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Background Wastewater-based epidemiology (WBE) surveillance as an early warning system (EWS) for monitoring community transmission of SARS-CoV-2 in low- and middle-income country (LMIC) settings, where diagnostic testing capacity is limited, needs further exploration. We explored the feasibility to conduct a WBE surveillance in Indonesia, one of the global epicenters of the COVID-19 pandemic in the middle of 2021, with the fourth largest population in the world where sewer and non-sewered sewage systems are implemented. The feasibility and resource capacity to collect samples on a weekly or fortnightly basis with grab and/or passive sampling methods, as well as to conduct qualitative and quantitative identification of SARS-CoV-2 ribonucleic acid (RNA) using real-time RT-PCR (RT-qPCR) testing of environmental samples were explored. Materials and methods We initiated a routine surveillance of wastewater and environmental sampling at three predetermined districts in Special Region of Yogyakarta Province. Water samples were collected from central and community wastewater treatment plants (WWTPs), including manholes flowing to the central WWTP, and additional soil samples were collected for the near source tracking (NST) locations (i.e., public spaces where people congregate). Results We began collecting samples in the Delta wave of the COVID-19 pandemic in Indonesia in July 2021. From a 10-week period, 54% (296/544) of wastewater and environmental samples were positive for SARS-CoV-2 RNA. The sample positivity rate decreased in proportion with the reported incidence of COVID-19 clinical cases in the community. The highest positivity rate of 77% in week 1, was obtained for samples collected in July 2021 and decreased to 25% in week 10 by the end of September 2021. Conclusion A WBE surveillance system for SARS-CoV-2 in Indonesia is feasible to monitor the community burden of infections. Future studies testing the potential of WBE and EWS for signaling early outbreaks of SARS-CoV-2 transmissions in this setting are required.

Type VII collagen, as a major component of anchoring fibrils found at basement membrane zones, is crucial in anchoring epithelial tissue layers to their underlying stroma. Recently, type VII collagen was discovered in the inner human retina by means of immunohistochemistry, while proteomic investigations demonstrated type VII collagen at the vitreoretinal interface of chicken. Because of its potential anchoring function at the vitreoretinal interface, we further assessed the presence of type VII collagen at this site. We evaluated the vitreoretinal interface of human donor eyes by means of immunohistochemistry, confocal microscopy, immunoelectron microscopy, and Western blotting. Firstly, type VII collagen was detected alongside vitreous fibers6 at the vitreoretinal interface. Because of its known anchoring function, it is likely that type VII collagen is involved in vitreoretinal attachment. Secondly, type VII collagen was found within cytoplasmic vesicles of inner retinal cells. These cells resided most frequently in the ganglion cell layer and inner plexiform layer. Thirdly, type VII collagen was found in astrocytic cytoplasmic inclusions, known as corpora amylacea. The intraretinal presence of type VII collagen was confirmed by Western blotting of homogenized retinal preparations. These data add to the understanding of vitreoretinal attachment, which is important for a better comprehension of common vitreoretinal attachment pathologies.

Azoospermia (the complete absence of spermatozoa in the semen) is a common cause of male infertility. The etiology of azoospermia is poorly understood. Whole-genome analysis of azoospermic men has identified a number of candidate genes, such as the X-linked testis-expressed 11 (TEX11) gene. Using a comparative genomic hybridization array, an exonic deletion (exons 10-12) of TEX11 had previously been identified in two non-apparent azoospermic patients. However, the putative impact of this genetic alteration on spermatogenesis and the azoospermia phenotype had not been validated functionally. We therefore used a CRISPR/Cas9 system to generate a mouse model (Tex11Ex9-11del/Y) with a partial TEX11 deletion that mimicked the human mutation. Surprisingly, the mutant male Tex11Ex9-11del/Y mice were fertile. The sperm concentration, motility, and morphology were normal. Similarly, the mutant mouse line's testis transcriptome was normal, and the expression of spermatogenesis genes was not altered. These results suggest that the mouse equivalent of the partial deletion observed in two infertile male with azoospermia has no impact on spermatogenesis or fertility in mice, at least of a FVB/N genetic background and until 10 months of age. Mimicking a human mutation does not necessarily lead to the same human phenotype in mice, highlighting significant differences species.

Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH model's relative performance, we additionally developed prediction models for acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) and compared the discriminative performance of the models. We included individuals aged ≥35 years without history of stroke from a Dutch routine care database (years 2007-2020) and defined outcomes aSAH, AIS and ICH using International Classification of Diseases (ICD) codes. Potential predictors included sociodemographic data, diagnoses, medications, and blood measurements. We cross-validated a Cox proportional hazards model with an elastic net penalty on derivation cohorts and reported the c-statistic and 10-year calibration on validation cohorts. We examined 1,040,855 individuals (mean age 54.6 years, 50.9% women) for a total of 10,173,170 person-years (median 11 years). 17,465 stroke events occurred during follow-up: 723 aSAH, 14,659 AIS, and 2,083 ICH. The aSAH model's c-statistic was 0.61 (95%CI 0.57-0.65), which was lower than the c-statistic of the AIS (0.77, 95%CI 0.77-0.78) and ICH models (0.77, 95%CI 0.75-0.78). All models were well-calibrated. The aSAH model identified 19 predictors, of which the 10 strongest included age, female sex, population density, socioeconomic status, oral contraceptive use, gastroenterological complaints, obstructive airway medication, epilepsy, childbirth complications, and smoking. Discriminative performance of the aSAH prediction model was moderate, while it was good for the AIS and ICH models. We conclude that it is currently not feasible to accurately identify individuals at increased risk for aSAH using EHR data.

The "princely" barrows of Łęki Małe, Greater Poland are the oldest such monuments within the distribution area of Únětice societies in Central Europe. While in the Circum-Harz group and in Silesia similar rich furnished graves under mounds have appeared as single monuments as early as 1950 BC, Łęki Małe represents a chain of barrows constructed between 2150 BC and 1800 BC. Of the original 14 mounds, only four were preserved well enough that their complex biographies can now be reconstructed. They included ritual activities (before, during, and after the funeral), and also subsequent incursions, including robberies. The long lasting barrow cemetery at Łęki Małe can be linked to a nearby fortified site, Bruszczewo. Together, Łęki Małe and Bruszczewo represent a stable, socially differentiated society that existed for no less than 350-400 years. Therefore, it can be argued that the Early Bronze Age societies of Greater Poland were extremely sustainable in comparison to those of other Únětice regions.

Vaccination willingness against COVID-19 is generally perceived as low. Moreover, there is large heterogeneity across and within countries. As a whole, Germany has average vaccination rates compared to other industrialized countries. However, vaccination rates in the 16 different German federal states differ by more than 20 percentage points. We describe variation in vaccination rates on the level of the 400 German counties using data on all vaccinations carried out until December 2022. Around 52-72% of that variation can be explained by regional differences in demographic characteristics, housing, education and political party preferences. We find indications that the remaining part may be due to differences in soft factors such as risk aversion, trust in the German government, trust in science, and beliefs in conspiracy theories regarding the origins of the Corona virus. We conclude that improving the trust in science and the fight against conspiracy theories may possibly be effective tools to improve vaccination rates and effectively fight pandemics.

In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins-complete tumor removal while attempting to preserve viable tissue-remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.

The utilisation of insect meal-based fish feed as a substitute for conventional fish meal-based fish feed is considered as a promising innovative alternative to boost circularity in aquaculture and aquaponics. Basic research on its use in aquaponics is limited. So far, no reports on the effects of fish waste water, derived from a recirculating aquaculture system using Black Soldier Fly (BSF) meal-based diets, were available on the growth performance of lettuce. Therefore, this study aimed to compare the effect of reusing fish waste water from tilapia culture (as a base for the nutrient solution) fed with a fish meal-based diet (FM) and a BSF meal-based diet on resource use and lettuce growth in decoupled aquaponic systems. A conventional hydroponics nutrient solution (HP) served as control, and inorganic fertilisers were added to all nutrient solutions to reach comparable target concentrations. The experiment was conducted in a controlled climate chamber in nine separate hydroponics units, three per treatment. Lettuce fresh and dry weight, number of leaves, relative leaf chlorophyll concentration, water consumption, and the usage of inorganic fertilisers were measured. Micro- and macronutrients in the nutrient solutions were monitored in time series. Similar lettuce yield was seen in all treatments, with no significant effects on fresh and dry weight, the number of leaves, and relative chlorophyll values. Water use per plant was also similar between treatments, while the amount of total inorganic fertiliser required was 32% lower in FM and BSF compared to HP. Higher sodium concentrations were found in the FM nutrient solutions compared to BSF and HP. The results confirm that BSF-based diet is a promising alternative to FM-based diet in aquaponics with no negative effects on lettuce growth. Additionally, BSF-based diet might be beneficial in intensive, professional aquaponics applications due to the lower sodium concentration in the nutrient solution.

Reference data is key to produce reliable crop type and cropland maps. Although research projects, national and international programs as well as local initiatives constantly gather crop related reference data, finding, collecting, and harmonizing data from different sources is a challenging task. Furthermore, ethical, legal, and consent-related restrictions associated with data sharing represent a common dilemma faced by international research projects. We address these dilemmas by building a community-based, open, harmonised reference data repository at global extent, ready for model training or product validation. Our repository contains data from different sources such as the Group on Earth Observations Global Agricultural Monitoring Initiative (GEOGLAM) Joint Experiment for Crop Assessment and Monitoring (JECAM) sites, the Radiant MLHub, the Future Harvest (CGIAR) centers, the National Aeronautics and Space Administration Food Security and Agriculture Program (NASA Harvest), the International Institute for Applied Systems Analysis (IIASA) citizen science platforms (LACO-Wiki and Geo-Wiki), as well as from individual project contributions. Data of 2016 onwards were collected, harmonised, and annotated. The data sets spatial, temporal, and thematic quality were assessed applying rules developed in this research. Currently, the repository holds around 75 million harmonised observations with standardized metadata of which a large share is available to the public. The repository, funded by ESA through the WorldCereal project, can be used for either the calibration of image classification deep learning algorithms or the validation of Earth Observation generated products, such as global cropland extent and maize and wheat maps. We recommend continuing and institutionalizing this reference data initiative e.g. through GEOGLAM, and encouraging the community to publish land cover and crop type data following the open science and open data principles.

BackgroundBone metastases are on the rise due to longer survival of cancer patients. Local tumor control is required for pain relief. Microwave ablation (MWA) is a technique for minimally invasive local tumor treatment. Tumor tissue is destroyed by application of local hyperthermia to induce necrosis. Given the most common setting of palliative care, it is generally considered beneficial for patients to start mobilizing directly following treatment. No data on mechanical strength in long bones after MWA have been published so far.Materials and methodsIn- and ex-vivo experiments on sheep tibias were performed with MWA in various combinations of settings for time and power. During the in-vivo part sheep were sacrificed one or six weeks after ablation. Mechanical strength was examined with a three-point bending test for ablations in the diaphysis and with an indentation test for ablations in the metaphysis.ResultsMWA does not decrease mechanical strength in the diaphysis. In the metaphysis strength decreased up to 50% six weeks after ablation, which was not seen directly after ablation.ConclusionMWA appears to decrease mechanical strength in long bone metaphysis up to 50% after six weeks, however strength remains sufficient for direct mobilization. The time before normal strength is regained after the remodeling phase is not known.

In Germany, nursing homes are characterised by challenging conditions for adequately supporting residents at their end of life, which have even amplified due to the COVID-19 pandemic. This article therefore analyses how hospice and palliative care in nursing homes has changed due to the COVID-19 pandemic and how the pandemic has affected residents, relatives and employees. Semi-structured interviews with employees, residents and relatives were conducted before and during the COVID-19 pandemic in two nursing homes in North Rhine-Westphalia, Germany. In a pre-post comparison, data were qualitatively evaluated using content analysis according to Mayring. Shifts, congruities and discrepancies in challenges in hospice and palliative care were identified between T0 and T1. Due to contact restrictions, important parts of end-of-life care were missing, and the roles of individuals providing hospice and palliative care were redefined. The interviewed groups experienced changes differently and contradictory statements on satisfaction and expectations about hospice and palliative care were reported. Employees and relatives predominantly perceived the pandemic to be very stressful, while residents endured this period more composedly. Employees stated that, despite the pandemic, they were mostly able to meet residents' requests. However, relatives and residents expressed that minor requests were not reliably fulfilled, neither at T0 nor at T1. Drawing together the different perspectives from employees, residents and relatives offers a bigger picture of challenges in hospice and palliative care in nursing homes and the pandemic effects. Stronger communication of requests and needs as well as greater collaboration, especially under crisis conditions, are essential for a better quality of end-of-life care. There is an urgent need to break down the taboos around the topics of dying and death in nursing homes.

Photographic identification catalogs of individual killer whales (Orcinus orca) over time provide a tool for remote health assessment. We retrospectively examined digital photographs of Southern Resident killer whales in the Salish Sea to characterize skin changes and to determine if they could be an indicator of individual, pod, or population health. Using photographs collected from 2004 through 2016 from 18,697 individual whale sightings, we identified six lesions (cephalopod, erosions, gray patches, gray targets, orange on gray, and pinpoint black discoloration). Of 141 whales that were alive at some point during the study, 99% had photographic evidence of skin lesions. Using a multivariate model including age, sex, pod, and matriline across time, the point prevalence of the two most prevalent lesions, gray patches and gray targets, varied between pods and between years and showed small differences between stage classes. Despite minor differences, we document a strong increase in point prevalence of both lesion types in all three pods from 2004 through 2016. The health significance of this is not clear, but the possible relationship between these lesions and decreasing body condition and immunocompetence in an endangered, non-recovering population is a concern. Understanding the etiology and pathogenesis of these lesions is important to better understand the health significance of these skin changes that are increasing in prevalence.

Non-physical barriers for migrating fish, such as effluent plumes discharged by sewage treatment plants (WWTPs), are hardly considered, and field studies on this topic are very scarce. The encounter with these plumes however may evoke behavioural responses in fish and could delay or (partially) block the migration. In this study, the behavioural responses of 40 acoustically-tagged silver eel (Anguilla anguilla) were monitored in situ, when confronting a WWTP effluent plume during their downstream migration in the canal Eems, the Netherlands. Their behavioural responses and the potential blocking effect of the plume were assessed using a 2D and 3D telemetry design displayed in the waterway, and matched to a modelled and calibrated WWTP effluent plume. When confronted with the WWTP effluent plume during their downstream migration, 22 of the silver eels (59%) showed an avoidance response, varying from lateral diverting to multiple turning in the vicinity of the effluent plume. Nineteen out of these 22 (86%) eventually passed the study site. No silver eel showed attraction to the plume. Delays in migration were from several hours up to several days. Due to the strong variation in discharged volumes and flow velocity of the receiving canal, the WWTP plume did not always flow over the full width of the canal. As a result, numerous migratory windows, where silver eels could pass the WWTP while avoiding direct contact with the plume, remained available in time. When discharge points cannot be avoided, reduced or restricted to areas that are not preferred as fish migration routes, discharge points should be designed such, that the chance is limited that a waterway is (temporarily) impacted over its full width.

Predicted lung volumes based on the Global Lung Function Initiative (GLI) model are used in pulmonary disease detection and monitoring. It is unknown how well the predicted lung volume corresponds with computed tomography (CT) derived total lung volume (TLV). The aim of this study was to compare the GLI-2021 model predictions of total lung capacity (TLC) with CT-derived TLV. 151 female and 139 male healthy participants (age 45-65 years) were consecutively selected from a Dutch general population cohort, the Imaging in Lifelines (ImaLife) cohort. In ImaLife, all participants underwent low-dose, inspiratory chest CT. TLV was measured by an automated analysis, and compared to predicted TLC based on the GLI-2021 model. Bland-Altman analysis was performed for analysis of systematic bias and range between limits of agreement. To further mimic the GLI-cohort all analyses were repeated in a subset of never-smokers (51% of the cohort). Mean±SD of TLV was 4.7±0.9 L in women and 6.2±1.2 L in men. TLC overestimated TLV, with systematic bias of 1.0 L in women and 1.6 L in men. Range between limits of agreement was 3.2 L for women and 4.2 L for men, indicating high variability. Performing the analysis with never-smokers yielded similar results. In conclusion, in a healthy cohort, predicted TLC substantially overestimates CT-derived TLV, with low precision and accuracy. In a clinical context where an accurate or precise lung volume is required, measurement of lung volume should be considered.

The pathogenesis of testicular germ cell tumours (GCTs) is still incompletely understood. Any progress in its understanding must derive from observational studies. Recently, it has been suggested that the incidence of GCTs may follow a seasonal pattern based on circannual changes in the Vitamin D serum levels, with maximum incidence rates in winter months. To examine this promising hypothesis, we studied monthly incidence rates of testicular GCTs in Germany by analysing 30,988 GCT cases aged 15-69 years, diagnosed during 2009-2019. Monthly incident case numbers with data regarding histology and patient age were obtained from the Robert Koch Institut, Berlin, along with annual male population counts. We used precision weighting for deriving pooled monthly incidence rates for GCTs of the period 2009-2019. We stratified pooled rates by histology (seminoma and nonseminoma) and age (15-39 and 40-69 years). By assuming a cyclical effect, we used an estimator of the intensity of seasonal occurrence and report seasonal relative risks (RR). The mean monthly incidence rate was 11.93/105 person-months. The seasonal RR for testicular cancer over-all is 1.022 (95% CI 1.000-1.054). The highest seasonal RR was found in the subgroup of nonseminoma aged 15-39 years, with a RR 1.044 (95% CI 1.000-1.112). The comparison of the pooled monthly rates of the winter months (October-March) with the summer months (April-September) revealed a maximum relative difference of 5% (95% CI 1-10%) for nonseminoma, aged 15-39 years. We conclude that there is no evidence of a seasonal variation of incidence rates of testicular cancer. Our results are at odds with an Austrian study, but the present data appear sound because the results were obtained with precision weighted monthly incidence rates in a large population of GCT cases.

BackgroundImproved survival of cancer patients leads to more skeletal metastatic lesions that need local therapies for tumor control and pain relief. Not all tumors are radiosensitive and alternative therapies are direly needed. Microwave ablation (MWA) is a technique for minimally invasive local tumor control by physical ablation. In soft tissue local temperature ablation is more common, but studies on bone tissue are limited. To ensure safe and effective treatment, studies on local tumor ablation in bone are needed.MethodMicrowave ablation was performed on sheep bone, for both in- and ex-vivo settings. Both a slow-cooking MWA protocol (gradually increasing wattage in the first two minutes of ablation) and a fast-cooking protocol (no warm-up period) were used. Heat distribution through the bone during ablation was determined by measuring temperature at 10- and 15mm from the ablation probe (= needle). Ablation size after procedure was measured using nitro-BT staining.ResultsIn-vivo ablations led to up to six times larger halos than ex-vivo with the same settings. Within both ex- and in-vivo experiments, no differences in halo size or temperature were found for different wattage levels (65W vs 80W). Compared to a fast cooking protocol, a two-minute slow cooking protocol led to increased temperatures and larger halos. Temperatures at 10- and 15mm distance from the needle no longer increased after six minutes. Halo sizes kept increasing over time without an evident plateau.ConclusionMicrowave ablation is technically effective for creating cell death in (sheep) long bone. It is recommended to start ablations with a slow-cooking period, gradually increasing the surrounding tissue temperature in two minutes from 40 to 90°C. Ex-vivo results cannot simply be translated to in-vivo.

Due to its close resemblance, the domesticated pig has proven to be a diverse animal model for biomedical research and genome editing tools have contributed to developing porcine models for several human diseases. By employing the CRISPR-Cas9 system, porcine embryos or somatic cells can be genetically modified to generate the desired genotype. However, somatic cell nuclear transfer (SCNT) of modified somatic cells and embryo manipulation are challenging, especially if the desired genotype is detrimental to the embryo. Direct in vivo edits may facilitate the production of genetically engineered pigs by integrating Cas9 into the porcine genome. Cas9 expressing cells were generated by either random integration or transposon-based integration of Cas9 and used as donor cells in SCNT. In total, 15 animals were generated that carried a transposon-based Cas9 integration and two pigs a randomly integrated Cas9. Cas9 expression was confirmed in muscle, tonsil, spleen, kidney, lymph nodes, oral mucosa, and liver in two boars. Overall, Cas9 expression was higher for transposon-based integration, except in tonsils and liver. To verify Cas9 activity, fibroblasts were subjected to in vitro genome editing. Isolated fibroblasts were transfected with guide RNAs (gRNA) targeting different genes (GGTA1, B4GALNT2, B2M) relevant to xenotransplantation. Next generation sequencing revealed that the editing efficiencies varied (2-60%) between the different target genes. These results show that the integrated Cas9 remained functional, and that Cas9 expressing pigs may be used to induce desired genomic modifications to model human diseases or further evaluate in vivo gene therapy approaches.

Population-based seroprevalence of chronic hepatitis B and C infections has not been examined in Lao People's Democratic Republic (PDR). Therefore, this study aimed to estimate the seroprevalence of these infections in the general population of Lao PDR and perform subgroup analysis. A nationwide seroprevalence survey was conducted in Lao PDR in June 2019 using the multistage cluster sampling method. Dried blood spot samples were collected onto WhatmanTM 903 filter paper by finger prick. A chemiluminescent microparticle immunoassay was used to measure the levels of hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCV-Ab). Samples in which the HBsAg level was above 0.05 IU/ml and HCV-Ab was above the signal/cutoff ratio of 1.0 were considered positive based on comparisons with the relative light unit value of a calibration sample. A total of 1,927 samples (male: 47.3%, mean age: 23.0 years) were included in the analysis. The prevalence was estimated to be 4.2% (95% confidence interval [CI]: 2.7-6.3) for HBsAg and 1.6% (95% CI: 0.5-5.3) for HCV-Ab. Multivariable analysis revealed that those aged 20-24 years (adjusted odds ratio (AOR): 2.3, 95% CI: 1.1-4.6), those aged 25-29 years (AOR: 2.7, 95% CI: 1.3-5.6), those from the Northern region (AOR: 2.8, 95% CI: 1.2-6.6), and those who were Khmu (AOR: 3.6, 95% CI: 2.0-6.8) or Hmong (AOR: 5.0, 95% CI: 3.3-7.5) were significantly more likely to be positive for HBsAg. Although there were no statistically significant differences in the HCV-Ab prevalence according to each variable, males (2.9%, 95% CI: 0.7-10.7), those aged ≥40 years (6.1%, 95% CI: 2.1-16.8), and those from the Southern region (3.3%, 95% CI: 0.6-15.3) tended to have a higher prevalence. This novel population-based survey found differences in the prevalence of chronic hepatitis B and hepatitis C virus infections in Lao PDR according to sex, age group, region, and ethnicity; however, the results of this study should be confirmed in future studies, and relevant responses tailored for each target also need to be determined to control the transmission of hepatitis B and C infections.

IntroductionSince the beginning of the pandemic in 2020, COVID-19 has changed the medical landscape. International recommendations for localized prostate cancer (PCa) include deferred treatment and adjusted therapeutic routines.Materials and methodsTo longitudinally evaluate changes in PCa treatment strategies in urological and radiotherapy departments in Germany, a link to a survey was sent to 134 institutions covering two representative baseline weeks prior to the pandemic and 13 weeks from March 2020 to February 2021. The questionnaire captured the numbers of radical prostatectomies, prostate biopsies and case numbers for conventional and hypofractionation radiotherapy. The results were evaluated using descriptive analyses.ResultsA total of 35% of the questionnaires were completed. PCa therapy increased by 6% in 2020 compared to 2019. At baseline, a total of 69 radiotherapy series and 164 radical prostatectomies (RPs) were documented. The decrease to 60% during the first wave of COVID-19 particularly affected low-risk PCa. The recovery throughout the summer months was followed by a renewed reduction to 58% at the end of 2020. After a gradual decline to 61% until July 2020, the number of prostate biopsies remained stable (89% to 98%) during the second wave. The use of RP fluctuated after an initial decrease without apparent prioritization of risk groups. Conventional fractionation was used in 66% of patients, followed by moderate hypofractionation (30%) and ultrahypofractionation (4%). One limitation was a potential selection bias of the selected weeks and the low response rate.ConclusionWhile the diagnosis and therapy of PCa were affected in both waves of the pandemic, the interim increase between the peaks led to a higher total number of patients in 2020 than in 2019. Recommendations regarding prioritization and fractionation routines were implemented heterogeneously, leaving unexplored potential for future pandemic challenges.

Background The incidence of keratinocyte carcinomas is high and rapidly growing. Approximately 80% of keratinocyte carcinomas consist of basal cell carcinomas (BCC) with 50% of these being considered as low-risk tumors. Nevertheless, 83% of the low-risk BCC patients were found to receive more follow-up care than recommended according to the Dutch BCC guideline, which is one visit post-treatment for this group. More efficient management could reduce unnecessary follow-up care and related costs. Objectives To study the efficacy, cost-utility, and budget impact of a personalized discharge letter for low-risk BCC patients compared with usual care (no personalized letter). Methods In a multi-center intervention study, a personalized discharge letter in addition to usual care was compared to usual care in first-time BCC patients. Model-based cost-utility and budget impact analyses were conducted, using individual patient data gathered via surveys. The outcome measures were number of follow-up visits, costs and quality adjusted life years (QALY) per patient. Results A total of 473 first-time BCC patients were recruited. The personalized discharge letter decreased the number of follow-up visits by 14.8% in the first year. The incremental costs after five years were -€24.45 per patient. The QALYs were 4.12 after five years and very similar in both groups. The national budget impact was -€2,7 million after five years. Conclusions The distribution of a personalized discharge letter decreases the number of unnecessary follow-up visits and implementing the intervention in a large eligible population would results in substantial cost savings, contributing to restraining the growing BCC costs.

Virtual reality (VR) has become a common tool and is often considered for sport-specific purposes. Despite the increased usage, the transfer of VR-adapted skills into the real-world (RW) has not yet been sufficiently studied, and it is still unknown how much of the own body must be visible to complete motoric tasks within VR. In addition, it should be clarified whether older adults also need to perceive their body within VR scenarios to the same extent as younger people extending the usability. Therefore, younger (18–30 years old) and elderly adults (55 years and older) were tested (n = 42) performing a balance-, grasping- and throwing task in VR (HMD based) accompanied with different body visualization types in VR and in the RW having the regular visual input of body’s components. Comparing the performances between the age groups, the time for completion, the number of steps (balance task), the subjective estimation of difficulty, the number of errors, and a rating system revealing movements’ quality were considered as examined parameters. A one-way ANOVA/Friedmann with repeated measurements with factor [body visualization] was conducted to test the influence of varying body visualizations during task completion. Comparisons between the conditions [RW, VR] were performed using the t-Tests/Wilcoxon tests, and to compare both age groups [young, old], t-Tests for independent samples/Mann-Whitney-U-Test were used. The analyses of the effect of body visualization on performances showed a significant loss in movement’s quality when no body part was visualized (p < .05). This did not occur for the elderly adults, for which no influence of the body visualization on their performance could be proven. Comparing both age groups, the elderly adults performed significantly worse than the young age group in both conditions (p < .05). In VR, both groups showed longer times for completion, a higher rating of tasks’ difficulty in the balance and throwing task, and less performance quality in the grasping task. Overall, the results suggest using VR for the elderly with caution to the task demands, and the visualization of the body seemed less crucial for generating task completion. In summary, the actual task demands in VR could be successfully performed by elderly adults, even once one has to reckon with losses within movement’s quality. Although more different movements should be tested, basic elements are also realizable for elderly adults expanding possible areas of VR applications.

German retailers offer a large variety of accessories for pets. However, not all products are suitable for pet husbandry. Several articles can negatively influence the wellbeing of pets or cause injuries, but empirical studies that evaluate accessories for small pets under animal welfare aspects are rare. In the present study, we assessed articles manufactured or sold in Germany in the product categories pet cages, hay racks, running wheels, exercise balls, harnesses and leashes, tube systems, and hamster bedding. To do so, we searched 28 German websites, visited 50 pet shops and 13 home improvement and garden centers on site and afterwards examined the animal welfare compliance of the products according to various evaluation criteria. Most of the examined products were rated not suitable for pet husbandry and were animal-welfare-adverse. This result applies to 86.1% (n = 87) of the 101 assessed running wheel models, 82.7% (n = 172) of the 208 assessed pet cage models and 55.6% (n = 40) of the 72 assessed hay rack models. The articles in the product categories exercise balls, harnesses and leashes, tube systems, and hamster bedding were also found unsuitable due to animal welfare concerns. Furthermore, we found clear shortcomings regarding article declarations. In some cases, relevant product information (e.g., dimensions) were missing, or the presented information was too general (e.g., rodent cage). Improperly declared pet accessories make it difficult for pet owners to decide whether a product is suitable or unsuitable for the species they keep. A declaration duty for manufacturers of pet products could ensure that German retailers only offer properly declared pet accessories and facilitate the decision for pet owners to purchase products appropriate for the pets they keep. Furthermore, a voluntary product certification for manufacturers would allow retailers to check the animal welfare compliance of articles before including them in their assortment. If a product is unsuitable for pet husbandry because it does not meet the set requirements, it must be considered animal-welfare-adverse and removed from the assortment. As done for the Austrian "animal welfare label," an independent, qualified third party could do the certification.

Dynamic contrast enhanced MRI (DCE-MRI) is a useful method to monitor therapy assessment in malignancies but must be reliable and comparable for successful clinical use. The aim of this study was to evaluate the inter- and intrarater reproducibility of DCE-MRI in lung cancer. At this IRB approved single centre study 40 patients with lung cancer underwent up to 5 sequential DCE-MRI examinations. DCE-MRI were performed using a 3.0T system. The volume transfer constant Ktrans was assessed by three readers using the two-compartment Tofts model. Inter- and intrarater reliability and agreement was calculated by wCV, ICC and their 95% confident intervals. DCE-MRI allowed a quantitative measurement of Ktrans in 107 tumors where 91 were primary carcinomas or intrapulmonary metastases and 16 were extrapulmonary metastases. Ktrans showed moderate to good interrater reliability in overall measurements (ICC 0.716–0.841; wCV 30.3–38.4%). Ktrans in pulmonary lesions ≥ 3 cm showed a good to excellent reliability (ICC 0.773–0.907; wCV 23.0–29.4%) compared to pulmonary lesions < 3 cm showing a moderate to good reliability (ICC 0.710–0.889; wCV 31.6–48.7%). Ktrans in intrapulmonary lesions showed a good reliability (ICC 0.761–0.873; wCV 28.9–37.5%) compared to extrapulmonary lesions with a poor to moderate reliability (ICC 0.018–0.680; wCV 28.1–51.8%). The overall intrarater agreement was moderate to good (ICC 0.607–0.795; wCV 24.6–30.4%). With Ktrans, DCE MRI offers a reliable quantitative biomarker for early non-invasive therapy assessment in lung cancer patients, but with a coefficient of variation of up to 48.7% in smaller lung lesions.

Background Most evidence on the relationship between sodium and potassium intake and cardiovascular disease originated from general population studies. This study aimed to evaluate the relation between estimated 24-hour sodium and potassium urinary excretion and the risk of recurrent vascular events and mortality in patients with vascular disease. Methods 7561 patients with vascular disease enrolled in the UCC-SMART cohort (1996–2015) were included. Twenty-four hour sodium and potassium urinary excretion were estimated (Kawasaki formulae) from morning urine samples. Cox proportional hazard models with restricted cubic splines were used to evaluate the relation between estimated urinary salt excretion and major adverse cardiovascular events (MACE; including myocardial infarction, stroke, cardiovascular mortality) and all-cause mortality. Results After a median follow-up of 7.4 years (interquartile range: 4.1–11.0), the relations between estimated 24-hour sodium urinary excretion and outcomes were J-shaped with nadirs of 4.59 gram/day for recurrent MACE and 4.97 gram/day for all-cause mortality. The relation between sodium-to-potassium excretion ratio and outcomes were also J-shaped with nadirs of 2.71 for recurrent MACE and 2.60 for all-cause mortality. Higher potassium urinary excretion was related to an increased risk of both recurrent MACE (HR 1.25 per gram potassium excretion per day; 95%CI 1.13–1.39) and all cause-mortality (HR 1.13 per gram potassium excretion per day; 95%CI 1.03–1.25). Conclusions In patients with established vascular disease, lower and higher sodium intake were associated with higher risk of recurrent MACE and all-cause mortality. Higher estimated 24-hour potassium urinary excretion was associated with a higher risk of recurrent MACE and all-cause mortality.

The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).

BackgroundLumbo-sacral transitional vertebrae (LSTV) are one of the most common congenital variances of the spine. They are associated with an increased frequency of degeneration in the cranial adjacent segment. Hypermobility and concomitant increased loads are discussed as a possible reason for segmental degeneration. We therefore examined the lumbar and segmental motion distribution in patients with LSTV with flexion-extension radiographs.MethodsA retrospective study of 51 patients with osteochondrosis L5/S1 with flexion and extension radiographs was performed. Of these, 17 patients had LSTV and were matched 1:1 for age and sex with patients without LSTV out of the collective of the remaining 34 patients. The lumbar and segmental range of motion (RoM) by segmental lordosis angle and the segmental wedge angle were determined. Normal distribution of parameters was observed by Kolmogorov-Smirnov-test. Parametric data were compared by paired T-test. Non-parametric data were compared by Wilcoxon-rank-sum-test. Correlations were observed using Spearman's Rank correlation coefficient. A p-value ResultsPatients with LSTV had mean age of 52.2±10.9, control group of 48.9±10.3. Both groups included 7 females and 10 males. Patients with LSTV presented with reduced RoM of the lumbar spine (LSTV 37.3°±19.2°, control 52.1°±20.5°, p = 0.065), however effects were statistically insignificant. LSTV significantly decreased segmental RoM in the transitional segment (LSTV 1.8°±2.7°, control 6.7°±6.0°, p = 0.003). Lumbar motion distribution differed significantly; while RoM was decreased in the transitional segment, (LSTV 5.7%, control 16.2%, p = 0.002), the distribution of lumbar motion to the cranial adjacent segment was increased (LSTV 30.7%, control 21.6%, p = 0.007).ConclusionPatients with LSTV show a reduced RoM in the transitional segment and a significantly increased motion distribution to the cranial adjacent segment in flexion-extension radiographs. The increased proportion of mobility in the cranial adjacent segment possibly explain the higher rates of degeneration within the segment.

This study aimed to provide volumetric choroidal readings regarding sex, origin, and eye side from healthy cynomolgus monkey eyes as a reference database using optical coherence tomography (OCT) imaging. A machine learning (ML) algorithm was used to extract the choroid from the volumetric OCT data. Classical computer vision methods were then applied to automatically identify the deepest location in the foveolar depression. The choroidal thickness was determined from this reference point. A total of 374 eyes of 203 cynomolgus macaques from Asian and Mauritius origin were included in the analysis. The overall subfoveolar mean choroidal volume in zone 1, in the region of the central bouquet, was 0.156 mm3 (range, 0.131-0.193 mm3). For the central choroid volume, the coefficient of variation (CV) was found of 6.3%, indicating relatively little variation. Our results show, based on analyses of variance, that monkey origin (Asian or Mauritius) does not influence choroid volumes. Sex had a significant influence on choroidal volumes in the superior-inferior axis (p ≤ 0.01), but not in the fovea centralis. A homogeneous foveolar choroidal architecture was also observed.

IntroductionLow back pain is a major health issue in elite rowers. High training volume, frequent flexion movements of the lower spine and rotational movement in sweep rowing contribute to increased spinal strain and neuropathological patterns. Perturbation-based trunk stabilization training (PTT) may be effective to treat neuromuscular deficits and low back pain.MethodsAll boat classes (8+, 4+/-, 2-) of the male German national sweep rowing team participated in this non-randomized parallel group study. We included 26 athletes (PTT: n = 12, control group: n = 14) in our analysis. Physical and Sports therapists conducted 16 individualized PTT sessions á 30-40 minutes in 10 weeks, while the control group kept the usual routines. We collected data before and after intervention on back pain intensity and disability, maximum isometric trunk extension and flexion, jump height and postural sway of single-leg stance.ResultsWe found less disability (5.3 points, 95% CI [0.4, 10.1], g = 0.42) for PTT compared to control. Pain intensity decreased similar in both groups (-14.4 and -15.4 points), yielding an inconclusive between-group effect (95% CI [-16.3, 14.3]). Postural sway, strength and jump height tend to have no between- and within-group effects.ConclusionPerturbation-based trunk stabilization training is possibly effective to improve the physical function of the lower back in elite rowers.

Objectives In alcoholic hepatitis (AH), dysfunctional T lymphocytes may contribute to the high mortality from infections. T lymphocyte activation is governed by the expression of co-stimulatory receptors such as 4-1BB balanced by inhibitory receptors such as Programmed Death receptor 1 (PD-1). 4-1BB expression is unaccounted for in AH, while PD-1 is elevated. We characterized expression of 4-1BB and PD-1 and the associated T lymphocyte functional status in AH and investigated whether these were associated with short-term mortality. Methods Thirty-five patients with AH (at diagnosis and days 7 and 90) were compared with healthy controls (HC). Spontaneous and in vitro stimulated receptor expression were quantified by flow cytometry, and plasma proteins by ELISA. Results At diagnosis, the patients showed increased stimulated 4-1BB responses of CD4+ T lymphocytes. Also, the frequencies of PD-1+ T lymphocytes both with and without co-expressed 4-1BB were increased. Further, interferon-gamma was predominantly produced in T lymphocytes co-expressing 4-1BB. A decrease in the frequency of spontaneous 4-1BB+ T lymphocytes and an increase in soluble 4-1BB during the first week after diagnosis were associated with higher mortality at day 90 in AH. PD-1 expression showed no systematic dynamics related to mortality. Conclusions We found an increased stimulated 4-1BB response of T lymphocytes in AH and early loss of these lymphocytes was associated with a higher short-term mortality. This suggests a role of T lymphocyte 4-1BB expression in the progression of AH.

Background Video analysis is one of the most commonly applied methods for analysing football injuries. Purpose The objective of this study was to assess the accuracy of video analysis for recording head injuries in professional football from official matches in the four highest men’s professional football leagues in Germany. Methods In this cohort study, head injuries detected by means of video analysis of all official matches over one season (2017–18) were compared to head injuries registered with the German statutory accident insurance. Results Our video analysis yielded 359 head injuries of 287 players. The comparison of head injuries found in our video analysis to those registered with the accident insurance only yielded a match in 23.1% (n = 83), which presents a rather low verification rate. The verification rates varied between the leagues (7.0–30.8%). All injuries documented in the accident insurance registry were found in the video analysis (100%). The types of head injury most often verified by the accident insurance registry (n = 83) were contusion (43.4%), bone fractures (19.3%) and skin lacerations (18.1%). Only 66 of the 359 head injuries (18.4%) resulted in absence from at least one training session and involved a mean time loss of 18.5 days (1–87 days). Conclusion The mismatch between the number of head injuries found in the video analysis and head injuries registered with the accident insurance is an important methodological issue in scientific research. The low verification rate seems to be due to the unclear correlation between injury severity and clinical consequences of head injuries detected by means of video analysis and the failure of football clubs to register minor head injuries with the accident insurance.

BackgroundTherapy of severely affected coronavirus patient, requiring intubation and sedation is still challenging. Recently, difficulties in sedating these patients have been discussed. This study aims to describe sedation practices in patients with 2019 coronavirus disease (COVID-19)-induced acute respiratory distress syndrome (ARDS).MethodsWe performed a retrospective monocentric analysis of sedation regimens in critically ill intubated patients with respiratory failure who required sedation in our mixed 32-bed university intensive care unit. All mechanically ventilated adults with COVID-19-induced ARDS requiring continuously infused sedative therapy admitted between April 4, 2020, and June 30, 2020 were included. We recorded demographic data, sedative dosages, prone positioning, sedation levels and duration. Descriptive data analysis was performed; for additional analysis, a logistic regression with mixed effect was used.ResultsIn total, 56 patients (mean age 67 (±14) years) were included. The mean observed sedation period was 224 (±139) hours. To achieve the prescribed sedation level, we observed the need for two or three sedatives in 48.7% and 12.8% of the cases, respectively. In cases with a triple sedation regimen, the combination of clonidine, esketamine and midazolam was observed in most cases (75.7%). Analgesia was achieved using sufentanil in 98.6% of the cases. The analysis showed that the majority of COVID-19 patients required an unusually high sedation dose compared to those available in the literature.ConclusionThe global pandemic continues to affect patients severely requiring ventilation and sedation, but optimal sedation strategies are still lacking. The findings of our observation suggest unusual high dosages of sedatives in mechanically ventilated patients with COVID-19. Prescribed sedation levels appear to be achievable only with several combinations of sedatives in most critically ill patients suffering from COVID-19-induced ARDS and a potential association to the often required sophisticated critical care including prone positioning and ECMO treatment seems conceivable.

BackgroundCritically ill patients with cardiogenic shock could benefit from ventricular assist device support using the Impella microaxial blood pump. However, recent studies suggested Impella not to improve outcomes. We, therefore, evaluated outcomes and predictors in a real-world scenario.MethodsIn this retrospective single-center trial, 125 patients suffering from cardiac arrest/cardiogenic shock between 2008 and 2018 were analyzed. 93 Patients had a prior successful cardiopulmonary resuscitation. The primary endpoint was hospital mortality. Associations of covariates with the primary endpoint were assessed by univariable and multivariable logistic regression. Adjusted odds ratios (aOR) and optimal cut-offs (using Youden index) were obtained.ResultsHospital mortality was high (81%). Baseline lactate was 4.7mmol/L [IQR = 7.1mmol/L]. In multivariable logistic regression, only age (aOR 1.13 95%CI 1.06-1.20; p3.3mmol/L and age >66 years. Patients were retrospectively stratified into three risk groups: Patients aged ≤66 years and lactate ≤3.3mmol (low-risk; n = 22); patients aged >66 years or lactate >3.3mmol/L (medium-risk; n = 52); and patients both aged >66 years and lactate >3.3mmol/L (high-risk, n = 51). Risk of death increased from 41% in the low-risk group, to 79% in the medium risk group and 100% in the high-risk group. The predictive abilities of this model were high (AUC 0.84; 95% 0.77-0.92).ConclusionMortality was high in this real-world collective of severely ill cardiogenic shock patients. Better patient selection is warranted to avoid unethical use of Impella. Age and lactate might help to improve patient selection.

Drawing on Jakarta, Metro Manila and Singapore as case studies, we explore the paradox of slow political action in addressing subsiding land, particularly along high-density urban coastlines with empirical insights from coastal geography, geodesy analysis, geology, and urban planning. In framing land subsidence as a classic 'wicked' policy problem, and also as a hybrid geological and anthropogenic phenomenon that is unevenly experienced across urban contexts, the paper uses a three-step analysis. First, satellite-derived InSAR maps are integrated with Sentinel-1A data in order to reveal the socio-temporal variability of subsidence rates which in turn pose challenges in uniformly applying regulatory action. Second, a multi-sectoral mapping of diverse policies and practices spanning urban water supply, groundwater extraction, land use zoning, building codes, tenurial security, and land reclamation reveal the extent to which the broader coastal governance landscape remains fragmented and incongruous, particularly in arresting a multi-dimensional phenomenon such as subsidence. Finally, in reference to distinct coastal identities of each city-the 'Sinking Capital' (Jakarta), 'Fortress Singapore', and the 'Disaster Capital' (Manila) the paper illustrates how land subsidence is portrayed across the three metropolises in markedly similar ways: as a reversible, quasi-natural, and/or a highly individualized problem.

BackgroundIntravenous cannulation is usually the first procedure performed in modern healthcare, although establishing peripheral intravenous access is challenging in some patients. The impact of the ratio between venous diameter and the size of the inserted catheter (catheter to vein ratio, CVR) on the first attempt success rate can be of added value in clinical. This study tries to give insight into the consideration that must be made when selecting the target vein and the type of catheter, and proved the null hypothesis that an optimal CVR would not be associated with increased first attempt cannulation success.MethodsThis was a post-hoc analyses on adult patients admitted for peripheral intravenous cannulation. Intravenous cannulation was performed according to practice guidelines, by applying the traditional landmark approach. The CVR was calculated afterwards for each individual patient by dividing the external diameter of the inserted catheter by the diameter of the target vein, which was multiplied by 100%.ResultsIn total, 610 patients were included. The median CVR was 0.39 (0.15) in patients with a successful first attempt, whereas patients with an unsuccessful first attempt had a median CVR of 0.55 (0.20) (P0.41 had a first attempt success rate of 65% (PConclusionThis first introduction of the CVR in relation to cannulation success should be further investigated. Although, measuring the venous diameter or detection of a vein with a specific diameter prior to cannulation may increase first attempt cannulation success.

BackgroundAnti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn's disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose response over time. To aid patient stratification, polygenetic risk scores have been identified as predictors of response to anti-TNFα therapy. We aimed to replicate the association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients, to establish its clinical validity.Materials and methodsPrimary non-response, primary response, durable response and loss of response to anti-TNFα therapy was retrospectively assessed for each patient using stringent definitions. Genome wide genotyping was performed and previously described polygenetic risk scores for primary non-response and durable response were calculated. We compared polygenetic risk scores between patients with primary response and primary non-response, and between patients with durable response and loss of response, using separate analyses for CD and UC.ResultsOut of 334 patients with CD, 15 (4%) patients met criteria for primary non-response, 221 (66%) for primary response, 115 (34%) for durable response and 35 (10%) for loss of response. Out of 112 patients with UC, 12 (11%) met criteria for primary non-response, 68 (61%) for primary response, 19 (17%) for durable response and 20 (18%) for loss of response. No significant differences in polygenetic risk scores were found between primary non-responders and primary responders, and between durable responders and loss of responders.ConclusionsWe could not replicate the previously reported association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients with CD or UC. Currently, there is insufficient evidence to use polygenetic risk scores to predict response to anti-TNFα therapy in patients with IBD.

IntroductionIn 2014, the Navajo Nation Healthy Diné Nation Act (HDNA) was passed, combining a 2% tax on foods of 'minimal-to-no-nutritional value' and waiver of 5% sales tax on healthy foods, the first-ever such tax in the U.S. and globally among a sovereign tribal nation. The aim of this study was to measure changes in pricing and food availability in stores on the Navajo Nation following the implementation of the HDNA.MethodsStore observations were conducted in 2013 and 2019 using the Nutrition Environment Measurement Survey-Stores (NEMS-S) adapted for the Navajo Nation. Observations included store location, type, whether healthy foods or HDNA were promoted, and availability and pricing of fresh fruits and vegetables, canned items, beverages, water, snacks and traditional foods. Differences between 2013 and 2019 and by store type and location were tested.ResultsThe matched sample included 71 stores (51 in the Navajo Nation and 20 in border towns). In 2019, fresh produce was available in the majority of Navajo stores, with 71% selling at least 3 types of fruit and 65% selling at least 3 types of vegetables. Compared with border town convenience stores, Navajo convenience stores had greater availability of fresh vegetables and comparable availability of fresh fruit in 2019. The average cost per item of fresh fruit decreased by 13% in Navajo stores (from $0.88 to $0.76) and increased in border stores (from $0.63 to $0.73), resulting in comparable prices in Navajo and border stores in 2019. While more Navajo stores offered mutton, blue corn and wild plants in 2019 compared to 2013, these changes were not statistically significant.DiscussionThe findings suggest modest improvements in the Navajo store environment and high availability of fruits and vegetables. Navajo stores play an important role in the local food system and provide access to local, healthy foods for individuals living in this rural, tribal community.

Yellow laccases lack the typical blue type 1 Cu absorption band around 600 nm; however, multi-copper oxidases with laccase properties have been reported. We provide the first evidence that the yellow laccase isolated from Sclerotinia sclerotiorum is obtained from a blue form by covalent, but nevertheless reversible modification with a phenolic product. After separating the phenolics from the extracellular medium, a typical blue laccase is obtained. With ABTS as model substrate for this blue enzyme, a non-natural purple adduct is formed with a spectrum nearly identical to that of the 1:1 adduct of an ABTS radical and Tyr. This modification significantly increases the stability and substrate affinity of the enzyme, not by acting primarily as bound mediator, but by structural changes that also alters the type 1 Cu site. The HPLC-MS analyses of the ABTS adduct trypsin digests revealed a distinct tyrosine within a unique loop as site involved in the modification of the blue laccase form. Thus, S. sclerotiorum yellow laccase seems to be an intrinsically blue multi-copper oxidase that boosts its activity and stability with a radical-forming aromatic substrate. This particular case could, at least in part, explain the enigma of the yellow laccases.

RATIONALE:A subset of patients with idiopathic pulmonary fibrosis (IPF) contains short leukocyte telomeres or telomere related mutations. We previously showed that alveolar type 2 cells have short telomeres in fibrotic lesions. Our objectives were to better understand how telomere shortening associates with fibrosis in IPF lung and identify a subset of patients with telomere-related disease. METHODS:Average telomere length was determined in multiple organs, basal and apical lung, and diagnostic and end-stage fibrotic lung biopsies. Alveolar type 2 cells telomere length was determined in different areas of IPF lungs. RESULTS:In IPF but not in controls, telomere length in lung was shorter than in other organs, providing rationale to focus on telomere length in lung. Telomere length did not correlate with age and no difference in telomere length was found between diagnostic and explant lung or between basal and apical lung, irrespective of the presence of a radiological apicobasal gradient or fibrosis. Fifteen out of 28 IPF patients had average lung telomere length in the range of patients with a telomerase (TERT) mutation, and formed the IPFshort group. Only in this IPFshort and TERT group telomeres of alveolar type 2 cells were extremely short in fibrotic areas. Additionally, whole exome sequencing of IPF patients revealed two genetic variations in RTEL1 and one in PARN in the IPFshort group. CONCLUSIONS:Average lung tissue telomere shortening does not associated with fibrotic patterns in IPF, however, approximately half of IPF patients show excessive lung telomere shortening that is associated with pulmonary fibrosis driven by telomere attrition.

Understanding and predicting how individuals perform in high-pressure situations is of importance in designing and managing workplaces. We investigate performance under pressure in professional darts as a near-ideal setting with no direct interaction between players and a high number of observations per subject. Analyzing almost one year of tournament data covering 32,274 dart throws, we find no evidence in favor of either choking or excelling under pressure.

BACKGROUND:Current guidelines underline the importance of high-quality chest compression during cardiopulmonary resuscitation (CPR), to improve outcomes. Contrary to this many studies show that chest compression is often carried out poorly in clinical practice, and long interruptions in compression are observed. This prospective cohort study aimed to analyse whether chest compression quality changes when a real-time feedback system is used to provide simultaneous audiovisual feedback on chest compression quality. For this purpose, pauses in compression, compression frequency and compression depth were compared. METHODS:The study included 292 out-of-hospital cardiac arrests in three consecutive study groups: first group, conventional resuscitation (no-sensor CPR); second group, using a feedback sensor to collect compression depth data without real-time feedback (sensor-only CPR); and third group, with real-time feedback on compression quality (sensor-feedback CPR). Pauses and frequency were analysed using compression artefacts on electrocardiography, and compression depth was measured using the feedback sensor. With this data, various parameters were determined in order to be able to compare the chest compression quality between the three consecutive groups. RESULTS:The compression fraction increased with sensor-only CPR (group 2) in comparison with no-sensor CPR (group 1) (80.1% vs. 87.49%; P < 0.001), but there were no further differences belonging compression fraction after activation of sensor-feedback CPR (group 3) (P = 1.00). Compression frequency declined over the three study groups, reaching the guideline recommendations (127.81 comp/min vs. 122.96 comp/min, P = 0.02 vs. 119.15 comp/min, P = 0.008) after activation of sensor-feedback CPR (group 3). Mean compression depth only changed minimally with sensor-feedback (52.49 mm vs. 54.66 mm; P = 0.16), but the fraction of compressions with sufficient depth (at least 5 cm) and compressions within the recommended 5-6 cm increased significantly with sensor-feedback CPR (56.90% vs. 71.03%; P = 0.003 and 28.74% vs. 43.97%; P < 0.001). CONCLUSIONS:The real-time feedback system improved chest compression quality regarding pauses in compression and compression frequency and facilitated compliance with the guideline recommendations. Compression depth did not change significantly after activation of the real-time feedback. Even the sole use of a CPR-feedback-sensor ("sensor-only CPR") improved performance regarding pauses in compression and compression frequency, a phenomenon known as the 'Hawthorne effect'. Based on this data real-time feedback systems can be expected to raise the quality level in some parts of chest compression quality. TRIAL REGISTRATION:International Clinical Trials Registry Platform of the World Health Organisation and German Register of Clinical Trials (DRKS00009903), Registered 09 February 2016 (retrospectively registered).

The European-Commission-funded project 'Citclops' (Citizens' observatory for coast and ocean optical monitoring) developed methods, tools and sensors, which can be used by citizens to monitor natural waters, with a strong focus on long-term data series related to environmental sciences. The new sensors, based on optical technologies, respond to a number of scientific, technical and societal objectives, ranging from more precise monitoring of key environmental descriptors of the aquatic environment (water colour, transparency and fluorescence) to an improved management of data collected with citizen participation. The sensors were tested, calibrated, integrated on several platforms, scientifically validated and demonstrated in the field. The new methods and tools were tested in a citizen-science context. The general conclusion is that citizens are valuable contributors in quality and quantity to the objective of collecting, integrating and analysing fragmented and diverse environmental data. An integration of these data into data-analysis tools has a large potential to support authoritative monitoring and decision-making. In this paper, the project's objectives, results, technical achievements and lessons learned are presented.

[This corrects the article DOI: 10.1371/journal.pone.0229431.].

All across the globe politically initiated research evaluations are based on "informed peer review" procedures. Scholars are appointed as evaluators and can apply self-defined quality standards in order to overcome shortcomings of standardized measures. Even though there are no binding criteria in these procedures and the quality standards of the scholars' disciplines vary, studies suggest that scholars, in their role as government-appointed research evaluators, assess research uniformly.By drawing on a small-N investigation, this study compares the quality standards scholars apply as government-appointed research evaluators with quality standards they follow as researchers. The study points to a paradox: Criteria scholars refer to while describing the excellence of their own research and criteria they use as evaluators differ and contradict each other. The results are discussed from different angles.

IntroductionAfter the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries.Material and methodsAn email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses.Results27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers-however, the number of COVID-19 patients and urologists did not reach double digits.ConclusionThe German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low.

Mental disorders (MD) are associated with an increased risk of developing coronary heart disease (CHD) and with higher CHD-related morbidity and mortality. There is a strong recommendation to routinely screen CHD patients for MDs, diagnosis, and treatment by recent guidelines. The current study aimed at mapping CHD patients' (1) state of diagnostics and, if necessary, treatment of MDs, (2) trajectories and detection rate in healthcare, and (3) the influence of MDs and its management on quality of life and patient satisfaction. The design was a cross-sectional study in three settings (two hospitals, two rehabilitation clinics, three cardiology practices). CHD patients were screened for MDs with the Hospital Anxiety and Depression Scale (HADS), and, if screened-positive, examined for MDs with the Structured Clinical Interview for DSM-IV (SCID-I). Quality of Life (EQ-5D), Patient Assessment of Care for Chronic Conditions (PACIC), and previous routine diagnostics and treatment for MDs were examined. Descriptive statistics, Chi-squared tests, and ANOVA were used for analyses. Analyses of the data of 364 patients resulted in 33.8% positive HADS-screenings and 28.0% SCID-I diagnoses. The detection rate of correctly pre-diagnosed MDs was 49.0%. Physicians actively approached approximately thirty percent of patients on MDs; however, only 6.6% of patients underwent psychotherapy and 4.1% medication therapy through psychotherapists/psychiatrists. MD patients scored significantly lower on EQ-5D and the PACIC. The state of diagnostic and treatment of comorbid MDs in patients with CHD is insufficient. Patients showed a positive attitude towards addressing MDs and were satisfied with medical treatment, but less with MD-related advice. Physicians in secondary care need more training inadequately addressing mental comorbidity.