Mires in the Maluti Mountains of Lesotho.

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Assessment of carnitine excretion and its ratio to plasma free carnitine as a biomarker for primary carnitine deficiency in newborns

In the Netherlands, newborns are referred by the newborn screening (NBS) Program when a low free carnitine (C0) concentration (&lt;5 μmol/l) is detected in their NBS dried blood spot. This leads to ~85% false positive referrals who all need an invasive, expensive and lengthy evaluation. We investigated whether a ratio of urine C0 / plasma C0 (RatioU:P) can improve the follow-up protocol for primary carnitine deficiency (PCD). A retrospective study was performed in all Dutch metabolic centres, using samples from newborns and mothers referred by NBS due to low C0 concentration. Samples were included when C0 excretion and plasma C0 concentration were sampled on the same day. RatioU:P was calculated as (urine C0 [μmol/mmol creatinine])/(plasma C0 [μmol/l]). Data were available for 59 patients with genetically confirmed PCD and 68 individuals without PCD. The RatioU:P in PCD patients was significantly higher (p value &lt; 0.001) than in those without PCD, median [IQR], respectively: 3.4 [1.2–9.5], 0.4 [0.3–0.8], area under the curve (AUC) 0.837. Classified for age (up to 1 month) and without carnitine suppletion (PCD; N = 12, Non-PCD; N = 40), medians were 6.20 [4.4–8.8] and 0.37 [0.24–0.56], respectively. The AUC for RatioU:P was 0.996 with a cut-off required for 100% sensitivity at 1.7 (yielding one false positive case). RatioU:P accurately discriminates between positive and false positive newborn referrals for PCD by NBS. RatioU:P is less effective as a discriminative tool for PCD in adults and for individuals that receive carnitine suppletion.</p

In-hospital versus postdischarge adverse events following carotid endarterectomy

ObjectiveMost studies based on state and nationwide registries evaluating perioperative outcome after carotid endarterectomy (CEA) rely on hospital discharge data only. Therefore, the true 30-day complication risk after carotid revascularization may be underestimated.MethodsWe used the National Surgical Quality Improvement Program database 2005-2010 to assess the in-hospital and postdischarge rate of any stroke, death, cardiac event (new Q-wave myocardial infarction or cardiac arrest), and combined stroke/death and combined adverse outcome (S/D/CE) at 30 days following CEA. Multivariable analyses were used to identify predictors for in-hospital and postdischarge events separately, and in particular, those that predict postdischarge events distinctly.ResultsA total of 35,916 patients who underwent CEA during 2005-2010 were identified in the National Surgical Quality Improvement Program database; 59% were male, median age was 72 years, and 44% had a previous neurologic event. Thirty-day stroke rate was 1.6% (n = 591), death rate was 0.8% (n = 272), cardiac event rate was 1.0% (n = 350), stroke or death rate was 2.2% (n = 794), and combined S/D/CE rate was 2.9% (n = 1043); 33% of strokes, 53% of deaths, 32% of cardiac events, 40% of combined stroke/death, and 38% of combined S/D/CE took place after hospital discharge. Patients with a prior stroke or transient ischemic attack had similar proportions of postdischarge events compared with patients without prior symptoms. Independent predictors for postdischarge events, but not for in-hospital events were female sex (stroke [odds ratio (OR), 1.6; 95% confidence interval (CI), 1.2-2.1] and stroke/death [OR, 1.4; 95% CI, 1.1-1.7]), renal failure (stroke [OR, 3.0; 95% CI, 1.4-6.2]) and chronic obstructive pulmonary disease (death [OR, 2.5; 95% CI, 1.6-3.7], stroke/death [OR, 1.8; 95% CI, 1.4-2.4], and S/D/CE [OR 1.8, 95% CI 1.4-2.3]).ConclusionsWith 38% of perioperative adverse events after CEA happening posthospitalization, regardless of symptoms status, we need to be alert to the ongoing risks after discharge particularly in women, patients with renal failure, or chronic obstructive pulmonary disease. This emphasizes the need for reporting and comparing 30-day adverse event rates when evaluating outcomes for CEA, or comparing carotid stenting to CEA

Long-Term Outcomes and Practical Considerations in the Pharmacological Management of Tyrosinemia Type 1

Tyrosinemia type 1 (TT1) is a rare metabolic disease caused by a defect in tyrosine catabolism. TT1 is clinically characterized by acute liver failure, development of hepatocellular carcinoma, renal and neurological problems, and consequently an extremely poor outcome. This review showed that the introduction of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) in 1992 has revolutionized the outcome of TT1 patients, especially when started pre-clinically. If started early, NTBC can prevent liver failure, renal problems, and neurological attacks and decrease the risk for hepatocellular carcinoma. NTBC has been shown to be safe and well tolerated, although the long-term effectiveness of treatment with NTBC needs to be awaited. The high tyrosine concentrations caused by treatment with NTBC could result in ophthalmological and skin problems and requires life-long dietary restriction of tyrosine and its precursor phenylalanine, which could be strenuous to adhere to. In addition, neurocognitive problems have been reported since the introduction of NTBC, with hypothesized but as yet unproven pathophysiological mechanisms. Further research should be done to investigate the possible relationship between important clinical outcomes and blood concentrations of biochemical parameters such as phenylalanine, tyrosine, succinylacetone, and NTBC, and to develop clear guidelines for treatment and follow-up with reliable measurements. This all in order to ultimately improve the combined NTBC and dietary treatment and limit possible complications such as hepatocellular carcinoma development, neurocognitive problems, and impaired quality of life

Sea buckthorn berries <i>Hippophae rhamnoides</i> L. predict size and composition of a great tit population <i>Parus major</i> L.

In seasonal environments variation in food abundance in the non-breeding season is thought to affect songbird population dynamics. In a unique tit-sea buckthorn berry system we can estimate the berry abundance and both the tit consumption and population dynamics. Six hundred nest boxes were available to great and blue tits Cyanistes caeruleus for breeding in spring and roosting in winter. We followed the dynamics including the recapture histories of individually marked great tits from 2008 to 2014. In each year we estimated 1) the winter sea buckthorn berry availability, 2) an index of berry consumption in December based on the colour of the faeces of roosting birds, 3) the number of breeding great and blue tits, 4) both recapture probability and the return rate of the great tits and 5) immigration rates. December berry abundance positively predicted the number of breeding pairs of both species in the subsequent season and great tit return rates in the second half of the winter. There was support for a sex specific berry effect on the adult return rate in the great tit: female return rate was associated less strongly to berry abundance than male return rate. This skewed the sex ratio of the local breeders in the following breeding season. Intriguingly, annual berry consumption in December was not related to berry abundance, and individuals consuming more berries tended to have slightly lower return rates. Reproductive rate was not related to berry abundance. There was hardly support for a relation between immigration rates of first year breeders and berry abundance. Taken together these results imply that berry stock not only affected population size but also the population composition through sex specific exchange with the surroundings. Since population density covaried with berry abundance, density dependent effects provide an alternative explanation for the patterns observed

Application of the Jacobi Davidson method for spectral low-rank preconditioning in computational electromagnetics problems

[EN] We consider the numerical solution of linear systems arising from computational electromagnetics applications. For large scale problems the solution is usually obtained iteratively with a Krylov subspace method. It is well known that for ill conditioned problems the convergence of these methods can be very slow or even it may be impossible to obtain a satisfactory solution. To improve the convergence a preconditioner can be used, but in some cases additional strategies are needed. In this work we study the application of spectral lowrank updates (SLRU) to a previously computed sparse approximate inverse preconditioner.The updates are based on the computation of a small subset of the eigenpairs closest to the origin. Thus, the performance of the SLRU technique depends on the method available to compute the eigenpairs of interest. The SLRU method was first used using the IRA s method implemented in ARPACK. In this work we investigate the use of a Jacobi Davidson method, in particular its JDQR variant. The results of the numerical experiments show that the application of the JDQR method to obtain the spectral low-rank updates can be quite competitive compared with the IRA s method.Mas Marí, J.; Cerdán Soriano, JM.; Malla Martínez, N.; Marín Mateos-Aparicio, J. (2015). Application of the Jacobi Davidson method for spectral low-rank preconditioning in computational electromagnetics problems. Journal of the Spanish Society of Applied Mathematics. 67:39-50. doi:10.1007/s40324-014-0025-6S395067Bergamaschi, L., Pini, G., Sartoretto, F.: Computational experience with sequential, and parallel, preconditioned Jacobi–Davidson for large sparse symmetric matrices. J. Comput. Phys. 188(1), 318–331 (2003)Carpentieri, B.: Sparse preconditioners for dense linear systems from electromagnetics applications. PhD thesis, Institut National Polytechnique de Toulouse, CERFACS (2002)Carpentieri, B., Duff, I.S., Giraud, L.: Sparse pattern selection strategies for robust Frobenius-norm minimization preconditioners in electromagnetism. Numer. Linear Algebr. Appl. 7(7–8), 667–685 (2000)Carpentieri, B., Duff, I.S., Giraud, L.: A class of spectral two-level preconditioners. SIAM J. Sci. Comput. 25(2), 749–765 (2003)Carpentieri, B., Duff, I.S., Giraud, L., Magolu monga Made, M.: Sparse symmetric preconditioners for dense linear systems in electromagnetism. Numer. Linear Algebr. Appl. 11(8–9), 753–771 (2004)Carpentieri, B., Duff, I.S., Giraud, L., Sylvand, G.: Combining fast multipole techniques and an approximate inverse preconditioner for large electromagnetism calculations. SIAM J. Sci. Comput. 27(3), 774–792 (2005)Darve, E.: The fast multipole method I: error analysis and asymptotic complexity. SIAM J. Numer. Anal. 38(1), 98–128 (2000)Fokkema, D.R., Sleijpen, G.L., Van der Vorst, H.A.: Jacobi–Davidson style QR and QZ algorithms for the reduction of matrix pencils. SIAM J. Sci. Comput. 20(1), 94–125 (1998)Greengard, L., Rokhlin, V.: A fast algorithm for particle simulations. J. Comput. Phys. 73(3), 325–348 (1987)Grote, M., Huckle, T.: Parallel preconditioning with sparse approximate inverses. SIAM J. Sci. Comput. 18(3), 838–853 (1997)Harrington, R.: Origin and development of the method of moments for field computation. IEEE Antenna Propag. Mag. (1990)Kunz, K.S., Luebbers, R.J.: The finite difference time domain method for electromagnetics. SIAM J. Sci. Comput. 18(3), 838–853 (1997)Maxwell, J.C.: A dynamical theory of the electromagnetic field. Roy. S. Trans. CLV, (1864). Reprinted in Tricker, R. A. R. The Contributions of Faraday and Maxwell to Electrial Science, Pergamon Press (1966)Marín, J., Malla M.: Some experiments preconditioning via spectral low rank updates for electromagnetism applications. In: Proceedings of the international conference on preconditioning techniques for large sparse matrix problems in scientific and industrial applications (Preconditioning 2007), Toulouse (2007)Meijerink, J.A., van der Vorst, H.A.: An iterative solution method for linear systems of which the coefficient matrix is a symmetric M-matrix. Math. Comput. 31, 148–162 (1977)Sorensen, D.C., Lehoucq, R.B., Yang, C.: ARPACK users’ guide: solution of large-scale eigenvalue problems with implicitly restarted Arnoldi methods. SIAM, Philadelphia (1998)Rao, S.M., Wilton, D.R., Glisson, A.W.: Electromagnetic scattering by surfaces of arbitrary shape. IEEE Trans. Antenna Propag. 30, 409–418 (1982)Saad, Y.: Iterative methods for sparse linear systems. PWS Publishing Company, Boston (1996)Silvester, P.P., Ferrari, R.L.: Finite elements for electrical engineers. Cambridge University Press, Cambridge (1990)Sleijpen, S.L., van der Vorst, H.A.: A Jacobi–Davidson iteration method for linear eigenvalue problems. SIAM J. Matrix Anal. Appl. 17, 401–425 (1996)van der Vorst, H.A.: Bi-CGSTAB: a fast and smoothly converging variant of Bi-CG for the solution of non-symmetric linear systems. SIAM J. Sci. Stat. Comput. 12(6), 631–644 (1992

Translation, cultural adaptation and validity assessment of the Dutch version of the eHealth Literacy Questionnaire: a mixed-method approach

Background: The digitalization of healthcare requires users to have sufficient competence in using digital health technologies. In the Netherlands, as well as in other countries, there is a need for a comprehensive, person-centered assessment of eHealth literacy to understand and address eHealth literacy related needs, to improve equitable uptake and use of digital health technologies. Objective: We aimed to translate and culturally adapt the original eHealth Literacy Questionnaire (eHLQ) to Dutch and to collect initial validity evidence. Methods: The eHLQ was translated using a systematic approach with forward translation, an item intent matrix, back translation, and consensus meetings with the developer. A validity-driven and multi-study approach was used to collect validity evidence on 1) test content, 2) response processes and 3) internal structure. Cognitive interviews (n = 14) were held to assess test content and response processes (Study 1). A pre-final eHLQ version was completed by 1650 people participating in an eHealth study (Study 2). A seven-factor Confirmatory Factor Analysis (CFA) model was fitted to the data to assess the internal structure of the eHLQ. Invariance testing was performed across gender, age, education and current diagnosis. Results: Cognitive interviews showed some problems in wording, phrasing and resonance with individual's world views. CFA demonstrated an equivalent internal structure to the hypothesized (original) eHLQ with acceptable fit indices. All items loaded substantially on their corresponding latent factors (range 0.51-0.81). The model was partially metric invariant across all subgroups. Comparison of scores between groups showed that people who were younger, higher educated and who had a current diagnosis generally scored higher across domains, however effect sizes were small. Data from both studies were triangulated, resulting in minor refinements to eight items and recommendations on use, score interpretation and reporting. Conclusion: The Dutch version of the eHLQ showed strong properties for assessing eHealth literacy in the Dutch context. While ongoing collection of validity evidence is recommended, the evidence presented indicate that the eHLQ can be used by researchers, eHealth developers and policy makers to identify eHealth literacy needs and inform the development of eHealth interventions to ensure that people with limited digital access and skills are not left behind.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Folate reference interval estimation in the Dutch general population

Background: Folate functions as an enzyme co-factor within the one-carbon metabolic pathway, providing key metabolites required for DNA synthesis and methylation. Hence, insufficient intake of folate can negatively affect health. As correct interpretation of folate status is dependent on a well-established reference interval, we set out to perform a new estimation following the restandardization of the Roche folate assay against the international folate standard. Materials and methods: The folate reference interval was estimated using samples obtained from the Dutch population-based Lifelines cohort. The reference interval was estimated using two methods: a nonparametric estimation combined with bootstrap resampling and by fitting the data to a gamma distribution. The lower reference limit was verified in a patient cohort by combined measurement of folate and homocysteine. Results: Dependent on the method used for estimation and in- or exclusion of individuals younger than 21 years of age, the lower reference limit ranged from 6.8 to 7.3 nmol/L and the upper reference limit ranged from 26 to 38.5 nmol/L. Applying a lower reference limit of 7.3 nmol/L resulted in the following percentage of folate deficiencies over a period of 12 months: general practitioner 15.5% (IQR 4.0%), general hospital 12.8% (IQR 5.3%), academic hospital 9.6% (IQR 4.3%). Conclusions: We estimated the folate reference interval in the Dutch general population which is not affected by a folic acid fortification program and verified the obtained lower reference limit by homocysteine measurements. Based on our results, we propose a folate reference interval independent of age of 7.3-38.5 nmol/