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Background At the entry site of respiratory virus infections, the oropharyngeal microbiome has been proposed as a major hub integrating viral and host immune signals. Early studies suggested that infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with changes of the upper and lower airway microbiome, and that specific microbial signatures may predict coronavirus disease 2019 (COVID-19) illness. However, the results are not conclusive, as critical illness can drastically alter a patient’s microbiome through multiple confounders. Methods To study oropharyngeal microbiome profiles in SARS-CoV-2 infection, clinical confounders, and prediction models in COVID-19, we performed a multicenter, cross-sectional clinical study analyzing oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate, and severe COVID-19 (n = 322 participants). Results In contrast to mild infections, patients admitted to a hospital with moderate or severe COVID-19 showed dysbiotic microbial configurations, which were significantly pronounced in patients treated with broad-spectrum antibiotics, receiving invasive mechanical ventilation, or when sampling was performed during prolonged hospitalization. In contrast, specimens collected early after admission allowed us to segregate microbiome features predictive of hospital COVID-19 mortality utilizing machine learning models. Taxonomic signatures were found to perform better than models utilizing clinical variables with Neisseria and Haemophilus species abundances as most important features. Conclusions In addition to the infection per se, several factors shape the oropharyngeal microbiome of severely affected COVID-19 patients and deserve consideration in the interpretation of the role of the microbiome in severe COVID-19. Nevertheless, we were able to extract microbial features that can help to predict clinical outcomes.

Digital media have become integral to the everyday life of people with disabilities. So far, research about disability and digital media use is rather scarce and narrowed on issues of accessibility and social media. This paper draws on qualitative interviews with people with visual or motoric impairments to provide an in-depth analysis of their everyday experiences relating to barriers and benefits of digital media. The findings reproduce previously identified barriers and extend these by adding novel sub-aspects of individual cognitive and attitudinal barriers like non-use of digital media due to their (perceived) complexity and a feeling of greater dependence on digital technology. However, the results also shed light on highly individualized ways that people with disabilities actively make use of digital media to improve their daily life. Despite persisting and new barriers, the general findings suggest that, with the appropriate training and support, digital media are largely beneficial.

Objective To determine the intraoperative and early postoperative opioid requirement after ultrasound-guided sciatic and/or femoral nerve block or epidural anaesthesia in dogs undergoing tibial plateau levelling osteotomy (TPLO). Study design Prospective, masked, pilot, randomized, clinical trial. Animals A total of 40 client-owned dogs undergoing TPLO. Methods Each dog was randomly assigned to group SF (combined sciatic and femoral nerve block), group S (sciatic nerve block), group F (femoral nerve block) or group E (epidural anaesthesia). A total of 0.3 mL kg���1 of ropivacaine 0.5% was administered to each nerve or in the epidural space. Intraoperatively, fentanyl (2 ��g kg���1) was administered intravenously when heart rate, mean arterial pressure or respiratory rate increased by >30% compared with baseline values. Postoperatively, a visual analogue scale (VAS) and a modified German version of the French pain scale (4AVet) were used to assess pain every 30 minutes for 150 minutes and again once the morning after surgery. Methadone (0.1 mg kg���1) was administered intravenously if the VAS was ��� 4 cm [maximal value 10 cm; median (interquartile range)] or the composite pain score was ���5 [maximal value 15; median (interquartile range)]. Significance was defined as p ��� 0.05. Results Groups SF and E required less total intraoperative and early postoperative opioid doses compared with groups S and F (p = 0.031). No dogs in group SF had a block failure or required postoperative methadone. A reduced methadone requirement was found in group SF compared with all the other groups up to 150 minutes after recovery (p = 0.041). Conclusions and clinical relevance Combined sciatic and femoral nerve block and epidural anaesthesia lead to less cumulative consumption of perioperative opioids than single nerve blockade. Sciatic or femoral nerve block alone might be insufficient to control nociception and early postoperative pain in dogs undergoing TPLO.

A functional hypersalivation reduces patient's quality of life by the need of repeated changes of cloths, skin damage around the mouth and reduced personal contacts. The indication to treat hypersalivation is justified furthermore when respiratory infections by saliva aspiration occur. Transnasal swallowing endoscopy allows to evaluate sufficiently dysphagia with limited risks. With this method therapy options can be judged for effectiveness. There are other additional radiologic assessments to complete diagnostic. Swallowing therapy should be initiated as first-line approach for hypersalivation and offers several treatment concepts to overcome the syndrome. Glycopyrrolate bromid received approval for children and adolescents as it reduces saliva flow relevantly with limited risk. Other anticholinergic drugs are restricted in use because of their side effects and off-label-use situation. Ultrasound guided injections of botulinum toxine in salivary glands are an established treatment option since decades. Meanwhile, the evidence for this method has improved, so Incobotulinum toxine is an approved therapy for chronic hypersalivation in adults, whereby new injections are needed about every four months. In the light of effective medical options, surgical approaches such as salivary duct relocation are recommended less often today because of invasiveness and failure. Radiotherapy is reserved mainly for neurodegenerative diseases and shows good response, but the cancer induction risks need to be discussed. A close follow-up regime is necessary to establish compliance not only by the patient, but also by his family and caregivers. By this, treatment effects can be optimized and therapies can be adjusted individually.

Background Concurrent extrahepatic autoimmune disorders (CEHAID) are frequently observed in autoimmune hepatitis (AIH). It is not clear whether there is any prognostic significance of CEHAID on AIH. The aim of this study was to examine the prognostic impact of CEHAID and the correlation with the disease severity of AIH. Methods This study included 65 hospitalized subjects who fulfilled the accepted criteria for AIH during an 8-year period (2009–2016). All records were manually screened for presence of associated autoimmune diseases. Disease severity of AIH was assessed by liver laboratory tests including the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) and liver histology. Results Among the enrolled patients, 52 (80%) were female (median age 61 years, IQR 45–75). Fifty-six (86.2%) were classified as type-1 AIH. In 26 (40%) patients at least one additional extrahepatic autoimmune disease was diagnosed. Thirty-four subjects were referred to our hospital because of acute presentation of AIH (supposed by an acute elevation of hepatic enzymes) for subsequent liver biopsy resulting in initial diagnosis of AIH. This group was stratified into 3 subgroups: (A) AIH alone (n = 14); (B) overlap with primary biliary cirrhosis (PBC) / primary sclerosing cholangitis (PSC) (n = 11); and (C) with CEHAID (n = 9). AST/ALT ratio was the lowest in subgroup C (median 0.64, IQR 0.51–0.94; P = 0.023), compared to subgroup A (median 0.91, IQR 0.66–1.10) and subgroup B (median 1.10, IQR 0.89–1.36). Patients with AIH alone showed a trend to the highest grade of fibrosis (mean 2.3; 95% CI: 1.5–3.0) with no statistical significance compared to subjects with CEHAID (lowest grade of fibrosis; mean 1.5; 95% CI: 0.2–2.8; P = 0.380) whereas the ongoing inflammation was comparable. Conclusions AST/ALT ratio and extent of fibrosis were lower in subjects with AIH and CEHAID, compared to subjects with only AIH. Therefore, the occurrence of CEHAID might be a predictor for lower disease severity of newly diagnosed acute onset AIH, possibly caused by an earlier diagnosis or different modes of damage.

Although the automatic synthesis of molecules has been established, each reaction class uses bespoke hardware. This means that the connection of multi-step syntheses in a single machine to run many different protocols and reactions is not possible, as manual intervention is required. Here we show how the Chemputer synthesis robot can be programmed to perform many different reactions, including solid-phase peptide synthesis, iterative cross-coupling and accessing reactive, unstable diazirines in a single, unified system with high yields and purity. Developing universal and modular hardware that can be automated using one software system makes a wide variety of batch chemistry accessible. This is shown by our system, which performed around 8,500 operations while reusing only 22 distinct steps in 10 unique modules, with the code able to access 17 different reactions. We also demonstrate a complex convergent robotic synthesis of a peptide reacted with a diazirine-a process requiring 12 synthetic steps.

Background House dust mites (HDMs) are among the most important allergen sources containing many different allergenic molecules. Analysis of patients from a double-blind, placebo-controlled allergen-specific immunotherapy (AIT) study indicated that patients may benefit from AIT to different extents depending on their molecular sensitization profiles. Objective Our aim was to investigate in a real-life setting whether stratification of patients with HDM allergy according to molecular analysis may enhance AIT success. Methods Serum and nasal secretion samples from patients with HDM allergy (n = 24) (at baseline, 7, 15, 33, and 52 weeks) who had received 1 year of treatment with a well-defined subcutaneous AIT form (Alutard SQ 510) were tested for IgE and IgG reactivity to 15 microarrayed HDM allergen molecules with ImmunoCAP Immuno-solid-phase Allergen Chip technology. IgG subclass levels to allergens and peptides were determined by ELISA, and IgG blocking was assessed by basophil activation. In vitro parameters were related to reduction of symptoms determined by combined symptom medication score and visual analog scale score. Results Alutard SQ 510 induced protective IgG mainly against Dermatophagoides pteronyssinus (Der p) 1 and Der p 2 and to a lesser extent to Der p 23, but not to the other important allergens such as Der p 5, Der p 7, and Der p 21, showing better clinical efficacy in patients sensitized only to Der p 1 and/or Der p 2 as compared with patients having additional IgE specificities. Conclusion Stratification of patients with HDM allergy according to molecular sensitization profiles and molecular monitoring of AIT-induced IgG responses may enhance the success of AIT.

Objective: To evaluate the prevalence of chronic postsurgical pain (CPSP) after tibial plateau leveling osteotomy (TPLO) in dogs and to determine the influence of preemptive locoregional analgesia on CPSP. Study design: Retrospective study. Animals: One hundred twenty client-owned dogs. Methods: Medical records of dogs that underwent TPLO between 2012 and 2016 were reviewed for demographic information and type of preemptive analgesia. Owners were contacted to retrospectively assess the quality of life of their dogs by using the Helsinki Chronic Pain Index (HCPI) before and 6 months after surgery and at the time of questioning. An HCPI score > 12 was considered indicative of CPSP. Medical records were reviewed for demographic information and type of preemptive analgesia. A cumulative logit model was used to assess correlation of type of perioperative analgesia, HCPI, and demographic data. Results: The HCPI score was consistent with CPSP in 41 of 101 dogs with long-term follow-up (2.9 ± 1.5 years after surgery). Chronic postsurgical pain was documented in 11 of 32 and 13 of 28 dogs that received a spinal or epidural injection, respectively, or in 28 of 80 and 25 of 67 dogs with sciatic-femoral block at 6 months or with long-term follow-up after TPLO, respectively (P > .05). A negative correlation was found between HCPI and both weight and age 6 months after surgery. Only weight remained negatively correlated 2.9 years after surgery. Conclusion: Forty-one percent of dogs that were evaluated exhibited HCPI values compatible with CPSP long-term after TPLO, regardless of the type of preemptive analgesia. Increased body weight was a negative prognostic factor for CPSP development. Clinical significance: Additional studies are required to evaluate CPSP development after TPLO.

The article studies whether foreign skilled workers have similar access to licensed and more credentialed occupations, and whether they profit from these regulations in terms of similar wages in these occupations to comparable domestic skilled workers. The theoretical foundations of this article are concepts of signaling and occupational closure. The analyses use a sample of 60,000 employed persons from the 2006, 2012 and 2018 Employment Surveys of the German Federal Institute for Vocational Education and Training (BIBB) and the Federal Institute for Occupational Safety and Health (BAuA), and a reweighting approach to account for the selection on observables. Results show an ambivalent picture of the regulation of occupations: on the one hand, at least foreign skilled men earn similar wages to domestic skilled men in more closed occupations; on the other hand, foreign skilled workers are less likely to enter these positions and they have monetary disadvantages compared with domestic skilled workers in less closed occupations.

Kann das neue Coronavirus SARS-CoV‑2 okulares Geweben infizieren und damit neben dem Kontaktrisiko ein Infektionsrisiko durch das Gewebe darstellen, ist die Frage, die die Augenheilkunde seit Beginn der Infektion beschaftigt. Um einen bestimmten Gewebetyp zu infizieren, muss jedes Virus seinen bestimmten Rezeptor und manchmal auch Korezeptoren oder andere Proteine vorfinden. Ziel dieser Ubersichtsarbeit war es, mithilfe der aktuellen, zuganglichen Literatur (Stand 28.05.2020) den aktuellen Forschungsstatus zusammenzufassen und wiederzugeben. Zum Zeitpunkt der Recherche waren eindeutig ACE2 als Rezeptor und TMPRSS2 als notwendige Protease identifiziert, um die Infektion einer humanen Zelle mit SARS-CoV‑2 zu ermoglichen. Im Auge werden sowohl ACE2 als auch TMPRSS2 exprimiert, wenn auch teilweise sehr schwach und unterschiedlich schwach in verschiedenen Geweben. Beachtenswert ist, dass mit verschiedenen Methoden sehr unterschiedliche Ergebnisse erzielt wurden. Hierfur kommen mehrere Grunde infrage: zum einen die Methode der Detektion bzw. der Konservierung des Gewebes, zum anderen die moglicherweise unterschiedliche Expression der getesteten Gewebeproben, des Weiteren ein moglicherweise rascher Rezeptorexpressionsverlusts post mortem. Eine Infektion des Auges erscheint daher moglich, woruber auch schon in diversen Publikationen berichtet wurde. Welche Virusmenge bzw. welche Rezeptorexpression notwendig ist, um eine Infektion zu ermoglichen, ist ungeklart. Aufgrund der geringeren ACE2- und TMPRSS2-Expression ist das Auge – nach aktuellem Wissenstand – aber nicht als Hochrisikogewebe anzusehen. Trotzdem sind entsprechende Schutzmasnahmen sowohl fur das medizinische Personal als auch fur die Patienten notwendig. Bei Hornhauttransplantation ist eine Infektion des Spendergewebes mit SARS-Cov‑2 auszuschliesen.

Objectives The current systematic review (SR) was undertaken to identify and summarise the published literature reporting on the clinical and economic value of automated in-hospital pharmacy services with a primary focus on systems supporting the dispensing of medicines. Methods Literature searches were conducted in MEDLINE, Embase and the Cochrane Library on 17 December 2017 to identify English-language publications investigating any automated dispensing systems (ADSs) in the inpatient setting to include central pharmacy and ward-based systems. Results 4320 publications were screened by title and abstract and 45 of 175 full publications screened were included. Grey literature searching identified an additional three publications. Therefore, 48 publications relating to ADSs were eligible for inclusion. Although a relatively large evidence base was identified as part of the current SR, the eligible studies were inconsistent in terms of their design and the format of reporting of outcomes. The studies demonstrate that both pharmacy and ward-based ADSs offer benefits over traditional manual dispensing methods in terms of clinical and economic outcomes. The primary benefits following implementation of an ADS include reductions in medication errors, medication administration time and costs. Studies examining optimisation/inventory management strategies/refill programmes for these systems suggest that optimal implementation of the ADS is required to ensure that clinical success and economic benefits are maximised. Conclusions The published evidence suggests positive impacts of ADS and should encourage hospitals to invest in automation, with a global strategy to improve the reliability and the efficiency of the medication process. However, one of the key findings of the current SR is the need for further data from adequately powered studies reporting clinically relevant outcomes which would allow for robust, evidence-based recommendations on the return on investment of the technologies. These studies would probably contribute to a larger adoption of these technologies by European hospitals.

Background: There is growing interest both in testing IgE in nasal secretions (NS) and in molecular diagnosis of seasonal allergic rhinitis (SAR). Yet, the reliability of nasal IgE detection with the newest molecular assays has never been assessed in a large cohort of pollen allergic patients. Objective: To investigate with microarray technology and compare the repertoires of specific IgE (sIgE) antibodies in NS and sera of a large population of children and adults with SAR. Methods: Nasal secretions were collected with an absorbent device (Merocel 2000��, Medtronic) and a minimal dilution procedure from 90 children and 71 adults with SAR. Total IgE (tIgE) (ImmunoCAP, Thermo Fisher Scientific (TFS)) and sIgE antibodies against 112 allergen molecules (ISAC-112, TFS) were measured in NS and serum. Results: Nasal sIgE was detectable in 68.3% of the patients. The detected nasal sIgE antibodies recognized airborne (88%), vegetable (10%), and animal food or other (

Lack of sex education in schools has been an ongoing issue in Russia, mainly due to conservative opposition to providing accurate sexual health information openly. Many adolescents may be misinform...

In modern 3D microscopy, holding and orienting arbitrary biological objects with optical forces instead of using coverslips and gel cylinders is still a vision. Although optical trapping forces are strong enough and related photodamage is acceptable, the precise (re-) orientation of large specimen with multiple optical traps is difficult, since they grab blindly at the object and often slip off. Here, we present an approach to localize and track regions with increased refractive index using several holographic optical traps with a single camera in an off-focus position. We estimate the 3D grabbing positions around several trapping foci in parallel through analysis of the beam deformations, which are continuously measured by defocused camera images of cellular structures inside cell clusters. Although non-blind optical trapping is still a vision, this is an important step towards fully computer-controlled orientation and feature-optimized laser scanning of sub-mm sized biological specimen for future 3D light microscopy., Optical manipulation of large objects is challenging as optical trap positions are blindly chosen. Here, the authors present off-focus interferometric tracking, which localises optimal grabbing positions with increased refractive index, by analysing the beam deformations of several holographic optical traps.

Aquaculture activities continue to expand in Vietnam, covering an estimated 700,000 ha, with 89% of these culture ponds located in the Mekong Delta. Since 2009, large-scale bacterial outbreaks have spread in response to this intensive farming. Antibiotics, even those considered a last resort, have only partially mitigated this problem. A side effect of the massive use of these chemicals is the appearance of mobile genetic elements associated with antibiotic resistance genes (ARGs). The large-scale emergence of a diverse bacterial resistome, accompanied by severe economic losses, has posed significant health risks to local residents. In this study, the seasonal and spatial distributions of the class I integrase (CL1) intl1 and the ARGs sul2 (sulfonamide), BLA-oxa1 (ß-lactams), and ermB (erythromycin) were quantified from water and sediment samples collected during two consecutive seasons along the Vam Co River and its tributary (Long An province, Vietnam). Results showed that CL1 was present in all river compartments, reaching 2.98×104 copies/mL and 1.07×106 copies/g of sediment, respectively. The highest relative copy abundances to the 16S rDNA gene were measured in water samples, with up to 3.02% for BLA-oxa1, followed by sul2 (1.16%) and ermB (0.46%). Strong seasonal (dry season vs. rainy season) and spatial trends were recorded for all resistance genes. Higher amounts of ARGs in river water could be associated with higher antibiotic use during the rainy season. In contrast, higher amounts of ARGs were recorded in river sediments during the dry season, making this habitat a potential reservoir of transient genes. Finally, the observations made in this study allowed us to clarify the environmental and anthropogenic influences that may promote the dispersal and persistence of ARGS in this riverine ecosystem.ABSTRACT ARTHIGHLIGHTSIn Vietnam, inland aquaculture massively relies on antibiotics to prevent epidemicsResistance genes were quantified along two rivers of the Mekong deltaSeasonal (dry and rainy seasons) and spatial distributions were registered by qPCRBLA-oxa1and sul2 reached highest abundances among bacterial communitiesStrong seasonal patterns and local variabilities were measured for CL1s and ARGs

Background Lupus disproportionately affects Black/African American (AA) and Latino/a patients, yet these underrepresented racial/ethnic minority populations often face challenges with accessing quality care.1,2 We aimed to explore patients’ and physicians’ perceptions on the treatment journey for underrepresented patients and identify barriers to quality care. Methods In-depth qualitative interviews were conducted with patients with lupus from underrepresented populations (Black/AA, Latino/a, Native American, Asian/Pacific Islander) and physicians (dermatology or rheumatology). Quota sampling was used to recruit patients from racially and ethnically diverse backgrounds and physicians with varied medical practices. Patient and physician participants provided informed consent. Semi-structured interviews explored patients’ experiences with the healthcare system and physicians’ challenges when treating patients with lupus. Results Interviews were conducted with 33 patients and 20 physicians. Age, region, education, employment status, and type/severity of lupus varied among patients, as did physicians’ work experience and practice settings (table 1). Patients reported challenges at each step of their journey. Prior to diagnosis, patients entered the healthcare system often lacking awareness of lupus disease and reported feeling initially ignored, dismissed, or misdiagnosed, which delayed treatment and triggered mistrust of the healthcare system. Lack of trust was cited by patients as a reason to discontinue treatment, despite persistent symptoms. Some patients reported perceived challenges with access to branded medications due to insurance coverage or delays in prior authorization and were concerned about losing their job and insurance. Patients communicated that treatment access might be improved by establishing support systems for reliable disease information (advocacy groups, community support), increasing cultural sensitivity in physician practices, and enabling an efficient and transparent treatment initiation process. From the physician perspective, barriers to treatment access included delayed diagnoses, patient concerns over side effects and the need for lifelong treatment, communication challenges with patients with limited English proficiency (LEP), and medication costs. Physicians suggested addressing perceived barriers by providing better patient information resources, having a live translator present during visits for patients with LEP, and navigating accessibility to medications through patient assistance programs to ensure access to branded therapies when needed. Conclusions Improving access to quality care for underrepresented patients is essential to reduce health disparities across racial/ethnic groups and build trust in the healthcare system. Increasing disease awareness among these diverse groups and physicians, establishing patient support networks, and improving patient-physician communication should be critical components of health equity efforts. References Arora. Rheum Dis Clin N Am. 2020;46:623-638. Maningding. Arthritis Care Res. 2020;72(5):622-629.

The ability to detect and quantify the state of charge (SoC) of lithium-ion (Li-ion) batteries - the most common energy sources for portable devices - using fast and nondestructive evaluation techniques is crucial for the technology. Ten factory-new 18650 batteries were imaged at 100% and 0% SoC using a Vantage-256 system (Verasonics, Inc.) equipped with a 5-MHz and 64-element ultrasound array (Imasonic SAS). Quantitative ultrasound spectroscopy (QUS) parameters, i.e., midbandfit (MBf), spectral slope (SS), and intercept (I0), were obtained from the normalized power spectra of the backscattered ultrasound signals. A significant impact (ANOVA, p

Transcranial direct current stimulation (tDCS) applied at the same intensity for an entire group of people results in wide interindividual variability, limiting stimulation efficacy. Evidence suggests that tDCS efficacy might be linked to individual corticospinal excitability (CSE) levels measured by transcranial magnetic stimulation (TMS). However, no study has attempted to individualize tDCS parameters according to the CSE level. We aimed to investigate whether the tDCS effect could be improved by individualizing stimulation intensity based on CSE measured at baseline. Fourteen participants were included in a crossover single-blinded design study where anodal (1 mA), individualized anodal (between 0.9 and 1.6 mA) and sham tDCS were applied for 14 min over the primary motor cortex. The resting motor threshold (RMT), stimulus intensity for a 1 mV response (SI1mV) and the input-output curve (I–O curve) were measured before, immediately after, 15 after and 30 min after tDCS using single pulses of TMS. The tDCS intensity in the individualized anodal condition was determined according to the RMT value at baseline (i.e., CSE level). RMT, SI1mV and I–O curve MEPs did not change after any tDCS paradigm. Our results are consistent with previous investigations that did not show an effect of tDCS on CSE and supports that tDCS protocols suffer from large interindividual variability and a lack of efficiency. This calls for further investigations to find the optimal tDCS setting to reduce the inconsistency in the results and obtain reproducible effects.

Photonic Force Microscopy (PFM) uses optically trapped particles to measure fluctuation based forces and potential landscapes. This feature makes it a very soft probing technique that is well suited to investigate surface interactions with biological samples. In addition, PFMs can be used in scan mode to create surface-profiles with a resolution better than the optical diffraction limit. In this talk we present an improved intermittent contact (tapping) mode PFM and a revised data analysis for more detailed surface height profiles.

Objectives The National Early Warning Score, Modified Early Warning Score, and quick Sepsis-related Organ Failure Assessment can predict clinical deterioration. These scores exhibit only moderate performance and are often evaluated using aggregated measures over time. A simulated prospective validation strategy that assesses multiple predictions per patient-day would provide the best pragmatic evaluation. We developed a deep recurrent neural network deterioration model and conducted a simulated prospective evaluation. Design Retrospective cohort study. Setting Four hospitals in Pennsylvania. Patients Inpatient adults discharged between July 1, 2017, and June 30, 2019. Interventions None. Measurements and main results We trained a deep recurrent neural network and logistic regression model using data from electronic health records to predict hourly the 24-hour composite outcome of transfer to ICU or death. We analyzed 146,446 hospitalizations with 16.75 million patient-hours. The hourly event rate was 1.6% (12,842 transfers or deaths, corresponding to 260,295 patient-hours within the predictive horizon). On a hold-out dataset, the deep recurrent neural network achieved an area under the precision-recall curve of 0.042 (95% CI, 0.04-0.043), comparable with logistic regression model (0.043; 95% CI 0.041 to 0.045), and outperformed National Early Warning Score (0.034; 95% CI, 0.032-0.035), Modified Early Warning Score (0.028; 95% CI, 0.027- 0.03), and quick Sepsis-related Organ Failure Assessment (0.021; 95% CI, 0.021-0.022). For a fixed sensitivity of 50%, the deep recurrent neural network achieved a positive predictive value of 3.4% (95% CI, 3.4-3.5) and outperformed logistic regression model (3.1%; 95% CI 3.1-3.2), National Early Warning Score (2.0%; 95% CI, 2.0-2.0), Modified Early Warning Score (1.5%; 95% CI, 1.5-1.5), and quick Sepsis-related Organ Failure Assessment (1.5%; 95% CI, 1.5-1.5). Conclusions Commonly used early warning scores for clinical decompensation, along with a logistic regression model and a deep recurrent neural network model, show very poor performance characteristics when assessed using a simulated prospective validation. None of these models may be suitable for real-time deployment.

Specifically designed resonant THz nano-structures absorb and locally enhance an incident THz pulse, thus, generating fields high enough to cause nonlinear material responses and thus give access to study nonlinear transport phenomena or to realize ultrafast electronic devices, such as efficient photovoltaic nano-cells, electroluminescent emitters, or highly sensitive photon detectors. Here, we study the ultrafast mode switching of metallic split ring resonators (SRRs) on semiconductor substrates, as shown in Fig. 1(a) . Mode switching occurs when the substrate underneath the gap region changes conductivity. For semiconductors, the electric field-induced conductivity is attributed to carrier generation via different mechanisms, e.g., inter-valley scattering (IVS) or impact ionization (IMI) [1] . However, mechanism and time scale by which mode switching occurs is still debated, despite several successful studies conducted to understand the underlying physics of field-induced nonlinear substrate behavior [1] - [2] . In the present work, by using semiconductor substrates with different bandgaps, we first show that impact ionization is indeed the most relevant carrier generation process. Second, we establish a mode switching time of 200 fs.

In recent years, it has been shown that intense THz pulses are powerful tools to manipulate, deflect or accelerate ultrashort electron bunches. The THz range is of interest, since the corresponding wavelengths are well-matched to a typical electron bunch size of several tens of microns. Here, we propose to use split-ring resonators (SRR) as key-elements to realize various tasks in electron accelerators. Through a judicious choice of shape and geometry these structure exhibit a considerable near-field enhancement, boosting the incident THz field strength by a factor of ten or more.

Die ersten Untersuchungen von humanen Hornhäuten von COVID‑19(Coronavirus Disease 2019/Coronaviruserkrankung 2019)-Spendern legen nahe, dass keine SARS-CoV-2(„severe acute respiratory syndrome-coronavirus-2“/schweres akutes respiratorisches Syndrom-Coronavirus-2)-RNA vorhanden ist. Derzeit wird nicht empfohlen, eine routinemäßige Testung von postmortalen Spendergeweben auf SARS-CoV-2-RNA durchzuführen. Dies begründet sich u. a. in den Faktoren, die das RT-PCR („reverse transcription polymerase chain reaction“/Reverse-Transkriptase-Polymerasekettenreaktion) Testergebnis beeinflussen können.

Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation of synovial joints, often resulting in irreversible structural damage. The activity of the disease is evaluated by clinical examinations, laboratory tests, and patient self-assessment. The long-term course of the disease is assessed with radiographs of hands and feet. The evaluation of the X-ray images performed by trained medical staff requires several minutes per patient. We demonstrate that deep convolutional neural networks can be leveraged for a fully automated, fast, and reproducible scoring of X-ray images of patients with rheumatoid arthritis. A comparison of the predictions of different human experts and our deep learning system shows that there is no significant difference in the performance of human experts and our deep learning model.

Background Early diagnosis is of substantial benefit for patients with Pompe disease. Yet underdiagnosing and substantial diagnostic delay are still frequent and the determinants of this are unknown. This study is the first to systematically investigate the diagnostic odyssey in Pompe disease from patients', parents', and physicians' perspectives. Methods Patients with infantile or late onset Pompe disease, their parents as well as their metabolic experts were invited to fill in respective surveys. The survey addressed perceived disease symptoms at onset and during the course of the disease, specialties of involved physicians, activities of patient-initiated search for diagnosis and the perceived impact of time to diagnosis on outcome. Results of experts' and patients'/parents' surveys were compared and expressed by descriptive statistics. Results and Discussion We collected data on 15 males and 17 females including 9 infantile and 23 late onset Pompe patients. All received the correct diagnosis at a metabolic or musculoskeletal expert center. Patients with direct referral to the expert center had the lowest diagnostic delay, while patients who were seen by several physicians, received the correct diagnosis after 44%-200% longer delay. The proportion of direct referral varied strongly between pediatricians (57%) and other disciplines (18%-36%). Conclusion Our study highlights a substantially larger diagnostic delay in Pompe patients that are not directly referred to expert centers for diagnostic work. Our findings may be used to develop more successful strategies for early diagnosis. Synopsis Diagnostic delay in Pompe disease is substantial particularly in patients that are not directly referred to expert centers for diagnostic workup, so facilitating direct referral may be a new strategy for early diagnosis.

ZusammenfassungHypersalivation bezeichnet einen übermäßigen Speichelfluss, der durch insuffiziente orofaziale Fähigkeiten, verminderte zentralnervöse Kontrolle und Koordination oder gestörte Schluckabläufe entstehen kann. Die Aktualisierung der S2k-Leitlinie soll den neuen diagnostischen und therapeutischen Kenntnisstand berücksichtigen.Die Diagnostik- und Therapiemaßnahmen sollten multidisziplinär erfolgen. Schwerpunkte sind die Abklärung von Schluckstörungen mit Speichelaspiration. Hier sind klinische Screeninguntersuchungen und die fiberendoskopische Schluckuntersuchung (FEES) hervorzuheben.Bei fast allen Ursachen sind die schlucktherapeutischen Übungsmaßnahmen zur Aktivierung und zum Erlernen von Kompensationsmechanismen unverzichtbar. Insbesondere bei Kindern mit hypotoner orofazialer Muskulatur sind myofunktionelle Therapiekonzepte indiziert, allerdings ist die Kompetenz zur Mitarbeit entscheidend. Zusätzlich können orale Stimulationsplatten durch die Veränderung der Zungenpositionierung zu einer Symptomreduktion führen. Sinnvolle medikamentöse Therapien sind insbesondere die verschiedenen Applikationsformen von Glycopyrrolat, von denen Sialanar® (Glycopyrronium) als Saft eine Genehmigung zur Behandlung bei Kindern ab 3 Jahren und Jugendlichen erhalten hat. Die Injektion von Botulinumtoxin in die Kopfspeicheldrüsen hat sich als effektive und sichere Behandlungsform mit einer langanhaltenden Speichelreduktion erwiesen. Für Incobotulinumtoxin A ist die Phase III-Studie bei Erwachsenen aktuell abgeschlossen und führte in den USA bereits zur Zulassungserweiterung bei Hypersalivation. Chirurgische Eingriffe der Speicheldrüsen bleiben Einzelfällen vorbehalten. Die Bestrahlung der Speicheldrüsen ist, insbesondere wenn sie in moderner 3-D-konformaler Technik zur Gewebeschonung durchgeführt wird, eine sichere und effektive Therapie. In einer regelhaften Nachsorge sind Therapieeffekte und mögliche Nebenwirkungen zu erfassen; insbesondere bei neurodegenerativen Erkrankungen ist die individuelle Dynamik der Symptomverschlechterung zu berücksichtigen.

An der Hornhaut konnen sich zahlreiche Systemerkrankungen manifestieren. Die korneale Manifestation ist mitunter das erste Zeichen des Allgemeinleidens. Sie ausert sich auf ganz unterschiedliche Art und Weise wie z. B. in einer peripheren Geschwurbildung oder einer kristallinen Keratopathie. Die Therapie ist interdisziplinar und richtet sich so weit wie moglich gegen das Grundleiden.

Aims The role of uncoupling protein 2 (UCP2) in cardiac adaptation to pressure overload remains unclear. In a classical model of left ventricular pressure overload genetic deletion of UCP2 (UCP2−/−) protected against cardiac hypertrophy and failure. However, in UCP2−/− mice increased proliferation of pulmonary arterial smooth muscle cells induces mild pulmonary hypertension, right ventricular (RV) hypertrophy, and reduced cardiac output. This suggests a different role for UCP2 in RV and left ventricular adaptation to pressure overload. To clarify this situation in more detail UCP2−/− and wild-type mice were exposed to pulmonary arterial banding (PAB). Methods and results Mice were analysed (haemodynamics, morphometry, and echocardiography) 3 weeks after PAB or sham surgery. Myocytes and non-myocytes were isolated and analysed separately. Cell shortening of myocytes and fura-2 loading of cardiomyocytes were used to characterize their function. Brd assay was performed to study fibroblast proliferation. Isolated mitochondria were analysed to investigate the role of UCP2 for reactive oxygen species (ROS) production. UCP2 mRNA was 2.7-fold stronger expressed in RV myocytes than in left ventricular myocytes and stronger expressed in non-myocytes compared with myocytes. Three weeks after PAB, cardiac output was reduced in wild type but preserved in UCP2−/− mice. UCP2−/− had increased RV wall thickness, but lower RV internal diameters and displayed a significant stronger fibrosis. Cardiac fibroblasts from UCP2−/− had reduced proliferation rates but higher collagen-1 expression. Myocytes isolated from mice after PAB banding showed preserved function that was further improved by UCP2−/−. Mitochondrial ROS production and respiration was similar between UCP2−/− or wild-type hearts. Conclusion Despite a mild pulmonary hypertension in UCP2−/− mice, hearts from these mice are well preserved against additional pressure overload (severe pulmonary hypertension). This—at least in part—depends on different behaviour of non-myocytes (fibroblasts).

BackgroundGray-scale, B-mode ultrasound (US) imaging is part of the standard clinical procedure for evaluating thyroid nodules (TNs). It is limited by its instrument- and operator-dependence and inter-observer variability. In addition, the accepted high-risk B-mode US TN features are more specific for detecting classic papillary thyroid cancer rather than the follicular variant of papillary thyroid cancer or follicular thyroid cancer. Quantitative ultrasound (QUS) is a technique that can non-invasively assess properties of tissue microarchitecture by exploiting information contained in raw ultrasonic radiofrequency (RF) echo signals that is discarded in conventional B-mode imaging. QUS provides quantitative parameter-value estimates that are a function of the properties of US scatterers and microarchitecture of the tissue. The purpose of this preliminary study was to assess the performance of QUS parameters in evaluating benign and malignant thyroid nodules.MethodsPatients from the Thyroid Health Center at the Boston Medical Center were recruited to participate. B-mode and RF data were acquired and analyzed in 225 TNs (24 malignant and 201 benign) from 208 patients. These data were acquired either before (167 nodules) or after (58 nodules) subjects underwent fine-needle biopsy (FNB). The performance of a combination of QUS parameters (CQP) was assessed and compared with the performance of B-mode risk-stratification systems.ResultsCQP produced an ROC AUC value of 0.857 ± 0.033 compared to a value of 0.887 ± 0.033 (p=0.327) for the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) and 0.880 ± 0.041 (p=0.367) for the American Thyroid Association (ATA) risk-stratification system. Furthermore, using a CQP threshold of 0.263 would further reduce the number of unnecessary FNBs in 44% of TNs without missing any malignant TNs. When CQP used in combination with ACR TI-RADS, a potential additional reduction of 49 to 66% in unnecessary FNBs was demonstrated.ConclusionThis preliminary study suggests that QUS may provide a method to classify TNs when used by itself or when combined with a conventional gray-scale US risk-stratification system and can potentially reduce the need to biopsy TNs.

Purpose To better assess clinical trajectories of patients with or without ocular comorbidity after Descemet membrane endothelial keratoplasty. Background: To report on the outcomes of eyes with differing starting conditions following surgery. Design: Retrospective study at a University Eye Hospital. Participants: 361 eyes separated into group 1 (n=229; eyes with endothelial disease only) and group 2 (n=132; eyes with additional ocular comorbid conditions, such as herpetic eye disease 18/132 (13.6%), glaucoma 16/132 (12.1%), dry age-related macular degeneration 14/132 (10.6%), epiretinal membranes 10/132 (7.6%), and wet age-related macular degeneration 9/132 (6.8%)). Methods Consecutive eyes that underwent Descemet membrane endothelial keratoplasty over a follow-up period of up to 7 years at a tertiary referral center were reviewed. Main outcome measures were best-corrected visual acuity, postoperative complications, graft survival, central corneal thickness, and endothelial cell density. Results Postoperative best-corrected visual acuity at year 1 improved in both groups significantly (Wilcoxon signed rank test: group 1, p =.002; .63 to .23 logMAR; group 2, p p =.009, Mann-Whitney-Wilcoxon). A decrease of the endothelial cell density and central corneal thickness was noted at postoperative year 1 for both groups (paired t-tests (group 1, p p =.045) and paired t-tests (group 1, p p =.003). Complications were less common, and graft longevity was superior in group 1. Conclusion Eyes with different starting conditions might experience a visual improvement and benefit from surgery. Descemet membrane endothelial keratoplasty is a valid treatment for endothelial disorders in manifold of eyes. Further long-term studies are required.

BACKGROUND Oro-facial dysfunctions (OFDs; oro-facial myofunctional disorders) in children and childhood apraxia of speech (CAS) often cause severe problems in articulation, chewing, swallowing and oral posture. OBJECTIVES Pathognomonic symptoms could yet not be identified, but central problems in planning, programming, timing and automating oro-facial, as well as other fine motor skills, are assumed to be affected. METHODS To investigate the nature of motor and coordinative deficits in OFD and CAS, digitomotography was applied. The testing focused on recording frequency, force, rhythm and regularity of the index finger including speeded and metronome tapping tasks. 25 children with OFD (7 girls and 18 boys, age 7.9 ± 2.3) and 5 children with CAS (0 girls and 5 boys, age 7.6 ± 2.3), and 31 healthy controls (12 girls and 19 boys, age 9.3 ± 2.2) were tested. Statistical significance was accepted at α = 0.05. ANOVA test, non-parametric Mann-Whitney U test, Kruskal-Wallis test and Spearman's rank correlation coefficient were used. RESULTS Cross-sectional data revealed consistent significant differences between children with OFD and healthy controls concerning frequency, force, rhythm and regularity of index finger tapping. Individuals with CAS showed particularly low results. Tapping results correlated with disease burden. CONCLUSION These findings support that underlying superordinated sensorimotor deficits exist. This may help phenotyping and influence diagnostical and therapeutical approaches.

Coronavirus 2 (SARS-CoV-2) infection and the resulting COVID-19 illness vary from asymptomatic disease, mild upper respiratory tract infection, pneumonia1, to a life-threatening multi-organ failure with case fatality rates ranging from 0.27–13.4%2,3. Despite increasing knowledge of the clinical and immunological features underlying COVID-191,4−6, biological variables explaining the course of infection and its severity remain elusive. At the entry site of SARS-CoV2, the oropharyngeal microbiome represents a hub integrating viral and immune signals at the start of the infection7–10. To evaluate the role of the oropharyngeal microbiome in COVID-19, we performed a multi-center, cross-sectional clinical study analyzing the oropharyngeal microbial metagenomes in healthy adults, patients with non-SARS-CoV-2 infections, or with mild, moderate and severe COVID-19 encompassing a total of 345 participants. Significantly reduced microbiome diversity and high dysbiosis were observed in hospitalized patients with severe COVID-19, which was further associated with a loss of microbial genes and metabolic pathways. In this cohort, diversity measures were also associated with need for intensive care treatments as major clinical parameters in COVID-19. We further applied random forest machine learning to unravel microbial features for segregating clinical outcomes in hospitalized cases, and observed oropharyngeal microbiome abundances of Haemophilus or Streptococcus species as most important features. These findings provide insights into the role of the oropharyngeal microbiome in SARS-CoV-2 infection, and may suggest new biomarkers for COVID-19 severity.

Repeated testing of a population is critical for limiting the spread of the SARS-CoV-2 virus and for the safe reopening of educational institutions such as K-12 schools and colleges. Many screening efforts utilize the CDC RT-PCR based assay which targets two regions of the novel Coronavirus nucleocapsid gene. The standard approach of testing each person individually, however, poses a financial burden to these institutions and is therefore a barrier to using testing for re-opening. Pooling samples from multiple individuals into a single test is an attractive alternate approach that promises significant cost savings - however the of specificity and sensitivity of such approaches needs to be assessed prior to deployment. To this end, we conducted a pilot study to evaluate the feasibility of analyzing samples in pools of eight by the established RT-PCR assay. Participants (1,576) were recruited from amongst the Tufts University community undergoing regular screening. Each volunteer provided two swabs, one analyzed separately and the other in a pool of eight. Because the positivity rate was very low, we spiked approximately half of the pools with laboratory-generated swabs produced from known positive cases outside the Tufts testing program. The results of pooled tests had 100% correspondence with those of their respective individual tests. We conclude that pooling eight samples does not negatively impact the specificity or sensitivity of the RT-PCR assay and suggest that his approach can be utilized by institutions seeking to reduce surveillance costs.

Is the new coronavirus SARS-CoV‑2 able to infect ocular tissue and thus poses a risk of infection through the tissue in addition to the risk of contact? This is the question that has occupied ophthalmologists since the beginning of the outbreak. In order to infect a certain type of tissue specific receptors for each virus and sometimes also coreceptors or other proteins must be present. The aim of this review was to summarize and reflect the current state of research with the help of the currently available literature as of 28 May 2020. At the time of the research, angiotensin-converting enzyme 2 (ACE2) was clearly identified as the receptor and transmembrane serine protease 2 (TMPRSS2) as the necessary protease to enable the infection of human cells with SARS-CoV‑2. In the eye both ACE2 and TMPRSS2 are expressed, although sometimes very weakly and with varying degrees in different tissues. It is noteworthy that very different results were obtained with different methods. Several reasons can account for this effect: Firstly, the method of detection or preservation of the tissue, secondly, the possibly different expression of the tested tissue samples and thirdly, a possibly rapid loss of receptor expression post-mortem. Therefore, an infection of the eye seems possible, which has already been reported in various publications. The amount of virus or receptor expression necessary to cause an infection is not known. According to current state of knowledge the eye is not considered to be a high-risk tissue due to the low ACE2 and TMPRSS2 expression. Nevertheless, appropriate protective measures are necessary for both medical personnel and patients. In cases of corneal transplantation an infection of the donor tissue with SARS-CoV‑2 must be excluded.Kann das neue Coronavirus SARS-CoV‑2 okulares Geweben infizieren und damit neben dem Kontaktrisiko ein Infektionsrisiko durch das Gewebe darstellen, ist die Frage, die die Augenheilkunde seit Beginn der Infektion beschäftigt. Um einen bestimmten Gewebetyp zu infizieren, muss jedes Virus seinen bestimmten Rezeptor und manchmal auch Korezeptoren oder andere Proteine vorfinden. Ziel dieser Übersichtsarbeit war es, mithilfe der aktuellen, zugänglichen Literatur (Stand 28.05.2020) den aktuellen Forschungsstatus zusammenzufassen und wiederzugeben. Zum Zeitpunkt der Recherche waren eindeutig ACE2 als Rezeptor und TMPRSS2 als notwendige Protease identifiziert, um die Infektion einer humanen Zelle mit SARS-CoV‑2 zu ermöglichen. Im Auge werden sowohl ACE2 als auch TMPRSS2 exprimiert, wenn auch teilweise sehr schwach und unterschiedlich schwach in verschiedenen Geweben. Beachtenswert ist, dass mit verschiedenen Methoden sehr unterschiedliche Ergebnisse erzielt wurden. Hierfür kommen mehrere Gründe infrage: zum einen die Methode der Detektion bzw. der Konservierung des Gewebes, zum anderen die möglicherweise unterschiedliche Expression der getesteten Gewebeproben, des Weiteren ein möglicherweise rascher Rezeptorexpressionsverlusts post mortem. Eine Infektion des Auges erscheint daher möglich, worüber auch schon in diversen Publikationen berichtet wurde. Welche Virusmenge bzw. welche Rezeptorexpression notwendig ist, um eine Infektion zu ermöglichen, ist ungeklärt. Aufgrund der geringeren ACE2- und TMPRSS2-Expression ist das Auge – nach aktuellem Wissenstand – aber nicht als Hochrisikogewebe anzusehen. Trotzdem sind entsprechende Schutzmaßnahmen sowohl für das medizinische Personal als auch für die Patienten notwendig. Bei Hornhauttransplantation ist eine Infektion des Spendergewebes mit SARS-Cov‑2 auszuschließen.

Translating satellite imagery into maps requires intensive effort and time, especially leading to inaccurate maps of the affected regions during disaster and conflict. The combination of availability of recent datasets and advances in computer vision made through deep learning paved the way toward automated satellite image translation. To facilitate research in this direction, we introduce the Satellite Imagery Competition using a modified SpaceNet dataset. Participants had to come up with different segmentation models to detect positions of buildings on satellite images. In this work, we present five approaches based on improvements of U-Net and Mask R-Convolutional Neuronal Networks models, coupled with unique training adaptations using boosting algorithms, morphological filter, Conditional Random Fields and custom losses. The good results—as high as AP=0.937 and AR=0.959—from these models demonstrate the feasibility of Deep Learning in automated satellite image annotation.

Transdermal patches allow a noninvasive and &ldquo, stress free&rdquo, analgesia in rabbits. As fentanyl uptake is dependent on exogenous and endogenous factors of the area where the patch is applied, this study investigated three different locations (neck, inner and outer surfaces of the ear) for fentanyl patch application to provide adequate and reliable fentanyl plasma concentrations above those previously shown to be analgesic. Fentanyl plasma concentration was measured at different time points (3, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120 h) and rabbits were assessed for their general conditions and treatment-related side effects. Practicability of the proposed methods was evaluated. Following patch application on the neck, fentanyl plasma concentrations equal to or above the analgesic value were measured in all rabbits between 6 and 72 h. Comparable concentrations were reached between 9 and 48 h in all animals for the outer ear surface. However, for the inner ear surface, analgesic concentrations were not reached, even if practicability was considered the best for this location. Preparation of the neck skin was judged as the most cumbersome due to the clipping of the dense fur and patch removal resulted in erythema. In summary, the application of the fentanyl patch on the neck and outer ear surface allowed the reach of reliable plasma concentrations above the analgesic threshold in rabbits. When applied on the neck, fentanyl patches provided the longest duration of analgesic plasma concentrations, whereas patch application and removal were easier on the outer ear surface.

Background Ehlers-Danlos Syndrome (EDS) comprises a heterogeneous group of diseases characterized by joint hypermobility, connective tissue friability, and vascular fragility. Reliable prognostic factors predicting vascular disease progression (e.g. arterial aneurysms, dissections, and ruptures) in EDS patients are still missing. Recently, applanation tonometry derived augmentation index (AIx), an indirect marker of arterial stiffness, has shown to be positively associated with progression of aortic disease in Marfan syndrome. In this study, we assessed aortic AIx in patients with EDS and matched healthy controls. Methods We performed noninvasive applanation tonometry in 61 adults with EDS (43 women and 18 men aged 39.3 ± 14.6 years) and 61 age-, gender-, height-, and weight-matched healthy controls. Radial artery pulse waveforms were recorded and analyzed using the SphygmoCor System (AtCor Medical, Sydney, NSW, Australia). Calculated AIx was adjusted to a heart rate of 75/min. Groups were compared and association between AIx and EDS was determined by univariate and multivariate regression analysis. Results EDS patients were categorized in classical type EDS (34%), hypermobile type EDS (43%), vascular type EDS (5%), or remained unassignable (18%) due to overlapping features. EDS patients showed a significantly increased aortic AIx compared to healthy controls (22.8% ± 10.1 vs 14.8% ± 14.0, p Conclusions Patients with EDS showed elevated AIx, indicating increased arterial stiffness when compared to healthy controls. Further investigations are needed in order to assess the prognostic value of increased AIx for cardiovascular outcomes in patients with EDS.

Photonic Force Microscopy (PFM) uses optically trapped nanoparticles to measure forces in the sub-piconewton range. This makes it a very soft probing technique that is perfectly suited to investigate surface interactions with biological samples. In addition, PFMs can be used in scan mode to create surface-profiles with a resolution better than the optical diffraction limit. A common problem for probing techniques that operate in contact mode is sticking of the probe to the sample. To overcome this problem, we present an intermittent contact mode PFM to improve the technique’s robustness by reducing contact times and binding between sample and probe.

Purpose: To examine corneal tissue for severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) positivity regarding implications for tissue procurement, processing, corneal transplantation, and ocular surgery on healthy patients. We performed quantitative reverse transcription-polymerase chain reaction qRT-PCR-testing for SARS-CoV-2 RNA on corneal stroma and endothelium, bulbar conjunctiva, conjunctival fluid swabs, anterior chamber fluid, and corneal epithelium of coronavirus disease 2019 (COVID-19) postmortem donors. Methods: Included in this study were 10 bulbi of 5 COVID-19 patients who died because of respiratory insufficiency. Informed consent and institutional review board approval was obtained before this study (241/2020BO2). SARS-CoV-2 was detected by using a pharyngeal swab and bronchoalveolar lavage. Tissue procurement and tissue preparation were performed with personal protective equipment (PPE) and the necessary protective measures. qRT-PCR-testing was performed for each of the abovementioned tissues and intraocular fluids. Results: The qRT-PCRs yielded no viral RNA in the following ocular tissues and intraocular fluid: corneal stroma and endothelium, bulbar-limbal conjunctiva, conjunctival fluid swabs, anterior chamber fluid, and corneal epithelium. Conclusions: In this study, no SARS-CoV-2-RNA was detected in conjunctiva, anterior chamber fluid, and corneal tissues (endothelium, stroma, and epithelium) of COVID-19 donors. This implicates that the risk for SARS-CoV-2 infection using corneal or conjunctival tissue is very low. However, further studies on a higher number of COVID-19 patients are necessary to confirm these results. This might be of high importance for donor tissue procurement, processing, and corneal transplantation.