Individualized immunosuppression in transplant patients: potential role of pharmacogenetics.

The immunosuppressive drugs used to prevent the rejection of transplanted organs have a narrow therapeutic index. Under treatment results in episodes of rejection leading to either damage or loss of the organ. Over immunosuppression increases the risk of infection and malignancy as well as drug specific complications including diabetes mellitus and nephrotoxicity. There is wide variation in the drug dose required to achieve target blood concentrations and there is often dissociation between pharmacokinetics and pharmacodynamics. Currently, immunosuppressive drug treatment is individualized based on a clinical assessment of the risk of rejection or toxicity. Therapeutic drug monitoring is routinely employed for several immunosuppressive drugs. Pharmacogenetics has the potential to complement therapeutic drug monitoring but clinical benefit has yet to be demonstrated. Novel biomarker-based approaches to risk stratification and pharmacodynamic monitoring are under development and are ready for clinical trials

Patient involvement in selection of immunosuppressive regimen following transplantation.

Transplantation has made a considerable difference to the lives of many patients. However, feedback from patients indicates that although having a transplant is a hugely positive experience, having to take medications indefinitely is one of the biggest challenges. An ideal scenario would be no medications following a transplant. A compromise would be a minimal number of medications, with minimal restrictions and as simple a regimen as possible. Although there is considerable research going into fine-tuning the management of the immune response to a transplant, to date there is no universal regimen that enables patients to remain free of immunosuppressant medications, making adherence paramount to maintain long-term allograft survival. This paper reviews the available immunosuppressant regimens and factors influencing choice from both the clinician's and the patient's perspective. Factors influencing the decision-making process, such as quality of life for patients, their satisfaction, acceptability, and adherence uptake are reviewed. We conclude with a further assessment of patient choice as a factor in regimen selection, its impact on adherence, and its implications

Action for the eleven dimensional multiple M-wave system

We present the covariant supersymmetric and kappa-symmetric action for a system of N nearly coincident M-waves (multiple M0-brane system) in flat eleven dimensional superspace.Comment: 4+ pages, RevTeX4, no figures. V2: misprints corrected, discussion extended, references added, LaTeX, 10 pages. V3: misprints corrected. V4, extended version, 1+13 pages, to appear in JHE

Nutritional Status of School Age Children (5-14 years) in a Rural Health Block of North India (Kashmir) Using WHO Z-Score System

Objective: To assess the nutritional status of school going children in Rural Block Hajin. Methods: School children from various primary and middle level educational facilities from a rural health block were surveyed during the School Health Program. Height and weight was measured following standard procedures. MS Excel and Interactive statistics page were used for analysis of data. Results: Both mean weight and height were higher in females than males. The overall prevalence of under nutrition was 19.2%. The prevalence of underweight was lowest in 5 year female (0.0%) and highest in 6 year male (21.5%). For Stunting 7 year males recorded the lowest (0.0%) and 12 year males the highest (28.5%) prevalence. The highest and lowest prevalence of wasting was recorded in 6 year old females (2.56%) and 9 year old males (24.6%) respectively. Prevalence of thinness was lowest in 13 year old females (14.2%) and highest in 13 year old males (47.1%).Conclusion: The nutritional status of school age children in this health block are comparatively better even though a large number of children still fall below the cutoff for various nutritional indicators

Direct evidence for charge stripes in a layered cobalt oxide

Recent experiments indicate that static stripe-like charge order is generic to the hole-doped copper oxide superconductors and competes with superconductivity. Here we show that a similar type of charge order is present in La5/3 Sr1/3 CoO4 , an insulating analogue of the copper oxide superconductors containing cobalt in place of copper. The stripe phase we have detected is accompanied by short-range, quasi-one-dimensional, antiferromagnetic order, and provides a natural explanation for the distinctive hour- glass shape of the magnetic spectrum previously observed in neutron scattering mea- surements of La2−xSrx CoO4 and many hole-doped copper oxide superconductors. The results establish a solid empirical basis for theories of the hourglass spectrum built on short-range, quasi-static, stripe correlations

Preon Prophecies by the Standard Model

The Standard Model of quarks and leptons is, at first sight, nothing but a set of {\it ad hoc} rules, with no connections, and no clues to their true background. At a closer look, however, there are many inherent prophecies that point in the same direction: {\it Compositeness} in terms of three stable preons.Comment: 13 pages, 8 eps-figures, invited talk at Beyond the Desert '03, Schloss Ringberg, Bavaria, June 2003; to be published in the Proceeding

Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions

Ergodicity properties of pp -adic (2,1)(2,1)-rational dynamical systems with unique fixed point

We consider a family of $(2,1)$-rational functions given on the set of $p$-adic field $Q_p$. Each such function has a unique fixed point. We study ergodicity properties of the dynamical systems generated by $(2,1)$-rational functions. For each such function we describe all possible invariant spheres. We characterize ergodicity of each $p$-adic dynamical system with respect to Haar measure reduced on each invariant sphere. In particular, we found an invariant spheres on which the dynamical system is ergodic and on all other invariant spheres the dynamical systems are not ergodic

(2,0) theory on circle fibrations

We consider (2,0) theory on a manifold M_6 that is a fibration of a spatial S^1 over some five-dimensional base manifold M_5. Initially, we study the free (2,0) tensor multiplet which can be described in terms of classical equations of motion in six dimensions. Given a metric on M_6 the low energy effective theory obtained through dimensional reduction on the circle is a Maxwell theory on M_5. The parameters describing the local geometry of the fibration are interpreted respectively as the metric on M_5, a non-dynamical U(1) gauge field and the coupling strength of the resulting low energy Maxwell theory. We derive the general form of the action of the Maxwell theory by integrating the reduced equations of motion, and consider the symmetries of this theory originating from the superconformal symmetry in six dimensions. Subsequently, we consider a non-abelian generalization of the Maxwell theory on M_5. Completing the theory with Yukawa and phi^4 terms, and suitably modifying the supersymmetry transformations, we obtain a supersymmetric Yang-Mills theory which includes terms related to the geometry of the fibration.Comment: 24 pages, v2 References added, typos correcte

Potentials in vegetable oils and various nutrients of eighteen varieties of Niger Cucurbitaceae

Citrullus Colocynthis and Lagenaria siceraria are two species of Cucurbitaceae whose seeds are used for the production of dough, cakes and edible oils in Niger. Yield in seeds of 18 varieties belonging to these two species were assessed on the Faculty experimental field. The average berries production was 17 berries per plant the first year in contrast 6 the second year. The best productivity was achieved with Citrullus colocynthis which gave 82 berries per plant the 1st year. The average yield in seeds was 180.15 kg/ha the first year and 704.30 kg/ha the second year. The determination of the physicochemical characteristics showed water, ashes, fat, and protein contents which vary respectively from 7 to 9.50%, 4.13 to 4.84%, 18 to 47% and 11 to 35%. The yield in seeds oil varied from 13.7 to 134 L per ha in the first year and 0.26 liters to 800 L per ha the 2nd year. These are the first studies on Cucurbitaceae which link agronomic and physicochemical characteristics of seeds. They showed very important nutrient contents and oil yield, and even higher than some conventionaloilseeds. Extraction of oils from these seeds could meet the need of the populations.Keywords: Cucurbitaceae, Niger, yield, seeds, oils, food security