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Latent semantic analysis (LSA) and correspondence analysis (CA) are two techniques that use a singular value decomposition for dimensionality reduction. LSA has been extensively used to obtain low-dimensional representations that capture relationships among documents and terms. In this article, we present a theoretical analysis and comparison of the two techniques in the context of document-term matrices. We show that CA has some attractive properties as compared to LSA, for instance that effects of margins, that is, sums of row elements and column elements, arising from differing document lengths and term frequencies are effectively eliminated so that the CA solution is optimally suited to focus on relationships among documents and terms. A unifying framework is proposed that includes both CA and LSA as special cases. We empirically compare CA to various LSA-based methods on text categorization in English and authorship attribution on historical Dutch texts and find that CA performs significantly better. We also apply CA to a long-standing question regarding the authorship of the Dutch national anthem Wilhelmus and provide further support that it can be attributed to the author Datheen, among several contenders.

Contains fulltext : 252388.pdf (Publisher’s version ) (Closed access) 26 juli 2022

Contains fulltext : 287165.pdf (Publisher’s version ) (Open Access) BACKGROUND AND OBJECTIVE: More than half of all drugs are still prescribed off-label to children. Pharmacokinetic (PK) data are needed to support off-label dosing, however for many drugs such data are either sparse or not representative. Physiologically-based pharmacokinetic (PBPK) models are increasingly used to study PK and guide dosing decisions. Building compound models to study PK requires expertise and is time-consuming. Therefore, in this paper, we studied the feasibility of predicting pediatric exposure by pragmatically combining existing compound models, developed e.g. for studies in adults, with a pediatric and preterm physiology model. METHODS: Seven drugs, with various PK characteristics, were selected (meropenem, ceftazidime, azithromycin, propofol, midazolam, lorazepam, and caffeine) as a proof of concept. Simcyp(®) v20 was used to predict exposure in adults, children, and (pre)term neonates, by combining an existing compound model with relevant virtual physiology models. Predictive performance was evaluated by calculating the ratios of predicted-to-observed PK parameter values (0.5- to 2-fold acceptance range) and by visual predictive checks with prediction error values. RESULTS: Overall, model predicted PK in infants, children and adolescents capture clinical data. Confidence in PBPK model performance was therefore considered high. Predictive performance tends to decrease when predicting PK in the (pre)term neonatal population. CONCLUSION: Pragmatic PBPK modeling in pediatrics, based on compound models verified with adult data, is feasible. A thorough understanding of the model assumptions and limitations is required, before model-informed doses can be recommended for clinical use.

Contains fulltext : 291086.pdf (Publisher’s version ) (Open Access) Physiologically based pharmacokinetic (PBPK) modeling can be an attractive tool to increase the evidence base of pediatric drug dosing recommendations by making optimal use of existing pharmacokinetic (PK) data. A pragmatic approach of combining available compound models with a virtual pediatric physiology model can be a rational solution to predict PK and hence support dosing guidelines for children in real-life clinical care, when it can also be employed by individuals with little experience in PBPK modeling. This comes within reach as user-friendly PBPK modeling platforms exist and, for many drugs and populations, models are ready for use. We have identified a list of drugs that can serve as a starting point for pragmatic PBPK modeling to address current clinical dosing needs. 01 januari 2023

An increasing number of firms are aiming to implement closed-loop supply chain (CLSC) management to contribute to a more circular economy. However, for many of these firms, it is difficult to translate this strategic aim into fruitful operational decisions. They need to address many deep uncertainties and dynamic complexities in their supply chain system, which make their transition towards CLSC management challenging. This article aims to develop a better understanding of how supply chain actors taking steps towards CLSC management could be supported to reach higher levels of maturity in dealing with deep uncertainty and dynamic complexity. This is investigated in a single, facilitated, embedded case study: a future-oriented decision-making process regarding the use of timber with four real-world actors in the construction industry. The process is structured and supported with analyses, following a methodology based on the capability maturity approach. In this empirical context, the selected approach is shown to have positive effects on clarifying the potential impact of transitions to CLSC management. Furthermore, it stimulates important learning processes during the transition, and as such supports actors to achieve higher levels of maturity and to take further steps towards CLSC management. In this context, a conceptual distinction is made between ‘situational maturity’ and ‘mental maturity’, which enriches double-loop learning theory in the context of transitions.

Randomized response (RR) is a well-known interview technique designed to eliminate evasive response bias that arises from asking sensitive questions. The most frequently asked questions in RR are either whether respondents were “ever” carriers of the sensitive characteristic, or whether they were carriers in a recent period, for instance, “last year”. The present paper proposes a design in which both questions are asked, and derives a multinomial model for the joint analysis of these two questions. Compared to the separate analyses with the binomial model, the model makes a useful distinction between last year and former carriers of the sensitive characteristic, it is more efficient in estimating the prevalence of last year carriers, and it has a degree of freedom that allows for a goodness-of-fit test. Furthermore, it is easily extended to a multinomial logistic regression model to investigate the effects of covariates on the prevalence estimates. These benefits are illustrated in two studies on the use of anabolic androgenic steroids in the Netherlands, one using Kuk and one using both the Kuk and forced response. A salient result of our analyses is that the multinomial model provided ample evidence of response biases in the forced response condition.

Contains fulltext : 293280.pdf (Publisher’s version ) (Open Access) Dose recommendations for lamivudine or emtricitabine in children with HIV and chronic kidney disease (CKD) are absent or not supported by clinical data. Physiologically based pharmacokinetic (PBPK) models have the potential to facilitate dose selection for these drugs in this population. Existing lamivudine and emtricitabine compound models in Simcyp(®) (v21) were verified in adult populations with and without CKD and in non-CKD paediatric populations. We developed paediatric CKD population models reflecting subjects with a reduced glomerular filtration and tubular secretion, based on extrapolation from adult CKD population models. These models were verified using ganciclovir as a surrogate compound. Then, lamivudine and emtricitabine dosing strategies were simulated in virtual paediatric CKD populations. The compound and paediatric CKD population models were verified successfully (prediction error within 0.5- to 2-fold). The mean AUC ratios in children (GFR-adjusted dose in CKD population/standard dose in population with normal kidney function) were 1.15 and 1.23 for lamivudine, and 1.20 and 1.30 for emtricitabine, with grade-3- and -4-stage CKD, respectively. With the developed paediatric CKD population PBPK models, GFR-adjusted lamivudine and emtricitabine dosages in children with CKD resulted in adequate drug exposure, supporting paediatric GFR-adjusted dosing. Clinical studies are needed to confirm these findings.

There is an ongoing forensic and security need for rapid, on-scene, easy-to-use, non-invasive chemical identification of intact energetic materials at pre-explosion crime scenes. Recent technological advances in instrument miniaturization, wireless transfer and cloud storage of digital data, and multivariate data analysis have created new and very promising options for the use of near-infrared (NIR) spectroscopy in forensic science. This study shows that in addition to drugs of abuse, portable NIR spectroscopy with multivariate data analysis also offers excellent opportunities to identify intact energetic materials and mixtures. NIR is able to characterize a broad range of chemicals of interest in forensic explosive investigations, covering both organic and inorganic compounds. NIR characterization of actual forensic casework samples convincingly shows that this technique can handle the chemical diversity encountered in forensic explosive investigations. The detailed chemical information contained in the 1350–2550 nm NIR reflectance spectrum allows for correct compound identification within a given class of energetic materials, including nitro-aromatics, nitro-amines, nitrate esters, and peroxides. In addition, the detailed characterization of mixtures of energetic materials, such as plastic formulations containing PETN (pentaerythritol tetranitrate) and RDX (trinitro triazinane), is feasible. The results presented illustrate that the NIR spectra of energetic compounds and mixtures are sufficiently selective to prevent false-positive results for a broad range of food-related products, household chemicals, raw materials used for the production of home-made explosives, drugs of abuse, and products that are sometimes used to create hoax improvised explosive devices. However, for frequently encountered pyrotechnic mixtures, such as black powder, flash powder, and smokeless powder, and some basic inorganic raw materials, the application of NIR spectroscopy remains challenging. Another challenge is presented by casework samples of contaminated, aged, and degraded energetic materials or poor-quality HMEs (home-made explosives), for which the spectral signature deviates significantly from the reference spectra, potentially leading to false-negative outcomes.

After World War II, large amounts of ammunition were dumped in surface waters worldwide, potentially releasing harmful and toxic compounds to the environment. To study their degradation, ammunition items dumped in the Eastern Scheldt in The Netherlands were surfaced. Severe damage due to corrosion and leak paths through the casings were observed, making the explosives in the ammunition accessible to sea water. Using novel techniques, the concentrations of ammunition-related compounds in the surrounding seabed and in the seawater were analyzed at 15 different locations. In the direct vicinity of ammunition, elevated concentrations of ammunition-related compounds (both metals and organic substances) were found. Concentrations of energetic compounds ranged from below the limit of detection (LoD) up to the low two-digit ng/L range in water samples, and from below the LoD up to the one-digit ng/g dry weight range in sediment samples. Concentrations of metals were found up to the low microgram/L range in water and up the low ng/g dry weight in sediment. However, even though the water and sediment samples were collected as close to the ammunition items as possible, the concentrations of these compounds were low and, as far as available, no quality standards or limits were exceeded. The presence of fouling, the low solubility of the energetic compounds, and dilution by the high local water current were concluded to be the main causes for the absence of high concentrations of ammunition-related compounds. As a conclusion, these new analytical methods should be applied to continuously monitor the Eastern Scheldt munitions dump site.

The increasing prevalence of urolithiasis in industrialized societies triggered considerable interest in how various species found in urine regulate the nucleation and growth of common kidney stone constituents such as calcium oxalate (CaOx). Yet, the role macromolecules play in kidney stone formation is often overlooked due to their low concentration in urine. In this study, we investigate the nucleation kinetics of CaOx in artificial urine with droplet-based microfluidic induction time measurements at varying concentrations of oxalate and hyaluronic acid (HA), a polysaccharide commonly found in urine. The formation of two pseudo-polymorphic forms of calcium oxalate crystals, calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD), are carefully monitored using polarized light microscopy in induction time experiments. COM and COD nucleated concomitantly in artificial urine yet with distinct kinetics. Our results indicate that higher oxalate concentrations favor the formation of COD, the metastable form, over COM, the most stable form. Moreover, COD is also the fastest nucleating form in droplets under studied conditions. Furthermore, increasing the concentration of HA at fixed calcium and oxalate concentrations favored the nucleation of COM. We observed that in droplets where COM nucleated first, COD was not formed within the experimental time scale. However, in the droplets where COD appeared first, COM crystals were also observed later. We hope our findings shed light on the role macromolecules such as HA plays in dictating the pseudo-polymorphic form of CaOx and guide next generation treatments. QC 20220601

Across Europe, ongoing changes in higher education, such as the stagnating (even decreasing) percentage of permanent or tenure-track jobs, and the reduced government budgets impress on us the need to conduct empirical research on the dynamics of the careers in this sector. In this study, we focussed on career success in higher education, and specifically examined the relationship of career commitment with objective and subjective career success, and the mediating role of employability in this relationship. Participants were drawn from across occupational roles including academic and support staff (N = 354) in a large Dutch university. Process macro's for SPSS were used to test our hypothesized model. We found that career commitment was particularly related to three out of the five dimensions of employability (i.e., anticipation and optimisation, personal flexibility, and corporate sense). There also was positive association between employability and objective and subjective career success. Furthermore, personal flexibility and corporate sense fully mediated the relationship between career commitment and objective career success. Corporate sense partially mediated the relationship between career commitment and subjective career success. Unexpectedly, staff status was not a moderator. Different explanatory mechanisms seem to operate between career commitment and forms of career success. Our study implies that for university staff, it is important to actively invest in their employability, with a special focus on one's corporate sense, and to be supported in this by their surrounding stakeholders (i.e., their family, friends, peers, direct supervisor, and employer). In this way, they will be able to increase their career success and add to the sustained competitive advantage of their employers.

Contains fulltext : 291096.pdf (Publisher’s version ) (Open Access) BACKGROUND: Peripheral pulmonary nodules are often detected as multiple nodules in one patient. Computed tomography (CT) guided transthoracic biopsy (TTNB) is the most widely implemented method for minimal invasive biopsy of pulmonary nodules, but generally only one nodule is sampled per procedure. Navigation bronchoscopy is an endobronchial procedure with very low complication rates, and uses high-end image guidance which allows for the sampling of multiple nodules in one session, while also allowing inspection of the central airways and endobronchial ultrasound (EBUS) guided staging in one session. This report presents a unique case with three different synchronous primary tumors treated with three different treatment modalities that highlights the added value of cone-beam CT guided navigation bronchoscopy (CBCT-NB) in the diagnostic work-up of suspected early-stage lung cancer. CASE DESCRIPTION: This case describes an asymptomatic patient with no history of prior lung cancer referred because of a shadow seen on a screening X-ray. CT and positron emission tomography (PET) showed two nodules for which a navigation procedure was performed. Both nodules were sampled, and on inspection, a third occult endobronchial lesion was also found. Pathology revealed three separate primary tumors, which were treated with three different treatment modalities: surgery, radiotherapy and endobronchial cryoablation. Current follow-up at 12 months shows no signs of recurrence. CONCLUSIONS: This case highlights that synchronous primary malignancies do occur and require a patient tailored approach to minimize treatment related morbidity and optimize survival. To this goal, image guided navigation bronchoscopy allows for a full and complete diagnostic evaluation and can be combined with a staging EBUS in one single session.

Previously, scholars have studied the need for implementing different human resource (HR) configurations that foster aging employees' outcomes, but there is a lack of evidence at the group level. Using the framework of Social Exchange Theory, coupled with the Selection, Optimization, and Compensation theory, we examine associations between bundles of HR practices, age (measured both as calendar age and proportion of an aging workforce), and performance, at both the individual and group levels. First, the outcomes of our multi-level analysis show that bundles of maintenance-enhancing HR practices are positively related to performance at both levels, whereas bundles of growth-enhancing HR practices associate with performance only at the group level. Second, age relates positively to performance, both at the individual and group levels. At the group level, there is an inverted U-shaped relationship between the proportion of an aging workforce and group performance, such that a group's performance benefits from the participation of older employees up to a maximum proportion of 56%. Finally, age negatively moderates the association between growth-enhancing HR bundles and performance at both the individual and group levels. Results highlight the value of older employees for working organizations, and the importance of adopting HR practices that consider maintenance and growth-related needs across the life-span, while also providing useful theoretical and practical implications for Human Resource Development scholars and professionals.

Introduction: The annual number of patients > 65 years old about whom the Dutch Poisons Information Center (DPIC) was consulted has more than doubled in the last decade. We aimed to gain insight in the type and circumstances of exposures reported to the DPIC involving older patients, in order to help prevent future poisonings. Methods: Enquiries to the DPIC involving patients > 65 years old were prospectively included from January 2019 to June 2019. Data were collected on patient characteristics (e.g., age, gender, and living situation) and exposure characteristics (e.g., type and exposure scenario). Results: In the first half of 2019, the DPIC was consulted about 1051 patients > 65 years old. The median age of the patients was 77 years old (range: 66–104 years) and women were over-represented (61%). A total of 1650 different substances were reported, 1213 pharmaceutical exposures (74%) and 437 non-pharmaceutical exposures (26%), mostly household products (n = 162). Most pharmaceutical exposures involved cardiovascular agents (n = 367, 30%), central and peripheral nervous system agents (n = 354, 29%), and analgesics (n = 152, 13%). In 71% of the patients exposed to pharmaceuticals, the drugs were taken unintentionally (n = 471), frequently caused by medication errors made by the patients themselves (n = 357, 76%). Most common scenarios included inadvertently taken/given a double (n = 140, 30%) or more than double (n = 94, 20%) dose or the wrong medication (n = 124, 26%). The most common scenario for unintentional exposure to non-pharmaceuticals was “mistook product for food/drink” (n = 122, 37%). Conclusions: The majority of intoxications in older adults are accidental and often involve medication errors. Unintentional poisoning is often preventable. If patients are cognitively impaired, potentially harmful substances should be kept out of their reach and medication should only be administered under direct supervision. Clear labelling, simplified drug regimens and the use of automatic medication dispensers could reduce the risk of medication errors in older patients.

We present a general methodology for the nonlinear dynamical modeling of a three-axis stabilized spacecraft equipped with flexible solar arrays. The large-span multi-panel solar arrays are modeled as flexible thin plates that are connected to the rigid central body of the spacecraft by means of nonlinear flexible hinges. We construct a low-dimensional yet accurate dynamical model by using a Galerkin expansion in terms of global modes of the system that we compute first by using the Rayleigh-Ritz method. The hinged connections between the rigid and flexible parts of the system are imposed by means of Lagrange multipliers. We use the model to study the spacecraft response triggered by various maneuvering scenarios. We in particular focus on the coupling between vibrations of the flexible components and the rigid motion of the spacecraft induced by hinge nonlinearities during these orbital and attitude maneuvering operations. In all cases considered we find that four global modes are sufficient to accurately compute the system’s response. We also observe other complicated nonlinear dynamical phenomena such as hysteresis and superharmonic resonance that may be of concern in spacecraft design. Our modeling approach can straightforwardly be applied to other multibody systems.

Whitehead et al. (2019) advance two key arguments in response to the Bales et al. (2015) article. The first is that Multiple Systems Estimation (MSE) is something other than a widely accepted metho...

The immunological response to meningococcal C conjugated vaccine can be evaluated by two different tests: the serum bactericidal antibody assay (SBA), which evaluates the qualitative bactericidal capacity of the antibodies, and the Enzyme-Linked Immunosorbent Assay (ELISA), which quantifies the specific serogroup C meningococcal immunoglobulin-G. Incompatibilities between the results of both tests have been reported. Technically, ELISA is simpler, safer, and easier to reproduce when compared to the SBA; thus, an assessment of the validity of ELISA as a protective correlate compared to the SBA gold standard should be performed. This study tested the validity of ELISA for the evaluation of the protective response to the C meningococcal conjugate vaccine in adolescents with HIV compared with the gold standard SBA, to evaluate the reliability of ELISA to infer the protection of the individual.

Background Vocal cord palsy after cervical mediastinoscopy is usually reported at less than 1%. However, its incidence might be underestimated and no follow-up studies are available. Our study aimed to evaluate the incidence of voice changes after cervical mediastinoscopy and report on long-term outcomes, including quality of life, after at least one-year follow-up. Methods A retrospective cohort study was performed, considering all patients who underwent cervical mediastinoscopy in our center between January 2011 and April 2016. Patients with pre-existing voice changes, voice changes only after pulmonary resection and patients who underwent neoadjuvant chemo(radio)therapy were excluded. Voice changes with full recovery within 14 days were attributed to intubation-related causes. Follow-up questionnaires, including the standardized Voice Handicap Index, were sent to patients with documented voice changes. Results Of 270 patients who were included for final analysis, 17 (6.3%) experienced voice changes after cervical mediastinoscopy, which persisted > 2 years in 4 patients (1.5%), causing mild to moderate disabilities in daily living. Twelve patients (out of 17, 71%) were referred for otolaryngology consultation, and paresis of the left vocal cord suggesting recurrent laryngeal nerve injury was confirmed in 10 (3.7% of our total study group). Additionally, 83% of the patients who were referred for otolaryngology consultation received voice treatment. Recovery rate after vocal exercises therapy and injection laryngoplasty was respectively 71% and 33%. Conclusions Voice changes after cervical mediastinoscopy is an underreported complication, with an incidence of at least 6.3% in our retrospective study, with persisting complaints in at least 1.5% of patients, leading to mild to moderate disabilities in daily living. These findings highlight the need for appropriate patient education for this underestimated complication, as well as the exploration of possible preventive measures.

ObjectivesTo determine if cone beam CT-guided navigation bronchoscopy (CBCT-NB) is a cost-effective diagnostic procedure in patients with a pulmonary nodule (PN) with an intermediate risk for lung cancer.Materials and methodsTwo decision analytical models were developed to compare the long-term costs, survival and quality of life. In the first model, CBCT-NB was compared with CT-guided transthoracic needle biopsy (TTNB) in TTNB eligible patients. In the second model, CBCT-NB was compared with direct treatment (without pathology proven lung cancer) in patients for whom TTNB is not suitable. Input data were gathered in-house, from literature and expert opinion. Effects were expressed in quality-adjusted life years (QALYs). Sensitivity analyses were used to assess uncertainty.ResultsCBCT-NB can be cost-effective in TTNB eligible patients with an incremental cost-effectiveness ratio of €18 416 in an expert setting. The probabilistic sensitivity analysis showed that in 69% and 90% of iterations CBCT-NB remained cost-effective assuming a willingness to pay (WTP) of €20 000 and €80 000 per QALY. CBCT-NB dominated in the treatment strategy in which TTNB is not suitable. The probabilistic sensitivity analysis showed that in 95% of iterations CBCT-NB remained the dominant strategy, and CBCT-NB remained cost-effective in 100% of iterations assuming a WTP limit of €20 000. In the comparison between CBCT NB and TTNB, the deterministic sensitivity analysis showed that the diagnostic properties and costs of both procedures have a large impact on the outcome.ConclusionsCBCT-NB seems a cost-effective procedure when compared with TTNB and when compared with a direct treatment strategy in patients with an intermediate risk PN.

Objective: To determine the associations between four validated multidimensional self-report frailty scales and nine indices of oral health in communitydwelling older persons. Materials and Methods: This pilot study was conducted in a sample of 208 older persons aged 70 years and older who visited two dental practices in the Netherlands. Frailty status was measured by four different self-report frailty questionnaires: Tilburg Frailty Indicator (TFI), Groningen Frailty Indicator (GFI), Sunfrail Checklist (SC), and the Sherbrooke Postal Questionnaire (SPQ). Oral health was assessed by two calibrated examiners. Results: The prevalence of frailty according to the four frailty measures TFI, GFI, SC, and SPQ was 32.8%, 31.5%, 24.5%, and 49.7%, respectively. The SC correlated with four oral health variables (DMFT, number of teeth, percentage of occlusal contacts, Plaque Index), the TFI with three (number of teeth, percentage of occlusal contacts, Plaque Index), the GFI only with DPSI, and the SPQ with the number of teeth and the number of occlusal contacts. Conclusion: Of the studiedmultidimensional frailty scales, the SC and TFIwere correlated with most oral health variables (four and three, respectively). However, it should be noticed that these correlations were small. Clinical relevance: The SCand TFImight help to identify older people with risk of poor oral health so that preventive care can be used to ensure deterioration of oral health and maintenance of quality of life. Vice versa early detection of frailty by oral care professionals could contribute to interprofessional management of frailty.

Standard reference terminology of diagnoses and risk factors is crucial for billing, epidemiological studies, and inter/intranational comparisons of diseases. The International Classification of Disease (ICD) is a standardized and widely used method, but the manual classification is an enormously time-consuming endeavor. Natural language processing together with machine learning allows automated structuring of diagnoses using ICD-10 codes, but the limited performance of machine learning models, the necessity of gigantic datasets, and poor reliability of terminal parts of these codes restricted clinical usability. We aimed to create a high performing pipeline for automated classification of reliable ICD-10 codes in the free medical text in cardiology. We focussed on frequently used and well-defined three- and four-digit ICD-10 codes that still have enough granularity to be clinically relevant such as atrial fibrillation (I48), acute myocardial infarction (I21), or dilated cardiomyopathy (I42.0). Our pipeline uses a deep neural network known as a Bidirectional Gated Recurrent Unit Neural Network and was trained and tested with 5548 discharge letters and validated in 5089 discharge and procedural letters. As in clinical practice discharge letters may be labeled with more than one code, we assessed the single- and multilabel performance of main diagnoses and cardiovascular risk factors. We investigated using both the entire body of text and only the summary paragraph, supplemented by age and sex. Given the privacy-sensitive information included in discharge letters, we added a de-identification step. The performance was high, with F1 scores of 0.76–0.99 for three-character and 0.87–0.98 for four-character ICD-10 codes, and was best when using complete discharge letters. Adding variables age/sex did not affect results. For model interpretability, word coefficients were provided and qualitative assessment of classification was manually performed. Because of its high performance, this pipeline can be useful to decrease the administrative burden of classifying discharge diagnoses and may serve as a scaffold for reimbursement and research applications.

Vocal cord palsy after cervical mediastinoscopy is usually reported at less than 1%. However, its incidence might be underestimated and no follow-up studies are available. Our study aimed to evaluate the incidence of voice changes after cervical mediastinoscopy and report on long-term outcomes, including quality of life, after at least one-year follow-up.A retrospective cohort study was performed, considering all patients who underwent cervical mediastinoscopy in our center between January 2011 and April 2016. Patients with pre-existing voice changes, voice changes only after pulmonary resection and patients who underwent neoadjuvant chemo(radio)therapy were excluded. Voice changes with full recovery within 14 days were attributed to intubation-related causes. Follow-up questionnaires, including the standardized Voice Handicap Index, were sent to patients with documented voice changes.Of 270 patients who were included for final analysis, 17 (6.3%) experienced voice changes after cervical mediastinoscopy, which persisted 2 years in 4 patients (1.5%), causing mild to moderate disabilities in daily living. Twelve patients (out of 17, 71%) were referred for otolaryngology consultation, and paresis of the left vocal cord suggesting recurrent laryngeal nerve injury was confirmed in 10 (3.7% of our total study group). Additionally, 83% of the patients who were referred for otolaryngology consultation received voice treatment. Recovery rate after vocal exercises therapy and injection laryngoplasty was respectively 71% and 33%.Voice changes after cervical mediastinoscopy is an underreported complication, with an incidence of at least 6.3% in our retrospective study, with persisting complaints in at least 1.5% of patients, leading to mild to moderate disabilities in daily living. These findings highlight the need for appropriate patient education for this underestimated complication, as well as the exploration of possible preventive measures.

Beyond fifth generation (5G) communication systems aim towards data rates in the tera bits per second range, with improved and flexible coverage options, introducing many new technological challenges in the fields of network architecture, signal processing, and radio frequency front-ends. One option is to move towards cell-free, or distributed massive Multiple-Input Multiple-Output (MIMO) network architectures and highly integrated front-end solutions. This paper presents an outlook on beyond 5G distributed massive MIMO communication systems, the signal processing, characterisation and simulation challenges, and an overview of the state of the art in millimetre wave antennas and electronics.

Methemoglobinemia is a rare cause of neonatal cyanosis in the newborn. It is considered a medical emergency. Failure of recognition or appropriated treatment could result in serious disease and neonatal death. Neonatal methemoglobinemia can be caused by both hereditary and acquired factors.We present two cases of newborns who developed severe cyanosis a few hours after birth due to methemoglobinemia. This was thought to be related to the local maternal perineal infiltration of prilocaine during childbirth. Though rare, prilocaine is the most potent agent to induce methemoglobinemia compared to other local aneasthetics. After intravenous administration of methylene blue, both newborns fully recovered.Neonatal methemoglobinemia is a rare and potentially fatal complication of local anesthetics, particularly prilocaine, administered to the mother during childbirth. Midwives, obstetricians, gynecologists and pediatricians should be aware of this complication. The use of other local anesthetics, including lidocaine, should be considered.

In Heliconius butterflies, wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes, cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knockouts in multiple Heliconius species and show that cortex is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified cis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the H. melpomene/timareta lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that cis-regulatory structural variation underlies these mimetic adaptations. Our work shows that cortex functionally controls scale colour fate and that its cis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion., eLife digest Heliconius butterflies have bright patterns on their wings that tell potential predators that they are toxic. As a result, predators learn to avoid eating them. Over time, unrelated species of butterflies have evolved similar patterns to avoid predation through a process known as Müllerian mimicry. Worldwide, there are over 180,000 species of butterflies and moths, most of which have different wing patterns. How do genes create this pattern diversity? And do butterflies use similar genes to create similar wing patterns? One of the genes involved in creating wing patterns is called cortex. This gene has a large region of DNA around it that does not code for proteins, but instead, controls whether cortex is on or off in different parts of the wing. Changes in this non-coding region can act like switches, turning regions of the wing into different colours and creating complex patterns, but it is unclear how these switches have evolved. Butterfly wings get their colour from tiny structures called scales, which each have their own unique set of pigments. In Heliconius butterflies, there are three types of scales: yellow/white scales, black scales, and red/orange/brown scales. Livraghi et al. used a DNA editing technique called CRISPR to find out whether the cortex gene affects scale type. First, Livraghi et al. confirmed that deleting cortex turned black and red scales yellow. Next, they used the same technique to manipulate the non-coding DNA around the cortex gene to see the effect on the wing pattern. This manipulation turned a black-winged butterfly into a butterfly with a yellow wing band, a pattern that occurs naturally in Heliconius butterflies. The next step was to find the mutation responsible for the appearance of yellow wing bands in nature. It turns out that a bit of extra genetic code, derived from so-called ‘jumping genes’, had inserted itself into the non-coding DNA around the cortex gene, ‘flipping’ the switch and leading to the appearance of the yellow scales. Genetic information contains the instructions to generate shape and form in most organisms. These instructions evolve over millions of years, creating everything from bacteria to blue whales. Butterfly wings are visual evidence of evolution, but the way their genes create new patterns isn't specific to butterflies. Understanding wing patterns can help researchers to learn how genetic switches control diversity across other species too.