Graph clustering by flow simulation

Dit proefschrift heeft als onderwerp het clusteren van grafen door middel van simulatie van stroming, een probleem dat in zijn algemeenheid behoort tot het gebied der clusteranalyse. In deze tak van wetenschap ontwerpt en onderzoekt men methoden die gegeven bepaalde data een onderverdeling in groepen genereren, waarbij het oogmerk is een onderverdeling in groepen te vinden die natuurlijk is. Dat wil zeggen dat verschillende data-elementen in dezelfde groep idealiter veel op elkaar lijken, en dat data-elementen uit verschillende groepen idealiter veel van elkaar verschillen. Soms ontbreken zulke groepjes helemaal; dan is er weinig patroon te herkennen in de data. Het idee is dat de aanwezigheid van natuurlijke groepjes het mogelijk maakt de data te categoriseren. Een voorbeeld is het clusteren van gegevens (over symptomen of lichaamskarakteristieken) van patienten die aan dezelfde ziekte lijden. Als er duidelijke groepjes bestaan in die gegevens, kan dit tot extra inzicht leiden in de ziekte. Clusteranalyse kan aldus gebruikt worden voor exploratief onderzoek. Verdere voorbeelden komen uit de scheikunde, taxonomie, psychiatrie, archeologie, marktonderzoek en nog vele andere disicplines. Taxonomie, de studie van de classificatie van organismen, heeft een rijke geschiedenis beginnend bij Aristoteles en culminerend in de werken van Linnaeus. In feite kan de clusteranalyse gezien worden als het resultaat van een steeds meer systematische en abstracte studie van de diverse methoden ontworpen in verschillende toepassingsgebieden, waarbij methode zowel wordt gescheiden van data en toepassingsgebied als van berekeningswijze. In de cluster analyse kunnen grofweg twee richtingen onderscheiden worden, naar gelang het type data dat geclassificeerd moet worden. De data-elementen in het voorbeeld hierboven worden beschreven door vectoren (lijstjes van scores of metingen), en het verschil tussen twee elementen wordt bepaald door het verschil van de vectoren. Deze dissertatie betreft cluster analyse toegepast op data van het type `graaf'. Voorbeelden komen uit de patroonherkenning, het computer ondersteund ontwerpen, databases voorzien van hyperlinks en het World Wide Web. In al deze gevallen is er sprake van `punten' die verbonden zijn of niet. Een stelsel van punten samen met hun verbindingen heet een graaf. Een goede clustering van een graaf deelt de punten op in groepjes zodanig dat er weinig verbindingen lopen tussen (punten uit) verschillende groepjes en er veel verbindingen zijn in elk groepje afzonderlijk

Operational sex ratio, sexual conflict and the intensity of sexual selection.

Modern sexual selection theory indicates that reproductive costs rather than the operational sex ratio predict the intensity of sexual selection. We investigated sexual selection in the polygynandrous common lizard Lacerta vivipara. This species shows male aggression, causing high mating costs for females when adult sex ratios (ASR) are male-biased. We manipulated ASR in 12 experimental populations and quantified the intensity of sexual selection based on the relationship between reproductive success and body size. In sharp contrast to classical sexual selection theory predictions, positive directional sexual selection on male size was stronger and positive directional selection on female size weaker in female-biased populations than in male-biased populations. Thus, consistent with modern theory, directional sexual selection on male size was weaker in populations with higher female mating costs. This suggests that the costs of breeding, but not the operational sex ratio, correctly predicted the strength of sexual selection

Umbilical cord procalcitonin to detect early-onset sepsis in newborns: a promising biomarker

Background: Up to 7% of neonates born in high-income countries receive antibiotics for suspected early-onset sepsis (EOS). Culture-proven neonatal sepsis has a prevalence of 0.2%, suggesting considerable overtreatment. We studied the diagnostic accuracy of umbilical cord blood and infant blood procalcitonin (PCT) in diagnosing EOS to improve antibiotic stewardship.Methods: Umbilical cord blood PCT was tested in newborns >= 32 weeks of gestation. Groups were defined as following: A) culture-proven or probable EOS (n = 25); B) Possible EOS, based on risk factors for which antibiotics were administered for = 32 weeks with a proven or probable EOS and low in newborns with risk factors for infection, but PCT seems not a reliable marker after maternal antibiotic treatment. PCT could be useful to distinguish infected from healthy newborns with or without EOS risk factors.Afdeling Klinische Chemie en Laboratoriumgeneeskunde (AKCL

Feasibility Study of Vascular Access and REBOA Placement in Quick Response Team Firefighters.

Early hemorrhage control using resuscitative endovascular balloon occlusion of the aorta (REBOA) can save lives. This study was designed to evaluate the ability to train Quick Response Team Fire Fighters (QRT-FF) to gain percutaneous femoral artery access and place a REBOA catheter in a model, using a comprehensive theoretical and practical training program.Six QRT-FF participated in the training. SOF medics from a previous training served as the control group. A formalized training curriculum included basic anatomy and endovascular materials for percutaneous access and REBOA placement. Key skills included (1) preparation of an endovascular toolkit, (2) achieving vascular access in the model, and (3) placement and positioning of REBOA.QRT-FF had significantly better scores compared with medics using endovascular materials (P = .003) and performing the procedure without unnecessary attempts (P = .032). Basic surgical anatomy scores for QRT-FF were significantly better than SOF medics (P = .048). QRT-FF subjects demonstrated a significantly higher overall technical skills point score than medics (P = .030). QRT-FF had a median total time from start of the procedure to REBOA inflation of 3:23 minutes, and medics, 5:05 minutes. All six QRT-FF subjects improved their procedure times-as did four of the five medics.Our training program using a task training model can be utilized for percutaneous femoral access and REBOA placement training of QRT-FF without prior ultrasound or endovascular experience. Training the use of advanced bleeding control options such as REBOA, as a secondary occupational task, has the potential to improve outcomes for severely bleeding casualties in the field

'We are planning to leave, all of us'-a realist study of mechanisms explaining healthcare employee turnover in rural Ethiopia

Background: We study healthcare employees' turnover intentions in the Afar National Regional State of Ethiopia. This rural region is experiencing the globally felt crisis in human resources, which is inhibiting its ability to meet health-related sustainable development goals. Methods: Realist case study which combines literature study and qualitative analysis of interview and focus group discussion data, following a realist case study protocol. Results: A large majority of employees has turnover intentions. Building on Herzberg's two-factor theory, person-environment fit theory, as well as recent sub-Saharan evidence, analysis of the collected data yields four turnover mechanisms: (1) lack of social and personal opportunities in the region, (2) dissonance between management logic and professional logic, (3) standards of service operations are hard to accept, and (4) lack of financial improvement opportunities. Conclusions: While the first and fourth mechanisms may be out of reach for local (human resource) management interventions, the second and third mechanisms proposed to explain health workforce turnover appear to be amenable to local (human resource) management interventions to strengthen healthcare. These mechanisms are likely to play a role in other remote sub-Saharan regions as well

Reduction of routine use of radiography in patients with ankle fractures leads to lower costs and has no impact on clinical outcome: an economic evaluation

Background: To evaluate the cost-effectiveness of a reduction in the number of routine radiographs in the follow-up of patients with ankle fractures.Methods: We performed an economic evaluation alongside the multicentre, randomised WARRIOR trial. Participants were randomised to a reduced imaging follow-up protocol (i.e. radiographs at week 6 and 12 follow-up obtained on clinical indication) or usual care (i.e. routine radiography at weeks 6 and 12). The Olerud & Molander Ankle Score (OMAS) was used to assess ankle function and the EQ-5D-3L was used to estimate Quality-Adjusted Life Years (QALYs). Costs and resource use were assessed using self-reported questionnaires and medical records, and analysed from a societal perspective. Multiple imputation was used for missing data, and data were analysed using seemingly unrelated regression analysis and bootstrapping.Results: In total, 246 patients had data available for analysis (reduced imaging = 118; usual care = 128). Fewer radiographs were obtained in the reduced imaging group (median = 4) compared with the usual-care group (median = 5). Functional outcome was comparable in both groups. The difference in QALYs was - 0.008 (95% CI:-0.06 to 0.04) and the difference in OMAS was 0.73 (95% CI:-5.29 to 6.76). Imaging costs were lower in the reduced imaging group (-(sic)48; 95% CI:- (sic)72 to -(sic)25). All other cost categories did not statistically differ between the groups. The probability of the reduced imaging protocol being cost-effectiveness was 0.45 at a wiliness-to-pay of (sic)20,000 per QALY.Conclusions: Reducing the number of routine follow-up radiographs has a low probability of being cost-effective compared with usual care. Functional outcome, health-related quality of life and societal costs were comparable in both groups, whereas imaging costs were marginally lower in the reduced imaging group. Given this, adherence to a reduced imaging follow-up protocol for those with routine ankle fractures can be followed without sacrificing quality of care, and may result in reduced costs.Trauma Surger

Controlling bias and inflation in epigenome- and transcriptome-wide association studies using the empirical null distribution

We show that epigenome- and transcriptome-wide association studies (EWAS and TWAS) are prone to significant inflation and bias of test statistics, an unrecognized phenomenon introducing spurious findings if left unaddressed. Neither GWAS-based methodology nor state-of-the-art confounder adjustment methods completely remove bias and inflation. We propose a Bayesian method to control bias and inflation in EWAS and TWAS based on estimation of the empirical null distribution. Using simulations and real data, we demonstrate that our method maximizes power while properly controlling the false positive rate. We illustrate the utility of our method in large-scale EWAS and TWAS meta-analyses of age and smoking

An interlaboratory study of TEX86 and BIT analysis of sediments, extracts and standard mixtures.

Two commonly used proxies based on the distribution of glycerol dialkyl glycerol tetraethers (GDGTs) are the TEX86 (TetraEther indeX of 86 carbon atoms) paleothermometer for sea surface temperature reconstructions and the BIT (Branched Isoprenoid Tetraether) index for reconstructing soil organic matter input to the ocean. An initial round-robin study of two sediment extracts, in which 15 laboratories participated, showed relatively consistent TEX86 values (reproducibility ±3-4°C when translated to temperature) but a large spread in BIT measurements (reproducibility ±0.41 on a scale of 0-1). Here we report results of a second round-robin study with 35 laboratories in which three sediments, one sediment extract, and two mixtures of pure, isolated GDGTs were analyzed. The results for TEX86 and BIT index showed improvement compared to the previous round-robin study. The reproducibility, indicating interlaboratory variation, of TEX86 values ranged from 1.3 to 3.0°C when translated to temperature. These results are similar to those of other temperature proxies used in paleoceanography. Comparison of the results obtained from one of the three sediments showed that TEX86 and BIT indices are not significantly affected by interlaboratory differences in sediment extraction techniques. BIT values of the sediments and extracts were at the extremes of the index with values close to 0 or 1, and showed good reproducibility (ranging from 0.013 to 0.042). However, the measured BIT values for the two GDGT mixtures, with known molar ratios of crenarchaeol and branched GDGTs, had intermediate BIT values and showed poor reproducibility and a large overestimation of the "true" (i.e., molar-based) BIT index. The latter is likely due to, among other factors, the higher mass spectrometric response of branched GDGTs compared to crenarchaeol, which also varies among mass spectrometers. Correction for this different mass spectrometric response showed a considerable improvement in the reproducibility of BIT index measurements among laboratories, as well as a substantially improved estimation of molar-based BIT values. This suggests that standard mixtures should be used in order to obtain consistent, and molar-based, BIT values

Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2-specific CD8(+) T cell responses following COVID-19

Systemic immune cell dynamics during coronavirus disease 2019 (COVID-19) are extensively documented, but these are less well studied in the (upper) respiratory tract, where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates(1-6). Here, we characterized nasal and systemic immune cells in individuals with COVID-19 who were hospitalized or convalescent and compared the immune cells to those seen in healthy donors. We observed increased nasal granulocytes, monocytes, CD11c(+) natural killer (NK) cells and CD4(+) T effector cells during acute COVID-19. The mucosal proinflammatory populations positively associated with peripheral blood human leukocyte antigen (HLA)-DRlow monocytes, CD38(+)PD1(+)CD4(+) T effector (T-eff) cells and plasmablasts. However, there was no general lymphopenia in nasal mucosa, unlike in peripheral blood. Moreover, nasal neutrophils negatively associated with oxygen saturation levels in blood. Following convalescence, nasal immune cells mostly normalized, except for CD127(+) granulocytes and CD38(+)CD8(+) tissue-resident memory T cells (T-RM). SARS-CoV-2-specific CD8(+) T cells persisted at least 2 months after viral clearance in the nasal mucosa, indicating that COVID-19 has both transient and long-term effects on upper respiratory tract immune responses.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care