Global and local sensitivity analysis to improve the understanding of physically-based urban wash-off models from high-resolution laboratory experiments.

Physically-based urban wash-off models are a promising means of studying the transport of finer suspended solids and their associated pollutants during rain events, considering spatial and temporal heterogeneities. This study contributes to the understanding of these models through an in-depth sensitivity analysis to provide the necessary information to simplify the model and deal with parameter identifiability. First, based on twelve tailored high-resolution experiments, the accurate measurement of input variables was used to study the parameters of the Hairsine-Rose sediment transport model through a global sensitivity analysis. Using Standardized Regression Coefficients (SRC) and Extended Fourier Amplitude Sensitivity Test (EFAST) methods, the analysis showed that both the total washed-off mass and the TSS peaks concentration are highly sensitive to the critical mass, which considers the reduction in the detachment of particles when the sediment available decreases and is scattered over the surface. In addition, the rain- and flow-driven detachment parameters were presented as key for smaller and larger sediment particles, respectively. Then, those uncertainties that are associated in field studies with the determination of the model input variables were also considered by conducting a local sensitivity analysis. The initial load of sediment and the mean grain size were seen to be the most important variables, thus underlining the need for very accurate measurements here. Moreover, a precise definition of Harsine-Rose parameters is also necessary to achieve reliable results in order to work on treatment and management techniques to minimize the impact of urban surface contaminants on urban environments.

Brown bear attacks on humans: a worldwide perspective.

The increasing trend of large carnivore attacks on humans not only raises human safety concerns but may also undermine large carnivore conservation efforts. Although rare, attacks by brown bears Ursus arctos are also on the rise and, although several studies have addressed this issue at local scales, information is lacking on a worldwide scale. Here, we investigated brown bear attacks (n = 664) on humans between 2000 and 2015 across most of the range inhabited by the species: North America (n = 183), Europe (n = 291), and East (n = 190). When the attacks occurred, half of the people were engaged in leisure activities and the main scenario was an encounter with a female with cubs. Attacks have increased significantly over time and were more frequent at high bear and low human population densities. There was no significant difference in the number of attacks between continents or between countries with different hunting practices. Understanding global patterns of bear attacks can help reduce dangerous encounters and, consequently, is crucial for informing wildlife managers and the public about appropriate measures to reduce this kind of conflicts in bear country.

ANP32E, a Protein Involved in Steroid-Refractoriness in Ulcerative Colitis, Identified by a Systems Biology Approach.

BACKGROUND AND AIMS: Steroid-refractoriness is a common and unpredictable phenomenon in ulcerative colitis [UC], but there are no conclusive studies on the molecular functions involved. We aimed to assess the mechanism of action related to steroid failure by integrating transcriptomic data from UC patients, and updated molecular data on UC and glucocorticoids. METHODS: MicroRNA [miRNA] and mRNA expression were evaluated by sequencing and microarrays, respectively, from rectal biopsies of patients with moderately-to-severe active UC, obtained before and on the third day of steroid treatment. The differential results were integrated into the mathematical models generated by a systems biology approach. RESULTS: This computational approach identified 18 proteins that stand out either by being associated with the mechanism of action or by providing a means to classify the patients according to steroid response. Their biological functions have been linked to inflammation, glucocorticoid-induced transcription and angiogenesis. All the selected proteins except ANP32E [a chaperone which has been linked to the exchange of H2A.z histone and promotes glucocorticoid receptor-induced transcription] had previously been related to UC and/or glucocorticoid-induced biological actions. Western blot and immunofluorescence assays confirmed the implication of this chaperone in steroid failure in patients with active UC. CONCLUSIONS: A systems biology approach allowed us to identify a comprehensive mechanism of action of steroid-refractoriness, highlighting the key role of steroid-induced transcription and the potential implication of ANP32E in this phenomenon.

Qualidade de vida e bem-estar subjetivo de sobreviventes de câncer ósseo: percepção de sobreviventes e familiares / Quality of life and subjetive well-being of bone cancer suvivors: perceptions of survivors and family

Em Psico-Oncologia, é crescente o interesse por estudos que fundamentem programas eficazesdestinados à etapa de sobrevivência. Destarte, objetivou-se conhecer e analisar a qualidade de vida e obem-estar subjetivo de sobreviventes, com diagnóstico anterior de câncer ósseo. Para tanto, 27sobreviventes e 25 familiares preencheram os seguintes instrumentos: Questionário de Avaliação daExperiência Oncológica do Sobrevivente, Escala de Qualidade de Vida para Sobreviventes de Câncere Escala de Bem-Estar Subjetivo. A percepção de qualidade de vida dos sobreviventes revelou-se maispositiva do que para seus familiares. O domínio psicológico foi estimado como de pior desempenho.A percepção de bem-estar subjetivo foi semelhante para sobreviventes e familiares. Não houvediferença quanto à idade, localização do tumor e renda entre sobreviventes(AU)

Central ventilatory control in the South American lungfish, Lepidosiren paradoxa: contributions of pH and CO(2).

Lungfish represent a probable sister group to the land vertebrates. Lungfish and tetrapods share features of respiratory control, including central, peripheral and intrapulmonary CO(2) receptors. We investigated whether or not central chemoreceptors in the lungfish, L. paradoxa, are stimulated by CO(2) and/or pH. Ventilation was measured by pneumotachography for diving animals. The fourth cerebral ventricle was equipped with two catheters for superfusion. Initially, two control groups were compared: (1) catheterized animals with no superfusion and (2) animals superfused with mock CSF solutions at pH = 7.45; PCO(2) = 21 mmHg. The two groups had virtually the same ventilation of about 40 ml BTPS kg(-1) h(-1) (P > 0.05). Next, PCO(2) was increased from 21 to 42 mmHg, while pH(CSF) was kept at 7.45, which increased ventilation from 40 to 75 ml BTPS kg(-1) h(-1). Conversely, a decrease of pH(CSF) from 7.45 to 7.20 (PCO(2) = 21 mmHg) increased ventilation to 111 ml BTPS kg(-1) h(-1). Further decreases of pH(CSF) had little effect on ventilation, and the combination of pH(CSF) = 7.10 and PCO(2) = 42 mmHg reduced ventilation to 63 ml BTPS kg(-1) h(-1).

Components to the acid-base related ventilatory drives in the South American lungfish Lepidosiren paradoxa.

Lungfish are closely related to terrestrial vertebrates (tetrapoda). Like tetrapods, the South American lungfish (Lepidosiren paradoxa) has central chemoreceptors involved in regulation of acid-base status. However, no data were available on peripheral CO(2)/[H(+)] receptors. Therefore, we tested the hypothesis that such receptors exist by measuring the ventilatory responses during a 5h exposure to combined aquatic/gas phase hypercarbia 7% (approximately 49 mmHg). Normocarbic control ventilation was 22 ml BTPS kg(-1)h(-1), and hypercarbia increased ventilation to 175 ml BTPS kg(-1)h(-1) at 5h. This procedure was repeated with the modification that normocarbic mock CSF (pH 7.45; P(CO2) = 20.7 mmHg) was applied to superfuse the cerebral ventricular system during the last 2h of the experiment. This served to eliminate the hypercarbic stimulus to the central chemoreceptors, while possible responses from peripheral chemoreceptors would remain intact. Peripheral receptors were detected, since ventilation became reduced to 62 ml BTPS kg(-1)h(-1) (P<0.05), which exceeds the initial normocarbic control ventilation (P<0.05). Based on this, the peripheral contribution accounted for 20% of the total response to hypercarbia, similar to the contribution of these receptors in man.

Effects of acute temperature changes on aerial and aquatic gas exchange, pulmonary ventilation and blood gas status in the South American lungfish, Lepidosiren paradoxa.

Lungfish (Dipnoi) are probably sister group relative to all land vertebrates (Tetrapoda). The South American lungfish, Lepidosiren paradoxa, depends markedly on pulmonary gas exchange. In this context, we report on temperature effects on aquatic and pulmonary respiration, ventilation and blood gases at 15, 25 and 35 degrees C. Lung ventilation increased from 0.5 (15 degrees C) to 8.1 ml BTPS kg(-1) min(-1) (35 degrees C), while pulmonary O(2)-uptake increased from 0.06 (15 degrees C) to 0.73 ml STPD kg(-1) min(-1) (35 degrees C). Meanwhile aquatic O(2)-uptake remained about the same ( approximately 0.01 ml STPD kg(-1) min(-1)) at all temperatures. Concomitantly, the pulmonary gas exchange ratio (R(E)) rose from 0.11 (15 degrees C) to 0.62 (35 degrees C), because a larger fraction of total CO(2) output became eliminated by the lung. Accordingly, PaCO(2) rose from 13 (15 degrees C) to 37 mm Hg (35 degrees C), leading to a significant decrease of pHa at higher temperature (pHa=7.58-15 degrees C; 7.33-35 degrees C). The acid-base status of L. paradoxa was characterized by a generally low pH (7.4-7.5), high bicarbonate level (20-25 mM) and PaO(2) ( approximately 80 mm Hg). The increased dependence on the lung at higher temperature parallels data for amphibians. Further, the effects of bimodal gas exchange on temperature-dependent acid-base regulation closely resemble those of anuran amphibians.

Micronuclei in lymphocytes of prostate cancer patients undergoing radiation therapy.

To further verify the applicability of the micronucleus (MN) assay in biodosimetry, we measured the MN yield in cytokinesis-blocked (CB) peripheral blood lymphocytes (PBL) of eight prostate cancer (PC) patients. These patients had no previous chemotherapy or radiotherapy (xRT). They were treated with standardized schemes of fractionated pelvic xRT. Before xRT, and at one random time-point during the course of xRT, blood samples were collected from each patient for the following purposes: (1) to verify the relationship between the MN yield in PBL and the estimated equivalent (EQ) total-body absorbed dose; and (2) to evaluate the individual differences of ex vivo radiation dose-response (1-4 Gy) relationship of MN yield in PBL before xRT. The number of xRT fractions, cumulative tumor dose, and EQ total-body absorbed doses of these patients represented a wide range. We found in PBL of these patients that (1) MN yield (Y) increased linearly with the estimated EQ total-body absorbed dose as Y=14.6+9.2D (R(2)=0.7, p=0.007); the distributions of MN yield were overdispersed; the ratio of relative increment of MN yield per 1000 binucleated (BN) PBL ranged from 0.9 to 8.2 (median: 4.1) folds above that of the respective baseline levels; and (2) before xRT, the MN yields also increased linearly with the ex vivo radiation dose; at each radiation dose level, the distributions of MN yield were overdispersed in most patients. In two of the three patients with xRT-induced early side effects (cystitis, diarrhea), the MN yield in PBL induced by ex vivo irradiation before xRT was significantly higher than in the other patients without xRT-induced side effects. These findings suggest that MN yields in CB PBL can be used as an in vivo biodosimeter. Since the differences in individual ex vivo radiation dose-response relationship of MN yield in PBL before xRT appeared to be significant, our preliminary results also suggest that it may be possible to identify individual intrinsic radiosensitivity before the start of xRT.

TrkA is necessary for the normal development of the murine thymus.

Nerve growth factor (NGF) and its signal-transducing receptor TrkA are expressed in the thymus. However, their possible role during thymic organogenesis is unknown. Here we analyze the thymus of trkA-kinase deficient 2-week-old mice. trkA-kinase +/+ and +/- mice had a normal thymus, whereas the thymus of trkA-kinase -/- mice showed lack of delimitation between the cortex and medulla, lower thymocyte density, and the presence of epithelial cell islands and numerous cysts lined with endodermal epithelium. The present results indicate that TrkA is necessary for the normal development of the thymus, and that its absence causes an arrest in the differentiation of endodermal epithelial cells. Whether this lack of differentiation has functional implication has yet to be determined.

Developmental changes in nerve growth factor (NGF) binding and NGF receptor proteins trkA and p75 in the facial nerve.

This study characterizes the temporal-spatial distribution of nerve growth factor (NGF) low (p75) and high-affinity (trkA) receptors in the facial nerve and geniculate ganglion (GG) of developing quail embryos (E-3 to E-14). We used 125I-labeled NGF (125I-NGF) to study binding dynamics in a temporal series of isolated primordia and an autoradiographic series of staged specimens to characterize the occurrence and distribution of NGF receptors in this cranial nerve and its ganglion. In addition, expression of trkA and p75 protein-like immunoreactivity in the facial nerve and GG was studied by Western blot, in order to distinguish between high- and low-affinity NGF receptors respectively. The quantitative study of binding show that isolated facial primordia ranging from E-3 to E-14 exhibit different levels of specific binding. High initial binding levels were observed on E-3 specimens, then an initial decrease on day 4 (E-4) followed by a steady increase from days E-4 to E-7. Maximum 125I-NGF binding was achieved on E-7, followed by a steady decline in binding on days 8 (E-8) and 9 (E-9), reaching near background levels on day 10 (E-10) of development and until the oldest stage assayed (E-14). Most of the cells bearing NGF receptors appeared to be non-neuronal crest-derived cells, but some placode-derived neurons and motor fibers of the VIIth cranial nerve transiently expressed the ability to bind 125I-NGF. The temporal pattern of p75 expression matches the pattern of quantitative binding of NGF, while the trkA expression is restricted to a few stages mainly E7 and E9, implying that most of the binding detected is via low-affinity receptors, except for a proportion of high-affinity receptors present at stages of maximum binding. This temporal pattern of NGF binding sites suggests that cells within the VIIth cranial nerve are responsive to and/or dependent upon NGF in vivo, so NGF may play a biological role during normal development of the facial nerve. In view of the developmental events that parallel the occurrence and type of NGF binding sites, we suggest that this role may be to modulate from earlier chemotaxis and cell proliferation to much later events, such as neuronal differentiation and neuron-glia interactions. The significance of these findings in regeneration during adult life remain to be investigated.

[Prophylactic effect of Misoprostol on gastric lesions induced by aspirin (ASA) in healthy subjects]. / Efecto profiláctico de Misoprostol sobre las lesiones gástricas inducidas por aspirina (AAS) en sujetos sanos.

Aspirin (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs), are extensively used for treating rheumatic diseases, inflammatory problems, and pain of different etiologies. However, their use is limited by the damage they may produce to the gastroduodenal mucosa. The purpose of this double-blind, multicenter, randomized, placebo-controlled study was to assess and corroborate the protective effect of misoprostol on the gastric mucosa against ASA injury. Following endoscopic screening, 60 healthy male and female subjects were assigned, at random, to one of two treatment groups. One group was treated with ASA (3.0 g/day, in three divided doses) and misoprostol (600 mcg/day, co-administered with ASA); the other with ASA and placebo. After six days of treatment, endoscopy was repeated and the gastric mucosa was graded on a 5 point endoscopic score. Protection was defined as mucosa having an endoscopic score of 2 or less (10 or fewer hemorrhages or erosions). Misoprostol produced a significant (p = 0.005) and profound protection of the gastric mucosa against ASA injury and was well tolerated. These results suggest that misoprostol should have significant therapeutic utility in the treatment and prevention of gastropathy due to NSAIDs.

A spreadsheet program for brachytherapy planning.

A computer program (brachy-spread) which allows spreadsheet-like interactive adjustment of the loading of any brachytherapy application has been implemented. Sources are collected into objects, each assigned an activity and duration of implant. Activities and times may be adjusted by moving a cursor to the datum to be edited and entering a new value from the keyboard. Alternatively, the desired total dose to a given calculation point may be edited resulting in a recalculation of the time for all objects. For each of a set of calculation points, dose rates, total doses, and the percent contribution of each object to the point are displayed and instantly updated as the times and activities are adjusted. The program design includes rapidly updated display of isodose curves in previously selected arbitrary planes. A strategy for providing rapid dose display involving precalculation of fractional dose tables is used. The program has significantly reduced the time required to determine the appropriate loading of GYN applications and of implants which involve a combination of line sources and seeds.

Sarcoma granulocitico (cloroma): compressao de medula espinal e envolvimento testicular. / Granulocytic sarcoma (chloroma): spinal cord compression and testicular involvement

Sao apresentados dois casos de sarcoma granulocitico (cloroma) com compressao de medula espinal, um deles com massa tumoral do testiculo. A revisao da literatura mostra que embora que embora a infiltracao microscopia do testiculo na leucemia mieloide seja frequente, massas tumorais sao raramente observadas. Os dois casos apresentados foram diagnosticados durante o curso de leucemia mieloide aguda. Os autores enfatizam a necessidade de identificacao da doenca na fase pre-leucemica quando o diagnostico histopatologico pode apresentar dificuldade sem o uso de coloracoes especificas