High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation.

Despite its common use in nonmyeloablative preparative regimens, the pharmacokinetics of fludarabine are poorly characterized in hematopoietic cell transplantation (HCT) recipients and exposure-response relationships remain undefined. The objective of this study was to evaluate the association between plasma F-ara-A exposure, the systemically circulating moiety of fludarabine, and engraftment, acute GVHD, TRM and OS after HCT. The preparative regimen consisted of CY 50 mg/kg/day i.v. day -6; plus fludarabine 30-40 mg/m²/day i.v. on days -6 to -2 and TBI 200 cGy on day -1. F-ara-A pharmacokinetics were carried out with the first dose of fludarabine in 87 adult patients. Median (range) F-ara-A area-under-the-curve (AUC((0-∞))) was 5.0 μg h/mL (2.0-11.0), clearance 15.3 L/h (6.2-36.6), C(min) 55 ng/mL (17-166) and concentration on day(zero) 16.0 ng/mL (0.1-144.1). Despite dose reductions, patients with renal insufficiency had higher F-ara-A exposures. There was strong association between high plasma concentrations of F-ara-A and increased risk of TRM and reduced OS. Patients with an AUC((0-∞)) greater than 6.5 μg h/mL had 4.56 greater risk of TRM and significantly lower OS. These data suggest that clinical strategies are needed to optimize dosing of fludarabine to prevent overexposure and toxicity in HCT

Ranking the Predictive Power of Clinical and Biological Features Associated With Disease Progression in Huntington's Disease

Huntington’s disease (HD) is characterised by a triad of cognitive, behavioural, and motor symptoms which lead to functional decline and loss of independence. With potential disease-modifying therapies in development, there is interest in accurately measuring HD progression and characterising prognostic variables to improve efficiency of clinical trials. Using the large, prospective Enroll-HD cohort, we investigated the relative contribution and ranking of potential prognostic variables in patients with manifest HD. A random forest regression model was trained to predict change of clinical outcomes based on the variables, which were ranked based on their contribution to the prediction. The highest-ranked variables included novel predictors of progression—being accompanied at clinical visit, cognitive impairment, age at diagnosis and tetrabenazine or antipsychotics use—in addition to established predictors, cytosine adenine guanine (CAG) repeat length and CAG-age product. The novel prognostic variables improved the ability of the model to predict clinical outcomes and may be candidates for statistical control in HD clinical studies

Drain tube migration into the anastomotic site of an esophagojejunostomy for gastric small cell carcinoma: short report

Intraluminal migration of a drain through an anastomotic site is a rare complication of gastric surgery. Case Presentation: We herein report the intraluminal migration of a drain placed after a lower esophagectomy and total gastrectomy with Roux-en-Y anastomosis for gastric small cell carcinoma. Persistent drainage was noted 1 month after surgery, and radiographic studies were consistent with drain tube migration. Endoscopy revealed the drain had migrated into the esophagojejunostomy anastomotic site. The drain was removed from outside of abdominal wound while observing the anastomotic site endoscopically. The patient was treated with suction via a nasogastric tube drain for 5 days, and thereafter had an uneventful recovery. Conclusions: Though drain tube migration is a rare occurrence, it should be considered in patients with persistent drainage who have undergone gastric surgery

Spatial Division Multiplexed Microwave Signal processing by selective grating inscription in homogeneous multicore fibers

[EN] The use of Spatial Division Multiplexing for Microwave Photonics signal processing is proposed and experimentally demonstrated, for the first time to our knowledge, based on the selective inscription of Bragg gratings in homogeneous multicore fibers. The fabricated devices behave as sampled true time delay elements for radiofrequency signals offering a wide range of operation possibilities within the same optical fiber. The key to processing flexibility comes from the implementation of novel multicavity configurations by inscribing a variety of different fiber Bragg gratings along the different cores of a 7-core fiber. This entails the development of the first fabrication method to inscribe high-quality gratings characterized by arbitrary frequency spectra and located in arbitrary longitudinal positions along the individual cores of a multicore fiber. Our work opens the way towards the development of unique compact fiber-based solutions that enable the implementation of a wide variety of 2D (spatial and wavelength diversity) signal processing functionalities that will be key in future fiber-wireless communications scenarios. We envisage that Microwave Photonics systems and networks will benefit from this technology in terms of compactness, operation versatility and performance stability.We thank Prof. Jose Capmany for the thoughtful discussions and recommendations that greatly contribute to this work. This research was supported by the Spanish MINECO Projects TEC2014-60378-C2-1-R and TEC2015-62520-ERC, the Valencian Research Excellency Award Program GVA PROMETEO 2013/012, the Spanish MECD FPU Scholarship (FPU13/04675) for J. Hervas, and the Spanish MINECO Ramon y Cajal Program (RYC-2014-16247) for I. Gasulla.Gasulla Mestre, I.; Barrera Vilar, D.; Hervás-Peralta, J.; Sales Maicas, S. (2017). Spatial Division Multiplexed Microwave Signal processing by selective grating inscription in homogeneous multicore fibers. Scientific Reports. 7(41727):1-10. https://doi.org/10.1038/srep41727S110741727Samsung Electronics Co, “5G Vision”, available at http://www.samsung.com/global/business-images/insights/2015/Samsung-5G-Vision-0.pdf (2015).Technology Focus on Microwave Photonics. Nat. Photonics 5, 723 (2011).J. Capmany, J. Mora, I. Gasulla, J. Sancho, J. Lloret & S. Sales . Microwave photonic signal processing. IEEE J. Lightw. Technol. 31, 571–586 (2013).Y. Long & J. Wang . Ultra-high peak rejection notch microwave photonic filter using a single silicon microring resonator. Opt. Express 23, 17739–17750 (2015).Y. Long & J. Wang . All-optical tuning of a nonlinear silicon microring assisted microwave photonic filter: theory and experiment. Opt. Express 23, 17758–17771 (2015).Y. Long, L. Zhou & J. Wang . Photonic-assisted microwave signal multiplication and modulation using a silicon Mach–Zehnder modulator. Sci. Reports 6, 20215 (2016).J. Sancho, J. Bourderionnet, J. Lloret, S. Combrié, I. Gasulla, S. Xavier, S. Sales, P. Colman, G. Lehoucq, D. Dolfi, J. Capmany & A. De Rossi . Integrable microwave filter based on a photonic crystal delay line. Nat. Commun. 3, 1075 (2012).F. Ohman, K. Yvind & J. Mørk . Slow Light in a Semiconductor Waveguide for True-Time Delay Applications in Microwave Photonics. IEEE Photon. Technol. Lett. 19, 1145–1157 (2007).P. A. Morton & J. B. Khurgin. Microwave photonic delay line with separate tuning of the optical carrier. IEEE Photon. Technol. Lett. 21, 1686–1688 (2009).D. Marpaung, C. Roeloffzen, R. Heideman, A. Leinse, S. Sales & J. Capmany . Integrated microwave photonics. Lasers Photon. Rev. 7, 506–538 (2013).I. Gasulla & J. Capmany . Microwave photonics applications of multicore fibers. Photonics J. 4, 877–888 (2012).S. Garcia & I. Gasulla . 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A comparison of transgenic rodent mutation and in vivo comet assay responses for 91 chemicals.

A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals

Feeding spectra and activity of the freshwater crab Trichodactylus kensleyi (Decapoda: Brachyura: Trichodactylidae) at La Plata basin

Background: In inland water systems, it is important to characterize the trophic links in order to identify the ‘trophic species’ and, from the studies of functional diversity, understand the dynamics of matter and energy in these environments. The aim of this study is to analyze the natural diet of Trichodactylus kensleyi of subtropical rainforest streams and corroborate the temporal variation in the trophic activity during day hours. Results: A total of 15 major taxonomic groups were recognized in gut contents. The index of relative importance identified the following main prey items in decreasing order of importance: vegetal remains, oligochaetes, chironomid larvae, and algae. A significant difference was found in the amount of full stomachs during day hours showing a less trophic activity at midday and afternoon. The index of relative importance values evidenced the consumption of different prey according to day moments. Results of the gut content indicate that T. kensleyi is an omnivorous crab like other trichodactylid species. Opportunistic behavior is revealed by the ingestion of organisms abundant in streams such as oligochaetes and chironomid larvae. The consumption of allochthonous plant debris shows the importance of this crab as shredder in subtropical streams. However, the effective assimilation of plant matter is yet unknown in trichodactylid crabs. Conclusions: This research provides knowledge that complements previous studies about trophic relationships of trichodactylid crabs and supported the importance of T. kensleyi in the transference of energy and matter from benthic community and riparian sources to superior trophic levels using both macro- and microfauna.Fil: Williner, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: de Azevedo Carvalho, Debora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Testing for Network and Spatial Autocorrelation

Testing for dependence has been a well-established component of spatial statistical analyses for decades. In particular, several popular test statistics have desirable properties for testing for the presence of spatial autocorrelation in continuous variables. In this paper we propose two contributions to the literature on tests for autocorrelation. First, we propose a new test for autocorrelation in categorical variables. While some methods currently exist for assessing spatial autocorrelation in categorical variables, the most popular method is unwieldy, somewhat ad hoc, and fails to provide grounds for a single omnibus test. Second, we discuss the importance of testing for autocorrelation in data sampled from the nodes of a network, motivated by social network applications. We demonstrate that our proposed statistic for categorical variables can both be used in the spatial and network setting

Comparison of prefrontal atrophy and episodic memory performance in dysexecutive Alzheimer’s disease and behavioural-variant frontotemporal dementia

Alzheimer’s disease (AD) sometimes presents with prominent executive dysfunction and associated prefrontal cortex atrophy. The impact of such executive deficits on episodic memory performance as well as their neural correlates in AD, however, remains unclear. The aim of the current study was to investigate episodic memory and brain atrophy in AD patients with relatively spared executive functioning (SEF-AD; n = 12) and AD patients with relatively impaired executive functioning (IEF-AD; n = 23). We also compared the AD subgroups with a group of behavioral-variant frontotemporal dementia patients (bvFTD; n = 22), who typically exhibit significant executive deficits, and age-matched healthy controls (n = 38). On cognitive testing, the three patient groups showed comparable memory profiles on standard episodic memory tests, with significant impairment relative to controls. Voxel-based morphometry analyses revealed extensive prefrontal and medial temporal lobe atrophy in IEF-AD and bvFTD, whereas this was limited to the middle frontal gyrus and hippocampus in SEF-AD. Moreover, the additional prefrontal atrophy in IEF-AD and bvFTD correlated with memory performance, whereas this was not the case for SEF-AD. These findings indicate that IEF-AD patients show prefrontal atrophy in regions similar to bvFTD, and suggest that this contributes to episodic memory performance. This has implications for the differential diagnosis of bvFTD and subtypes of AD