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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.

IntroductionCritically ill patients show large variability in drug disposition due to e.g., age, size, disease and treatment modalities. Physiologically-based pharmacokinetic (PBPK) models can be used to design individualized dosing regimens taking this into account. Dexamethasone, prescribed for the prevention post-extubation stridor (PES), is metabolized by the drug metabolizing enzyme CYP3A. As CYP3A4 undergoes major changes during childhood, we aimed to develop age-appropriate dosing recommendations for children of dexamethasone for PES, as proof of concept for PBPK modeling to individualize dosing for critically ill patients.MethodsAll simulations were conducted in Simcyp™ v21 (a population-based PBPK modeling platform), using an available dexamethasone compound model and pediatric population model in which CYP3A4 ontogeny is incorporated. Published pharmacokinetic (PK) data was used for model verification. Evidence for the dose to prevent post-extubation stridor was strongest for 2–6 year old children, hence simulated drug concentrations resulting from this dose from this age group were targeted when simulating age-appropriate doses for the whole pediatric age range.ResultsDexamethasone plasma concentrations upon single and multiple intravenous administration were predicted adequately across the pediatric age range. Exposure-matched predictions of dexamethasone PK indicated that doses (in mg/kg) for the 2–6 years olds can be applied in 3 month-2 year old children, whereas lower doses are needed in children of other age groups (60% lower for 0–2 weeks, 40% lower for 2–4 weeks, 20% lower for 1–3 months, 20% lower for 6–12 year olds, 40% lower for 12–18 years olds).DiscussionWe show that PBPK modeling is a valuable tool that can be used to develop model-informed recommendations using dexamethasone to prevent PES in children. Based on exposure matching, the dose of dexamethasone should be reduced compared to commonly used doses, in infants

This narrative review examines the existing literature on minimally invasive image-guided sampling techniques of mediastinal lesions gathered from international databases (Medline, PubMed, Scopus, and Google Scholar). Original studies, systematic reviews with meta-analyses, randomized controlled trials, and case reports published between January 2009 and November 2023 were included. Four authors independently conducted the search to minimize bias, removed duplicates, and selected and evaluated the studies. The review focuses on the recent advancements in mediastinal sampling techniques, including EBUS-TBNA, EUS-FNA and FNB, IFB, and nodal cryobiopsy. The review highlights the advantages of an integrated approach using these techniques for diagnosing and staging mediastinal diseases, which, when used competently, significantly increase diagnostic yield and accuracy.

IntroductionMolecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting.MethodsThis multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated.ResultsTotal accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (pConclusionThis study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients.

IntroductionThis paper reports on the effects of a 9-week vitality training that employed behaviour-change techniques and was evaluated using a randomised controlled trial (RCT) in three large companies based in the Netherlands.MethodsA total of 84 adult employees from three participating organisations in the Netherlands were enrolled in the study. A parallel group RCT design was employed and participants were assigned using individual random assignment to either an intervention (n = 38) or a waitlist control group (n = 46). The intervention consisted of a 9-week vitality training employing the behaviour-change techniques of self-persuasion, implementation intentions, and self-efficacy, which was delivered in-house over five fortnightly 2-hour sessions. Primary outcomes (i.e., reported energy and stress) and secondary outcomes (i.e., reported daily life satisfaction and work capacity) were assessed prior to, immediately after, and 3 months following the intervention.ResultsA mixed MANOVA revealed a significant interaction effect between treatment group and time period for the combination of reported energy, stress, daily life satisfaction, and work capacity. Subsequent univariate ANOVAs revealed significant interactions between treatment group and time period for reported energy, stress, and daily life satisfaction; however, not for reported work capacity. Improvements in outcomes were observed for both groups following their completion of the vitality training; however, not all improvements reached statistical significance. Reported self-efficacy regarding managing work-life balance was found to mediate the relationship between the effects of the intervention and reported energy; however, such an effect was not found for stress.DiscussionAn intervention drawing upon evidence-based behaviour-change techniques shows promise for improving indicators associated with burnout; although, it is recommended that in future research a larger-scale evaluation be conducted over a longer time period with an active control group to establish effectiveness.Clinical trial registration:https://www.anzctr.org.au/, ACTRN12622001268730.

Objectives To 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 methods Two 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.Results CBCT-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.Conclusions CBCT-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.

Primary Sjögren's syndrome (pSS) is a systemic auto-immune disease typified by dryness of the mouth and eyes. A majority of patients with pSS have a type-I interferon (IFN)-signature, which is defined as the increased expression of IFN-induced genes in circulating immune cells and is associated with increased disease activity. As plasmacytoid dendritic cells (pDC) are the premier type-I IFN-producing cells and are present at the site of inflammation, they are thought to play a significant role in pSS pathogenesis. Considering the lack of data on pDC regulation and function in pSS patients, we here provided the first in-depth molecular characterization of pSS pDCs. In addition, a group of patients with non-Sjögren's sicca (nSS) was included; these poorly studied patients suffer from complaints similar to pSS patients, but are not diagnosed with Sjögren's syndrome. We isolated circulating pDCs from two independent cohorts of patients and controls (each n = 31) and performed RNA-sequencing, after which data-driven networks and modular analysis were used to identify robustly reproducible transcriptional “signatures” of differential and co-expressed genes. Four signatures were identified, including an IFN-induced gene signature and a ribosomal protein gene-signature, that indicated pDC activation. Comparison with a dataset of in vitro activated pDCs showed that pSS pDCs have higher expression of many genes also upregulated upon pDC activation. Corroborating this transcriptional profile, pSS pDCs produced higher levels of pro-inflammatory cytokines, including type-I IFN, upon in vitro stimulation with endosomal Toll-like receptor ligands. In this setting, cytokine production was associated with expression of hub-genes from the IFN-induced and ribosomal protein gene-signatures, indicating that the transcriptional profile of pSS pDCs underlies their enhanced cytokine production. In all transcriptional analyses, nSS patients formed an intermediate group in which some patients were molecularly similar to pSS patients. Furthermore, we used the identified transcriptional signatures to develop a discriminative classifier for molecular stratification of patients with sicca. Altogether, our data provide in-depth characterization of the aberrant regulation of pDCs from patients with nSS and pSS and substantiate their perceived role in the immunopathology of pSS, supporting studies that target pDCs, type-I IFNs, or IFN-signaling in pSS.

In view of the aging and dejuvenation of the working population and the expected shortages in employees’ skills in the future, it is of utmost importance to focus on older workers’ employability in order to prolong their working life until, or even beyond, their official retirement age. The primary aim of the current study was to examine the relationship between older workers’ employability (self-)perceptions and their intention to continue working until their official retirement age. In addition, we studied the role of potential antecedents of their perceived employability at three different levels: training and education in current expertise area as well as in an adjacent expertise area (individual level factor), learning value of the job (job level factor), and organizational career management practices (organizational level factor). Data were collected by means of e-questionnaires that were distributed among two groups of Dutch older (45-plus) white collar workers. The samples consisted of 223 employees of an insurance company, and 325 university workers, respectively. Our research model was tested separately in each sample using Structural Equation Modeling. We controlled for effects of respondents’ (self-)perceived health and (self-)perceived financial situation. Similar results were found for both samples. First, the relationship of perceived employability with the intention to continue working until one’s retirement age was positive, whereas the relationship between a perceived good financial situation with the intention to continue working until one’s retirement age was negative. Secondly, as regards the potential antecedents, results showed that the learning value of the job was positively related to perceived employability. In addition, an employee’s perception of good health is a relevant correlate of perceived employability. So, whereas perceived employability contributes to the intention to continue working until one’s retirement age, a good financial situation is a push factor to retire early. In order to promote the labor participation of older workers, this study indicates that organizations should focus on the learning possibilities that are inherent to one’s job rather than on providing additional training or career management. Further research is needed to test the generalizability of our results to other samples.

The “aging population” implies an increased proportion of older professionals and a growing demand for healthcare services. Healthcare professionals are often highly committed to their work which can be reflected in high levels of workaholism, being a double-edged sword that can prompt both positive and negative mechanisms, differently affecting younger and older healthcare workers. The present study aims to gain insights into the relationships between healthcare professionals' age, workaholism and job satisfaction, by estimating the sequential mediating roles of workload perceptions and emotional exhaustion. We used original survey data, including information on 750 healthcare professionals. Overall, the negative relationship between workaholism and job satisfaction was shown to be sequentially (and partially) mediated by workload perceptions and emotional exhaustion. Multi-Group SEM analyses revealed differences across three age groups (under 35; between 35 and 50; over 50). Only in the two younger age groups, we found a direct and positive relationship between workaholism and job satisfaction. In all age groups, we found the negative relationship between workaholism and job satisfaction to be sequentially (and partially) mediated by workload perceptions and emotional exhaustion. The indirect effects were relatively stronger in the younger age group. Workaholism can prompt both a “gain spiral” and “a loss spiral” among healthcare professionals. The first reflects workaholism to function as a job resource fostering job satisfaction (only for the two younger age groups). The second reflects workaholism to function as a job demand reducing job satisfaction. This mechanism was shown to be stronger with an increasing age.

At present, individuals increasingly have to take ownership of their working lives. This situation requires them to self-manage and plan their careers. However, individuals’ career management does not happen in a vacuum. Studies have therefore stressed the importance of organizations introducing Sustainable Human Resource Management to share the responsibility for individuals’ employability. This is expected to motivate especially disadvantaged workers, such as older workers (≥ 50 years) and those working in lower-skilled jobs, to work longer across the life-span. In view of the growing scholarly and societal attention for Sustainable Career Development (SCD), the present study examines the relationships between workers’ chronological age (comparing older workers with younger and middle-aged groups, respectively) and dimensions of self-reported employability, and how perceptions of negative (meta-)stereotyping regarding older workers’ productivity, reliability, and personal adaptability moderate these relationships. To examine how possible underlying psychological mechanisms can affect individuals’ labor market decisions and behaviors, we developed hypotheses derived from socio-emotional selectivity and self-categorization theory, which we tested using data collected among supermarket workers in various age groups (N = 98). Moderated regression analyses showed that, in line with our hypotheses, perceptions of negative age-based (meta-)stereotyping amplifies the negative effect of older workers’ age on their self-perceived employability. In particular, we found that: (1) the older worker group reported lower levels of three of the distinguished employability dimensions (i.e., anticipation and optimization, corporate sense, and balance, but not occupational expertise and personal flexibility) and (2) perceptions of stronger negative (meta-)stereotypes regarding older workers in the organization had a moderating effect on the relationship between age group and four of the distinguished employability dimensions (i.e., occupational expertise, anticipation and optimization, corporate sense, and balance, but not personal flexibility). We conclude that age group membership as well as negative age-based (meta-)stereotypes deter older workers from enhancing their employability, which may potentially impact their career decisions and opportunities, especially in view of swift changing labor market demands. We argue, therefore, that Sustainable HR practices should focus on opposing negative age-based (meta-)stereotyping and on creating an inclusive work climate, meanwhile enhancing workers’ ambitions and career opportunities over the life cycle.

Accurate Calcium Oxalate Monohydrate (COM) solubility measurements are essential for elucidating the physiochemical mechanism behind the formation of kidney stones, nephrolithiasis. Yet the reported solubility values of COM in ultrapure water, arguably the simplest solvent relevant for nephrolithiasis, vary significantly depending on implemented method. To address this variation, we present an experimental study of the solubility of COM validated by a model based on the Debye–Hückel theory describing the solution chemistry and the complex formation. We also carefully monitor potential pseudopolymorphic/hydrate transitions during the solubility measurements with in-situ and ex-situ methods. Our results indicate that the solubility of COM in ultrapure water is a weak function of temperature. However, the measured solubility varies significantly in buffer solutions across physiologically relevant pH values at body temperature. The proposed model explains observed trends as a combined effect of ionic strength, protonation reactions, and soluble complex formation. Moreover, it predicts solubility of COM in buffer solutions remarkably well using our measurements in ultrapure water as input, demonstrating the consistency of presented approach. The presented study parleying experiments and modelling provides a solid stepping stone to extend the physiochemical understanding of nephrolithiasis to more realistic solutions laden with biological complexity.

In addition to acquiring occupation-specific knowledge and skills, students need to develop a set of career self-management skills – or resources – that helps them to successfully maneuver the various career-related challenges they face and that stimulate their well-being, engagement, and performance in studying tasks. In the current study, we apply the Job Demands-Resources (JD-R) theory in an educational setting and suggest that career adaptability and career competencies are important career resources that predict both life satisfaction and academic performance via students’ satisfaction with the choice of their major and study engagement. Undergraduate students (N = 672) from nine different colleges and universities in Lithuania participated in the study. The results revealed that career adaptability and career competencies were positively linked to students’ life satisfaction, both directly and via study engagement. In addition, these career resources were positively, yet indirectly, related to academic performance via study engagement. Overall, the results suggest that career resources contribute to study engagement, life satisfaction, and academic performance. The results of our study further support JD-R theorizing and its applicability in student samples. Further theoretical and practical implications are discussed.

This two-wave complete panel study aims to examine human resource management (HRM) bundles of practices in relation to social support [i.e., leader–member exchange (LMX), coworker exchange (CWX)] and employee outcomes (i.e., work engagement, employability, and health), within a context of workers aged 65+. Based upon the social exchange theory and the Job Demands-Resources (JD-R) framework, it was hypothesized that HRM bundles at Time 1 would increase bridge workers' outcomes at Time 2, and that this relationship would be mediated by perceptions of LMX and CWX at Time 2. Using a longitudinal design, hypotheses were tested in a unique sample of Dutch bridge employees (N = 228). Results of several structural equation modeling analyses revealed no significant associations between HRM bundles, and social support, moreover, no significant associations were found in relation to employee outcomes. However, the results of the best-fitting final model revealed the importance of the impact of social support on employee (65+) outcomes over time.

Respondent-driven detection is a chain recruitment method used to sample contact persons of infected persons in order to enhance case finding. It starts with initial individuals, so-called seeds, who are invited for participation. Afterwards, seeds receive a fixed number of coupons to invite individuals with whom they had contact during a specific time period. Recruitees are then asked to do the same, resulting in successive waves of contact persons who are connected in one recruitment tree. However, often the majority of participants fail to invite others, or invitees do not accept an invitation, and recruitment stops after several waves. A mathematical model can help to analyse how various factors influence peer recruitment and to understand under which circumstances sustainable recruitment is possible. We implemented a stochastic simulation model, where parameters were suggested by empirical data from an online survey, to determine the thresholds for obtaining large recruitment trees and the number of waves needed to reach a steady state in the sample composition for individual characteristics. We also examined the relationship between mean and variance of the number of invitations sent out by participants and the probability of obtaining a large recruitment tree. Our main finding is that a situation where participants send out any number of coupons between one and the maximum number is more effective in reaching large recruitment trees, compared to a situation where the majority of participants does not send out any invitations and a smaller group sends out the maximum number of invitations. The presented model is a helpful tool that can assist public health professionals in preparing research and contact tracing using online respondent-driven detection. In particular, it can provide information on the required minimum number of successfully sent invitations to reach large recruitment trees, a certain sample composition or certain number of waves.

[This corrects the article DOI: 10.1371/journal.pone.0161749.].

Though the importance of sustainable employability throughout people's working life is undisputed, up till now only one attempt for a conceptual definition has been made (van der Klink et al., 2016). Following the suggestions to further refine and improve this definition recently put forward by Fleuren et al. (2016), we propose an approach to sustainable employability that is based on the Ability-Motivation-Opportunity (AMO) framework, and incorporates three indicators: the ability, the motivation, and the opportunity to continue working, respectively. As sustainable employability is considered to be an important aspect of successful aging at work, this study used four different conceptualizations of aging at work to set up convergent and divergent validity of our operationalization of sustainable employability: calendar age, organizational age (job and organizational tenure), functional age (work ability), and life-span age (partner and children). We formulated several hypotheses that were tested by analyzing data from an online survey among 180 employees from Dutch public service organizations who filled out a questionnaire on different age concepts, and their ability, motivation, and opportunity to continue working. Multiple regression analyses were performed, and results showed that the four conceptualizations of aging were differently related to the three indicators of sustainable employability. Life-span age, in terms of having children, had the strongest negative relationship with the ability to continue working, organizational age (i.e., organizational tenure) had the strongest negative relationship with the motivation to continue working, and functional age had the strongest negative relationship with the opportunity to continue working. Moreover, functional age was significantly negatively related to the other two indicators of sustainable employability too, while life-span age appeared to enhance the ability and motivation to continue working (in terms of having children) and the perceived opportunity to continue working (in terms of having a partner). Calendar age was only important for the opportunity to continue working and appeared to have a negative association with this outcome variable. These results lend support to our proposed operationalization of sustainable employability by showing that the three indicators are differently related to different age conceptualizations thus expanding previous research on the conceptualization of sustainable employability.

In the contemporary workplace, insight into retirement behaviors is of crucial importance. Previous empirical evidence has found mixed results regarding the relationship between work attitudes, such as job satisfaction, and retirement behaviors, suggesting that further scholarly examination incorporating moderating and mediating variables into retirement models is needed. Drawing on comparative models of attitude to retirement, we hypothesized a direct relationship between job satisfaction and intended retirement age for workers with a high household income and an indirect relationship between job satisfaction and intended retirement age, via retirement attitude, for workers with a low or mean household income. We collected data from a sample of 590 United Kingdom workers aged 50+. Using conditional process analysis, we found that the underlying mechanisms in our research model differ according to socio-economic status. We found no direct effect between job satisfaction and intended retirement age. However, an indirect effect was observed between job satisfaction and intended retirement age, via retirement attitude, for both low- and mean-household income individuals. Specifically, the relationship between job satisfaction and retirement attitude differed according to socio-economic group: for high-household income older workers, there was no relationship between job satisfaction and retirement attitude. However, for low- and mean-household income older workers, we observed a negative relationship between job satisfaction and retirement attitude. Otherwise stated, increases in job satisfaction for mean and low household income workers are likely to make the prospect of retirement less attractive. Therefore, we argue that utmost care must be taken around the conditions under which lower income employees will continue their work when getting older in order to protect their sustainable employability.