers on paintings could be used to uncover hidden perceptual cues by visualizing the features used by the classifiers. We conclude that our dataset of painterly material depictions is a rich source for gaining insights into the depiction and perception of materials across multiple disciplines and hope that the release of this dataset will drive multidisciplinary research.

Background:. Worldwide, many scar contracture release surgeries are performed to improve range of motion (ROM) after a burn injury. There is a particular need in low- and middle-income countries (LMICs) for such procedures. However, well-designed longitudinal studies on this topic are lacking globally. The present study therefore aimed to evaluate the long-term effectiveness of contracture release surgery performed in an LMIC. Methods:. This pre-/postintervention study was conducted in a rural regional referral hospital in Tanzania. All patients undergoing contracture release surgery during surgical missions were eligible. ROM data were indexed to normal values to compare various joints. Surgery was considered effective if the ROM of all planes of motion of a single joint increased at least 25% postoperatively or if the ROM reached 100% of normal ROM. Follow-ups were at discharge and at 1, 3, 6, and 12 months postoperatively. Results:. A total of 70 joints of 44 patients were included. Follow-up rate at 12 months was 86%. Contracture release surgery was effective in 79% of the joints (P < 0.001) and resulted in a mean ROM improvement from 32% to 90% of the normal value (P < 0.001). A predictive factor for a quicker rehabilitation was lower age (R2 = 11%, P = 0.001). Complication rate was 52%, consisting of mostly minor complications. Conclusions:. This is the first study to evaluate the long-term effectiveness of contracture release surgery in an LMIC. The follow-up rate was high and showed that contracture release surgery is safe, effective, and sustainable. We call for the implementation of outcome research in future surgical missions.

Background: In burn patients, wound healing is often accompanied by hypertrophic scar (HS) development, resulting in both functional and aesthetic problems. HSs are characterised by abundant presence of myofibroblasts that contribute to overproduction of extracellular matrix (ECM) that is regulated by the TGF-β signalling pathway. Studies have shown that inhibition of TGF-β receptors in fibrotic diseases reduces the fibrotic load. In the present study, we aim to inactivate ALK5, also known as TGF-β receptor I, in human HS fibroblasts by exon skipping using antisense oligonucleotides (AONs). Methods: HS biopsies were used to isolate and set up fibroblast monocultures. AONs targeting ALK5 were supplemented to the fibroblast cultures to induce exon skipping, while pharmacological ALK5 inhibition was induced using SB431542. AON delivery in HS fibroblasts was examined using immunofluorescence (IF), while TGF-β signalling downstream targets, such as Smad2/3, PAI-1, ACTA2, COL1A1 and COL3A1, were analysed using touchdown polymerase chain reaction (PCR), quantitative PCR (qPCR), IF or western blotting. Results: Our data clearly demonstrate that AONs were successfully delivered in the nuclei of HS fibroblasts and that functional exon skipping of ALK5 took place as confirmed with touchdown PCR and qPCR. In addition, exon skipping affected the expression of ECM-related genes, such as type I/III collagens, PAI-1 and CCN2. Moreover, AON treatment did not affect the migration of HS fibroblasts in a model for wound healing. Conclusion: Exon skipping is a promising tool to modulate the TGF-β signalling pathway in HS. This would open a therapeutic window for the treatment of patients suffering from HSs.

Abstract Background Deep dermal burns require tangential excision of non-viable tissue and skin grafting to improve wound healing and burn-scar quality. Tangential excision is conventionally performed with a knife, but during the last decade hydrosurgery has become popular as a new tool for tangential excision. Hydrosurgery is generally thought to be a more precise and controlled manner of burn debridement leading to preservation of viable tissue and, therefore, better scar quality. Although scar quality is considered to be one of the most important outcomes in burn surgery today, no randomized controlled study has compared the effect of these two common treatment modalities with scar quality as a primary outcome. The aim of this study is, therefore, to compare long-term scar quality after hydrosurgical versus conventional tangential excision in deep dermal burns. Methods/design A multicenter, randomized, intra-patient, controlled trial will be conducted in the Dutch burn centers of Rotterdam, Beverwijk, and Groningen. All patients with deep dermal burns that require excision and grafting are eligible. Exclusion criteria are: a burn wound 30%, full-thickness burns, chemical or electrical burns, infected wounds (clinical symptoms in combination with positive wound swabs), insufficient knowledge of the Dutch or English language, patients that are unlikely to comply with requirements of the study protocol and follow-up, and patients who are (temporarily) incompetent because of sedation and/or intubation. A total of 137 patients will be included. Comparable wound areas A and B will be appointed, randomized and either excised conventionally with a knife or with the hydrosurgery system. The primary outcome is scar quality measured by the observer score of the Patient and Observer Scar Assessment Scale (POSAS); a subjective scar-assessment instrument, consisting of two separate six-item scales (observer and patient) that are both scored on a 10-point rating scale. Discussion This study will contribute to the optimal surgical treatment of patients with deep dermal burn wounds. Trial registration Dutch Trial Register, NTR6232. Registered on 23 January 2017.

Traditional on-site missions of plastic surgeons from "high-income countries" in "low- and middle-income countries" are often limited in time and lack proper follow-up. Regular digital collaboration could lead to a more impactful and durable exchange of knowledge for plastic surgeons and residents in both settings. The aim of this study was to evaluate the satisfaction of the first twelve months of weekly digital meetings, explore advantages/disadvantages, and to provide tools for similar initiatives. Weekly meetings started from August 2021. An encrypted digital connection allowed residents and plastic surgeons from Uganda and the Netherlands to discuss cases for educational purposes, where treatment options were considered. After twelve months, a survey was sent to participants from both countries to indicate the meetings' strengths, weaknesses, and possible improvements. A total of 18 participants responded to the questionnaire (ten plastic surgeons, six residents, and two researchers). The strengths of the meetings were the accessibility of the meetings, knowledge exchange and practice for residents' final exams. Possible improvements included having a clear format for patient discussion, a session moderator and better internet connectivity. Moreover, a database to assess the impact of the given intervention on the patient cases by evaluating postoperatively (e.g. three months), could further improve clinical care. Virtual patient discussions subjectively contributed to medical education at both locations. Improved digital infrastructure and a collaborative database could further maximize learning capacity. Furthermore, digital proctoring is a promising way to establish sustainable collaborations between high- and low-resource countries. [ABSTRACT FROM AUTHOR]

Wound healing is an essential process to restore tissue integrity after trauma. Large skin wounds such as burns often heal with hypertrophic scarring and contractures, resulting in disfigurements and reduced joint mobility. Such adverse healing outcomes are less common in the oral mucosa, which generally heals faster compared to skin. Several studies have identified differences between oral and skin wound healing. Most of these studies however focus only on a single stage of wound healing or a single cell type. The aim of this review is to provide an extensive overview of wound healing in skin versus oral mucosa during all stages of wound healing and including all cell types and molecules involved in the process and also taking into account environmental specific factors such as exposure to saliva and the microbiome. Next to intrinsic properties of resident cells and differential expression of cytokines and growth factors, multiple external factors have been identified that contribute to oral wound healing. It can be concluded that faster wound closure, the presence of saliva, a more rapid immune response, and increased extracellular matrix remodeling all contribute to the superior wound healing and reduced scar formation in oral mucosa, compared to skin.

Background:. Measurements of scar quality are essential to evaluate the effectiveness of scar treatments and to monitor scars. A large number of scar scales and measurement devices have been developed, which makes instrument selection challenging. The aim of this study was to provide an overview of the content (ie, included items) of all outcome measurement instruments that measure scar quality in different types of scars (burn, surgical, keloid, and necrotizing fasciitis), and the frequency at which the instruments and included items are used. Methods:. A systematic search was performed in PubMed and Embase.com up to October 31, 2018. All original studies reporting on instruments that measured at least 1 characteristic of scar quality were included and the instrument’s content was extracted. Results:. We included 440 studies for data extraction. Included instruments (N = 909) were clinician-reported scales (41%), measurement devices (30%), patient-reported scales (26%), and combined clinician- and patient-reported scales (3%). The Observer scale of the Patient and Observer Scar Assessment Scale, the Cutometer, the Patient Scale of the Patient and Observer Scar Assessment Scale, and the modified Vancouver Scar Scale were the most often used instrument in each of these categories, respectively. The most frequent assessed items were thickness, vascularity, pigmentation, pliability, pain, and itch. Conclusion:. The results of this study lay the foundation for our future research, which includes an international Delphi study among many scar experts, and an international focus group study among scar patients, aiming to elucidate how scar quality must be defined and measured from both professional and patient perspectives.

Background:. In the human ear and nose, cartilage plays a key role in establishing its form and function. Interestingly, there is a noticeable paucity on biochemical, structural, and mechanical studies focused on facial cartilage. Such studies are needed to provide elementary knowledge that is fundamental to tissue engineering of cartilage. Therefore, in this study, a comparison is made of the biochemical, structural, and mechanical differences between ear, ala nasi, and septum on the extracellular matrix (ECM) level. Methods:. Cartilage samples were harvested from 10 cadaveric donors. Each sample was indented 10 times with a nanoindenter to determine the effective Young’s modulus. Structural information of the cartilage was obtained by multiple-photon laser scanning microscopy capable of revealing matrix components at subcellular resolution. Biochemistry was performed to measure glycosaminoglycan (GAG), DNA, elastin, and collagen content. Results:. Significant differences were seen in stiffness between ear and septal cartilage (P = 0.011) and between ala nasi and septal cartilage (P = 0.005). Elastin content was significantly higher in ear cartilage. Per cartilage subtype, effective Young’s modulus was not significantly correlated with cell density, GAG, or collagen content. However, in septal cartilage, low elastin content was associated with higher stiffness. Laser microscopy showed a distinct difference between ear cartilage and cartilage of nasal origin. Conclusion:. Proposed methods to investigate cartilage on the ECM level provided good results. Significant differences were seen not only between ear and nasal cartilage but also between the ala nasi and septal cartilage. Albeit its structural similarity to septal cartilage, the ala nasi has a matrix stiffness comparable to ear cartilage.

Fauna Europaea provides a public web-service with an index of scientific names (including important synonyms) of all extant multicellular European terrestrial and freshwater animals and their geographical distribution at the level of countries and major islands (east of the Urals and excluding the Caucasus region). The Fauna Europaea project comprises about 230,000 taxonomic names, including 130,000 accepted species and 14,000 accepted subspecies, which is much more than the originally projected number of 100,000 species. Fauna Europaea represents a huge effort by more than 400 contributing taxonomic specialists throughout Europe and is a unique (standard) reference suitable for many user communities in science, government, industry, nature conservation and education. The Diptera–Brachycera is one of the 58 Fauna Europaea major taxonomic groups, and data have been compiled by a network of 55 specialists. Within the two-winged insects (Diptera), the Brachycera constitute a monophyletic group, which is generally given rank of suborder. The Brachycera may be classified into the probably paraphyletic 'lower brachyceran grade' and the monophyletic Eremoneura. The latter contains the Empidoidea, the Apystomyioidea with a single Nearctic species, and the Cyclorrhapha, which in turn is divided into the paraphyletic 'aschizan grade' and the monophyletic Schizophora. The latter is traditionally divided into the paraphyletic 'acalyptrate grade' and the monophyletic Calyptratae. Our knowledge of the European fauna of Diptera–Brachycera varies tremendously among families, from the reasonably well known hoverflies (Syrphidae) to the extremely poorly known scuttle flies (Phoridae). There has been a steady growth in our knowledge of European Diptera for the last two centuries, with no apparent slow down, but there is a shift towards a larger fraction of the new species being found among the families of the nematoceran grade (lower Diptera), which due to a larger number of small-sized species may be considered as taxonomically more challenging. Most of Europe is highly industrialised and has a high human population density, and the more fertile habitats are extensively cultivated. This has undoubtedly increased the extinction risk for numerous species of brachyceran flies, yet with the recent re-discovery of Thyreophora cynophila (Panzer), there are no known cases of extinction at a European level. However, few national Red Lists have extensive information on Diptera. For the Diptera–Brachycera, data from 96 families containing 11,751 species are included in this paper.

Despite advances in turbulence modelling, the Smagorinsky model remains a popular choice for large eddy simulation (LES) due to its simplicity and ease of use. The dissipation in turbulence energy that the model introduces, is proportional to the Smagorinsky constant, of which many different values have been proposed. These values have been derived for certain simulated test-cases while using a specific set of numerical schemes, to obtain the correct dissipation in energy simply because an incorrect value of the Smagorinsky constant would lead to an incorrect dissipation. However, it is important to bear in mind that numerical codes may suffer from numerical or artificial dissipation, which occurs spuriously through a combination of spatio-temporal and iterative errors. The latter can be controlled through more iterations, the former however, depends on the grid resolution and the time step. Recent research suggests that a complete energy-conserving (EC) spatio-temporal discretisation guarantees zero numerical dissipation for any grid resolution and time step. Therefore, using an EC scheme would ensure that dissipation occurs primarily through the Smagorinsky model (and errors in its implementation) than through the discretisation of the Navier-Stokes (NS) equations. To evaluate the efficacy of these schemes for engineering applications, the article first discusses the use of an EC temporal discretisation as regards to accuracy and computational effort, to ascertain whether EC time advancement is advantageous or not. It was noticed that a simple non-EC explicit method with a smaller time step not only reduces the numerical dissipation to an acceptable level but is computationally cheaper than an implicit-EC scheme for wide range of time steps. Secondly, in terms of spatial discretisation on uniform grids (popular in LES), a simple central-difference scheme is as accurate as an EC spatial discretisation. Finally, following the removal of numerical dissipation with any of the methods mentioned above, one is able to choose a Smagorinsky constant that is nearly independent of the grid resolution (within realistic bounds, for OpenFOAM and an in-house code). This article provides impetus to the efficient use of the Smagorinsky model for LES in fields such as wind farm aerodynamics and atmospheric simulations, instead of more comprehensive and computationally demanding turbulence models.

Background: The population of elderly patients with burn injuries is growing. Insight into long-term mortality rates of elderly after burn injury and predictors affecting outcome is limited. This study aimed to provide this information. Methods: A multicentre observational retrospective cohort study was conducted in all three Dutch burn centres. Patients aged ≥65 years, admitted with burn injuries between 2009 and 2018, were included. Data were retrieved from electronic patient records and the Dutch Burn Repository R3. Mortality rates and standardized mortality ratios (SMRs) were calculated. Multivariable logistic regression was used to assess predictors for in-hospital mortality and mortality after discharge at 1 year and five-year. Survival analysis was used to assess predictors of five-year mortality. Results: In total, 682/771 admitted patients were discharged. One-year and five-year mortality rates were 8.1 and 23.4%. The SMRs were 1.9(95%CI 1.5–2.5) and 1.4(95%CI 1.2–1.6), respectively. The SMRs were highest in patients aged 75–80 years at 1 year (SMRs 2.7, 95%CI 1.82–3.87) and five-year in patients aged 65–74 years (SMRs 10.1, 95%CI 7.7–13.0). Independent predictors for mortality at 1 year after discharge were higher age (OR 1.1, 95%CI 1.0–1.1), severe comorbidity, (ASA-score ≥ 3) (OR 4.8, 95%CI 2.3–9.7), and a non-home discharge location (OR 2.0, 95%CI 1.1–3.8). The relative risk of dying up to five-year was increased by age (HR 1.1, 95%CI 1.0–1.1), severe comorbidity (HR 2.3, 95%CI 1.6–3.5), and non-home discharge location (HR 2.1, 95%CI 1.4–3.2). Conclusion: Long-term mortality until five-year after burn injury was higher than the age and sex-matched general Dutch population, and predicted by higher age, severe comorbidity, and a non-home discharge destination. Next to pre-injury characteristics, potential long-lasting systemic consequences on biological mechanisms following burn injuries probably play a role in increased mortality. Decreased health status makes patients more prone to burn injuries, leading to early death. [ABSTRACT FROM AUTHOR]

Discrete-time forward interest rate curve models are studied, where the curves are driven by a random field. Under the assumption of no-arbitrage, the maximum likelihood estimator of the volatility parameter is given and its asymptotic behaviour is studied. First, the so-called martingale models are examined, but we will also deal with the general case, where we include the market price of risk in the discount factor.