Stock allocation in general multi-echelon distribution systems with (R, S) order-up-to-policies

In this paper we analyze stock allocation policies in general N-echelon distribution systems, where it is allowed to hold stock at all levels in the network. The goal is to achieve differentiated target customer service levels (fill rates). Various allocation rules and accompanying numerical methods that have already been developed for smaller networks are extended and compared in an extensive numerical experiment. We conclude that the extension of Balanced Stock rationing (see Van der Heijden (1996)) is the most accurate method, in particular in cases of relatively high imbalance. If the imbalance is not too high, the extension of Consistent Appropriate Share rationing (see De Kok et al., 1994; Verrijdt and De Kok, 1996) performs good as well

Allocation policies in general multi-echelon distribution systems with (R, S) order-up-to-policies

In this paper we analyze stock allocation policies in general N-echelon distribution systems, where it is allowed to hold stock at all levels in the network. The goal is to achieve differentiated target customer service levels (fill rates). Various allocation rules and accompanying numerical methods that have already been developed for smaller networks are extended and compared in an extensive numerical experiment. We conclude that the extension of Balanced Stock rationing (see Van der Heijden [1996]) is the most accurate method, in particular in cases of relatively high imbalance. If the imbalance is not too high, the extension of Consistent Appropriate Share rationing (see [De Kok, Lagodimos & Seidel, 1994; Verrijdt & De Kok, 1996]) performs good as well. Keywords: Multi-echelon, inventory, allocation, rationing, divergent

Binaural detection with spectrally nonoverlapping signals and maskers: evidence for masking by aural distortion products

Thresholds were measured for diotic tonal signals in the presence of interaurally delayed bands of Gaussian noise. When the signal frequency was 525 Hz, the spectrum of the noise was either below (highest frequency, 450 Hz) or above (lowest frequency, 600 Hz) the frequency of the signal. When the signal frequency was 450 Hz, the spectrum of the noise was always above the signal frequency (lowest frequency, 600 Hz). Signals had a 250-ms duration and were temporally centered within the 300-ms long bursts of noise. The spectrum level of the noise was 60 dB. Thresholds obtained in all three conditions varied essentially sinusoidally with the interaural delay of the noise. For signals below the spectrum of the noise, the periodicities within the data were close to, but not identical with, the periodicities of the signals. This outcome is discussed in terms of masking produced by aural distortion products stemming from interactions within the bands of noise [cf. van der Heijden and Kohlrausch, J. Acoust. Soc. Am. 98, 3125–3134 (1995)]. For signals above the spectrum of the noise, the periodicities in the data suggested that masking was produced by components within the band of noise. Patterns within the data are also discussed in terms of limitations concerning the magnitude of external delays that can be matched by internal delays that are incorporated in modern models of binaural processing

Citrullination of synovial proteins in murine models of rheumatoid arthritis

Item does not contain fulltextOBJECTIVE: Antibodies directed to citrulline-containing proteins are highly specific for rheumatoid arthritis (RA) and can be detected in up to 80% of patients with RA. Citrulline is a nonstandard amino acid that can be incorporated into proteins only by posttranslational modification of arginine by peptidylarginine deiminase (PAD) enzymes. The objective of this study was to investigate the presence of anticitrulline antibodies, PAD enzymes, and citrullinated antigens in mouse models of both acute and chronic destructive arthritis: streptococcal cell wall (SCW)-induced arthritis and collagen-induced arthritis (CIA), respectively. METHODS: Synovial tissue biopsy specimens were obtained from naive mice, mice with CIA, and mice with SCW-induced arthritis. The expression of messenger RNA (mRNA) for PAD enzymes was analyzed by reverse transcriptase-polymerase chain reaction; the presence of PAD proteins and their products (citrullinated proteins) was analyzed by Western blotting and by immunolocalization. The presence of anticitrullinated protein antibodies was investigated by an anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay (ELISA) and an ELISA using in vitro citrullinated fibrinogen. RESULTS: In both mouse models, PAD type 2 (PAD2) mRNA was present in the synovium but was not translated into PAD2 protein. In contrast, PAD4 mRNA, although absent from healthy synovium, was readily transcribed and translated by polymorphonuclear neutrophils infiltrating the synovial tissue during inflammation. As a consequence, several synovial proteins were subjected to citrullination. One of these proteins was identified as fibrin, which has been reported to be citrullinated also in synovium of patients with RA. Although generation of citrullinated antigens during synovial inflammation in the mice was eminent, no anti-CCP antibodies could be detected. CONCLUSION: Citrullination of synovial antigens is an active process during joint inflammation in both mice and humans, but the induction of autoantibodies directed to these proteins is a more specific phenomenon, detectable only in human RA patients

Understanding personality pathology in a clinical sample of youth: study protocol for the longitudinal research project 'APOLO'

Introduction We propose that a dimensional, multilayered perspective is well suited to study maladaptive personality development in youth. Such a perspective can help understand pathways to personality pathology and contribute to its early detection. The research project 'APOLO' (a Dutch language acronym for Adolescents and their Personality Development: a Longitudinal Study) is designed based on McAdams' integrative three-layered model of personality development and assesses the interaction between dispositional traits, characteristic adaptations, the narrative identity and functioning. Methods and analysis APOLO is a longitudinal research project that takes place in two outpatient mental healthcare centres. Participants are youth between 12 years and 23 years and their parents. Data collection is set up to build a data set for scientific research, as well as to use the data for diagnostic assessment and systematic treatment evaluation of individual patients. Measurements are conducted half-yearly for a period of 3 years and consist of self-report and informant-report questionnaires and a semistructured interview. The included constructs fit the dimensional model of personality development: maladaptive personality traits (dispositional traits), social relations, stressful life events (characteristic adaptations), a turning point (narrative identity) and functioning (eg, achievement of youth specific milestones). Primary research questions will be analysed using structural equation modelling. Ethics and dissemination The results will contribute to our understanding of (the development of) personality pathology as a complex phenomenon in which both structural personality characteristics as well as unique individual adaptations and experiences play a role. Furthermore, results will give directions for early detection and timely interventions. This study has been approved by the ethical review committee of the Utrecht University Faculty for Social and Behavioural Sciences (FETC17-092). Data distribution will be anonymous and results will be disseminated via communication canals appropriate for diverse audiences. This includes both clinical and scientific conferences, papers published in national and international peer-reviewed journals and (social) media platforms

Features of the citrullinating peptidylarginine deiminase enzymes

Contains fulltext : 58471.pdf (publisher's version ) (Open Access

Predictors of undergoing multivisceral resection, margin status and survival in Dutch patients with locally advanced colorectal cancer

Background: The aim of this nationwide observational study was to evaluate factors associated with multivisceral resection (MVR), margin status and overall survival in locally advanced colorectal cancer (CRC). Material and methods: Patients with (y)pT4, cM0 CRC between 2006 and 2017 were selected from the Netherlands Cancer Registry. Cox-proportional hazards modelling was used for survival analysis, stratified for T4a and T4b. Annual hospital volume cut-off was 75 for colon and 40 for rectal resections. Results: A total of 11.930 patients were included and 2410 patients (20.2%) underwent MVR. Factors associated with MVR for colon and rectal cancer besides cT4 category were more recent diagnosis (OR 3.61, CI 95% 3.06–4.25 (colon) and OR 2.72, CI 95% 1.82–4.08 (rectum)) and high hospital volume (OR 1.20, CI 95% 1.05–1.38 (colon) and OR 2.17, CI 95% 1.55–3.04 (rectum)). Patients ≥70 year were less likely to undergo MVR for colon cancer (OR 0.80, 95% CI 0.70–0.90). Risk factors for incomplete resection were cT4 (OR 3.08, CI 95% 2.35–4.04 (colon) and OR 1.82, CI 95% 1.13–2.94 (rectum)) and poor/undifferentiated tumors (OR 1.41, CI 95% 1.14–1.72 (colon) and OR 1.69, CI 95% 1.05–2.74 (rectum)). More recent diagnosis was independently associated with less incomplete resections in colon cancer (OR 0.58, CI 95% 0.40–0.76). Independent predictors of survival were age, resection margin, nodal status and adjuvant chemotherapy, but not MVR. Conclusion: Treatment of locally advanced CRC with MVR at population level was influenced by year of diagnosis and hospital volume. Margin status in colon cancer improved substantially over time.</p

Youth’s Social Environments: Associations with Mental Problems and Achievement of Developmental Milestones in Times of Crises

So far, many studies indicated that youth experience mental problems during crises, such as the COVID-19 crisis, but little attention has been paid to the relation to age-adequate functioning and its association to layered social environments. This study addresses this gap by investigating the association between social environments (i.e., household, friends, and neighbourhood) during the COVID-19 crisis with youth’s mental problems and age-adequate functioning. In total, 673 youth (mean age = 19.87, 73.4% girls) were surveyed online during the COVID-19 outbreak. In line with predictions, worse contact with household members was associated with more internalizing symptoms. A lack of privacy was associated with more internalizing and externalizing symptoms and difficulties achieving personal and school and professional milestones. Living with a vulnerable other was associated with more internalizing symptoms and difficulties achieving school and professional milestones. Worse contact with friends was associated with difficulty achieving social milestones. Additionally, neighbourhood risk moderated the association between living with a vulnerable other and school and professional milestones. A lack of privacy stood out as the most important factor associated to youth’s mental problems and achievement of developmental milestones. Future research should indicate to what extent these findings are COVID-19 crisis-specific or can generalize to other crises

Predictors of undergoing multivisceral resection, margin status and survival in Dutch patients with locally advanced colorectal cancer

Background: The aim of this nationwide observational study was to evaluate factors associated with multivisceral resection (MVR), margin status and overall survival in locally advanced colorectal cancer (CRC). Material and methods: Patients with (y)pT4, cM0 CRC between 2006 and 2017 were selected from the Netherlands Cancer Registry. Cox-proportional hazards modelling was used for survival analysis, stratified for T4a and T4b. Annual hospital volume cut-off was 75 for colon and 40 for rectal resections. Results: A total of 11.930 patients were included and 2410 patients (20.2%) underwent MVR. Factors associated with MVR for colon and rectal cancer besides cT4 category were more recent diagnosis (OR 3.61, CI 95% 3.06–4.25 (colon) and OR 2.72, CI 95% 1.82–4.08 (rectum)) and high hospital volume (OR 1.20, CI 95% 1.05–1.38 (colon) and OR 2.17, CI 95% 1.55–3.04 (rectum)). Patients ≥70 year were less likely to undergo MVR for colon cancer (OR 0.80, 95% CI 0.70–0.90). Risk factors for incomplete resection were cT4 (OR 3.08, CI 95% 2.35–4.04 (colon) and OR 1.82, CI 95% 1.13–2.94 (rectum)) and poor/undifferentiated tumors (OR 1.41, CI 95% 1.14–1.72 (colon) and OR 1.69, CI 95% 1.05–2.74 (rectum)). More recent diagnosis was independently associated with less incomplete resections in colon cancer (OR 0.58, CI 95% 0.40–0.76). Independent predictors of survival were age, resection margin, nodal status and adjuvant chemotherapy, but not MVR. Conclusion: Treatment of locally advanced CRC with MVR at population level was influenced by year of diagnosis and hospital volume. Margin status in colon cancer improved substantially over time.</p

Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes

Introduction Although associations of total plasma N-glycome (TPNG) with type 2 diabetes have been reported, little is known on the role of TPNG in type 2 diabetes complications, a major cause of type 2 diabetes-related morbidity and mortality. Here, we assessed TPNG in relation to type 2 diabetes complications in subsamples of two Dutch cohorts using mass spectrometry (n=1815 in DiaGene and n=1518 in Hoorn Diabetes Care System).Research design and methods Blood plasma samples and technical replicates were pipetted into 96-well plates in a randomized manner. Peptide:N-glycosidase F (PNGase F) was used to release N-glycans, whereafter sialic acids were derivatized for stabilization and linkage differentiation. After total area normalization, 68 individual glycan compositions were quantified in total and were used to calculate 45 derived traits which reflect structural features of glycosylation. Associations of glycan features with prevalent and incident microvascular or macrovascular complications were tested in logistic and Cox regression in both independent cohorts and the results were meta-analyzed.Results Our results demonstrated similarities between incident and prevalent complications. The strongest association for prevalent cardiovascular disease was a high level of bisection on a group of diantennary glycans (A2FS0B; OR=1.38, p=1.34x10(-11)), while for prevalent nephropathy the increase in 2,6-sialylation on triantennary glycans was most pronounced (A3E; OR=1.28, p=9.70x10(-6)). Several other TPNG features, including fucosylation, galactosylation, and sialylation, firmly demonstrated associations with prevalent and incident complications of type 2 diabetes.Conclusions These findings may provide a glance on how TPNG patterns change before complications emerge, paving the way for future studies on prediction biomarkers and potentially disease mechanisms.Molecular Epidemiolog