De grenzen van het verschoningsrecht voor advocaten in het Nederlands strafprocesrecht getoetst aan artikel 8 EVRM:Een rechtswetenschappelijk onderzoek naar de grenzen van het verschoningsrecht voor advocaten in het Nederlands strafproces in het licht van artikel 8 EVRM

Wanneer het gaat om de bevoegdheid van verschoningsrecht voor advocaten, zoals bedoeld in artikel 218 Sv wordt hierbij geen onderscheid gemaakt tussen meer of minder vertrouwelijke gegevens. Ook wordt geen onderscheid gemaakt of deze vertrouwelijke communicatie geschiedt in het kader van advies of in het kader van een juridisch proces. Nederland geeft daarmee een ruime bescherming aan het verschoningsrecht van een advocaat wat in overeenstemming is met de benadering van het EHRM. Met betrekking tot de beperkingen zoals bedoeld in artikel 98 lid 5 Sv en in zeer uitzonderlijke omstandigheden, voldoen deze regelingen aan het beoordelingskader van artikel 8 lid 2 EVRM. Echter, het beoordelingskader tot doorbreking van verschoningsrecht (in zeer uitzonderlijke omstandigheden) lijkt in Nederland strenger dan het beoordelingskader tot doorbreking van verschoningsrecht (in bijzondere omstandigheden) voortvloeiende uit artikel 8 EVRM volgens het EHRM. In tegenstelling tot een redelijke grond dat de vertrouwensrelatie wordt misbruikt is in Nederland het enkele feit dat een advocaat wordt verdacht van een ernstig feit onvoldoende om het verschoningsrecht te doorbreken

T cell communication in kidney transplantation

The findings described in this thesis provide new perspectives in the mechanisms by which T follicular helper (Tfh) cells and tissue-resident memory T (TRM) cells modulate an alloimmune response after kidney transplantation. Both cell types have an effector memory phenotype and are able to mount an alloreactive response in which the function of IL-21 is involved. Moreover, these IL-21 driven T cells are active in the kidney allograft where they directly contribute to the process of rejection via the communication to CD8+ cytotoxic T cells and B cells. Furthermore, we found a broad effect of IL-21R blockade in our in vitro and in vivo transplant models all pointing to the same direction. Namely, blockade of IL-21R signaling has inhibiting effects on both the humoral and cellular arm of the alloimmune response. Overall, in this thesis we functionally characterized Tfh cells and TRM cells to gain knowledge about their role in alloreactivity after organ transplantation in patients. Our studies show that these T cell subsets communicate to other immune competent cells to enhance the alloimmune response via the formation of DSA, proinflammatory cytokines, and cytotoxins such as granzyme B and perforin. Modeling cell-to-cell communication networks of the T cells might help us to improve immunosuppressive treatment strategies, ultimately leading to enhanced kidney transplant outcomes

Surgery in the Elderly: Does age matter?

De demografische verschuiving in het aantal ouderen zorgt voor een oudere behandelgroep. De chirurgische behandeling van vasculaire en trauma gerelateerde aandoeningen in deze oudere populatie is niet eenvoudig. Zorgvuldige patiëntselectie zou wel eens de sleutel kunnen zijn tot betere behandelresultaten van vasculaire en trauma gerelateerde aandoeningen binnen deze oudere bevolkingsgroep. Het eerste deel van dit proefschrift bespreekt de uitkomst van verschillende vasculaire chirurgische interventies. Oudere dialysepatiënten zijn wellicht beter af zijn met een elleboogshunt gezien de betere patency, hoewel de kwaliteit van leven hierbij nog nader onderzocht dient te worden. Verder wordt aangetoond dat de mortaliteit van perifere bypass chirurgie bij met name 80-plussers erg hoog is met een postoperatieve sterfte van 22%. Met betrekking tot de behandeling van een abdominaal aneurysma is de mortaliteit na electieve endovasculaire behandeling van een abdominaal aneurysma bij patiënten ouder dan 80 jaar significant hoger in vergelijking met een jongere groep, echter als we de mortaliteit van deze behandeling vergelijken met de in de literatuur beschreven mortaliteit na open behandeling van een abdominaal aneurysma lijkt een endovasculaire behandeling in deze populatie gerechtvaardigd. In het tweede deel worden uitkomsten van verschillende trauma gerelateerde chirurgische behandelingen besproken. De vergrijzing zorgt voor een toename van het aantal ziekenhuisopnames ten gevolge van een bekkenfractuur, om gerelateerde kosten voor de gezondheidszorg in de toekomst te reduceren blijf

IL-21 receptor antagonist inhibits differentiation of B cells toward plasmablasts upon alloantigen stimulation

Interaction between T follicular helper (Tfh) cells and B cells is complex and involves various pathways, including the production of IL-21 by the Tfh cells. Secretion of IL-21 results in B cell differentiation toward immunoglobulin-producing plasmablasts. In patients after kidney transplantation, the formation of alloantibodies produced by donor antigen-activated B cells are a major cause of organ failure. In this allogeneic response, the role of IL-21-producing Tfh cells that regulate B cell differentiation is unknown. Here, we tested, in an alloantigen-driven setting, whether Tfh cell help signals control B cell differentiation with its dependency on IL-21. Pre-transplantation patient PBMCs were sorted into pure CD4posCXCR5pos Tfh cells and CD19posCD27pos memory B cells and stimulated with donor antigen in the presence or absence of an IL-21 receptor (IL-21R) antagonist (αIL-21R). Donor antigen stimulation initiated expression of the activation markers inducible co-stimulator (ICOS) and programmed death 1 (PD-1) on Tfh cells and a shift toward a mixed Tfh2 and Tfh17 phenotype. The memory B cells underwent class switch recombination and differentiated toward IgM- and IgG-producing plasmablasts. In the presence of αIL-21R, a dose-dependent inhibition of STAT3 phosphorylation was measured in both T and B cells. Blockade of the IL-21R did not have an effect on PD-1 and ICOS expression on Tfh cells but significantly inhibited B cell differentiation. The proportion of plasmablasts decreased by 78% in the presence of αIL-21R. Moreover, s

Denominator identities for finite-dimensional Lie superalgebras and Howe duality for compact dual pairs

We provide formulas for the denominator and superdenominator of a basic classical type Lie superalgebra for any set of positive roots. We establish a connection between certain sets of positive roots and the theory of reductive dual pairs of real Lie groups. As an application of our formulas, we recover the Theta correspondence for compact dual pairs. Along the way we give an explicit description of the real forms of basic classical type Lie superalgebras.Comment: Latex, 75 pages. Minor corrections. Final version, to appear in the Japanese Journal of Mathematic

Mortality after major amputation in elderly patients with critical limb ischemia

Background: Owing to the aging population, the number of elderly patients with critical limb ischemia (CLI) has increased. The consequence of amputation is immense. However, at the moment, information about the mortality after amputation in the elderly vascular patients is unknown. For this reason, this study evaluated mortality rates and patient-related factors associated with mortality after a major amputation in elderly patients with CLI. Methods: From 2006 to 2013, we included patients aged >70 years who were treated for chronic CLI by primary or secondary major amputation within or after 3 months of initial therapy (revascularization or conservative management). Outcome measurements were mortality after major amputation and factors associated with mortality (age, comorbidity and timing of amputation). Results: In total, 168/651 patients (178 legs; 26%) underwent a major amputation. Patients were stratified by age: 70–80 years (n=86) and > 80 years (n=82). Overall mortality after major amputation was 44%, 66% and 85% after 1, 3 and 5 years, respectively. The 6-month and 1-year mortality in patients aged 80 years or older was, respectively, 59% or 63% after a secondary amputation 3 months. Per year of age, the mortality rate increased by 4% (P=0.005). No significant difference in mortality after major amputation was found in the presence of comorbidity or according to Rutherford classification. Conclusion: Despite developments in the treatment of CLI by revascularization, amputation rates remain high and are associated with tremendous mortality rates. Secondary amputation after a failed attempt of revascularization causes a higher mortality. Further research concerning timing of amputation and patient-related outcome is needed to evaluate if selected patients might benefit from primary amputation

Multiple sums and integrals as neutral BKP tau functions

We consider multiple sums and multi-integrals as tau functions of the BKP hierarchy using neutral fermions as the simplest tool for deriving these. The sums are over projective Schur functions $Q_\alpha$ for strict partitions $\alpha$. We consider two types of such sums: weighted sums of $Q_\alpha$ over strict partitions $\alpha$ and sums over products $Q_\alpha Q_\gamma$. In this way we obtain discrete analogues of the beta-ensembles ($\beta=1,2,4$). Continuous versions are represented as multiple integrals. Such sums and integrals are of interest in a number of problems in mathematics and physics.Comment: 16 page

Discovering and Visualizing Disease-Specific Electrocardiogram Features Using Deep Learning: Proof-of-Concept in Phospholamban Gene Mutation Carriers

BACKGROUND: ECG interpretation requires expertise and is mostly based on physician recognition of specific patterns, which may be challenging in rare cardiac diseases. Deep neural networks (DNNs) can discover complex features in ECGs and may facilitate the detection of novel features which possibly play a pathophysiological role in relatively unknown diseases. Using a cohort of PLN (phospholamban) p.Arg14del mutation carriers, we aimed to investigate whether a novel DNN-based approach can identify established ECG features, but moreover, we aimed to expand our knowledge on novel ECG features in these patients. METHODS: A DNN was developed on 12-lead median beat ECGs of 69 patients and 1380 matched controls and independently evaluated on 17 patients and 340 controls. Differentiating features were visualized using Guided Gradient Class Activation Mapping++. Novel ECG features were tested for their diagnostic value by adding them to a logistic regression model including established ECG features. RESULTS: The DNN showed excellent discriminatory performance with a c-statistic of 0.95 (95% CI, 0.91-0.99) and sensitivity and specificity of 0.82 and 0.93, respectively. Visualizations revealed established ECG features (low QRS voltages and T-wave inversions), specified these features (eg, R- and T-wave attenuation in V2/V3) and identified novel PLN-specific ECG features (eg, increased PR-duration). The logistic regression baseline model improved significantly when augmented with the identified features (P<0.001). CONCLUSIONS: A DNN-based feature detection approach was able to discover and visualize disease-specific ECG features in PLN mutation carriers and revealed yet unidentified features. This novel approach may help advance diagnostic capabilities in daily practice