To reduce cytotoxicity when testing the virucidal activity of chemical disinfectants and biocides: The "T-25 method" as an alternative to "large-volume-plating".

When testing the virucidal activity of biocides, the non-inactivated residual virus is titrated on cell cultures by the end point dilution method on 96-well tissue culture plates. However, residues of the biocide to be tested also come into contact with the cell cultures in varying concentrations and thus can lead to cytotoxic effects even at high levels of dilution. In the European standards for testing biocides, in particular disinfectants, methods such as Large-Volume-Plating (LVP) method and, in some guidelines, gel filtration procedures are described for reducing cytotoxic effects in the case of highly cytotoxic products, if the classical dilution method proves to be impractical. In order to enable the testing of highly cytotoxic biocides for their activity against viruses, an alternative method for reducing cytotoxicity is introduced, which is based on a procedure of isolating infectious viruses from cytotoxic patients' materials such as stool and can be applied when the other methods fail.

X-ray Fourier transform holography with beam shaping optical elements.

Holography is a powerful method for achieving 3D images of objects. Extending this method to short wavelengths potentially offers significantly higher resolution than visible light holography. However, current X-ray holography setups employ nanoscale pinholes to form the reference wave. This approach is relatively inefficient and limited to very small sample size. Here, we propose a new setup for X-ray holography based on a binary diffractive optical element (DOE), which forms at the same time the object illumination and the reference wave. This optic is located separately from the sample plane, which permits investigation of larger sample areas. Using an extended test sample, we demonstrate a resolution of 90 nm (half-pitch) at an undulator beamline at BESSY II. The new holography setup can be directly transferred to free electron laser sources enabling time-resolved nanoscale imaging for ultra-fast processes.

[COVID-19 in Routine Rheumatologic Care]. / COVID-19 in der rheumatologischen Routineversorgung.

Since the first case of coronavirus infection with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and the associated COVID-19 (corona virus disease 2019) it has become a worldwide pandemic. This leads to persistent and far-reaching consequences for the health system and society as a whole. Our patients with inflammatory rheumatic diseases were initially considered to be at high risk of contracting SARS-CoV­2, especially if they were on immunosuppressive and/or immunomodulatory therapy (DMARD). It was assumed that a severe COVID-19 course could occur in case of infection. Although PCR diagnosis is generally considered the gold standard for early diagnosis of active infection with SARS-CoV­2, it has been shown that it should not always be used to confirm the diagnosis of COVID-19. Therefore, complementary antibody testing for SARS-CoV­2 could be useful in cases of clinical suspicion and negative PCR for diagnostic confirmation of COVID-19, even retrospectively. Apparently, patients with inflammatory rheumatic disease and under DMARD therapy are not particularly at risk in case of SARS-CoV­2 infection. Whether this is due to better hygiene measures or increased contact restrictions of patients with underlying inflammatory rheumatic disease, or whether ongoing DMARD therapy offers some protection against a severe course of COVID-19, is still to be clarified. The important questions about the tolerability and efficacy of COVID-19 vaccination have yet to be answered. In summary, there is still a clear need for research to better advise our patients.

[Elective treatment of inguinal hernia in university surgery-an economic challenge]. / Elektive Versorgung von Leistenhernien in der universitären Chirurgie ­ eine ökonomische Herausforderung.

INTRODUCTION: Elective and emergency inguinal hernia surgery is a central task for general and abdominal surgeons. As a standard procedure it is regarded as having a relatively low income in the German diagnosis-related groups (DRG) system. This can lead to an economic imbalance, especially in a cost-intensive environment of a university hospital. The aim of this analysis was to investigate the influence of clinical factors on costs and the contribution margin as well as the overall economic evaluation of elective inguinal hernia surgery at a university hospital. MATERIAL AND METHODS: All patients undergoing elective inguinal hernia surgery at two locations of the Charité University Medicine Berlin in 2014 and 2015 were included in the analysis. The influence of clinical, patient and surgical factors on the economic outcome of the cases was evaluated. RESULTS: A total of 419 patients were included, mostly after a Lichtenstein operation (44.9%) and laparoscopic transabdominal preperitoneal (TAPP) surgery (53.9%). The greatest impact on the economic outcome was the occurrence of postoperative complications. Also, a patient clinical complexity level (PCCL) value of >1, more than 8 encoded secondary diagnoses and a duration of hospital stay of less than 2 days had a significantly negative impact on the contribution margin. Overall, elective inguinal hernia surgery led to a negative contribution margin of €â€¯651 per case. CONCLUSION: Elective inguinal hernia surgery in the environment of a university hospital has a high financial deficit; however, since a complete discontinuation of this treatment is not an alternative multifactorial approaches are required to improve the economic outcome.

Interlaboratory reproducibility of a test method following 4-field test methodology to evaluate the susceptibility of Clostridium difficile spores.

BACKGROUND: Sporicidal surface disinfection is recommended to control transmission of Clostridium difficile in healthcare facilities. EN 17126 provides a method to determine the sporicidal activity in suspension and has been approved as a European standard. In addition, a sporicidal surface test has been proposed. AIM: To determine the interlaboratory reproducibility of a test method for evaluating the susceptibility of a C. difficile spore preparation to a biocidal formulation following the 4-field test (EN 16615 methodology). METHODS: Nine laboratories participated. C. difficile NCTC 13366 spores were used. Glutaraldehyde (1% and 6%; 15 min) and peracetic acid (PAA; 0.01% and 0.04%; 15 min) were used to determine the spores' susceptibility in suspension in triplicate. FINDINGS: One-percent glutaraldehyde revealed a mean decimal log10 reduction of 1.03 with variable results in the nine laboratories (0.37-1.49) and a reproducibility of 0.38. The effect of 6% glutaraldehyde was stronger (mean: 2.05; range: 0.96-4.29; reproducibility: 0.86). PAA revealed similar results. An exemplary biocidal formulation based on 5% PAA was used at 0.5% (non-effective concentration) and 4% (effective concentration) to determine the sporicidal efficacy (4-field test) under clean conditions in triplicate with a contact time of 15 min. When used at 0.5% it demonstrated an overall log10 reduction of 2.68 (range: 2.35-3.57) and at 4% of 4.61 (range: 3.82-5.71). The residual contamination on the three primarily uncontaminated test fields was <50 cfu/25 cm2 in one out of nine laboratories (0.5%) and in seven out of nine laboratories (4%). CONCLUSION: The interlaboratory reproducibility seems to be robust.

Laparoscopic versus open hemihepatectomy-a cost analysis after propensity score matching.

INTRODUCTION: Cost efficiency is important for hospitals in order to provide high-quality health care for all patients. As hemihepatectomies are increasingly being performed laparoscopically, the aims of this study were to evaluate the costs of laparoscopic hemihepatectomy and to compare them to conventional open techniques. PATIENTS AND METHODS: This is a retrospective analysis of clinical outcomes and financial calculations of all patients who underwent hemihepatectomy between January 2015 and December 2016 at the Department of Surgery, Campus Charité Mitte and Campus Charité Virchow-Klinikum, Berlin, Germany, being allocated to the DRG (diagnosis-related group) H01A (complex operations of the liver and pancreas with complex intensive care treatment) or H01B (operations of the liver and pancreas without complex intensive care treatment). To overcome selection bias, a 1:1 propensity score matching (PSM) analysis was performed. RESULTS: After PSM, a total of 64 patients were identified; 32 patients underwent laparoscopic hemihepatectomy (LH); and 32 patients received open hemihepatectomy (OH). After PSM, no significant differences were observed in clinical baseline characteristics. The duration of surgery was significantly longer for patients undergoing LH compared to OH (LH, 334 min, 186-655 min; OH, 274 min, 176-454 min; p = 0.005). Patients in the LH group had a significantly shortened median hospital stay of 5 d, when compared to OH (LH, 9.5 d, 3-35 d; OH, 14.5 d, 7-37d; p = 0.005). We observed a significant higher rate of postoperative complication in the OH group (p = 0.022). Cost analysis showed median overall costs of 17,369.85€ in the LH group and 16,103.64€ in the OH group (p = 0.390). CONCLUSION: Our data suggest that higher intraoperative costs of laparoscopic liver surgery, e.g., for surgical devices and due to longer operation times, are compensated by fewer postoperative complications and consecutive shorter length of stay when compared with OH.

The important role of marine debris networks to prevent and reduce ocean plastic pollution.

Societal change is needed to prevent and reduce the growth in the amount of solid waste entering the sea. Marine debris networks cover a broad range of activities in order to protect our oceans. By following a common vision and a collective systematic approach they are capable of creating synergies between all relevant stakeholders that result in reducing the flow of waste into our oceans. Thus, they are key to achieving the Sustainable Development Goals. During the 6th International Marine Debris Conference in San Diego in 2018, different marine debris networks from different parts of the world presented their activities, achievements and challenges. This led to network representatives agreeing to collaborate as members of an International Waste Platform. This platform aims to harmonize objectives, share knowledge, join forces and help new networks to emerge.

Association between baseline clinical and imaging findings and the development of digital ulcers in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) can lead to ischemic complications such as digital ulcers (DUs). The aim of the study was to find predictors of DUs by clinical and new imaging methods. PATIENTS AND METHODS: All 79 SSc patients included in the study received a clinical, colour Doppler ultrasound (CDUS), fluorescence optical imaging (FOI) and capillaroscopy examination at baseline, and their capacity to predict new DU development was analysed in 76 patients at 12 months follow-up. RESULTS: Twenty-two of 76 patients (28.9%) developed new ulcers during follow-up (diffuse SSc 48.1%; limited SSc 18.4%). Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 0.7576 for DU development, with a specificity of 87% and a sensitivity of 54.6% (p = 0.0003, OR = 8.1 [95%CI 2.5-25.6]) at a cut-off of ≥ 21 points (ACR/EULAR classification criteria for SSc). Capillaroscopy and CDUS had high sensitivity (100% and 95.5%) but low specificity (28.9% and 22.2%) for ulcer occurrence when used alone, but better specificity (46.3%) when combined (OR = 18.1 [95%CI 2.3-144.4]; p = 0.0004). Using FOI, fingers with pathologic staining had a higher risk for new ulcer development in the same finger (p = 0.0153). General future DU (i.e. DU also in other fingers) was associated with a missing FOI signal in the right digit III at baseline (p = 0.048). CONCLUSION: New imaging modalities can predict digital ulcer development in SSc patients with high sensitivity for capillaroscopy and CDUS and enhanced specificity when combined. A missing signal of FOI in the right digit III at baseline was associated with general future DU.

Service use and perceptions of service effectiveness by parents of individuals with intellectual disabilities: comparing Jewish and Arab Israeli parental caregivers.

BACKGROUND: The relationship between ethnicity, service use and perceptions of service effectiveness is inconclusive. This study examined differences in service use and perceptions of service effectiveness between Israeli Jewish (Jewish) and Israeli Arab (Arab) parental caregivers of individuals with intellectual disabilities and dual diagnosis of psychopathology. METHODS: Parental caregivers (n = 186) of individuals with intellectual disabilities or dual diagnosis, aged 10 to 30 years, completed a self-report questionnaire. RESULTS: Arab parental caregivers perceived health services to be more accessible than did Jewish caregivers, but there was no difference between the two groups in the use of the services. Overall, greater enabling factors and accessibility were associated with higher use of education and social services. No differences were found between the groups in their perceptions of service effectiveness. CONCLUSION: Arab family caregivers use education and social services less than do their Jewish peers, possibly because they have fewer enabling resources. The finding that both groups reported similar use of health services may be explained by a shared perception that informal help may not be suitable for dealing with situations of psychopathology. The similar perceptions of service effectiveness may be explained by extensive services available in Israel, to the satisfaction of both groups, or by the fact that participants perceived these services as their only alternative, and therefore fear losing them.

Committing to quantum resistance: a slow defence for Bitcoin against a fast quantum computing attack.

Quantum computers are expected to have a dramatic impact on numerous fields due to their anticipated ability to solve classes of mathematical problems much more efficiently than their classical counterparts. This particularly applies to domains involving integer factorization and discrete logarithms, such as public key cryptography. In this paper, we consider the threats a quantum-capable adversary could impose on Bitcoin, which currently uses the Elliptic Curve Digital Signature Algorithm (ECDSA) to sign transactions. We then propose a simple but slow commit-delay-reveal protocol, which allows users to securely move their funds from old (non-quantum-resistant) outputs to those adhering to a quantum-resistant digital signature scheme. The transition protocol functions even if ECDSA has already been compromised. While our scheme requires modifications to the Bitcoin protocol, these can be implemented as a soft fork.

Nutritional depletion of total mixed rations by European starlings: Projected effects on dairy cow performance and potential intervention strategies to mitigate damage.

European starlings are an invasive bird species in North America that are known to cause damage to commercial dairies through the consumption of total mixed rations (TMR) destined for dairy cows. We hypothesized that large foraging flocks of starlings alter the physical composition of TMR, and that this change may be significant enough to affect milk production. To better determine if production losses could potentially occur in commercial dairies as a consequence of feed consumption by foraging flocks of starlings, we conducted controlled feeding experiments using a TMR sourced from a commercial dairy that is chronically plagued with seasonal starling damage. European starlings selected the high-energy fraction of the TMR and reduced starch and crude fat availability. Using the dairy National Research Council production model equations, the nutritional changes measured in the controlled feeding experiments could potentially reduce the productivity of dairies. Model output suggests that for Holsteins producing 32 kg of milk/d, total required net energy intake (NEI) was 31.5 Mcal/d. Within the reference TMR, NEI supplied was 29.3 Mcal/d, whereas within the starling-consumed TMR NEI supplied was 27.7 Mcal/d. Following our nutrition experiments, we assessed the efficacy of pelleted feed as a deterrent strategy for bird damage management in commercial dairies. Six different pelleted feed treatments of differing diameter were offered to starlings. All pellets of 0.95 cm diameter or larger inhibited starling consumption by ≥79%.

Can interpersonal contact help improve attitudes toward soldiers with intellectual disability? An Israeli study.

BACKGROUND: It has been argued that interpersonal contact is the best intervention for reducing negative attitudes and discrimination toward individuals with intellectual disabilities (ID). In Israel, the Equal in Uniform project makes it possible for individuals with ID to serve alongside soldiers without ID in ordinary military units in the Israeli Defense Forces. The project provided the opportunity to examine the effect of contact on the attitudes of soldiers without ID. METHODS: Data analyses are based on data collected from 220 soldiers without ID via a self-administered questionnaire based on the Multidimensional Attitudes Scale. Of these, 138 were in contact with soldiers with ID as part of the project. RESULTS: A mediation model showed that the impact of contact with a soldier with ID on withdrawal behaviour was mediated by cognitive attributions and negative affect. Contact was directly associated with prosocial behaviour. DISCUSSION: Results support the importance of contact between soldiers with and without ID to bring about improved attitudes toward the former.

Principles of effective communication with patients who have intellectual disability among primary care physicians.

OBJECTIVE: Examine physicians' implementation of effective communication principles with patients with intellectual disabilities (ID) and its predictors. METHODS: Focus groups helped construct a quantitative questionnaire. The questionnaire (completed by 440 physicians) examined utilization of effective communication principles, attitudes toward individuals with ID, subjective knowledge and number of patients with ID. RESULTS: Subjective knowledge of ID and more patients with ID increased utilization of effective communication principles. Provision of knowledge that allows patients to make their own medical decisions was predicted by more patients with ID, lower attitudes that treatment of this population group is not desirable, less negative affect and greater perception that treatment of this group is part of the physician's role. Effective preparation of patients with ID for treatment was predicted by higher perception of treatment of this group as part of the physician's role, lower perception of this field as undesirable and higher perception of these individuals as unable to make their own choice. Simplification of information was predicted by a greater perception of treatment of this group as part of the physician's role and more negative affect. CONCLUSION: Greater familiarity may enhance care for these patients. PRACTICE IMPLICATIONS: Increase exposure to patients with ID within training.

Injuries in Swedish floorball: a cost analysis.

The epidemiology of sport injuries is well documented. However, the costs are rarely discussed. Previous studies have presented such costs in specific sports or localization. No study has investigated the costs related to injuries in elite floorball. Thus, the aim of this study was to estimate cost of injuries in Swedish elite floorball players. During 1 year, 346 floorball players were prospectively followed. All time-loss injures were recorded. The injured players were asked to complete a questionnaire regarding their costs tied to the injury. Mean costs were calculated by multiplying the total resource use with the collected unit costs and dividing these total costs with the number of injuries as well as players. The results showed that the average cost per injury increased with the level of severity and ranged from 332 to 2358 Euros. The mild and moderate overuse injuries were costlier than the corresponding traumatic injuries. However, the severe traumatic injuries were associated with higher costs than overuse injuries. Knee injuries were the costliest. Our results indicate that there are costs to be saved, if floorball injuries can be avoided. They should be of interest to decision makers deciding whether to invest in preventive interventions.

Social workers' attributions towards individuals with dual diagnosis of intellectual disability and mental illness.

BACKGROUND: The present study aimed to explore the applicability of the attribution model to social workers' attributions towards clients with dual diagnosis of intellectual disability and psychiatric illness. Specifically, the study examined the relations between social workers' attribution of responsibility, causality, stereotypes of dangerousness, their emotional reactions and behavioural reactions towards clients with dual diagnosis. METHOD: Social workers (N = 279) completed questionnaires measuring attributions of responsibility, causation and dangerousness, and reported on their emotional and behavioural reactions to clients diagnosed with DD. RESULTS: Most social workers reported high levels of helping behaviours. The strongest predictor of discriminatory behaviours was the stereotype of dangerousness. Social workers who reported feeling less anger and more pity towards clients with DD tended to report higher levels of helping behaviour. But contrary to attribution theory, fear and anger did not predict discriminatory behaviours. CONCLUSION: The results are discussed in relation to the core values of social work and to professional identity.

Efficacy and safety of a VWF/FVIII concentrate (wilate® ) in inherited von Willebrand disease patients undergoing surgical procedures.

INTRODUCTION: Surgical procedures in von Willebrand disease (VWD) patients may require prophylactic treatment with exogenous von Willebrand factor (VWF) and coagulation factor VIII (FVIII) to prevent excessive bleeding. Wilate® is a plasma-derived, double virus-inactivated, highly purified, freeze-dried VWF/FVIII concentrate, containing both factors in a physiological activity ratio of 1:1. AIM: To investigate the efficacy and safety of wilate® in maintaining haemostasis in VWD patients undergoing surgical procedures. METHODS: This prospective, open-label multinational clinical study documents 28 individuals who underwent 30 surgical procedures managed with wilate® . Twenty-one patients had VWD Type 3, and 21 surgeries were major. Efficacy was assessed intra- and postoperatively by the surgeon and investigator, respectively, and adjudicated by an Independent Data Monitoring Committee, using an objective scale based on blood loss, transfusion requirements and postoperative bleeding and oozing. Treatment success (primary endpoint) was determined using a composite assessment algorithm and was formally assessed. RESULTS: Surgical prophylaxis with wilate® was successful in 29 of 30 procedures. The overall rate of success was 96.7% (98.75% CI: 0.784, 1.000). All 21 surgeries in patients with VWD Type 3 were managed successfully. There was no accumulation of VWF or FVIII after multiple dosing, and no thromboembolic events or inhibitors to VWF or FVIII were observed. CONCLUSIONS: Wilate® demonstrated effective prevention and treatment of bleeding in inherited VWD patients undergoing surgery, with no clinically significant safety concerns.

Applicability domain: towards a more formal definition.

In recent years the applicability domain (AD) of a prediction system has become an important concern in (Q)SAR modelling, especially in the context of human safety assessment. Today AD is an active research topic, and many methods have been designed to estimate the adequacy of a model and the confidence in its outcome for a given prediction task. Unfortunately, the wide spectrum of techniques developed for this purpose is based on various definitions of the concept of AD, often taking into account different types of information. This variety of methodologies confuses the end users and makes the comparison of the AD for different models almost impossible. In this article, we demonstrate that AD is not a monolithic concept and can be broken down into three well-defined sub-domains assessing confidence at the model, prediction and decision levels, respectively. By leveraging this separation of concerns we have an opportunity to clarify, formalize and extend the definition of AD. We propose a framework that captures this new vision with the aim to initiate a global effort to converge towards a common AD definition within the (Q)SAR community.

Analysis of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-reactive CD8(+) T cell responses in children with NPM-ALK(+) anaplastic large cell lymphoma.

Cellular immune responses against the oncoantigen anaplastic lymphoma kinase (ALK) in patients with ALK-positive anaplastic large cell lymphoma (ALCL) have been detected using peptide-based approaches in individuals preselected for human leucocyte antigen (HLA)-A*02:01. In this study, we aimed to evaluate nucleophosmin (NPM)-ALK-specific CD8(+) T cell responses in ALCL patients ensuring endogenous peptide processing of ALK antigens and avoiding HLA preselection. We also examined the HLA class I restriction of ALK-specific CD8(+) T cells. Autologous dendritic cells (DCs) transfected with in-vitro-transcribed RNA (IVT-RNA) encoding NPM-ALK were used as antigen-presenting cells for T cell stimulation. Responder T lymphocytes were tested in interferon-gamma enzyme-linked immunospot (ELISPOT) assays with NPM-ALK-transfected autologous DCs as well as CV-1 in Origin with SV40 genes (COS-7) cells co-transfected with genes encoding the patients' HLA class I alleles and with NPM-ALK encoding cDNA to verify responses and define the HLA restrictions of specific T cell responses. NPM-ALK-specific CD8(+) T cell responses were detected in three of five ALK-positive ALCL patients tested between 1 and 13 years after diagnosis. The three patients had also maintained anti-ALK antibody responses. No reactivity was detected in samples from five healthy donors. The NPM-ALK-specific CD8(+) T cell responses were restricted by HLA-C-alleles (C*06:02 and C*12:02) in all three cases. This approach allowed for the detection of NPM-ALK-reactive T cells, irrespective of the individual HLA status, up to 9 years after ALCL diagnosis.

Decoupling of a neutron interferometer from temperature gradients.

Neutron interferometry enables precision measurements that are typically operated within elaborate, multi-layered facilities which provide substantial shielding from environmental noise. These facilities are necessary to maintain the coherence requirements in a perfect crystal neutron interferometer which is extremely sensitive to local environmental conditions such as temperature gradients across the interferometer, external vibrations, and acoustic waves. The ease of operation and breadth of applications of perfect crystal neutron interferometry would greatly benefit from a mode of operation which relaxes these stringent isolation requirements. Here, the INDEX Collaboration and National Institute of Standards and Technology demonstrates the functionality of a neutron interferometer in vacuum and characterize the use of a compact vacuum chamber enclosure as a means to isolate the interferometer from spatial temperature gradients and time-dependent temperature fluctuations. The vacuum chamber is found to have no depreciable effect on the performance of the interferometer (contrast) while improving system stability, thereby showing that it is feasible to replace large temperature isolation and control systems with a compact vacuum enclosure for perfect crystal neutron interferometry.

Analysis of distribution and severity of inflammation in patients with osteoarthitis compared to rheumatoid arthritis by ICG-enhanced fluorescence optical imaging and musculoskeletal ultrasound: a pilot study.

BACKGROUND: In rheumatoid arthritis (RA), hand synovitis appears especially in wrist, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. In hand osteoarthritis (OA), potential inflammatory changes are mainly present in PIP and distal interphalangeal (DIP) joints. Joint inflammation can be visualised by fluorescence optical imaging (FOI) and musculoskeletal ultrasound (US). OBJECTIVE: Comparison of the amount and distribution of inflammatory signs in wrist and finger joints of the clinically dominant hand in patients with OA and RA by FOI and gray-scale (GSUS) and power Doppler US (PDUS). METHODS: FOI and GSUS/PDUS were performed in 1.170 joints (wrists, MCP, PIP, DIP) in 90 patients (67 RA, 23 OA). Joint inflammation was graded by a semiquantitative score (0-3) for each imaging method. RESULTS: GSUS/PDUS showed wrist and MCP joints mostly affected in RA. DIP joints were graded higher in OA. In FOI, RA and OA featured inflammatory changes in the respective joint groups depending on the phase of fluorescence dye flooding. CONCLUSIONS: US and FOI detected inflammation in both RA and OA highlighting the inflammatory component in the course of OA. The different inflammatory patterns and various shapes of fluorescence enhancement in FOI may offer opportunities to distinguish and determine the inflammatory status in both diseases.