Young adults in Neither in Employment, Education nor Training (NEET) are at risk of adverse labour market outcomes. Earlier studies often measured NEET status at one time point or compared persistent ...NEETs with non-NEETs, neglecting other patterns of NEET status. Evidence on early life factors associated with NEET patterns is lacking. This study aims to (i) identify patterns of NEET status over time and (ii) examine whether factors in childhood and adolescence are associated with these patterns.
Data were used from 1499 participants of the TRacking Adolescents' Individual Lives Survey (TRAILS), a Dutch prospective cohort study with 15-year follow-up. NEET status was assessed at ages 19, 22 and 26. Socioeconomic status of parents (SES), intelligence and negative life events were measured at age 11, educational attainment at age 26 and mental health problems at ages 11, 13.5 and 16. Data were analyzed using multinomial logistic regression analysis.
Four NEET patterns were identified: (i) non-NEETs (85.2%), (ii) early NEETs (4.5%), (iii) late NEETs (5.7%) and (iv) persistent NEETs (4.5%). Reporting internalizing problems at age 11 was a risk factor for early and late NEETs odds ratio (OR) 2.77, 95% confidence interval (CI) 1.16-6.62; OR 5.00, 95% CI 2.22-11.3, respectively. Low parental SES, lower intelligence scores and negative life events (≥3) were risk factors for persistent NEETs (OR 4.45, 95% CI 2.00-9.91; OR 0.96, 95% CI 0.94-0.98; OR 4.42, 95% CI 1.62-12.08, respectively).
The results highlight the importance of timing and duration of NEET status and emphasize the need for tailored interventions to prevent specific NEET patterns.
Improved ways to diagnose acute respiratory viral infections could decrease inappropriate antibacterial use and serve as a vital triage mechanism in the event of a potential viral pandemic. ...Measurement of the host response to infection is an alternative to pathogen-based diagnostic testing and may improve diagnostic accuracy. We have developed a host-based assay with a reverse transcription polymerase chain reaction (RT-PCR) TaqMan low-density array (TLDA) platform for classifying respiratory viral infection. We developed the assay using two cohorts experimentally infected with influenza A H3N2/Wisconsin or influenza A H1N1/Brisbane, and validated the assay in a sample of adults presenting to the emergency department with fever (n = 102) and in healthy volunteers (n = 41). Peripheral blood RNA samples were obtained from individuals who underwent experimental viral challenge or who presented to the emergency department and had microbiologically proven viral respiratory infection or systemic bacterial infection. The selected gene set on the RT-PCR TLDA assay classified participants with experimentally induced influenza H3N2 and H1N1 infection with 100 and 87% accuracy, respectively. We validated this host gene expression signature in a cohort of 102 individuals arriving at the emergency department. The sensitivity of the RT-PCR test was 89% 95% confidence interval (CI), 72 to 98%, and the specificity was 94% (95% CI, 86 to 99%). These results show that RT-PCR-based detection of a host gene expression signature can classify individuals with respiratory viral infection and sets the stage for prospective evaluation of this diagnostic approach in a clinical setting.
Background
Respiratory motion presents a challenge in radiotherapy of thoracic and upper abdominal tumors. Techniques to account for respiratory motion include tracking. Using magnetic resonance ...imaging (MRI) guided radiotherapy systems, tumors can be tracked continuously. Using conventional linear accelerators, tracking of lung tumors is possible by determining tumor motion on kilo voltage (kV) imaging. But tracking of abdominal tumors with kV imaging is hampered by limited contrast. Therefore, surrogates for the tumor are used. One of the possible surrogates is the diaphragm. However, there is no universal method for establishing the error when using a surrogate and there are particular challenges in establishing such errors during free breathing (FB). Prolonged breath‐holding might address these challenges.
Purpose
The aim of this study was to quantify the error when using the right hemidiaphragm top (RHT) as surrogate for abdominal organ motion during prolonged breath‐holds (PBH) for possible application in radiation treatments.
Methods
Fifteen healthy volunteers were trained to perform PBHs in two subsequent MRI sessions (PBH‐MRI1 and PBH‐MRI2). From each MRI acquisition, we selected seven images (dynamics) to determine organ displacement during PBH by using deformable image registration (DIR). On the first dynamic, the RHT, right and left hemidiaphragm, liver, spleen and right and left kidney were segmented. We used the deformation vector fields (DVF), generated by DIR, to determine the displacement of each organ between two dynamics in inferior‐superior (IS), anterior‐posterior (AP), left‐right (LR) direction and we calculated the 3D vector magnitude (|d|). The displacements of the RHT, both hemidiaphragms and the abdominal organs were compared using a linear fit to determine the correlation (R2 of the fit) and the displacement ratio (DR, slope of the fit) between displacements of the RHT and each organ. We quantified the median difference between the DRs of PBH‐MRI1 and PBH‐MRI2 for each organ. Additionally, we estimated organ displacement in the second PBH by applying the DR from the first PBH to the displacement of the RHT measured during the second PBH. We compared the estimated organ displacement to the measured organ displacement during the second PBH. The difference between the two values was defined as the estimation error of using the RHT as a surrogate and assuming a constant DR over MRI sessions.
Results
The linear relationships were confirmed by the high R2 values of the linear fit between the displacements of the RHT and the abdominal organs (R2 > 0.96) in the IS and AP direction and |d|, and high to moderate correlations in the LR direction (0.93 > R2 > 0.64). The median DR difference between PBH‐MRI1 and PBH‐MRI2 varied between 0.13 and 0.31 for all organs. The median estimation error of the RHT as a surrogate varied between 0.4 and 0.8 mm/min for all organs.
Conclusion
The RHT could serve as an accurate surrogate for abdominal organ motion during radiation treatments, for example, in tracking, provided the error of the RHT as motion surrogate is taken into account in the margins.
Trial registration
The study was registered in the Netherlands Trial Register (NL7603).
The presence of ESBL/AmpC-producing E. coli in cattle has been reported previously, however information on veal calves is limited. This study describes the prevalence and molecular characteristics of ...E. coli with non-wild type susceptibility to cefotaxime in veal calves at slaughter.
Faecal samples from 100 herds, 10 individual animals per herd, were screened for E. coli with non-wild type susceptibility for cefotaxime. Molecular characterization of ESBL/AmpC genes and plasmids was performed on one isolate per herd by microarray, PCR and sequence analysis.
66% of the herds were positive for E. coli with non-wild type susceptibility for cefotaxime. Within-herd prevalence varied from zero to 90%. 83% of E. coli producing ESBL/AmpC carried bla(CTX-M) genes, of which bla(CTX-M-1), bla(CTX-M-14) and bla(CTX-M-15) were most prevalent. The dominant plasmids were IncI1 and IncF-type plasmids.
A relatively high prevalence of various bla(CTX-M) producing E. coli was found in veal calves at slaughter. The genes were mainly located on IncI1 and IncF plasmids.
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are associated with a variety of cellular alterations that mitigate cardiovascular disease. However, pinpointing the positive therapeutic effects is ...challenging due to inconsistent clinical trial results and overly simplistic in vitro studies. Here we aimed to develop realistic models of n-3 PUFA effects on platelet function so that preclinical results can better align with and predict clinical outcomes. Human platelets incubated with the n-3 PUFAs docosahexaenoic acid and eicosapentaenoic acid were stimulated with agonist combinations mirroring distinct regions of a growing thrombus. Platelet responses were then monitored in a number of ex-vivo functional assays. Furthermore, intravital microscopy was used to monitor arterial thrombosis and fibrin deposition in mice fed an n-3 PUFA-enriched diet. We found that n-3 PUFA treatment had minimal effects on many basic ex-vivo measures of platelet function using agonist combinations. However, n-3 PUFA treatment delayed platelet-derived thrombin generation in both humans and mice. This impaired thrombin production paralleled a reduced platelet accumulation within thrombi formed in either small arterioles or larger arteries of mice fed an n-3 PUFA-enriched diet, without impacting P-selectin exposure. Despite an apparent lack of robust effects in many ex-vivo assays of platelet function, increased exposure to n-3 PUFAs reduces platelet-mediated thrombin generation and attenuates elements of thrombus formation. These data support the cardioprotective value of-3 PUFAs and strongly suggest that they modify elements of platelet function in vivo.
Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved ...by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization
. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
The characteristics-based ssolution. It is easy to verify thatectional method (CBSM) offers an Eulerian description of an internally mixed aerosol. It was shown to be robust and capable of exact ...preservation of lower order moments, allowing for highly skewed sectional droplet size distributions. In this paper we apply CBSM to a spatially varying flow, by incorporating the fractional step method. In this way an accurate time integration of the spatial terms in the transport equations for the velocity, mass fractions and sectional droplet concentrations is achieved. Integrating CBSM into the compressible PISO (Pressure-Implicit with Splitting of Operators) algorithm allows for phase change and corresponding changes in pressure. We apply CBSM to a lid-driven cavity flow. First, the steady state isothermal flow solution is validated against published data. Next, by releasing a saturated vapor into the cavity while cooling the walls, we simulate the formation of aerosol. The accuracy of the solution is studied, as well as the performance of the CBSM scheme in the spatially varying context. The solution of the velocity is shown to be accurate, even at CFL (Courant–Friedrichs–Lewy) numbers of unity. The feasibility of the developed method is demonstrated in a 3D complex geometry studying the aerosol generation via nucleation of hot vapors cooled by a dilution stream of cold air in a double-mixing tee system. The sectional approach delivers detailed information about the aerosol formation and size distribution of the droplets in the domain.
•Characteristics-based sectional method (CBSM) was extended to spatially varying flow.•Aerosol formation through nucleation and condensation was simulated in lid-driven cavity flow.•Accuracy and performance of the method was shown.•Applicability and feasibility of the method in a 3D complex geometry was shown by simulation of aerosol formation in the Vitrocell® exposure system.
Abstract
Background
Little is known about factors that may explain the association between depressive symptoms and poor labour market participation (LMP). The aim of this study is to examine the ...mediation and interaction effects of social support on the association between depressive symptoms and LMP.
Methods
Data were used from 985 participants (91% of the initial cohort) of the Northern Swedish Cohort, a longitudinal study of Swedish participants followed from adolescence throughout adulthood. Depressive symptoms were measured at age 16, social support at age 21 and LMP from age 30 to 43. Poor LMP was defined as being unemployed for a total of 6 months or more between the ages of 30 and 43. A four-way decomposition approach was applied to identify direct, mediation and interaction effects, together and separately.
Results
Both depressive symptoms during adolescence and social support at young adulthood were associated with poor LMP odds ratio (OR) = 1.70, 95% confidence interval (CI) 1.17–2.47 and OR = 2.56, 95% CI 1.78-3.68 respectively. The association between depressive symptoms and poor LMP was partially mediated by a lack of social support. No interaction effect of a lack of social support was found.
Conclusion
The results suggest that depressive symptoms influence not only later LMP but also the intermediary level of social support, and in turn influencing later LMP. Recommendations for public health are to detect and treat depressive symptoms at an early stage and to focus on the development of social skills, facilitating the increased availability of social support, thereby improving future LMP.
Background
rVIII‐SingleChain, a novel recombinant factor VIII (rFVIII), has been designed as a B‐domain truncated construct with covalently bonded heavy and light chains, aiming to increase binding ...affinity to von Willebrand factor (VWF). Preclinical studies confirmed greater affinity for VWF, giving improved pharmacokinetic and pharmacodynamic properties compared with full‐length rFVIII.
Aim
To investigate the pharmacokinetics of rVIII‐SingleChain and compare them against those of full‐length rFVIII.
Methods
This study enrolled 27 patients with severe haemophilia A in the AFFINITY clinical trial programme. After a 4‐day washout period, all patients received a single infusion of 50 IU kg−1 octocog alfa (Advate®); after a ≥4‐day postinfusion washout period, they received a single infusion of 50 IU kg−1 rVIII‐SingleChain. Blood samples for pharmacokinetic assessments of each product were collected before infusion (predose) and at 0.5, 1, 4, 8, 10, 24, 32, 48 and 72 h postinfusion for both products.
Results
rVIII‐SingleChain had a longer mean half‐life (t1/2) (14.5 vs. 13.3 h), lower mean clearance (CL) (2.64 vs. 3.68 mL h−1 kg−1), higher mean residence time (20.4 vs. 17.1 h) and larger mean AUCinf (2090 vs. 1550 IU?h dL−1) than octocog alfa, respectively. The mean AUCinf after rVIII‐SingleChain infusion was ~35% larger than after octocog alfa. A similar pattern was observed for AUC0‐last. No serious adverse events or inhibitors were reported.
Conclusions
rVIII‐SingleChain has a favourable pharmacokinetic profile compared with octocog alfa and was well tolerated. The prolonged t1/2, larger AUC and reduced CL of rVIII‐SingleChain may permit longer dosing intervals, thereby improving patient adherence to prophylactic treatment.
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