Intestinal parasites, both helminths and protozoa, are commonly found in domestic animals, and the possible transmission of enteric parasites from dogs and cats to humans may constitute a global ...potential health risk worldwide. In the present study, we analysed 148 stool samples from dogs (
n
=
126) and cats (
n
=
22) collected from animal shelters and veterinary clinics, in the district of Évora, Portugal. Microscopic examination confirmed that
Giardia was the most frequent parasite in the studied population (34/148; 23%). Other parasites such as
Ancylostoma sp.,
Isospora spp.,
Toxocara,
Trichuris spp.,
Toxascaris and
Toxoplasma were also found. Furthermore, molecular characterization of
Giardia duodenalis analysis targeting the small subunit ribosomal RNA (
ssu-rRNA) was performed revealing the presence of host-specific (C and D) and zoonotic assemblages (A and B). This work points out to the importance of protozoan parasites in companion animals, and reanalyses the need for parasite prophylaxis.
Molecular crystals cannot be designed in the same manner as macroscopic objects, because they do not assemble according to simple, intuitive rules. Their structures result from the balance of many ...weak interactions, rather than from the strong and predictable bonding patterns found in metal-organic frameworks and covalent organic frameworks. Hence, design strategies that assume a topology or other structural blueprint will often fail. Here we combine computational crystal structure prediction and property prediction to build energy-structure-function maps that describe the possible structures and properties that are available to a candidate molecule. Using these maps, we identify a highly porous solid, which has the lowest density reported for a molecular crystal so far. Both the structure of the crystal and its physical properties, such as methane storage capacity and guest-molecule selectivity, are predicted using the molecular structure as the only input. More generally, energy-structure-function maps could be used to guide the experimental discovery of materials with any target function that can be calculated from predicted crystal structures, such as electronic structure or mechanical properties.
We present and discuss VARSEDIG, an algorithm which identifies the morphometric features that significantly discriminate two taxa and validates the morphological distinctness between them via a ...Monte-Carlo test. VARSEDIG is freely available as a function of the RWizard application PlotsR (http://www.ipez.es/RWizard) and as R package on CRAN. The variables selected by VARSEDIG with the overlap method were very similar to those selected by logistic regression and discriminant analysis, but overcomes some shortcomings of these methods. VARSEDIG is, therefore, a good alternative by comparison to current classical classification methods for identifying morphometric features that significantly discriminate a taxon and for validating its morphological distinctness from other taxa. As a demonstration of the potential of VARSEDIG for this purpose, we analyze morphological discrimination among some species of the Neotropical freshwater family Characidae.
It has been observed that there is an imperative to develop predictive human systems that more effectively study and/or prevent the onset of liver disease and decompensated organ function. A ...serum‐free, scalable, and shippable cell‐based model that faithfully predicts the potential for human liver injury has been developed. Such a resource has direct application in human modeling, and, in the future, could play an important role in developing renewable cell‐based therapies.
Despite major progress in the knowledge and management of human liver injury, there are millions of people suffering from chronic liver disease. Currently, the only cure for end‐stage liver disease is orthotopic liver transplantation; however, this approach is severely limited by organ donation. Alternative approaches to restoring liver function have therefore been pursued, including the use of somatic and stem cell populations. Although such approaches are essential in developing scalable treatments, there is also an imperative to develop predictive human systems that more effectively study and/or prevent the onset of liver disease and decompensated organ function. We used a renewable human stem cell resource, from defined genetic backgrounds, and drove them through developmental intermediates to yield highly active, drug‐inducible, and predictive human hepatocyte populations. Most importantly, stem cell‐derived hepatocytes displayed equivalence to primary adult hepatocytes, following incubation with known hepatotoxins. In summary, we have developed a serum‐free, scalable, and shippable cell‐based model that faithfully predicts the potential for human liver injury. Such a resource has direct application in human modeling and, in the future, could play an important role in developing renewable cell‐based therapies.
Pluripotent stem cells were differentiated to hepatocytes. Upon hepatic specification, cells were replated onto a synthetic surface, which stabilized cell function for more than 2 weeks in vitro. The ...goal of these studies was the accurate prediction of cellular toxicity in response to specific pharmacological compounds. Importantly, stem cell‐derived hepatocytes displayed equivalence to primary human material. Moreover, this approach was capable of modeling metabolic differences observed in the population. These studies provide robust hepatocyte models which will likely contribute to improvements in drug safety testing.
Faithfully recapitulating human physiology “in a dish” from a renewable source remains a holy grail for medicine and pharma. Many procedures have been described that, to a limited extent, exhibit human tissue‐specific function in vitro. In particular, incomplete cellular differentiation and/or the loss of cell phenotype postdifferentiation play a major part in this void. We have developed an interdisciplinary approach to address this problem, using skill sets in cell biology, materials chemistry, and pharmacology. Pluripotent stem cells were differentiated to hepatocytes before being replated onto a synthetic surface. Our approach yielded metabolically active hepatocyte populations that displayed stable function for more than 2 weeks in vitro. Although metabolic activity was an important indication of cell utility, the accurate prediction of cellular toxicity in response to specific pharmacological compounds represented our goal. Therefore, detailed analysis of hepatocellular toxicity was performed in response to a custom‐built and well‐defined compound set and compared with primary human hepatocytes. Importantly, stem cell‐derived hepatocytes displayed equivalence to primary human material. Moreover, we demonstrated that our approach was capable of modeling metabolic differences observed in the population. In conclusion, we report that pluripotent stem cell‐derived hepatocytes will model toxicity predictably and in a manner comparable to current gold standard assays, representing a major advance in the field.
Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large ...randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage.
MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0–3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046.
Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0–3 at 365 days (adjusted risk difference 4% 95% CI −4 to 12; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six 2% of 255 patients vs three 1% of 251 patients; p=0·33 for symptomatic bleeding; two 1% of 255 patients vs 0 0% of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012).
For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons.
National Institute of Neurological Disorders and Stroke and Genentech.
Online topology estimation of graph-connected time series is challenging in practice, particularly because the dependencies between the time series in many real-world scenarios are nonlinear. To ...address this challenge, we introduce a novel kernel-based algorithm for online graph topology estimation. Our proposed algorithm also performs a Fourier-based random feature approximation to tackle the curse of dimensionality associated with kernel representations. Exploiting the fact that real-world networks often exhibit sparse topologies, we propose a group-Lasso based optimization framework, which is solved using an iterative composite objective mirror descent method, yielding an online algorithm with fixed computational complexity per iteration. We provide theoretical guarantees for our algorithm and prove that it can achieve sublinear dynamic regret under certain reasonable assumptions. In experiments conducted on both real and synthetic data, our method outperforms existing state-of-the-art competitors.
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