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Postmortem detection of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) after the exhumation of a corpse can become important, e.g. in the case of subsequent medical malpractice allegations. To date, data on possible detection periods [e.g. by reverse transcription polymerase chain reaction (RT-PCR)] or on the potential infectivity of the virus after an exhumation are rare. In the present study, these parameters were examined in two cases with a time span of approximately 4 months between day of death and exhumation. Using SARS-CoV-2 RT-PCR on swabs of both lungs and the oropharynx detection was possible with cycle threshold (Ct) values of about 30 despite signs of beginning decay. RT-PCR testing of perioral and perinasal swabs and swabs collected from the inside of the body bag, taken to estimate the risk of infection of those involved in the exhumation, was negative. Cell culture-based infectivity testing was negative for both, lung and oropharyngeal swabs. In one case, RT-PCR testing at the day of death of an oropharyngeal swab showed almost identical Ct values as postmortem testing of an oropharyngeal swab, impressively demonstrating the stability of viral RNA in the intact corpse. However, favorable climatic conditions in the grave have to be taken into account, as it was wintertime with constant low temperatures. Nevertheless, it was possible to demonstrate successful postmortem detection of SARS-CoV-2 infection following exhumation even after months in an earth grave.

Background Burn wound progression is a significant problem as burns initially thought to be superficial can actually become full thickness over time. Cooling is an efficient method to reduce burn wound conversion. However, if the cooling agent is below room temperature, depending on the wound size the patient is at risk of hypothermia. Additionally, tissue perfusion is reduced leading to an aggravation of burn wound progression. We investigated if wound dressings based on non-pre-cooled bacterial nanocellulose (BNC) with a high water content cool a burn just by evaporation and reduce the intradermal damages in the skin. Material and methods In a human ex-vivo model, skin explants underwent contact burns using a 100 °C hot steel block. The burned areas were divided into two groups of which one was cooled with a BNC-based wound dressing. Intradermal temperature probes measured temperature in cooled and uncooled burn sites over 24 h. For histological assessments of the burned areas biopsies were taken at different time points. High mobility group box-1 (HMBG1) staining served as marker for cell vitality and necrosis in the different skin layers. Results Intradermal temperature measurement showed that application of the BNC-based wound dressing reduced temperature significantly in burned skin. This cooling effect resulted in a maximum temperature difference of 6.4 ± 1.9 °C and a significant mean reduction of the area under the curve in the first hour after burn of 62% (p Conclusion Based on our results, BNC-based wound dressings cool a burn. Intradermal temperature as well as thermal damage of the tissue was reduced. The tested BNC-based wound dressing can be used without pre-cooling to cool a burn as well as to reduce the burn BNC-based wound progression through its evaporation cooling effect.

Background Bacterial nanocellulose (BNC) is considered a promising carrier for various substances and novel approaches using BNC in combination with antiseptics are well documented. However, the difference in the molecular weight of these molecules influences their uptake by and release from BNC. Analysing the diffusion of standard molecules with different weight, e.g. dextrans, offers the possibility to investigate the mobility of various molecules. We aimed to test the use of BNC regarding uptake and release of different standard molecules as well as two commercially available antiseptics for possible applications in future wound dressings. Material and methods Diffusion profiles, uptake and release of three FITC-dextran molecules differing in weight as well as octenidine (Octenisept®) and povidone-iodine (Betaisodona®)-based antiseptics were tested with BNC-based wound dressings. Furthermore, the antiseptic efficacy of BNC in combination with antiseptics against Staphylococcus aureus was tested. Results Uptake and release capacity for FITC-dextran molecules showed a molecular weight-dependent mobility from BNC into an agarose gel. The loading capacity of BNC was also inversely proportional to the molecular weight of the antiseptics. The release test for octenidine showed a sustained and prolonged delivery into a solid matrix, whereas povidone-iodine was released faster. Both antiseptic solutions combined with BNC showed a good dose-dependent efficacy against S. aureus. Conclusion Results obtained from the mobility of FITC-dextran molecules in the BNC matrix could open possible applications for the combination of BNC with other molecules for medical applications. Combination of both tested antiseptics with BNC showed to be an efficient approach to control bacterial infections.

Purpose To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (µOCT) imaging and to assess µOCT's clinical potential as a screening tool for corneal and systemic diseases. Methods An experimental high-resolution (1.5 × 1.5 × 1 µm) µOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in µOCT were compared to β3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ. Results Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the µOCT scans as approximately 88% in multiple image recordings of the same cornea. Conclusions Compared to the current gold standard of FCM, µOCT's larger field of view of currently 1 × 1 mm increases the conclusiveness of density measurements, which, coupled with µOCT's feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy). Translational Relevance Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.

Decarbonization of industry is a key challenge to achieve the Paris climate goals. Digitalization of the industry is a cornerstone of this journey. In this paper we present our modelling work towards the creation of a Digital Energy Twin of the energy supply system of a printed boarding circuit manufacturing by means of a classical use case, system design optimization. The simulation approach allowed us to fairly compare the improvements done in the energy supply system by evaluating those under the same operating conditions. Integration of waste chiller’s waste heat can cover most of the low temperature grid heat demand while the additional generation of chilled water reduces the amount of water pump from and back to the river.

Background and objectives A recent generation of 5,500 nm wavelength carbon monoxide (CO) lasers could serve as a novel tool for applications in medicine and surgery. At this wavelength, the optical penetration depth is about three times higher than that of the 10,600 nm wavelength carbon dioxide (CO2 ) laser. As the amount of ablation and coagulation is strongly influenced by the wavelength, we anticipated that CO lasers would provide extended coagulation zones, which could be beneficial for several medical applications, such as tissue tightening effects after laser skin resurfacing. Until now, the 1,940 nm wavelength thulium fiber (Tm:fiber) laser is primarily known as a non-ablative laser with an optical penetration depth that is eight times higher than that of the CO2 laser. The advantage of lasers with shorter wavelengths is the ability to create smaller spot sizes, which has a determining influence on the ablation outcome. In this study, the ablation and coagulation characteristics of a novel CO laser and a high power Tm:fiber laser were investigated to evaluate their potential application for fractional ablation of the skin. Study design/materials and methods Laser-tissue exposures were performed using a novel CO laser, a modified, pulse-width-modulated CO2 laser, and a Tm:fiber laser. We used discarded ex vivo human skin obtained from abdominoplasty as tissue samples. Similar exposure parameters, such as spot size (108-120 μm), pulse duration (2 milliseconds), and pulse energy (~10-200 mJ) were adjusted for the different laser systems with comparable temporal pulse structures. Laser effects were quantified by histology. Results At radiant exposures 10-fold higher than the ablation threshold, the CO laser ablation depth was almost two times deeper than that of the CO2 laser. At 40-fold of the ablation threshold, the CO laser ablation was 47% deeper. The ablation craters produced by the CO laser exhibited about two times larger coagulation zones when compared with the CO2 laser. In contrast, the Tm:fiber laser exhibited superficial ablation craters with massive thermal damage. Conclusions The tissue ablation using the Tm:fiber laser was very superficial in contrast to the CO laser and the CO2 laser. However, higher etch depths should be obtainable when the radiant exposure is increased by using higher pulse energies and/or smaller spot sizes. At radiant exposures normalized to the ablation threshold, the CO laser was capable of generating deeper ablation craters with extended coagulation zones compared with the CO2 laser, which is possibly desirable depending on the clinical goal. The effect of deep ablation combined with additional thermal damage on dermal remodeling needs to be further confirmed with in vivo studies. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Continuous subcutaneous insulin infusion (CSII) is a widely used treatment for diabetes patients. Insulin infusion sets (CSII-catheters) are continuously optimized regarding size, handling and safety, but recurring dysfunction (kinking or occlusion), due to different user situations, behavior or chain of events, demand new ways to improve the functionality and safety in patients experiencing these issues. A novel CSII-catheter design (Lantern) features additional lateral perforations, which guarantee functionality even in case of kinking or occlusion. This study aimed to compare functionality, insulin distribution, and failure rate of Lantern and standard catheters using excised human adipose tissue samples. Novel Lantern CSII-catheters (open and artificially occluded) and commercially available standard CSII-catheters were inserted into adipose tissue samples. A mixture of insulin and contrast agent was infused as single bolus (7 IU) with an insulin infusion pump at highest flow rate (1 IU/s). Microtomography images and surface-to-volume ratios were used to assess insulin distribution and depot volume indicating the functionality of CSII-catheters. Failure rate was measured by flow-stop alerts of the pump. We found no difference in the volume of insulin depots compared with the nominal volume of 70 μL. Surface-to-volume ratios showed no significant difference among CSII-catheters. None of the catheters triggered any flow-stop alarm. The novel Lantern CSII-catheter design achieved similar insulin distribution as commercially available CSII-catheters. Moreover, functionality of Lantern CSII-catheters was guaranteed during occlusion, which is an improvement compared with standard CSII-catheters. We conclude that the novel CSII-catheter design has the potential to provide a valuable contribution to patient well-being and safety.

Background/objectives Standard optical coherence tomography angiography (OCTA) has been limited to imaging blood vessels actively undergoing perfusion, providing a temporary picture of surface microvasculature. Capillary perfusion in the skin is dynamic and changes in response to the surrounding tissue's respiratory, nutritional, and thermoregulatory needs. Hence, OCTA often represents a given perfusion state without depicting the actual extent of the vascular network. Here we present a method for obtaining a more accurate anatomic representation of the surface capillary network in human skin using OCTA, along with proposing a new parameter, the Relative Capillary Capacity (RCC), a quantifiable proxy for assessing capillary dilation potential and permeability. Methods OCTA images were captured at baseline and after compression of the skin. Baseline images display ambient capillary perfusion, while images taken upon capillary refill display the network of existing capillaries at full capacity. An optimization-based automated vessel segmentation method was used to automatically analyze and compare OCTA image sequences obtained from two volunteers. RCC was then compared with visual impressions of capillary viability. Results Our OCTA imaging sequence provides a method for mapping cutaneous capillary networks independent of ambient perfusion. Differences between baseline and refill images clearly demonstrate the shortcomings of standard OCTA imaging and produce the RCC biometric as a quantifiable proxy for assessing capillary dilation potential and permeability. Conclusion Future dermatological OCTA diagnostic studies should implement the Capillary Refill Methods over standard imaging techniques and further explore the relevance of RCC to differential diagnosis and dermatopathology. Lasers Surg. Med. © The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

The agenesis of one or both upper thyroid horns (UTH) cannot be considered rare with an incidence ranging between 0.8–9.4%. Studies so far have mostly described frequencies, yet surveys on its morphology and traumatology are missing. It is unknown to what extent this anatomical variant impacts the overall symmetry of the larynx. For the trauma reconstruction after cervical trauma this knowledge is required as an asymmetric larynx can show a different fracture pattern. In this investigation, larynxes with unilateral (n = 21)/bilateral (n = 5) agenesis of the upper thyroid horn(s) and a control group with regular larynxes (n = 23) were juxtaposed. Various measurements were taken after μ-CT scanning. In total 10 distances/angles for the thyroid cartilage and 8 for the cricoid cartilage were compared. Using intra-individual and matched pair comparisons the symmetry was assessed. The results of this investigation showed significant differences in the intra-individual and pairwise comparison for the opening angle and the length of the thyroid alae although the lateral inclination of the thyroid alae showed no significant difference. Combining these three parameters into one symmetry score, the comparison was not significant. This research demonstrates that neither unilateral nor bilateral agenesis of the UTH is related to a structural disbalance of the larynx. Thus, different fracture patterns or vulnerabilities are not to be expected.

Background Trisomy 21 is the most common human chromosomal abnormality. Its manifestation includes intellectual impairment and more or less typical anatomical malformations and functional deficiencies that can cause sudden or unexpected deaths. Typical medicolegal questions at autopsy are related to medical malpractice, improper care, neglect, or abuse, and, depending on the cause of death, whether the death might have been avoidable. The aim of this study was to examine whether the causes of death in individuals with trisomy 21 were linked to the known health risks for this condition and to consider how these deaths might have been prevented. Material and methods A retrospective study was performed at the Institutes for Legal Medicine in Giessen and Frankfurt am Main, Hesse, Germany. All records for forensic autopsy cases within a 20-year period from 1998 to 2017 were reviewed for the diagnosis trisomy 21”, respectively, “Down’s syndrome”. Results Twenty-three cases complied with the inclusion criteria trisomy 21 and autopsy. The age of the deceased ranged from 23 days to 61 years. Infectious diseases, mainly respiratory, were the leading cause of death, followed by accidental deaths. Conclusion The medicolegal relevance of the known health risks in Down’s syndrome could be illustrated by the autopsy findings and the results of the additional examinations. The known high susceptibility to infections, with an increased risk of a rapid course and lethal outcome, in individuals with Down’s syndrome could be confirmed in our study. A sound knowledge of the risks and abnormalities associated with trisomy 21 are helpful in medicolegal assessments, particularly, in relation to medical malpractice charges.

Zusammenfassung Misshandlung und sexueller Missbrauch von Kindern hinterlassen u.a. physische Verletzungen. Diese können bei zeitnaher Dokumentation entscheidend sein für eine Beweisführung u.a. vor Gericht. Dabei werden körperliche Untersuchungen von verschiedenen Institutionen in Auftrag gegeben (Jugendamt, Polizei, Staatsanwaltschaft, Gericht) und es werden Gewaltformen unterschieden: stumpfe Gewalt (z.B. Schläge), thermische Gewalt (z.B. Verbrennen durch eine Zigarette), scharfe Gewalt (z.B. durch ein Messer). Hinzu kommen spezielle Formen der Kindesmisshandlung: u.a. das Schütteltrauma-Syndrom und das Münchhausen-Syndrom by proxy.

Introduction The estimation of age-at-death of unidentified cadavers is a central aspect of the identification process. With increasing age, the incidence of glomerulosclerosis and the thickness of the carotid wall have been observed to also increase. This correlation has been demonstrated in various international histological studies. The aim of our study was to assess whether these correlations also apply to a Western European population. Methodology In this retrospective observational study, kidney and common carotid artery samples from 216 cases autopsied at the Institute of Legal Medicine at the Justus-Liebig University in Giessen, Germany, were examined. Only cases with available tissue samples from both body sides were included. Exclusion criteria were poor sample quality and an age younger than 21 years. After histological processing, the tissue samples were assessed and digitally evaluated. Regression and classification analyses were used to investigate the correlation between age-at-death and intima-media thickness and age-at-death and the incidence of renal glomerular sclerosis. Results Of the 216 autopsy cases, 183 were included for evaluation. Analysis of the carotid artery segments showed a strong correlation (Pearson correlation coefficient r = 0.887) between the intima-media-complex thickness and chronological age. Classification of the glomerulosclerotic incidence showed a correlation of 37.7–43.1% with the predicted age group. Discussion Both the intima-media thickness and the proportion of sclerotic glomeruli can be used to estimate age in Western European cadavers. On the basis of these results, both methods are suited to supplement other already established methods for age-at-death estimation in the identification of an unknown cadaver.

The treatment of macular diseases requires frequent monitoring by optical coherence tomography (OCT). Home monitoring would reduce the burden of frequent clinical visits and increase therapy adherence. In a pilot study with 47 patients having different macular diseases we tested a proprietary self-examination low-cost full-field OCT (SELFF-OCT). For comparison, scans with a standard clinical spectral domain OCT were taken. Data was graded by a reading center. Patients were able to successfully acquire images that were clinically gradable for 85% of the included eyes. The sensitivity and specificity for an anti-VEGF treatment decision based on the SELFF-OCT was 0.94 and 0.95, respectively.

Burn injuries initiate numerous processes such as heat shock response, inflammation and tissue regeneration. Reliable burn models are needed to elucidate the exact sequence of local events to be able to better predict when local inflammation triggers systemic inflammatory processes. In contrast to other ex vivo skin culture approaches, we used fresh abdominal skin explants to introduce contact burn injuries. Histological and ultrastructural analyses confirmed a partial-thickness burn pathology. Gene expression patterns and cytokine production profiles of key mediators of the local inflammation, heat shock response, and tissue regeneration were analyzed for 24 h after burn injury. We found significantly increased expression of factors involved in tissue regeneration and inflammation soon after burn injury. To investigate purely inflammation-mediated reactions we injected lipopolysaccharide into the dermis. In comparison to burn injury, lipopolysaccharide injection initiated an inflammatory response while expression patterns of heat shock and tissue regeneration genes were unaffected for the duration of the experiment. This novel ex vivo human skin model is suitable to study the local, early responses to skin injuries such as burns while maintaining an intact overall tissue structure and it gives valuable insights into local mechanisms at the very beginning of the wound healing process after burn injuries.

In April 2020, the QUality Assessment and REProducibility for Instruments and Images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models, and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper 1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; 2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers, and observers of such; 3) outlines the current actions of the QUAREP-LiMi initiative, and 4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics., Comment: 17 pages, 3 figures, shortened abstract, Co-Lead Authors: Glyn Nelson and Ulrike Boehm, Corresponding author: Roland Nitschke

To investigate the difference in clinical efficacy in AD patients between two topical PDE4 inhibitors using dermal open flow microperfusion and cAMP as a pharmacodynamic read-out in fresh human skin explants. Clinical formulations were applied to intact or barrier disrupted human skin explants and both skin biopsy samples and dermal interstitial fluid was sampled for measuring drug concentration. Furthermore, cAMP levels were determined in the skin biopsies as a measure of target engagement. Elevated cAMP levels were observed with LEO 29102 while no evidence of target engagement was obtained with LEO 39652. In barrier impaired skin the dISF concentration of LEO 29102 was 2100 nM while only 33 nM for LEO 39652. For both compounds the concentrations measured in skin punch biopsies were 7–33-fold higher than the dISF concentrations. Low unbound drug concentration in dISF in combination with minimal target engagement of LEO 39652 in barrier impaired human skin explants supports that lack of clinical efficacy of LEO 39652 in AD patients is likely due to insufficient drug availability at the target. We conclude that dOFM together with a pharmacodynamic target engagement biomarker are strong techniques for establishing skin PK/PD relations and that skin biopsies should be used with caution.

Purpose Dermal open flow microperfusion (dOFM) has previously demonstrated its utility to assess the bioequivalence (BE) of topical drug products in a clinical study. We aimed to characterize the sources of variability in the dermal pharmacokinetic data from that study. Methods Exploratory statistical analyses were performed with multivariate data from a clinical dOFM-study in 20 healthy adults evaluating the BE, or lack thereof, of Austrian test (T) and U.S. reference (R) acyclovir cream, 5% products. Results The overall variability of logAUC values (CV: 39% for R and 45% for T) was dominated by inter-subject variability (R: 82%, T: 91%) which correlated best with the subject’s skin conductance. Intra-subject variability was 18% (R) and 9% (T) of the overall variability; skin treatment sites or methodological factors did not significantly contribute to that variability. Conclusions Inter-subject variability was the major component of overall variability for acyclovir, and treatment site location did not significantly influence intra-subject variability. These results support a dOFM BE study design with T and R products assessed simultaneously on the same subject, where T and R treatment sites do not necessarily need to be next to each other. Localized variation in skin microstructure may be primarily responsible for intra-subject variability.

The goal of this study was to investigate the usefulness of various photographic techniques in visualizing previous tattoos under cover-up tattoos. Ten volunteers with 11 known cover-up tattoos were examined using different photographic techniques: A Canon EOS 6D full-frame digital single-lens reflex camera used in conjunction with a SB600 off-camera flash system and an extension cord; and a Leica M8 digital imaging system camera in conjunction with two different infrared filters (715 nm and 850 nm) and a Metz CL-45 handle-mount flash. A Lumatec Superlite 400 forensic light source was used along with the Canon EOS 6D as a third system. The best results for black cover-up tattoos were achieved with the full-frame digital single-lens reflex camera in conjunction with the off-camera flash system and, for colored cover-up tattoos, with IR-photography at a wavelength of 850 nm. The Lumatec Superlite 400 light source did not provide better results for conventional photography than those obtained with flash lighting. In nine out of eleven cover-up tattoos, the previous tattoos could, at least, be partially visualized. The quality of the visualization depended on the color, pattern, density, and quality of the cover-up tattoo as well as on the photographic technique. None of the examined photographic techniques could satisfactorily image the previous tattoo if the cover-up tattoo was large and black, especially not if it was densely inked. Depending on the color of the cover-up tattoo, a full-frame digital single-lens reflex camera in conjunction with a SB600 off-camera flash system (for black cover-ups) or infrared photography with flash lighting and an 850 nm filter (for colored cover-ups) proved to be the best of the investigated techniques to visualize a previous tattoo under a cover-up tattoo.

Nach todlich verlaufenen Fallen eines Schutteltraumas mussen Befunde, die die entsprechende Gewalteinwirkung belegen, im Rahmen der Obduktion und durch nachfolgende histologische Untersuchungen erhoben werden. Dies gilt v. a. fur jene Schutteltraumaopfer, bei denen zu Lebzeiten keine klinische Diagnostik mehr erfolgen konnte. Aber auch ein antemortal bekannter Verdacht auf ein Schutteltrauma mit klassischen Befunden, wie z. B. einem subduralen Hamatom und retinalen Blutungen, gelegentlich auch mit paravertebralen Rippenfrakturen und subkutanen Einblutungen (Thorax, Oberarme), bedarf der autoptischen Beweissicherung. Wurde das Schutteltrauma zunachst uberlebt, konnen Fragen der Altersbestimmung von Verletzungen relevant werden.

BACKGROUND Traditionally, fractional laser treatments are performed with focused laser sources operating at a fixed wavelength. Using a tunable laser in the mid-infrared wavelength range, wavelength-dependent absorption properties on the ablation process and thermal damage formation were assessed with the goal to obtain customizable tissue ablations to provide guidance in finding optimized laser exposure parameters for clinical applications. METHODS Laser tissue experiments were carried out on full thickness ex vivo human abdominal skin using a mid-infrared tunable chromium-doped zinc selenide/sulfide chalcogenide laser. The laser has two independent channels: a continuous wave (CW) output channel which covers a spectrum ranging from 2.4 μm to 3.0 μm with up to 9.2 W output power, and a pulsed output channel which ranges from 2.35 μm to 2.95 μm. The maximum pulse energy of the pulsed channel goes up to 2.8 mJ at 100 Hz to 1,000 Hz repetition rate with wavelength-dependent pulse durations of 4-7 ns. RESULTS Total ablation depth, ablation efficiency, and coagulation zone thickness were highly correlated to wavelength, pulse width, and pulse energy. Using the same total radiant exposure at 2.85 μm wavelength resulted in 10-times smaller coagulation zones and 5-times deeper ablation craters for one hundred 6 ns pulses compared to one 100 ms pulse. For a fixed pulse duration of 6 ns and a total radiant exposure of 2.25 kJ/cm2 the ablation depth increased with longer wavelengths. CONCLUSION The tunable laser system provides a useful research tool to investigate specific laser parameters such as wavelength on lesion shape, ablation depth and thermal tissue damage. It also allows for customization of the characteristics of laser lesions and therefore facilitates the selection of suitable laser parameters for optimized fractional laser treatments. Lasers Surg. Med. 50:961-972, 2018.© 2018 Wiley Periodicals, Inc.

The demographic development in Germany shows a steady increase to senior citizens. The driving suitability of older road-users is of large social and political concern, because awareness and reactivity can be influenced by age-related diseases and potential medication, particularly in combination with the consumption of alcohol. This study provides an overview of senior road-users under the influence of alcohol. Therefore, 404 cases of drunken-driving by road-users aged 70 and over within the purview of the Institute of Legal Medicine at Justus-Liebig-University, Giessen, from the years 2009-2013 were evaluated in retrospect. The vast majority of the drivers were male (88.4% of the cases). Distribution of the blood alcohol concentrations were almost equally in male and female drivers with 62.8% of all cases showing a blood alcohol concentration (BAC) of more than 1.1‰ and 10.9% a BAC of more than 2.0‰. In 48.5% of the cases, drunk driving was associated with an accident. 54.5% of the drivers stated suffering from at least one disease and 60% admitted a regular medication or an intake prior to the incident. Moreover, the collected data includes aspects such as the kind of traffic participation as well as neurological and physiological deficits of the road-users. If accidents were caused by drunk driving, the external circumstances and consequences of these accidents were analyzed, too. The evaluation revealed, that the standard medical examination protocol proved to be improbable to cover polypharmacy and multimorbidity of older alcoholized drivers. So, an evaluation and adaptation of the common medical examination protocol must be considered.

Previous studies have demonstrated that filled intervals are perceived as being longer than empty intervals of the same duration (i.e., the filled - duration illusion). In the present study, we asked whether the motor actions involved in filled and empty reproductions (a single continuous key press vs. two discrete key presses) would affect time estimates in a similar way. We hypothesized that reproductions of intervals of the same duration should be shorter for filled than empty reproductions (i.e., a filled - reproduction illusion). In two experiments, participants reproduced filled and empty intervals (ranging from 400 to 1,600 ms) using filled and empty reproductions. The results provided evidence for both kinds of illusions, even though the evidence was clearer for the filled - duration than for the filled - reproduction illusion. The present study demonstrates that in a situation in which both illusions work in concert, reproductions of the same interval can vary dramatically depending on the combination of interval and reproduction type.

Morbus Osler (hereditare hamorrhagische Teleangiektasie, HHT) bezeichnet eine erbliche Erkrankung der Blutgefase, bei der es zu Teleangiektasien und vaskularen Malformationen kommen kann. Insbesondere pulmonale arteriovenose Malformationen konnen mit lebensbedrohlichen oder letalen Komplikationen einhergehen. Vorgestellt wird der Todesfall einer 13-Jahrigen, bei der es plotzlich und unerwartet zur Ruptur einer bis dahin unbekannten vaskularen Malformation der linken Lunge gekommen ist. Histologisch wies die etwa 1 cm durchmessende Gefasveranderung eine unterschiedlich dicke Gefaswand und Unterbrechungen der Lamina elastica interna, passend zu einer arteriovenosen Malformation, auf.

In forensic case work, blood stain pattern analysis frequently aids in deducing the chain of actions or parts thereof taking place during an event leading to blood loss. Wiped single blood stains and/or groups of blood stains are seen at a majority of complex crime scenes. The appearance of wiped blood stains depends on droplet volume and stain age (as a function of blood viscosity and the degree of stain skeletonization) and characteristics of the stained surface (i.e., texture, temperature). Furthermore, based on the biochemical and biophysical properties of blood, not only the drying processes, but also complex coagulation cascades are relevant to the assessment of wiped blood stains. This study was designed to determine if anticoagulation therapies markedly affect the wipeability of blood stains over times elapsed since deposition and the overall drying process. A total of 813 blood stains, originating from donors being treated with acetylsalicylic acid (ASA), clopidogrel + ASA, low-molecular-weight heparin, or rivaroxaban, were dropped on common household tiles. Wipeability at an ambient temperature of 20 °C was tested for 22 time periods (1, 2, 3, 5, 10, 15…105 min since deposition). Whereas stains consisting of untreated blood were dried within 55 min, wipeability of all droplets originating from donors with prior anticoagulation treatment showed pronounced delays compared with the control, ranging from 20 min (ASA and clopidogrel + ASA) to 45 min (rivaroxaban). This pronounced effect was not seen in earlier studies, which might be explained by the higher volume of droplets used in this study, which resulted in a shift in relevance from drying to clotting processes. Significant differences between the drying times of the various anticoagulation regimes might be attributed to anticoagulant activity against different targets in the coagulation cascades. In conclusion, anticoagulation treatment prior to blood loss significantly affected the wipeability of blood stains. Anticoagulation therapy should therefore be taken into account in the analysis of blood stain patterns.

Background Following the legal provisions on the termination of pregnancies in Art. 13 of the SFHG (Law on the Assistance for Pregnant Women and Families, passed on 27.07.1992, BGBl. I, p. 1398) the so-called embryopathic indication for termination was abandoned. Since then, sec. 218a para. 2 of the German Criminal Code (StGB) states that for late terminations, i.e., terminations after the 12th week of gestation post conception, the pregnant woman must be in exceptional distress “according to medical opinion”. Method Between 01.05.2012 and 25.07.2016, a total of 160 pregnancy terminations were carried out in Giesen University Hospital under sec. 218a para. 2 StGB. The following data were obtained from the patientsʼ files: age of the pregnant woman, number of pregnancies, type of fetal disease or malformation, time of diagnosis, medical and psychosocial counseling given to the pregnant woman, time of termination or delivery, type of termination, fetal gender. Results 160 pregnant women (mean age: 31.6 years) underwent termination of pregnancy between the 13th – 37th week of gestation. Chromosomal anomalies were diagnosed prenatally in 60 cases, and anomalies were diagnosed on ultrasonography in 100 cases, with the preponderance of cases presenting with developmental disorders of the central nervous system and cardiovascular system. Conclusion In addition to recording intrauterine fetal disorders, when pregnancies are terminated under sec. 218a para. 2 StGB, treating physicians are expected to give plausible reasons why “according to medical opinion” the pregnancy represents a danger to the life of the pregnant woman or of grave injury to her physical or mental health and enter these reasons in the patientʼs medical records.

Introduction Cooling of burn injuries is most important, not only to reduce pain but also to reduce the intradermal damage as well as the burn wound conversion. Studies have shown that cooling for about 20 to 30 minutes using only plain tap water at moderate temperature is most efficient resulting in least intradermal damage. However, many burn injuries reach the hospital without any pre-clinical cooling, possibly due to the lack of a cooling agent. After a pilot study, we investigated if a bacterial nanocellulose (BNC)-based wound dressing containing about 95% water can cool a burn injury and if so the effect suffices to reduce the damage in the skin. Methods Skin explants from human donors were burned with inflicted a contact burn injury, of which half were treated with a BNC-based wound dressing and a paraffin gauze dressing. Intradermal temperature sensors measured the temperature changes in the dermis over the course of 24 hours. Biopsies were taken for histological evaluation at different time points. Results The intradermal measurements show high temperature spikes at the moment of the burn injuries. After the application of a BNC-based wound dressing the intradermal skin temperature was significantly reduced. The area under the curve in the treated group was significantly less than the untreated. The histological assessment showed according results with less damage in the treated group in comparison to the untreated. Conclusions Bacterial nanocellulose-based wound dressings with high water content significantly lower the intradermal temperature after a contact burn and reduce the thermal damage inflicted to the skin. A secondary dressing that permits the water to evaporate slower additionally prolongs the cooling effect. The use of such a wound dressing could find use in a preclinical setting where other cooling options are not available. Applicability of Research to Practice The findings of this experiment should be tested in an in-vivo setting prior to clinical use to investigate the possibility of inducing hypothermia with this treatment.

Aberration-corrected imaging of human photoreceptor cells, whether hardware or software based, presently requires a complex and often expensive setup. Here, we demonstrate a simple and inexpensive off-axis full-field time-domain optical coherence tomography approach to acquire volumetric data of in vivo human retina. Full volumetric, laterally phase stable data are recorded. The lateral phase stability allows computational aberration correction, which enables us to visualize single photoreceptor cells. In addition, our approach is able to correct large aberrations and is thus feasible for the numerical correction of ametropia in post processing. Our implementation of full-field OCT combines a low technical complexity with the possibility to use the phase of the recorded light for computational image correction.

Two-Photon Microscopy (TPM) can provide three-dimensional morphological and functional contrast in vivo. Through proper staining, TPM can be utilized to create virtual, H&E equivalent images and thus can improve throughput in histology-based applications. We previously reported on a new light source for TPM that employs a compact and robust fiber-amplified, directly modulated laser. This laser is pulse-to-pulse wavelength switchable between 1064 nm, 1122 nm, and 1186 nm with an adjustable pulse duration from 50ps to 5ns and arbitrary repetition rates up to 1MHz at kW-peak powers. Despite the longer pulse duration, it can achieve similar average signal levels compared to fs-setups by lowering the repetition rate to achieve similar cw and peak power levels. The longer pulses lead to a larger number of photons per pulse, which yields single shot fluorescence lifetime measurements (FLIM) by applying a fast 4 GSamples/s digitizer. In the previous setup, the wavelengths were limited to 1064 nm and longer. Here, we use four wave mixing in a non-linear photonic crystal fiber to expand the wavelength range down to 940 nm. This wavelength is highly suitable for imaging green fluorescent proteins in neurosciences and stains such as acridine orange (AO), eosin yellow (EY) and sulforhodamine 101 (SR101) used for histology applications. In a more compact setup, we also show virtual H&E histological imaging using a direct 1030 nm fiber MOPA.

There is an increasing number of reports concerning lethal courses following consumption of 3,4-Methylenedioxymethamphetamine (MDMA), namely Ecstasy. Autopsy findings in cases of MDMA intoxications are described, however Ecstasy-associated pathological findings should be separated from Ecstasy-induced findings. This case report presents typical Ecstasy-induced findings due to an obviously genetic disposition leading to malignant hyperthermia and severe rhabdomyolysis. Medicolegal aspects are relevant because there is a therapeutic option to save life by injecting Dantrolene when first symptoms are recognized.

Cerebral open flow microperfusion (cOFM) is a new in-vivo technique for continuous sampling of the interstitial fluid in brain tissue. cOFM can be used to monitor substance transport across the blood-brain barrier (pharmacokinetics) and to investigate metabolic changes in brain tissue after drug application (pharmacodynamics). The possibility of long-term implantation into the brain makes cOFM an outstanding tool in the development of brain relevant pharmaceutics.

Aconitum plants have long played a major role in traditional Asian medicine and cuisine. The roots are often eaten or used to prepare a soup for culinary or traditional medicinal reasons. Thus, many cases of aconitine poisoning have been reported in China and nearby countries. However, only few cases have been described in Europe. We present two unrelated cases of aconitine poisoning. A 44 year and a 56 year old man were found dead in their beds. In both cases, residual plant material was found in close proximity to the body. The autopsies revealed gastric contents interspersed with plant components, blood congestion, hemorrhages in the lung tissue, lung edema and brain edema. Additionally, we found fine-vacuolar fat-negative intracytoplasmatic transformation of hepatocytes. Aconitine was detected in all analyzed samples (blood, urine, gastric content and kidney) and quantified in femoral blood with 86.2 μg/L (case 1) and 2.3 μg/L (case 2), respectively. In both forensic cases, the scenery suggested a suicidal ingestion of Aconitum plant material.

Introduction Repatriated corpses may have been autopsied abroad. The aim of the study was to compare the findings from second medico-legal autopsies with those from primary autopsies abroad to spotlight possible implications for the management of repatriated corpses. Material and Methods All autopsies from a 20-year period at the Institute of Legal Medicine in Frankfurt am Main on repatriated corpses of German citizens were reviewed. The results were compared with the information from the body passports, the protocols of the autopsies in the country of death, and the police files. Results In total, 151 corpses repatriated from 56 different countries were autopsied. The interval between death and autopsy in Germany was 2–603 days (median: 11 days). 91 of the repatriated corpses (59.5%) had previously been autopsied abroad. Three body cavities had been opened in 78.0% (71/91) of the original autopsies; among them, there were 11 cases (15.5%) with dissection of all organs, as opposed to 7 cases (9.9%) with all organs intact and in situ. Of the previously autopsied corpses, 62.6% were accompanied by a body passport that noted the cause of death. In nearly 75% of these cases, the stated cause of death was compatible with that established at second autopsy. In 5 cases (10.2%), the cause of death established in the second autopsy disagreed with that on the body passport. The most prominent disparity was a cranial gunshot wound rather than the stated fatal fall. Discussion This analysis of individual cases spotlights the problematics of an uncritical approval of the body passport. In light of the different procedural autopsy standards around the world, the validity of an autopsy abroad is discussed in the context of the second autopsy results. Conclusion A second external postmortem examination by qualified medical practitioners should be obligatory in all cases of repatriated corpses, with notification of the criminal police in all cases of non-natural or undetermined death. A timely second autopsy is recommended even in cases with previous autopsy abroad.

Background With the increase of antimicrobial resistance in recent decades, other methods of preventing and fighting infections must be considered. Burn patients, whose wound areas are often extensive, are especially prone to wound infections. The loading of bacterial nanocellulose (BNC) with antiseptics has already been successfully performed but unfortunately, the described procedure is time-consuming and thus not applicable in a clinical emergency setting. Therefore, a clinically feasible approach was established. Material and methods Sheets of BNC-based wound dressings were placed into antiseptic solutions containing PHMB (Prontosan® and LAVANID® 2) and were left to soak for up to two hours. At different time points, samples were analysed for their concentration of PHMB and antiseptic efficacy. Results Within 30 min, clinically relevant concentrations of PHMB were achieved in the BNC-based wound dressing. The 30-min PHMB uptake for Prontosan® and LAVANID® 2 resulted in concentrations of 0.05% and 0.019%, respectively. Samples from the PHMB loaded dressing showed a dose dependent antiseptic efficacy for Staphylococcus aureus. Conclusion This experiment showed that the loading of BNC-based wound dressings with PHMB-containing antiseptics was achieved by a simple and quick procedure. According to studies a PHMB concentration of 0.001% can already inhibits all bacterial growth, indicating that the concentrations of PHMB in the BNC-based wound dressings after 30 min are higher than the minimal inhibitory concentration and the antiseptic efficacy after 120 min loading analysed by an standardized bacterial disk diffusion assay was shown to be comparable to the clinically used Suprasorb® X + PHMB wound dressing.

Introduction Bacterial nanocellulose (BNC) is a novel wound dressing that consists of nearly 95% water. This hydrophilicity allows this matrix to absorb and release aqueous substances. We investigated how well BNC can absorb antiseptic substances in order to create on demand antimicrobial wound dressings. Methods Sheets of BNC-based wound dressings were placed in four different antiseptic substances. Punch biopsies were taken at different time points and the concentrations of the antiseptic agent was measured. Two PHMB-containing solutions, one octenidine-containing and one povidone-iodine-containing solution were tested. In addition, the release of the substances from the punch biopsies was examined. To test the efficacy of these novel wound dressing, the antimicrobial activity of the BNC sheets loaded with the antiseptic solutions were tested against Staphylococcus aureus. Results All antiseptic solutions showed excellent uptake into the BNC as well as release. Especially the PHMB- and octenidine-containing solutions already showed high values after only 30 minutes. The overall achieved concentrations were all highly effective against Staphylococcus aureus and were all higher than the minimal bactericidal concentration against MRSA. Conclusions Antiseptic, water-based solutions are excellently absorbed in a very short time and are released steadily over a period of time dependant on the size of the molecules. All tested antiseptic solutions reached effective antibacterial concentrations making them all suitable for the making of antiseptic BNC-based wound dressings. However, when using a commercially available solution and not a solution containing only the active ingredient, it must be taken into consideration that all ingredients have an effect on the uptake of the active substance and thus influence the maximum uptake and release concentration. Applicability of Research to Practice The findings of this experiment are ready to be used in practice.

Introduction Inflammation is part of the physiological phases of wound healing. It serves the purpose to attract different immune cells in order to clean the wound from pathogens and debris and create an ideal environment for fibroblasts and keratinocytes to differentiate, migrate and divide in order to close the wound. Pathological inflammation caused by many different factors is often the underlying cause of prolonged wound healing and unfavourable outcome in burn patients. We wanted to investigate what influence an induced hyper-inflammation on wound healing has in a controlled environment. Methods In a porcine wound model, pigs received full-thickness wounds on their backs where hyper-inflammation was induced by application of a chemotherapeutic for 6 days. Control wounds were left without induction. Wound were scored on a daily basis for 16 days in total and biopsies were taken for RNA analysis as well as histological assessment. Results The results showed a rise in inflammation of the wounds and the surrounding tissue due to the induction. The wounds healed slower, needing up to seven more days to completely heal. The results of the RNA analysis showed high values of pro-inflammatory cytokines after the induction in comparison to the baseline and control wounds. Histological assessment showed thick layers of necrosis, adipocyte as well as leucocyte infiltration in the hyper-inflamed wounds compared to completely healed control wounds with all layers of epidermis visible. Conclusions Hyper-inflammation, even just for a short period of time, can significantly prolong the time of wound healing. These findings underline the importance of preventing and treating wound infections of burn patients in order to support physiological wound healing as well as to avert complications such as infections with multi-resistant microbes that are associated with prolonged hospital stays. Applicability of Research to Practice The findings of these experiments cannot be directly applied to practice however, the influence of inflammation should kept in mind when treating burn patients.

The ability to image the physiology of microvasculature with high spatial resolution in three dimensions while investigating structural changes of skin, is essential for understanding the complex processes of skin aging, wound healing and disease development. Further, the quantitative, automatic assessment of these changes enables to analyze large amounts of image data in an abstract but comprehensive manner. However, previous work using OCT with methods of angiography was imaging less scattering, hence more challenging tissue than skin, such as brain and retina tissue. The published methods for capillary segmentation were mostly non-automatic, poorly benchmarked against state-of-the-art methods of computer vision and not applied to investigate medical processes and studies in a comprehensive fashion. Here, segmentation of capillaries in skin is reported and its efficacy is demonstrated in both, a longitudinal mouse study and a preliminary study in humans. By combining state-of-the-art image processing methods in an optimized way, we were able to improve the segmentation results and analyze the impact of each post-processing step. Furthermore, this automatic segmentation enabled us to analyze big amounts of datasets automatically and derive meaningful conclusions for the planning of clinical studies. With this work, optical coherence tomography is combined with methods of computer vision to a diagnostic tool with unique capabilities to characterize vascular diversity and provide extraordinary opportunities for dermatological investigation in both, clinics and research.

The transfer of academic innovation to clinical practice and industry is taking on an increasingly important role in academic centers, but significant challenges remain. This work identifies some of the pivotal elements that are required to assemble, manage and accelerate the pace of successful translational research. These elements can be incorporated in new models of translational research facilitation that improve the process of converting academic innovations to commercial products where they can be used to benefit patient health on a large scale.

An elaborated diffusion process model (a Diffusion Model for Conflict Tasks, DMC) is introduced that combines conceptual features of standard diffusion models with the notion of controlled and automatic processes. DMC can account for a variety of distributional properties of reaction time (RT) in conflict tasks (e.g., Eriksen flanker, Simon, Stroop). Specifically, DMC is compatible with all observed shapes of delta functions, including negative-going delta functions that are particularly challenging for the class of standard diffusion models. Basically, DMC assumes that the activations of controlled and automatic processes superimpose to trigger a response. Monte Carlo simulations demonstrate that the unfolding of automatic activation in time largely determines the shape of delta functions. Furthermore, the predictions of DMC are consistent with other phenomena observed in conflict tasks such as error rate patterns. In addition, DMC was successfully fitted to experimental data of the standard Eriksen flanker and the Simon task. Thus, the present paper reconciles the prominent and successful class of diffusion models with the empirical finding of negative-going delta functions.

Objective The inability of leptin to suppress food intake in diet-induced obesity, sometimes referred to as leptin resistance, is associated with several distinct pathological hallmarks. One prevailing theory is that impaired transport of leptin across the blood–brain barrier (BBB) represents a molecular mechanism that triggers this phenomenon. Recent evidence, however, has challenged this notion, suggesting that leptin BBB transport is acquired during leptin resistance. Methods To resolve this debate, we utilized a novel cerebral Open Flow Microperfusion (cOFM) method to examine leptin BBB transport in male C57BL/6J mice, fed a chow diet or high fat diet (HFD) for 20 days. Results Basal plasma leptin levels were 3.8-fold higher in HFD-fed mice (p, Highlights • Cerebral Open Flow Microperfusion can be utilized to assess hypothalamic leptin levels. • Twenty days of high-fat diet feeding causes functional resistance to exogenous leptin. • Transport of leptin across the BBB is not impaired by HFD-induced leptin resistance.

Background Pregnancy-associated deaths are extremely rare in Germany. Most deaths are from natural causes, and a range of causes are possible. Method The deaths of 22 women who died of pregnancy-associated causes and who were autopsied in the Institute of Forensic Medicine of Justus-Liebig University Gießen between 1992 and 2016 were analyzed. Results The autopsy results and histological examinations for the majority of women who died of pregnancy-associated causes between 1992 and 2016 showed that they had died of natural causes, although complications of pregnancy were a leading cause of death. Conclusion The death of a pregnant woman should not automatically raise the suspicion of malpractice, although the question does arise in cases of bleeding complications only detected at very late stages. Experts must prove that a real mistake was made during treatment and provide evidence of the causality between malpractice and patient death. Particularly when well-known complications of pregnancy were present, this is only the case if poor monitoring resulted in the complication being detected too late or if treatment was not in accordance with accepted standards of care. The majority of pregnancy-associated deaths are from natural causes and the death of a pregnant woman does not mean that medical malpractice was involved, although this accusation is often levelled in cases where rupture was not immediately diagnosed or in cases of fatal postpartum hemorrhage.

The neuroprotective blood-brain barrier (BBB) keeps many drug candidates below therapeutic levels in the central nervous system. Glutathione PEGylated liposomal doxorubicin (2B3-101) has been developed to safely enhance the delivery of doxorubicin to brain tumors. However, doxorubicin concentration in extracellular brain fluid cannot yet be reliably measured using conventional techniques. Cerebral open flow microperfusion (cOFM), a recently developed sampling technique, allows monitoring of drug concentrations in the brain independent of molecular weight and lipophilicity. In combination with cOFM sampling, sodium fluorescein (NaF) is used as a marker for BBB integrity. Rats received one intravenous dose of 7 mg/kg of either 2B3-101 or PEGylated liposomal doxorubicin (generic Caelyx(®)). Blood and cOFM sampling was performed for 5 h after dose injection. NaF concentration in the brain was monitored and remained low indicating an intact BBB. The brain-to-blood ratio of doxorubicin was 4.8-fold higher after administration of 2B3-101 as compared with generic Caelyx(®) (p = 0.0016). In conclusion, by using cOFM it was possible to show that 2B3-101 leads to enhanced doxorubicin concentration in the brain without affecting the BBB integrity.

Drugs for neurological diseases have to cross the blood-brain barrier (BBB) to induce their therapeutic effect. In vivo drug quantification in the brain is challenging, because invasive methods damage the BBB and measurement results may be confounded by drug leakage from the blood into the brain through the disrupted BBB. Cerebral open flow microperfusion (cOFM) is an in vivo sampling technique that allows BBB healing and re-establishment after probe implantation and before sampling is performed. It therefore provides the opportunity to sample compounds in cerebral interstitial fluid with an intact BBB. This article comprehensively describes the experimental setup and procedures, perfusate requirements, critical parameters, common problems that may occur, and their causes and solutions. Typical results from a cOFM sampling experiment are presented and discussed. This protocol provides a tool for performing pharmacokinetic and pharmacodynamic studies in mouse or rat brain with an intact BBB. © 2019 by John Wiley & Sons, Inc.

Optical coherence tomography angiography (OCTA) provides in-vivo images of microvascular perfusion in high resolution. For its application to basic and clinical research, an automatic and robust quantification of the capillary architecture is mandatory. Only this makes it possible to reliably analyze large amounts of image data, to establish biomarkers, and to monitor disease developments. However, due to its optical properties, OCTA images of skin often suffer from a poor signal-to-noise ratio and contain imaging artifacts. Previous work on automatic vessel segmentation in OCTA mostly focuses on retinal and cerebral vasculature. Its applicability to skin and, furthermore, its robustness against imaging artifacts had not been systematically evaluated. We propose a segmentation method that improves the quality of vascular quantification in OCTA images even if corrupted by imaging artifacts. Both the combination of image processing methods and the choice of their parameters are systematically optimized to match the manual labeling of an expert for OCTA images of skin. The efficacy of this optimization-based vessel segmentation is further demonstrated on sample images as well as by a reduced error of derived quantitative vascular network characteristics.