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Objectives Head trauma may cause dislodgement of otoconia and development of benign paroxysmal positional vertigo (BPPV). The risk of developing BPPV is expected to be highest shortly after the trauma, then decrease and approach the risk seen in the general population. The aim of this study was to estimate the risk-time curve of BPPV development after head trauma. Study design Prospective observational study. Methods Patients with minimal, mild, or moderate head trauma treated at the Department of Neurosurgery or the Department of Orthopedic Emergency at Oslo University Hospital, were interviewed and examined for BPPV using the Dix-Hallpike and supine roll maneuvers. BPPV was diagnosed according to the International diagnostic criteria of the Barany Society. Telephone interviews were conducted at 2, 6, and 12 weeks after the first examination. Results Out of 117 patients, 21% developed traumatic BPPV within 3 months after the trauma. The corresponding numbers were 12% with minimal trauma, 24% with mild, and 40% with moderate trauma. The difference in prevalence between the groups was significant (P = .018). During the first 4 weeks after the trauma, it was observed 20, 3, 0, and 1 BPPV onsets, respectively. No BPPV cases were seen for the remainder of the 3-month follow-up. Conclusion The risk of developing BPPV after minimal-to-moderate head trauma is considerable and related to trauma severity. Most cases occur within few days after the trauma, but any BPPV occurring within the first 2 weeks after head trauma are likely due to the traumatic event. Level of evidence 3 Laryngoscope, 2021.

Background In-hospital fall incidents are common and sensitive to nursing care. It is therefore important to have easy access to valid patient data to evaluate and follow-up nursing care. The aim of the study was to validate the nursing documentation, using a specific term in the registered nurses´ (RNs´) discharge note, regarding inpatient falls according to the outcome of a digitalized data extraction tool and the discharge note itself. Methods At a teaching hospital, 31,571 episodes of care were eligible for inclusion in this retrospective cohort study. A stratified sampling including five groups was used, two with random sampling and three with total sampling. In total, 1232 episodes of care were reviewed in the electronic patient record using a study-specific protocol. Descriptive statistics were used. Results In total, 590 episodes of care in the study cohort included 714 falls. When adjusted for the stratified sampling the cumulative incidence for the study population was 1.9%. The positive predictive value in total for the data extraction tool regarding the presence of any fall, in comparison with the record review, was 87.4%. Discrepancies found were, for example, that the RNs, at discharge, stated that the patient had fallen but no documented evidence of that could be detected during admission. It could also be the opposite, that the RNs correctly had documented that no fall had occurred, but the data extraction tool made an incorrect selection. When the latter had been withdrawn, the positive predictive value was 91.5%. Information about minor injuries due to the fall was less accurate. In the group where RNs had stated that the patient had fallen without injury, minor injuries had actually occurred in 28.3% of the episodes of care. Conclusions The use of a specific term regarding fall in the RNs´ discharge note seems to be a valid and reliable data measurement and can be used continuously to evaluate and follow-up nursing care.

There is growing evidence that people with serious mental illness have impaired capacity for processing sensory inputs which affects daily occupation. Although this is known, research regarding the target groups experiences of sensory inputs in daily occupations is lacking.To investigate the experience of sensory input and strategies used in daily occupations among people with serious mental illness.Fourteen people with serious mental illness were interviewed regarding their experiences of sensory processing and strategies for managing sensory inputs in daily occupations. Data were analysed using content analysis.Sensory processing issues affected occupational engagement and strategies to control inputs were intuitively used to cope with sensory challenges. Informants either ignored, reduced or avoided sensory inputs. Informants also enabled daily life through strategies such as creating a home that provides rest, finding a safe place, using nature and animals for relaxing and using effects of calming and alerting occupations.Specific sensory inputs were difficult to process, which was experienced as stressful and affected occupations negatively. The results imply a need for further research exploring the management of sensory input and the use of sensory modulation approaches to enable engagement in daily activities.

This chapter provides a due process examination of the investigatory powers granted to national supervisory authorities under MiFID II. It focuses on the power to carry out on-site inspections and the possibilities of holding the authorities accountable for any arbitrary or disproportionate measures taken in relation to these inspections. Absent clear and adequate procedural safeguards, there is an apparent risk that any measures taken will infringe both the right to privacy and the defence rights of those targeted. Without adequate safeguards, any decisions taken by the authorities risk being contestable on procedural grounds. Moreover, the threat of having to pay hefty fines may already deter some from accepting a managerial function in an investment firm. If the enforcement rules are allowed to be applied in an arbitrary or inconsistent way, allowing the supervisory authorities to escape accountability, it will no doubt become even more difficult to recruit managers and board members in the future. Thus, while lenient procedural safeguards would, in theory, further the interests of effectiveness and efficiency, the reality may be the opposite.

BACKGROUND A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome. OBJECTIVE The Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated. METHODS The PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid–based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis. RESULTS A pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020. CONCLUSIONS The findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment. CLINICALTRIAL ClinicalTrials.gov NCT03900091; https://clinicaltrials.gov/ct2/show/NCT03900091 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/21430

Respiratory viral infections often mimic the symptoms of infections caused by bacteria; however, restricted and targeted administration of antibiotics is needed to combat growing antimicrobial resistance. This is particularly relevant in low-income settings. In this work, we describe the use of isothermal amplification of viral DNA at 37 °C coupled to a paper-based vertical flow microarray (VFM) setup that utilizes a colorimetric detection of amplicons using functionalized gold nanoparticles. Two oligonucleotide probes, one in-house designed and one known adenoviral probe were tested and validated for microarray detection down to 50 nM using a synthetic target template. Furthermore, primers were shown to function in a recombinase polymerase amplification reaction using both synthetic template and viral DNA. As a proof-of-concept, we demonstrate adenoviral detection with four different adenoviral species associated with respiratory infections using the paper-based VFM format. The presented assay was validated with selected adenoviral species using the in-house probe, enabling detection at 1 ng of starting material with intra- and inter-assay %CV of ≤ 9% and ≤ 13%. Finally, we validate our overall method using clinical samples. Based on the results, the combination of recombinase polymerase amplification, paper microarray analysis, and nanoparticle-based colorimetric detection could thus be a useful strategy towards rapid and affordable multiplexed viral diagnostics. Electronic supplementary material The online version of this article (10.1007/s00216-018-1503-y) contains supplementary material, which is available to authorized users.

The Petri dish and microtiter plate are the golden standard for selection and screening of bacteria in microbiological research. To improve on the limited resolution and throughput of these methods, we developed a universal, user-friendly platform for selection and high-resolution phenotypic screening based on the nanowell slide. This miniaturized platform has an optimal ratio between throughput and assay complexity, holding 672 nanowells of 500 nl each. As monoclonality is essential in bacterial genetics, we used FACS to inoculate each nanowell with a single bacterium in 15 min. We further extended the protocol to select and sort only bacteria of interest from a mixed culture. We demonstrated this by isolating single transposon mutants generated by a custom-made transposon with dual selection for GFP fluorescence and kanamycin resistance. Optical compatibility of the nanowell slide enabled phenotypic screening of sorted mutants by spectrophotometric recording during incubation. By processing the absorbance data with our custom algorithm, a phenotypic screen for growth-associated mutations was performed. Alternatively, by processing fluorescence data, we detected metabolism-associated mutations, exemplified by a screen for β-galactosidase activity. Besides spectrophotometry, optical compatibility enabled us to perform microscopic analysis directly in the nanowells to screen for mutants with altered morphologies. Despite the miniaturized format, easy transition from nano- to macroscale cultures allowed retrieval of bacterial mutants for downstream genetic analysis, demonstrated here by a cloning-free single-primer PCR protocol. Taken together, our FACS-linked nanowell slide replaces manual selection of mutants on agar plates, and enables combined selection and phenotypic screening in a one-step process. The versatility of the nanowell slide, and the modular workflow built on mainstream technologies, makes our universal platform widely applicable in microbiological research.

The aim of this work was to investigate how manufacturing conditions influence phase-separated films of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) with different molecular weights of HPC. Two HPC grades, SSL and M, with weight average molecular weights (M

We present a droplet PCR workflow for detection of multiple pathogen DNA biomarkers using fluorescent color-coded Luminex® beads. This strategy enables encoding of multiple singleplex droplet PCRs using a commercially available bead set of several hundred distinguishable fluorescence codes. This workflow provides scalability beyond the limited number offered by fluorescent detection probes such as TaqMan probes, commonly used in current multiplex droplet PCRs. The workflow was validated for three different Luminex bead sets coupled to target specific capture oligos to detect hybridization of three microorganisms infecting poultry: avian influenza, infectious laryngotracheitis virus and Campylobacter jejuni. In this assay, the target DNA was amplified with fluorescently labeled primers by PCR in parallel in monodisperse picoliter droplets, to avoid amplification bias. The color codes of the Luminex detection beads allowed concurrent and accurate classification of the different bead sets used in this assay. The hybridization assay detected target DNA of all three microorganisms with high specificity, from samples with average target concentration of a single DNA template molecule per droplet. This workflow demonstrates the possibility of increasing the droplet PCR assay detection panel to detect large numbers of targets in parallel, utilizing the scalability offered by the color-coded Luminex detection beads.

Background: There is a need to better distinguish viral infections from antibiotic-requiring bacterial infections in children presenting with clinical community-acquired pneumonia (CAP) to assist health care workers in decision making and to improve the rational use of antibiotics. Objective: The overall aim of the Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) study is to improve the differential diagnosis of bacterial and viral etiologies in children aged below 5 years with clinical CAP, by evaluating myxovirus resistance protein A (MxA) as a biomarker for viral CAP and by evaluating an existing (multianalyte point-of-care antigen detection test system [mariPOC respi] ArcDia International Oy Ltd.) and a potential future point-of-care test for respiratory pathogens. Methods: Children aged 1 to 59 months with clinical CAP as well as healthy, hospital-based, asymptomatic controls will be included at a pediatric emergency hospital in Stockholm, Sweden. Blood (analyzed for MxA and C-reactive protein) and nasopharyngeal samples (analyzed with real-time polymerase chain reaction as the gold standard and antigen-based mariPOC respi test as well as saved for future analyses of a novel recombinase polymerase amplification–based point-of-care test for respiratory pathogens) will be collected. A newly developed algorithm for the classification of CAP etiology will be used as the reference standard. Results: A pilot study was performed from June to August 2017. The enrollment of study subjects started in November 2017. Results are expected by the end of 2019. Conclusions: The findings from the TREND study can be an important step to improve the management of children with clinical CAP. International Registered Report Identifier (IRRID): DERR1-10.2196/12705

Cell culture is a ubiquitous and flexible research method. However, it heavily relies on plastic consumables generating millions of tonnes of plastic waste yearly. Plastic waste is a major and growing global concern. Here we describe a new cell culture dish that offers a culture area equivalent to three petri dishes but that is on average 61% lighter and occupies 67% less volume. Our dish is composed of a lid and three thin containers surrounded by a light outer shell. Cell culture can be performed in each of the containers sequentially. The outer shell provides the appropriate structure for the manipulation of the dish as a whole. The prototype was tested by sequentially growing cells in each of its containers. As a control, sequential cultures in groups of 3 petri dishes were performed. No statistical differences were found between the prototype and the control in terms of cell number, cell viability or cell distribution.

The potential of using droplet microfluidics for screening mammalian cell factories has been limited by the difficulty in achieving continuous cell division during cultivation in droplets. Here, we report the influence of droplet size on mammalian cell division and viability during cultivation in droplets. Chinese Hamster Ovary (CHO) cells, the most widely used mammalian host cells for biopharmaceuticals production were encapsulated and cultivated in 33, 180 and 320 pL droplets for 3 days. Periodic monitoring of the droplets during incubation showed that the cell divisions in 33 pL droplets stopped after 24 h, whereas continuous cell division was observed in 180 and 320 pL droplets for 72 h. The viability of the cells cultivated in the 33 pL droplets also dropped to about 50% in 72 h. In contrast, the viability of the cells in the larger droplets was above 90% even after 72 h of cultivation, making them a more suitable droplet size for 72-h cultivation. This study shows a direct correlation of microfluidic droplet size to the division and viability of mammalian cells. This highlights the importance of selecting suitable droplet size for mammalian cell factory screening assays.

Gewebe- oder Organmodelle konnen als nutzliche In-vitro-Plattformen systematische und quantitative Untersuchungen von Wirkstoffen und Chemikalien erleichtern. Oberstes Ziel bei ihrer Entwicklung ist die Nachbildung der wichtigen physiologischen Funktionen, was ublicherweise komplexe Kultursysteme erforderlich macht. Biodrucktechniken bieten interessante Perspektiven fur den Aufbau von Gewebe- und Organmodellen, da sie eine reproduzierbare, automatisierte Produktion komplexer lebender Gewebe ermoglichen. Auf diese Weise erhaltene Modelle haben Potenzial fur das Screening neuer Verbindungen oder fur die Vorhersage von Toxizitaten, da in ihnen die raumliche und chemische Komplexitat von nativen Geweben oder Organen nachgebildet werden kann. Hier zeigen wir, wie Gewebe- und Organmodelle durch 3D-Biodruck in vitro hergestellt werden konnen, wie sich ihre Vergleichbarkeit mit dem nativen Gewebe charakterisieren lasst, und wie sie bei der Auswahl von Leitstrukturen, bei Toxizitatstests und als Krankheits- oder Tumormodelle von Nutzen sein konnen.

The characterization of the pore structure in pharmaceutical coatings is crucial for understanding and controlling mass transport properties and function in controlled drug release. Since the drug release rate can be associated with the film permeability, the effect of the pore structure on the permeability is important to study. In this paper, a new approach for characterizing the pore structure in polymer blended films was developed based on an image processing procedure for given two-dimensional scanning electron microscopy images of film cross-sections. The focus was on different measures for characterizing the complexity of the shape of a pore. The pore characterization developed was applied to ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) blended films, often used as pharmaceutical coatings, where HPC acts as the pore former. It was studied how two different HPC viscosity grades influence the pore structure and, hence, mass transport through the respective films. The film with higher HPC viscosity grade had been observed to be more permeable than the other in a previous study; however, experiments had failed to show a difference between their pore structures. By instead characterizing the pore structures using tools from image analysis, statistically significant differences in pore area fraction and pore shape were identified. More specifically, it was found that the more permeable film with higher HPC viscosity grade seemed to have more extended and complex pore shapes than the film with lower HPC viscosity grade. This result indicates a greater degree of connectivity in the film with higher permeability and statistically confirms hypotheses on permeability from related experimental studies.

BACKGROUND There is a need to better distinguish viral infections from antibiotic-requiring bacterial infections in children presenting with clinical community-acquired pneumonia (CAP) to assist health care workers in decision making and to improve the rational use of antibiotics. OBJECTIVE The overall aim of the Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) study is to improve the differential diagnosis of bacterial and viral etiologies in children aged below 5 years with clinical CAP, by evaluating myxovirus resistance protein A (MxA) as a biomarker for viral CAP and by evaluating an existing (multianalyte point-of-care antigen detection test system [mariPOC respi] ArcDia International Oy Ltd.) and a potential future point-of-care test for respiratory pathogens. METHODS Children aged 1 to 59 months with clinical CAP as well as healthy, hospital-based, asymptomatic controls will be included at a pediatric emergency hospital in Stockholm, Sweden. Blood (analyzed for MxA and C-reactive protein) and nasopharyngeal samples (analyzed with real-time polymerase chain reaction as the gold standard and antigen-based mariPOC respi test as well as saved for future analyses of a novel recombinase polymerase amplification–based point-of-care test for respiratory pathogens) will be collected. A newly developed algorithm for the classification of CAP etiology will be used as the reference standard. RESULTS A pilot study was performed from June to August 2017. The enrollment of study subjects started in November 2017. Results are expected by the end of 2019. CONCLUSIONS The findings from the TREND study can be an important step to improve the management of children with clinical CAP. INTERNATIONAL REGISTERED REPOR DERR1-10.2196/12705

Additional file 11. Spearman correlation’s for antibodies targetting the same protein. Table of presented antibodies targetting the same protein with Spearman’s Rho > 0.70. The table also includes the gene and gene description of the target protein of the antibodies.

Additional file 1. Clinical patient characteristics. Table summarizing the clinical characteristics for all the 541 included patients, divided by disease subcategory. Information about sex, age, nutrition status (based on WHO reference z-score), temperature and dehydration status are provided.

Paper-based biosensors offer a promising technology to be used at the point of care, enabled by good performance, convenience and low-cost. In this article, we describe a colorimetric vertical-flow DNA microarray (DNA-VFM) that takes advantage of the screening capability of DNA microarrays in a paper format together with isothermal amplification by means of Recombinase Polymerase Amplification (RPA). Different assay parameters such as hybridization buffer, flow rate, printing buffer and capture probe concentration were optimized. A limit of detection (LOD) of 4.4 nM was achieved as determined by tabletop scanning. The DNA-VFM was applied as a proof of concept for detection of Neisseria meningitidis, a primary cause of bacterial meningitis. The LOD was determined to be between 38 and 2.1 × 10

In recent years there has been a rapid expansion in the number of jurisdictions with competition laws. In the late 1980s only 20 jurisdictions had adopted competition laws. Two decades later, the number had surpassed 110. With competition legislation in place in many parts of the world, focus is shifting towards enforcement issues and questions on how to ensure an effective application of the competition rules. The EU is no exception. Through the adoption of Regulation 1/2003, a system of parallel enforcement powers was established and the national competition authorities (‘the NCAs’) have since become an essential pillar of the application of the EU competition rules. The reform has resulted in a stronger and more active enforcement of the rules, but it has also revealed that some of the NCAs lack the tools required to ensure effective enforcement in their jurisdictions. With the explicit aim to enhance the effectiveness of the NCAs, the European Commission (‘the Commission’) has now presented a proposal for a directive (‘the Proposal’) which would align the national enforcement rules to their EU equivalent and ensure a level playing field throughout the EU.