Incidence, severity and prognosis associated with hypernatremia in dogs and cats.

BackgroundHypernatremia has been associated with substantial morbidity and death in human patients. The incidence and importance of hypernatremia in dogs and cats has not been determined.Hypothesis/objectivesTo describe the incidence of and prognosis associated with hypernatremia in dogs and cats at a university teaching hospital.AnimalsA total of 16,691 dogs and 4,211 cats with measured blood or serum sodium concentration.MethodsRetrospective study. Medical records of animals with a blood or serum sodium concentration measured during a 60-month period were reviewed to determine the severity of hypernatremia and its associated case fatality rate. Cases with moderate (11-15 mmol/L above the reference range) or severe hypernatremia (≥16 mmol/L above the reference range) were further reviewed.ResultsA total of 957 dogs (5.7%) and 338 cats (8.0%) were diagnosed with hypernatremia. Case fatality rates of dogs and cats with hypernatremia was 20.6 and 28.1%, respectively compared to 4.4 and 4.5% with a normal blood or serum sodium concentration (P < .0001). The magnitude of hypernatremia was linearly associated with a higher case fatality rate (P < .0001). Hypernatremia was associated with a higher case fatality rate than hyponatremia. Among the animals with moderate or severe hypernatremia, 50% of dogs and 38.5% of cats presented with community-acquired hypernatremia, and 50% of dogs and 61.5% of cats developed hospital-acquired hypernatremia.Conclusions and clinical importanceHypernatremia was found infrequently in this population but was associated with increased case fatality rates in dogs and cats. Presence and severity of hypernatremia might be useful as a prognostic indicator

Genetic determinants of the response to bezafibrate treatment in the lower extremity arterial disease event reduction (LEADER) trial.

Genetic determinants of baseline levels and the fall in plasma triglyceride and fibrinogen levels in response to bezafibrate treatment were examined in 853 men taking part in the lower extremity arterial disease event reduction (LEADER) trial. Three polymorphisms in the peroxisome proliferator activated receptor alpha (PPARalpha) gene were investigated (L162V, G>A in intron 2 and G>C in intron 7), two in the apolipoprotein CIII (APOC3) gene (-482C>T and -455T>C) and one in the beta-fibrinogen (FIBB) gene (-455G>A). The presence of diabetes (n=158) was associated with 15% higher triglyceride levels at baseline compared to non-diabetics (n=654) (PC substitution. In the non-diabetic patients, the PPARalpha V162 allele was significantly associated with 9% higher baseline triglyceride levels (P<0.03) and a similar, but non-significant trend was seen for the intron 7 polymorphism. Overall, triglyceride levels fell by 26% with 3 months of bezafibrate treatment, and current smokers showed a poorer response compared to ex/non-smokers (23% fall compared to 28% P=0.03), but none of the genotypes examined had a significant influence on the magnitude of response. Carriers of the -455A polymorphism of the FIBB gene had, as expected, marginally higher baseline fibrinogen levels, 3.43 versus 3.36 g/l (P=0.055), but this polymorphism did not affect response to treatment. Overall, fibrinogen levels fell by 12%, with patients with the highest baseline fibrinogen levels showing the greatest decrease in response to bezafibrate. For both the intron 2 and the L162V polymorphisms of the PPARalpha gene there was a significant interaction (both P<0.01) between genotype and baseline levels of fibrinogen on the response of fibrinogen levels to bezafibrate, such that individuals carrying the rare alleles in the lowest tertile showed essentially no overall decrease compared to a 0.18 g/l fall in homozygotes for the common allele. Thus while these genotypes are a minor determinant of baseline triglyceride and fibrinogen levels, there is little evidence from this study that the magnitude of response to bezafibrate treatment in men with peripheral vascular disease is determined by variation at these loci

Large-Scale Modelling of the Environmentally-Driven Population Dynamics of Temperate Aedes albopictus (Skuse)

The Asian tiger mosquito, Aedes albopictus, is a highly invasive vector species. It is a proven vector of dengue and chikungunya viruses, with the potential to host a further 24 arboviruses. It has recently expanded its geographical range, threatening many countries in the Middle East, Mediterranean, Europe and North America. Here, we investigate the theoretical limitations of its range expansion by developing an environmentally-driven mathematical model of its population dynamics. We focus on the temperate strain of Ae. albopictus and compile a comprehensive literature-based database of physiological parameters. As a novel approach, we link its population dynamics to globally-available environmental datasets by performing inference on all parameters. We adopt a Bayesian approach using experimental data as prior knowledge and the surveillance dataset of Emilia-Romagna, Italy, as evidence. The model accounts for temperature, precipitation, human population density and photoperiod as the main environmental drivers, and, in addition, incorporates the mechanism of diapause and a simple breeding site model. The model demonstrates high predictive skill over the reference region and beyond, confirming most of the current reports of vector presence in Europe. One of the main hypotheses derived from the model is the survival of Ae. albopictus populations through harsh winter conditions. The model, constrained by the environmental datasets, requires that either diapausing eggs or adult vectors have increased cold resistance. The model also suggests that temperature and photoperiod control diapause initiation and termination differentially. We demonstrate that it is possible to account for unobserved properties and constraints, such as differences between laboratory and field conditions, to derive reliable inferences on the environmental dependence of Ae. albopictus populations

Taxonomic revision of lizards from the Paleocene deposits of the Qianshan Basin, Anhui, China

Although the Late Cretaceous lizard fauna of China and Mongolia is relatively well-known, information on Paleocene lizards from the same region is currently limited. Several species of lizards have been reported from the Paleocene Wanghudun and Doumu formations of Qianshan Basin on the basis of fragmentary specimens, namely Agama sinensis Hou, 1974, Anhuisaurus huainanensis Hou, 1974, Anqingosaurus brevicephalus Hou, 1976, Changjiangosaurus huananensis Hou, 1976, Qianshanosaurus huangpuensis Hou, 1974, and Tinosaurus doumuensis Hou, 1974. In this paper, we review all the reported material of these taxa with the aid of new technology, including CT scanning, and according to current views of squamate relationships and classification. Revised descriptions and classifications are given for each taxon, leading to changes in our understanding of faunal composition. This, in turn, reveals greater morphological and ecological diversity among the Paleocene lizards of the Qianshan Basin, including the occurrence of a varaniform (IVPP V 22767), and the reinterpretation of Anqingosaurus as a possible burrower. Further work on the Paleocene Qianshan lizards is ongoing and the discovery of new specimens may help to solve the puzzles these strange lizards have posed

Disposable Integrated Microfluidic Biochip for Blood Typing by Plastic Microinjection Moulding

Blood typing is the most important test for both transfusion recipients and blood donors. In this paper, a low cost disposable blood typing integrated microfluidic biochip has been designed, fabricated and characterized. In the biochip, flow splitting microchannels, chaotic micromixers, reaction microchambers and detection microfilters are fully integrated. The loaded sample blood can be divided by 2 or 4 equal volumes through the flow splitting microchannel so that one can perform 2 or 4 blood agglutination tests in parallel. For the purpose of obtaining efficient reaction of agglutinogens on red blood cells (RBCs) and agglutinins in serum, we incorporated a serpentine laminating micromixer into the biochip, which combines two chaotic mixing mechanisms of splitting/recombination and chaotic advection. Relatively large area reaction microchambers were also introduced for the sake of keeping the mixture of the sample blood and serum during the reaction time before filtering. The gradually decreasing multi-step detection microfilters were designed in order to effectively filter the reacted agglutinated RBCs, which show the corresponding blood group. To achieve the cost-effectiveness of the microfluidic biochip for disposability, the biochip was realized by the microinjection moulding of COC (cyclic olefin copolymer) and thermal bonding of two injection moulded COC substrates in mass production with a total fabrication time of less than 20 min. Mould inserts of the biochip for the microinjection moulding were fabricated by SU-8 photolithography and the subsequent nickel electroplating process. Human blood groups of A, B and AB have been successfully determined with the naked eye, with 3 mu l of the whole sample bloods, by means of the fabricated biochip within 3 min.X11100104sciescopu

Demonstration of the Presence of the "Deleted" MIR122 Gene in HepG2 Cells

MicroRNA 122 (miR-122) is highly expressed in the liver where it influences diverse biological processes and pathways, including hepatitis C virus replication and metabolism of iron and cholesterol. It is processed from a long non-coding primary transcript (~7.5 kb) and the gene has two evolutionarily-conserved regions containing the pri-mir-122 promoter and pre-mir-122 hairpin region. Several groups reported that the widely-used hepatocytic cell line HepG2 had deficient expression of miR-122, previously ascribed to deletion of the pre-mir-122 stem-loop region. We aimed to characterise this deletion by direct sequencing of 6078 bp containing the pri-mir-122 promoter and pre-mir-122 stem-loop region in HepG2 and Huh-7, a control hepatocytic cell line reported to express miR-122, supported by sequence analysis of cloned genomic DNA. In contrast to previous findings, the entire sequence was present in both cell lines. Ten SNPs were heterozygous in HepG2 indicating that DNA was present in two copies. Three validation isolates of HepG2 were sequenced, showing identical genotype to the original in two, whereas the third was different. Investigation of promoter chromatin status by FAIRE showed that Huh-7 cells had 6.2 ± 0.19- and 2.7 ± 0.01- fold more accessible chromatin at the proximal (HNF4α-binding) and distal DR1 transcription factor sites, compared to HepG2 cells (p=0.03 and 0.001, respectively). This was substantiated by ENCODE genome annotations, which showed a DNAse I hypersensitive site in the pri-mir-122 promoter in Huh-7 that was absent in HepG2 cells. While the origin of the reported deletion is unclear, cell lines should be obtained from a reputable source and used at low passage number to avoid discrepant results. Deficiency of miR-122 expression in HepG2 cells may be related to a relative deficiency of accessible promoter chromatin in HepG2 versus Huh-7 cells

Chemical potential oscillations from a single nodal pocket in the underdoped high-Tc superconductor YBa2Cu3O6+x

The mystery of the normal state in the underdoped cuprates has deepened with the use of newer and complementary experimental probes. While photoemission studies have revealed solely `Fermi arcs' centered on nodal points in the Brillouin zone at which holes aggregate upon doping, more recent quantum oscillation experiments have been interpreted in terms of an ambipolar Fermi surface, that includes sections containing electron carriers located at the antinodal region. To address the question of whether an ambipolar Fermi surface truly exists, here we utilize measurements of the second harmonic quantum oscillations, which reveal that the amplitude of these oscillations arises mainly from oscillations in the chemical potential, providing crucial information on the nature of the Fermi surface in underdoped YBa2Cu3O6+x. In particular, the detailed relationship between the second harmonic amplitude and the fundamental amplitude of the quantum oscillations leads us to the conclusion that there exists only a single underlying quasi-two dimensional Fermi surface pocket giving rise to the multiple frequency components observed via the effects of warping, bilayer splitting and magnetic breakdown. A range of studies suggest that the pocket is most likely associated with states near the nodal region of the Brillouin zone of underdoped YBa2Cu3O6+x at high magnetic fields.Comment: 7 pages, 4 figure

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub

Supervision-by-Registration: An Unsupervised Approach to Improve the Precision of Facial Landmark Detectors

© 2018 IEEE. In this paper, we present supervision-by-registration, an unsupervised approach to improve the precision of facial landmark detectors on both images and video. Our key observation is that the detections of the same landmark in adjacent frames should be coherent with registration, i.e., optical flow. Interestingly, coherency of optical flow is a source of supervision that does not require manual labeling, and can be leveraged during detector training. For example, we can enforce in the training loss function that a detected landmark at framet-1 followed by optical flow tracking from framet-1 to framet should coincide with the location of the detection at framet. Essentially, supervision-by-registration augments the training loss function with a registration loss, thus training the detector to have output that is not only close to the annotations in labeled images, but also consistent with registration on large amounts of unlabeled videos. End-to-end training with the registration loss is made possible by a differentiable Lucas-Kanade operation, which computes optical flow registration in the forward pass, and back-propagates gradients that encourage temporal coherency in the detector. The output of our method is a more precise image-based facial landmark detector, which can be applied to single images or video. With supervision-by-registration, we demonstrate (1) improvements in facial landmark detection on both images (300W, ALFW) and video (300VW, Youtube-Celebrities), and (2) significant reduction of jittering in video detections