Personalized immunosuppression in elderly renal transplant recipients

The number of elderly people has increased considerably over the last decades, due to a rising life expectancy and ageing populations. As a result, an increased number of elderly with end-stage-renal-disease are diagnosed, for which the preferred treatment is renal transplantation. Over the past years the awareness of the elderly as a specific patient population has grown, which increases the importance of research in this group.Elderly patients often receive kidneys from elderly donors while younger donor kidneys are preferentially reserved for younger recipients. Although the rate of acute rejection after transplantation is lower in the elderly, these rejections may lead to graft loss more frequently, as kidneys from elderly donors have marginal reserve capacity. To prevent acute rejection, immunosuppressive therapy is needed. On the other hand, elderly patients have a higher risk to die from infectious complications, and thus less immunosuppression would be preferable.Immunosuppressive treatm

Clinical Validation of a Dried Blood Spot Assay for 8 Antihypertensive Drugs and 4 Active Metabolites

BACKGROUND: Drug nonadherence is one of the major challenges faced by resistant hypertension patients, and identification of this problem is needed for optimizing pharmacotherapy. Dried blood spot (DBS) sampling is a minimally invasive method designed to detect and determine the degree of nonadherence. In this study, a DBS method for qualifying 8 antihypertensive drugs (AHDs) and 4 active metabolites was developed and validated using ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). METHOD: The DBS assay was validated analytically and clinically, in accordance with FDA requirements. Analytical validation was accomplished using UHPLC-MS/MS. For clinical validation, paired peak and trough levels of DBS and plasma samples were simultaneously collected and comparatively analyzed using Deming regression and Bland-Altman analyses. All concentrations below the set lower limit were excluded. Deming regression analysis was used to predict comparison bias between the collected plasma and DBS samples, with DBS concentrations corrected accordingly. RESULTS: The UHPLC-MS/MS method for simultaneously measuring 8 AHDs and their metabolites in DBS, was successfully validated. With Deming regression no bias was observed in N = 1; constant bias was seen in N = 6 and proportional bias in N = 11 of the AHDs and metabolites. After correction for bias, only one metabolite (canrenone) met the 20% acceptance limit for quantification, after Bland-Altman analyses. In addition, amlodipine, valsartan, and [enalaprilate] met the 25% acceptance limit. CONCLUSIONS: A novel DBS assay for simultaneously qualifying and quantifying 8 AHDs and their metabolites, has been successfully developed and validated. The DBS assay is therefore a suitable method to detect drug nonadherence. However, with the exception of canrenone, the interchangeable use of plasma and DBS sa

Uniqueness of roots up to conjugacy for some affine and finite type Artin groups

Let $G$ be one of the Artin groups of finite type ${\mathbf B}_n={\mathbf C}_n$, and affine type $\tilde{\mathbf A}_{n-1}$ and $\tilde{\mathbf C}_{n-1}$. In this paper, we show that if $\alpha$ and $\beta$ are elements of $G$ such that $\alpha^k=\beta^k$ for some nonzero integer $k$, then $\alpha$ and $\beta$ are conjugate in $G$. For the Artin group of type $\mathbf A_n$, this was recently proved by J. Gonz\'alez-Meneses. In fact, we prove a stronger theorem, from which the above result follows easily by using descriptions of those Artin groups as subgroups of the braid group on $n+1$ strands. Let $P$ be a subset of $\{1,...,n\}$. An $n$-braid is said to be \emph{$P$-pure} if its induced permutation fixes each $i\in P$, and \emph{$P$-straight} if it is $P$-pure and it becomes trivial when we delete all the $i$-th strands for $i\not\in P$. Exploiting the Nielsen-Thurston classification of braids, we show that if $\alpha$ and $\beta$ are $P$-pure $n$-braids such that $\alpha^k=\beta^k$ for some nonzero integer $k$, then there exists a $P$-straight $n$-braid $\gamma$ with $\beta=\gamma\alpha\gamma^{-1}$. Moreover, if $1\in P$, the conjugating element $\gamma$ can be chosen to have the first strand algebraically unlinked with the other strands. Especially in case of $P=\{1,...,n\}$, our result implies the uniqueness of root of pure braids, which was known by V. G. Bardakov and by D. Kim and D. Rolfsen.Comment: 15 pages, 8 figures; version published by Math.

Abstract Datatypes for Real Numbers in Type Theory

Abstract. We propose an abstract datatype for a closed interval of real numbers to type theory, providing a representation-independent approach to programming with real numbers. The abstract datatype requires only function types and a natural numbers type for its formulation, and so can be added to any type theory that extends Gödel’s System datatype is equivalent in power to programming intensionally with representations of real numbers. We also consider representing arbitrary real numbers using a mantissa-exponent representation in which the mantissa is taken from the abstract interval.