Journals
2016 EN
Pietersen Lars C. · Dulk A. Claire · Braat Andries E.
+7 more
The aim of the present study was to assess whether flushing the donor liver with urokinase immediately before implantation reduces the incidence of nonanastomotic biliary strictures (NASs) after liver transplantation, without causing increased blood loss, analyzed as a historical cohort study. Between January 2005 and October 2012, all liver (re‐)transplantations were included. Of the 185 liver transplant recipients included, 63 donor livers between January 2010 and October 2012 received urokinase (study group), whereas the donor liver of 122 consecutive recipients, who served as a historical control group, between January 2005 and January 2010 did not receive urokinase. Basic donor (Eurotransplant donor risk index) and recipient (age, body mass index, laboratory Model for End‐Stage Liver Disease score) characteristics did not significantly differ in both groups. Thirty‐three recipients developed NASs: 22 in the control group (18%) and 11 (17.5%) in the study group ( P = 0.68). Analyzed separately for donation after circulatory death ( P = 0.42) or donation after brain death ( P = 0.89), there was no difference between the groups in incidence of NAS. Of all the recipients developing NAS, 7 (21%) needed retransplantation and all others were treated conservatively. Autologous blood transfusion requirements did not differ significantly between both groups ( P = 0.91), whereas interestingly, more heterologous blood transfusions were needed in the control group ( P < 0.001). This study has its limitations by its retrospective character. A multi‐institutional prospective study could clarify this issue. In conclusion, arterial flushing of the liver with urokinase immediately before implantation did not lead to a lower incidence of NAS in this study, nor did it lead to increased blood loss. Liver Transplantation 22 420‐426 2016 AASLD
Lippincott Williams & Wilkins
Journals
2016 EN
Walker Lawrence R. · Hoyt David W. · Walker S. Michael
+3 more
A hybrid 1D 1 H NMR/ESI MS 1 approach is introduced that allows accurate and unambiguous identification of catalogued, that is, known metabolites detected in 1D 1 H NMR and direct infusion ESI MS 1 spectra of the same sample. The approach provides more accurate identification than individual analysis of 1D 1 H NMR and ESI MS 1 spectra. Moreover, we developed a software tool for the approach, which works with Chenomx NMR Suite.
Journals
2016 EN
Pugatsch Thea · Shoseyov David · CohenCymberknoh Malena
+4 more
Summary Background Clinical trials are all based on the assumption that patients are adherent to the study protocol. Many reports indicate that general adherence of patients with CF to their daily routine therapies is poor. However, no data exists on adherence to study drug regimens. Methods All clinical trials carried out at the Hadassah CF Center from 2008 to 2013 were reviewed. Actual adherence as determined by counted drugs was analyzed according to drug administration mode, study lengths and number of study visits. A subset of patients answered a two‐part questionnaire covering study specific and general treatment specific issues. Results Eight studies including 118 patients, with patient numbers varying between 4 and 32 per trial were analyzed. For 7/8 studies mean adherence was between 78% to 100%. Comparison with administration mode showed that adherence decreased substantially if the drugs were not provided as “ready to be used” (63%). Study length influenced adherence, the longer the study the poorer the adherence (82% trial beginning, 44% post 36 months [two combined studies with identical drug]). A substantial decrease was noted over Holiday periods and during the summer vacation months. No correlation was found between number of study visits and adherence to study drug. Conclusion Adherence to study drug is generally higher than that for regular treatment. Study length, mode of administration, and timing according to Holidays and vacations adversely affect adherence. Pediatr Pulmonol. 2016;51:143–146. © 2015 Wiley Periodicals, Inc.
Journals
2016 EN
Reiter Joel · Szafranski Przemyslaw · Breuer Oded
+4 more
Summary Background Heterozygous mutations in the FOXF1 transcription factor gene are implicated in alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a developmental disorder of the lungs classically presenting with pulmonary hypertension and early demise. Evidence has suggested haploinsufficiency and partial paternal imprinting. We present a family with several affected members with an extremely variable phenotype. Patients The index patient presented several hours after birth with severe pulmonary hypertension. She is now 3‐years old, thriving on maximal pulmonary hypertension therapy, chronic steroids, and oxygen. One of the patient's siblings died at 16 days with pulmonary hypertension and an annular pancreas, consistent with classical ACDMPV. Methods Whole exome sequencing was performed in the index case. The identified variant was confirmed by Sanger sequencing, and tested in the remaining family members. Parental origin was determined by PCR amplification and cloning, sequencing, and identification of adjacent single nucleotide polymorphisms. Echocardiography was performed in the asymptomatic carriers. Results Whole exome analysis revealed a novel, predictably pathogenic heterozygous missense mutation, g.chr16:86544406 C>A NM_001451, c.C231A, p.F77L, in the FOXF1 gene. The mutation arose in the father, de novo, early postzygotically, with 70% somatic mosaicism in the blood, on the grandpaternal chromosome. It was also present in the proband's asymptomatic sister, found to have partial anomalous pulmonary venous return. Conclusion FOXF1 mutations may have an extremely variable phenotype, possibly as a result of somatic mosaicism and complex gene regulation including unorthodox imprinting of the gene locus. The prolonged survival of the proband suggests the need for aggressive treatment. Pediatr Pulmonol. 2016; 51:921–927 . © 2016 Wiley Periodicals, Inc.
Book Series
2016 EN
Kerem Akartunalı · Ashwin Arulselvan
In a single item dynamic lot-sizing problem, we are given a time horizon and demand for a single item in every time period. The problem seeks a solution that determines how much to produce and carry at each time period, so that we will incur the least amount of production and inventory cost. When the remanufacturing option is included, the input comprises of number of returned products at each time period that can be potentially remanufactured to satisfy the demands, where remanufacturing and inventory costs are applicable. For this problem, we first show that it cannot have a fully polynomial time approximation scheme (FPTAS). We then provide a pseudo-polynomial algorithm to solve the problem and show how this algorithm can be adapted to solve it in polynomial time, when we make certain realistic assumptions on the cost structure. We finally give a computational study for the capacitated version of the problem and provide some valid inequalities and computational results that indicate that they significantly improve the lower bound for a certain class of instances.
Springer Science+Business Media
Journals
2016 EN
Kerem Pekkan · Brian Y. Chang · Fazil E. Uslu
+3 more
The hydrodynamics of suction feeding is critical for the survival of fish larvae; failure to capture food during the onset of autonomous feeding can rapidly lead to starvation and mortality. Fluid mechanics experiments that investigate the suction feeding of suspended particles are limited to adult fishes, which operate at large Reynolds numbers. This manuscript presents the first literature results in which the external velocity fields generated during suction feeding of early zebrafish larvae (2500–20,000 μm total length) are reported using time-resolved microscopic particle image velocimetry. For the larval stages studied, the maximum peak suction velocity of the inflow bolus is measured at a finite distance from the mouth tip and ranges from 1 to 8 mm/s. The average pressure gradient and the velocity profile proximal to the buccal (mouth) cavity are calculated, and two distinct trends are identified. External recirculation regions and reverse flow feeding cycles are also observed and quantified. One of the unresolved questions in fish suction feeding is the shape and dynamics of the buccal cavity during suction feeding; optical coherence tomography imaging is found to be useful for reconstructing the mouth kinematics. The projected area of the mouth cavity during the feeding cycle varies up to 160 and 22 % for the transverse and mid-sagittal planes, respectively. These findings can inspire novel hydrodynamically efficient biomedical and microfluidic devices
Springer Science+Business Media
Journals
2016 EN
Przemysław Szafrański · Tomasz Gambin · Avinash V. Dharmadhikari
+90 more
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV.
Springer Science+Business Media
Journals
2016 EN
Semih Atakan · Kerem Bülbül · Nilay Noyan
The vast majority of the machine scheduling literature focuses on deterministic problems in which all data is known with certainty a priori. In practice, this assumption implies that the random parameters in the problem are represented by their point estimates in the scheduling model. The resulting schedules may perform well if the variability in the problem parameters is low. However, as variability increases accounting for this randomness explicitly in the model becomes crucial in order to counteract the ill effects of the variability on the system performance. In this paper, we consider single-machine scheduling problems in the presence of uncertain parameters. We impose a probabilistic constraint on the random performance measure of interest, such as the total weighted completion time or the total weighted tardiness, and introduce a generic risk-averse stochastic programming model. In particular, the objective of the proposed model is to find a non-preemptive static job processing sequence that minimizes the value-at-risk (VaR) of the random performance measure at a specified confidence level. We propose a Lagrangian relaxation-based scenario decomposition method to obtain lower bounds on the optimal VaR and provide a stabilized cut generation algorithm to solve the Lagrangian dual problem. Furthermore, we identify promising schedules for the original problem by a simple primal heuristic. An extensive computational study on two selected performance measures is presented to demonstrate the value of the proposed model and the effectiveness of our solution method
Springer Science+Business Media
Journals
2016 EN
Kerem Akartunalı · Philip A. Knight
Systems for allocating seats in an election offer a number of socially and mathematically interesting problems. We discuss how to model the allocation process as a network flow problem, and propose a wide choice of objective functions and allocation schemes. Biproportional rounding, which is an instance of the network flow problem, is used in some European countries with multi-seat constituencies. We discuss its application to single seat constituencies and the inevitable consequence that seats are allocated to candidates with little local support. However, we show that variants can be selected, such as regional apportionment, to mitigate this problem. In particular, we introduce a parameter based family of methods, which we call Balanced Majority Voting, that can be tuned to meet the public's demand for local and global ``fairness''. Using data from the 2010 and 2015 UK General Elections, we study a variety of network models and implementations of biproportional rounding, and address conditions of existence and uniqueness
Springer Science+Business Media
Journals
2016 EN
Anthony Journault · FrançoisXavier Standaert · Kerem Varıcı
LS-designs are a family of bitslice ciphers aiming at efficient masked implementations against side-channel analysis. This paper discusses their security against invariant subspace attacks, and describes an alternative family of eXtended LS-designs (XLS-designs), that enables additional options to prevent such attacks. LS- and XLS-designs provide a large family of ciphers from which efficient implementations can be obtained, possibly enhanced with countermeasures against physical attacks. We argue that they are interesting primitives in order to discuss the general question of \"how simple can block ciphers be?\".