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AN AUGUST 1, 2004 FIRE IN A TWO-STORY, UNSPRINKLERED Paraguayan supermarket that killed more than 400 people and injured more than 360 people (1), has highlighted the problem of building [...]

Trained monkeys performed a two-choice perceptual decision-making task in which they reported the perceived orientation of a dynamic Glass pattern, before and after unilateral, reversible, inactivation of a brainstem area—the superior colliculus (SC)—involved in preparing eye movements. We found that unilateral SC inactivation produced significant decision biases and changes in reaction times consistent with a causal role for the primate SC in perceptual decision-making. Fitting signal detection theory and sequential sampling models to the data showed that SC inactivation produced a decrease in the relative evidence for contralateral decisions, as if adding a constant offset to a time-varying evidence signal for the ipsilateral choice. The results provide causal evidence for an embodied cognition model of perceptual decision-making and provide compelling evidence that the SC of primates (a brainstem structure) plays a causal role in how evidence is computed for decisions—a process usually attributed to the forebrain.

Despite proclamations that the Internet would make branch banking obsolete, the Federal Deposit Insurance Corp. reports that the number of bank offices has grown eight percent in the past 10 [...]

The RET receptor tyrosine kinase plays important roles in regulating cellular proliferation, migration, and survival in the normal development of neural crest derived tissues. However, aberrant activation of RET, through oncogenic mutations or overexpression, can contribute to tumourigenesis, regional invasion, and metastasis of several human cancers. RET is expressed as two main isoforms with unique C-terminal sequences that differ in protein interactions and subcellular trafficking in response to RET activation, and which also have distinct oncogenic potentials. The long isoform, termed RET51, is internalized from the membrane in response to stimulation by its ligand, GDNF, but is known to recycle back to the surface via RAB11 endosomes. However, the mechanisms regulating this process and its cellular effects have not been defined. Here, we show that recycling of RET51 requires a multicomponent complex that includes the endosomal-sorting protein GGA3, which mediates GDNF-dependent slow recycling of RET51 receptors to the plasma membrane. Our data show that the GRB2 adapter associates with RET51 through interactions with its C-terminal sequences, facilitating recruitment of active ARF6 and GGA3 interaction, and that depletion of GGA3 or ARF6 reduced RET51 recycling. Further, GGA3 knockdown accelerated RET51 degradation and also attenuated RET-mediated AKT activation. Finally, we showed that recycling of RET51 to the cell surface through association with GGA3 and ARF6 contributes to RET51-dependent cell motility, migration, and invasion. Our data establish RET recycling as a mechanism coordinating location and duration of RET signals in order to direct cell movement and invasion.

Relative density has been shown to be useful for interpreting soil behaviour and for estimating the strength and other soil characteristics in geotechnical engineering. Previous studies have shown that the index void ratios (maximum and minimum void ratios) used to determine relative density depend on the particle shape and the shape of the grain size distribution. However, the effect of the median grain size on the index void ratios has not been resolved. In this study, the effects of the particle weight and the particle size relative to the inter-particle attractive forces are examined by conducting maximum void ratio (emax) tests in elevated gravity fields through the use of a centrifuge. The results indicate that both an increasing particle size and increasing gravity affect emax, providing evidence that inter-particle forces affect the packing of materials in this limit state. The change in emax, occurring in an elevated gravity field, implies that the relative densities estimated for centrifuge model experiments may not be accurate.

Ten years ago, before the proliferation of Internet financial services, branches were a bank's most effective sales channel. Today, a visible presence on Main Street is still the key to [...]

Financial services companies are working hard today to create brand consistency at all customer points of contact -- be it the Internet, direct mail, TV advertising, or in-store merchandising. It [...]

The utility industry has seen a large jump in merger and acquisition (M&A) activity lover the last couple of years. Intensifying pressures to achieve scale and lower costs have driven [...]

Fungal peritonitis is a relatively uncommon infection in peritoneal dialysis patients. However, it can be associated with significant morbimortality. In recent reports, Candidaspecies and other filamentous fungi have been reported as being aetiological agents. Thermoascusspecies are ubiquitous, thermophilic fungi, with an anamorph in the Paecilomycesgenus. Here we present the first report of fungal peritonitis by Thermoascus crustaceusfrom Chile.

ABSTRACTOrgan-like microenviroment and 3-dimensional (3D) cell culture conformations have been suggested as promising approaches to mimic in a micro-scale a whole organ cellular functions and interactions present in vivo. We have used this approach to examine biologic features of hepatocellular carcinoma (HCC) cells. In this study, we demonstrate that hepatocellular carcinoma (HCC) cells, fibroblasts, endothelial cells and extracellular matrix can generate organoid-like spheroids that enhanced numerous features of human HCC observed in vivo. We show that the addition of non-parenchymal cells such as fibroblast and endothelial cells is required for spheroid formation as well as the maintenance of the tissue-like structure. Furthermore, HCC cells cultured as spheroids with non-parenchymal cells express more neo-angiogenesis-related markers (VEGFR2, VEGF, HIF-α), tumor-related inflammatory factors (CXCR4, CXCL12, TNF-α) and molecules-related to induced epithelial-mesenchymal transition (TGFβ, Vimentin, MMP9) compared with organoids containing only HCC cells.These results demonstrate the importance of non-parenchymal cells in the cellular composition of HCC organoids. The novelty of the multicellular-based organotypic culture system strongly supports the integration of this approach in a high throughput approach to identified patient-specific HCC malignancy and accurate anti-tumor therapy screening after surgery.

ABSTRACTStem cell research has significantly evolved over the last few years, allowing the differentiation of pluripotent cells into almost any kind of lineage possible. Studies that focus on the liver have considerably taken a leap into this novel technology, and hepatocyte-like cells are being generated that are close to resembling actual hepatocytes both genotypically and phenotypically. The potential of this extends from disease models to bioengineering, and even also innovative therapies for end-stage liver disease. Nonetheless, too few attention has been given to the non-parenchymal cells which are also fundamental for normal liver function. This includes cholangiocytes, the cells of the biliary epithelium, without whose role in bile modification and metabolism would impair hepatocyte survival. Such can be observed in diseases that target them, so called cholangiopathies, for which there is much yet to study so as to improve therapeutical options. Protocols that describe the induction of human induced pluripotent stem cells into cholangiocytes are scarce, although progress is being achieved in this area as well. In order to give the current view on this emerging research field, and in hopes to motivate further advances, we present here a review on the known differentiation strategies with sight into future applications.

Scedosporiumspecies are considered emerging agents causing illness in immunocompromised patients. In Chile, only Scedosporium apiospermum, Scedosporium boydiiand Lomentospora prolificanshaven been reported previously.

Describir las variaciones del haze corneal morfométrico, posterior a tratamiento con excímer láser de superficie, y su relación con la ametropía a tratar.

Your current and potential customers have access to myriad in-branch and on-line financial services-to the point of confusion on how to select from among all the financial advisors available to [...]

Saksenaea erythrosporais a filamentous fungus belonging to the order Mucorales. Cases of cutaneous mucormycosis caused by Saksenaeaspp. have previously been reported in immunocompetent and immunosuppressed people. A premature, 1-day-old bull calf from Texas with numerous plaque-like and ulcerative lesions in the skin was found at necropsy to have multiple areas of mycotic dermatitis and abomasitis. Fungal culture of the skin followed by morphological characterization and genetic analysis identified the etiologic agent as S. erythrospora.

Background: Over-expression of epidermal growth factor receptor in esophageal cancer is associated with poor prognosis. The present study was conducted to evaluate safety and preliminary efficacy of nimotuzumab, a humanized anti-EGFR antibody in combination with radiation and chemotherapy in advanced esophageal tumours.Patients and Methods: A Phase II clinical trial was conducted, where patients received cisplatin, 5-fluorouracil, and radiotherapy, either alone or combined with six weekly infusions of nimotuzumab at the dose of 200 mg. Safety was the primary endpoint. The antitumoral objective response rate was the secondary endpoint. Epidermal growth factor receptor expression, KRAS mutation status and anti-idiotypic response were also evaluated.Results: Sixty-three patients were included in the study. Thirty patients were entered into the control group, and thirty-three patients received the treatment with nimotuzumab. The antibody was very well tolerated. Objective response rate was 47.8 % (nimotuzumab group) and 15.4 % (control group). Disease control rate was 60.9 % (nimotuzumab group) and 26.9 % (control group). Response and disease control rate were higher in patients with EGFR overexpressing tumors.Conclusion: Nimotuzumab plus chemoradiotherapy was safe and provided statistically significant objective response. A Phase III in patients with similar characteristics will be launched.

The in vitro susceptibility of 17 strains of Mucor circinelloides to amphotericin B and posaconazole was ascertained by using broth microdilution and disk diffusion methods and by determining the minimal fungicidal concentration (MFC). We evaluated the efficacy of posaconazole at 40 mg/kg of body weight/day and amphotericin B at 0.8 mg/kg/day in a neutropenic murine model of disseminated infection by M. circinelloides by using 6 different strains tested previously in vitro. In general, most of the posaconazole MICs were within the range of susceptibility or intermediate susceptibility, while the small inhibition zone diameters (IZDs) were indicative of nonsusceptibility for all isolates tested. The MFCs were ≥3 dilutions higher than the corresponding MICs. In contrast, amphotericin B showed good activity against all of the strains tested regardless of the method used. The in vivo studies demonstrated that amphotericin B was effective in prolonging survival and reducing the fungal load. Posaconazole showed poor in vivo efficacy with no correlation with the MIC values. The results suggested that posaconazole should be used with caution in the treatment of infections caused by Mucor circinelloides or by strains of Mucor not identified to the species level.

ABSTRACTThe in vitrosusceptibility of 17 strains of Mucor circinelloidesto amphotericin B and posaconazole was ascertained by using broth microdilution and disk diffusion methods and by determining the minimal fungicidal concentration (MFC). We evaluated the efficacy of posaconazole at 40 mg/kg of body weight/day and amphotericin B at 0.8 mg/kg/day in a neutropenic murine model of disseminated infection by M. circinelloidesby using 6 different strains tested previously in vitro. In general, most of the posaconazole MICs were within the range of susceptibility or intermediate susceptibility, while the small inhibition zone diameters (IZDs) were indicative of nonsusceptibility for all isolates tested. The MFCs were ≥3 dilutions higher than the corresponding MICs. In contrast, amphotericin B showed good activity against all of the strains tested regardless of the method used. The in vivostudies demonstrated that amphotericin B was effective in prolonging survival and reducing the fungal load. Posaconazole showed poor in vivoefficacy with no correlation with the MIC values. The results suggested that posaconazole should be used with caution in the treatment of infections caused by Mucor circinelloidesor by strains of Mucornot identified to the species level.

Background:The prognosis of medulloblastoma in children under 3 years of age is poor. Methods:A retrospective analysis was performed to evaluate children under 3 years of age with medulloblastoma. Overall survival (OS) and progression-free survival (PFS) were assessed in children with and without metastasis. Results:A total of 534 children were diagnosed with medulloblastoma during the study period, 49 (9.1%) of whom were under 3 years of age and were evaluated. Their ages ranged from 5 to 35 months with a mean of 18.5 months. In 39 (79.6%) of these patients the tumors were staged as T3M0 or under, while 10 (20.4%) had metastasis at diagnosis. The OS was 38% and PFS 37% in the whole series, while PFS was 32% in those with metastasis and 40% in those without (P=0.78). For those who received radiotherapy the PFS was 62%, and in those not treated with radiotherapy PFS was nil (P=0.0001). When the children were divided into those who received surgical treatment plus chemotherapy and those who received surgery plus radiotherapy plus chemotherapy, the PFS was nil and 66%, respectively (P=0.00001). Conclusion:Because of the high morbidity of radiotherapy in children under 3 years old, surgery continues to be the basis of improved prognosis, followed by chemotherapy.

This paper describes the automatic three-dimensional (3D) graphic possibilities that are supplied by the Neurosurgical Deep Recording System (NDRS) to facilitate anatomic-physiological targeting during stereotactic and functional neurosurgery using depth recording. This software has been developed to substitute the complex electronic equipment ordinarily used for deep brain electrical recording, display and processing by a personal computer. It may also help to improve on-line graphic analysis, automatic management of the recorded information and flexibility to implement different forms of signal analysis. It can automatically show a 2D or 3D representation of the electrode track, with the electrophysiological findings superimposed as well as the corresponding sagittal, coronal and axial views of a brain atlas using automatic scaling. The NDRS has already successfully been applied during more than 300 neurosurgeries in Spain and Cuba, enabling improved targeting accuracy and safety.

The histological diagnosis of non-Hodgkin's lymphoma (Burkitt's lymphoma excluded) in 147 children was reviewed. The most common site of presentation was in the abdomen (32.6). The most frequent site of metastatic disease at diagnosis was the bone marrow (27.2). The most common histology was diffuse undifferentiated non-Burkitt type (37.4). According to the Murphy staging system, 40.1 were stage III and 27.2 were stage IV. In a nonrandomized prospective study, 121 patients were submitted to a treatment regimen (protocol 8001) and compared with 26 historical controls treated with the COP regimen, consisting of cyclophosphamide, vincristine and prednisone. Of those patients treated with protocol 8001, nine had intestinal perforation at the site of primary disease. All patients in this group were malnourished at the time of perforation. The overall rate of initial complete remission in those patients treated with protocol 8001 was 90.7. The duration of remission was from 16 to 108 months, with a median of 39 months. The actuarial rate of disease-free survival was 69 at 2 years and 63 at 6 years, compared with 36 at 6 years of the control group (COP) (p < 0.01). None of the patients have relapsed after 4 years.

Acute on Chronic Liver Failure (ACLF) is characterized by organ failure and high 28-day mortality. Identifying clinical predictors associated with early mortality could have implications for the treatment of patients with ACLF.

Introduction:

In integral medicine the spectral and vibration knowledge of the vital field in all points and parts of the human body, which is feasible in the application of their pharmacists in a space of states of energy (Chopra, 1989, Quantum Healing: Exploring the Frontiers of Mind/Body Medicine, Bantam Books, New York; Bulnes et al., 2010, “Integral Medicine: New Methods of Organ-Regeneration by Cellular Encoding Through Path Integrals Applied to the Quantum Medicine,” J. Nanotechnol. Eng. Med., 1, p. 031009) encoding points or regions of the human body, requires to recover the alignment, connectivity, and continuity of the field, and of that form to obtain the cure of different affections and sufferings. Using the spectral-vibration characteristic of the singularities of the vital field (Bulnes, F., 1998, Treatise of Advanced Mathematics (Monograph of Analysis of Systems and Sign Vol. I), 1st ed., Faculty of Sciences, UNAM, Mexico), and their medical similitude (Stumpf, 1990, Homoopathie, Everest, Grafe und Unzer GmbH, Munich, Germany), the design and development of an electronic device with the capacity of detection and diagnosis of a suffering in all parts of body are proposed. Afterward, wanting to unify the concepts of recovering the vital field of the human body (recovering of their alignment, connectivity, and continuity), under a same principle of the stability of their atoms, an electronic theory using an electronic bundle that can realize the synergic action of all and each of the formulas and pharmacists in integral medicine, to the cure of all sufferings, is proposed.

The integral medicine is a subarea of the alternative medicine that bases its cure methods and preservation of the health on the appropriate canalization of the energy code of the human body carrying out correctives actions on the vital field of a person to regenerate it and to recompose him, bringing with it the total reestablishment of the health in the affected part. The present work consists on using certain tools of mathematics called path integrals of the quantum mechanics to code the cellular information coming from its energy nuclei (mitocondrial energy) using the quantum contributions of the integral medicine. As examples, they considered several successful clinical cases of cure under the use of these methods in integral medicine.