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The PAU (Physics of the Accelerating Universe) project goal is the study of dark energy with a new photometric technique aiming at obtaining photo-z resolution for Luminous Red Galaxies (LRGs) roughly one order of magnitude better than current photometric surveys. To accomplish this, a new large field of view camera (PAUCam) has been built and commissioned at the William Herschel Telescope (WHT). With the current WHT corrector, the camera covers ~1 degree diameter Field of View (FoV). The focal plane consists of 18 2kx4k Hamamatsu fully depleted CCDs, with high quantum efficiency up to 1 μm. To maximize the detector coverage within the FoV, filters are placed in front of the CCD's inside the camera cryostat (made of carbon fiber material) using a challenging movable tray system. The camera uses a set of 40 narrow band filters ranging from ~4400 to ~8600 angstroms complemented with six standard broad-band filters, ugrizY. Here, we describe the camera and its first commissioning results. The PAU project aims to cover roughly 100 square degrees and to obtain accurate photometric redshifts for galaxies down to iAB ~ 22:5 detecting also galaxies down to iAB ~ 24 with less precision in redshift. With this data set we will obtain competitive constraints in cosmological parameters using both weak lensing and galaxy clustering as main observational probes.

Regulatory T-cell (Treg) modulation is developing as an important therapeutic opportunity for the treatment of a number of important diseases, including cancer, autoimmunity, infection, and organ transplant rejection. However, as demonstrated with IL-2 and TGN-1412, our understanding of the complex immunological interactions that occur with Treg modulation in both non-clinical models and in patients remains limited and appears highly contextual. This lack of understanding will challenge our ability to identify the patient population who might derive the highest benefit from Treg modulation and creates special challenges as we transition these therapeutics from non-clinical models into humans. Thus, in vivo testing in the most representative animal model systems, with careful progress in the clinic, will remain critical in developing therapeutics targeting Treg and understanding their clinical utility. Moreover, toxicology models can inform some of the potential liabilities associated with Treg modulation,...

Background Schistosomiasis is to a degree a disease of contact with fecally contaminated surface waters, rather than ingestion. Repeated treatments with praziquantel reduce schistosomiasis prevalence and morbidity; however, transmission persists and prevalence of infection often recover within a few years. Methods In a community in rural Bahia, Brazil that straddles a shallow river, we surveyed and treated all individuals that tested positive for schistosomiasis by Kato Katz in stools in 2009, 2012, 2013, 2015, and 2017. Upstream and downstream, as well as common water contact sites along the river were sampled and analyzed by microbial source tracking for human fecal indicator markers. The location of each home and water contact site was registered with a handheld GPS unit. Spatial analyses were performed by using QGIS software, version 2.14. Results The population in the village was 460 in 2009, with minimal fluctuation over the study period. In 2009, schistosomiasis prevalence was 45%. After successive rounds of community-wide treatment with praziquantel, in the years 2012, 2013, 2015, and 2017, prevalence decreased to 24%, 16%, 13%, and 1.6%, respectively. Among the river water samples, human fecal indicator markers were detectable in minimal quantities upstream of the village. The highest concentrations were found in the downstream sections of the village. Hotspot analysis, raster calculator, and nearest neighbor analysis were used to display and analyze the prevalence of schistosomiasis. Distribution of infection was widespread initially and clustered in the downstream sections of the village after successive treatments. Conclusion In this rural community in Brazil, sustained decrease in schistosomiasis prevalence was seen after multiple community-wide treatments over 5 years. Reinfection was not distributed randomly but concentrated in the downstream portion of the village, where human fecal water contamination is increased. Targeting sanitation in key areas may decrease sources of transmission persistence after cessation of community-wide treatment efforts. Disclosures All authors: No reported disclosures.

During manufacturing of an exemplary CD19-directed CAR-T cell product, patient T cells were transduced with a viral vector encoding the CD19-directed, 41BBζ endodomain-containing chimeric antigen receptor (CAR) construct, enabling permanent genetic modification of the target T cells. Lentiviral transduction with a self-inactivating (SIN) vector can offer certain advantages in safety and consistency over other DNA delivery methods. Although the integration patterns of wildtype HIV-1 have been well-characterized and shown to have a low risk of insertional transformation, the addition of an artificial construct may have the potential to affect integration patterns. Existing techniques for viral integration mapping, such as ligation-mediated polymerase chain reaction (LM-PCR), have limitations precluding comprehensive, unbiased, high-throughput insertion site mapping. To characterize insertional events in engineered CAR-T cells, we developed an unbiased NGS assay and computational pipeline capable of characterizing viral integration events genome-wide. The method leverages Tn5 transposase, coupled with a long terminal repeat-specific PCR, to map integration events down to nulceotide resolution. This assay identified over 150,000 high-confidence integration events across 23 patient-derived CAR-T cell products. Analysis of these sites revealed a similar integration preference to lentiviruses described in the literature: driven by GC content, local nucleotide content, chromatin status, and transcriptional activity, with no indication of preferential integration at oncogenic loci. In conclusion, in this assay a CD19-directed, CAR-containing lentivirus exhibited a low risk integration profile with no significant evidence of construct-specific risk factors. Furthermore, the findings suggest that the NGS assay may be useful for more efficient, cost-effective, and sensitive measurement of CAR-T integration events for a range of constructs. Citation Format: Timothy G. Johnstone, Rajagopal Chari, David Koppstein, Ronald J. Hause, Rafael Ponce, Adrian W. Briggs, Francois Vigneault. Directed, unbiased mapping of lentiviral integrations with next generation sequencing in CAR-T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1541.

Ancient human hair specimens can shed light on the extent of pre-historic exposures to methylmercury and provide valuable comparison data with current-day exposures, particularly for Indigenous Peoples who continue to rely upon local traditional food resources. Human hair from ancient Aleutian Island Native remains were tested for total and methylmercury (Hg, MeHg) and were radiocarbon dated. The remains were approximately 500 years old (1450 A.D.). For four adults, the mean and median total hair mercury concentration was 5.8 ppm (SD=0.9). In contrast, MeHg concentrations were lower with a mean of 1.2 ppm (SD=1.8) and a median of 0.54 ppm (0.12–3.86). For the five infants, the mean and median MeHg level was 1.2 ppm (SD=1.8) and 0.20 ppm (0.007–4.61), respectively. Segmental analyses showed variations in MeHg concentrations in 1-cm segments, consistent with fluctuations in naturally occurring exposure to mercury through dietary sources. The levels are comparable to or lower than those found in fish and marine mammal-eating populations today who rely far less on subsistence food than pre-historic humans. The findings are, therefore, compatible with increased anthropogenic release of trace metals during the past several centuries.

Dietary factors influence the development of cardiovascular disease (CVD). The diet of Alaskan Eskimos differs from that of other populations. We surveyed Eskimo adults in Northwest Alaska to document their usual dietary intakes, differences based on gender and age, and sources of selected nutrients, and to generate appropriate dietary advice to reduce CVD. Interviewers surveyed 850 men and women 17-92 y old, using a quantitative food-frequency instrument. We observed many significant (chi(2) analysis P < 0.05) differences in nutrient intakes among 3 age-groups. Energy intake from carbohydrate was negatively related to participant age-group (P < or = 0.01). Energy intake from all fats (P < 0.001) and polyunsaturated fat (P < or = 0.01) was positively related to age-group among both men and women in contrast to other studies in which age differences were either not observed or decreased with age. Native foods were major sources of monounsaturated and polyunsaturated fats, including 56% of (n-3) fatty acids primarily from seal oil and salmon. However, Native foods contributed significantly less to the diets of young adults than to those of elders, especially among women. Store-bought foods were the main sources of energy, carbohydrate, fat, saturated fat, and fiber for all adults. Based on their nutrient density and potential to inhibit CVD, continued consumption of traditional foods is recommended. Variations in intake by age may portend changing eating patterns that will influence CVD as participants age. These data will contribute to understanding dietary risk factors for cardiovascular disease in this population.

In this paper the Fast-Means algorithm, an enhanced version of the K-Means algorithm; inspired by the Early Classification algorithm; is presented. After analyzing the Early Classification algorithm it was found that the higher centroid displacement at each iteration can be used as mean to define whether an object remains in the same cluster for subsequent iterations, also we found that the reduction strategy can be applied from the beginning to the end of the algorithm execution unlike the Early Classification algorithm where the strategy is applied from the second to the last iteration. Results show that the Fast-Means outperforms the standard version because it reaches a time reduction up to 99.02% with only a quality reduction of 7.62% for the Transaction dataset. Additionally, Fast-Means compared to Early Classification reached an improvement in time reduction up to 41.92% with only a difference of 2.73% in quality reduction.

Background The relationship between poor sanitation and the parasitic infection schistosomiasis is well-known, but still rarely investigated directly and quantitatively. In a Brazilian village we correlated the spatial concentration of human fecal contamination of its main river and the prevalence of schistosomiasis. Methods We validated three bacterial markers of contamination in this population by high throughput sequencing of the 16S rRNA gene and qPCR of feces from local residents. The qPCR of genetic markers from the 16S rRNA gene of Bacteroides-Prevotella group, Bacteroides HF8 cluster, and Lachnospiraceae Lachno2 cluster as well as sequencing was performed on georeferenced samples of river water. Ninety-six percent of residents were examined for schistosomiasis. Findings Sequence of 16S rRNA DNA from stool samples validated the relative human specificity of the HF8 and Lachno 2 fecal indicators compared to animals. The concentration of fecal contamination increased markedly along the river as it passed an increasing proportion of the population on its way downstream as did the sequence reads from bacterial families associated with human feces. Lachnospiraceae provided the most robust signal of human fecal contamination. The prevalence of schistosomiasis likewise increased downstream. Using a linear regression model, a significant correlation was demonstrated between the prevalence of S. mansoni infection and local concentration of human fecal contamination based on the Lachnospiraceae Lachno2 cluster (r2 0.53) as compared to the correlation with the general fecal marker E. coli (r2 0.28). Interpretation Fecal contamination in rivers has a downstream cumulative effect. The transmission of schistosomiasis correlates with very local factors probably resulting from the distribution of human fecal contamination, the limited movement of snails, and the frequency of water contact near the home. In endemic regions, the combined use of human associated bacterial markers and GIS analysis can quantitatively identify areas with risk for schistosomiasis as well as assess the efficacy of sanitation and environmental interventions for prevention., Author Summary People tend to live close to natural water bodies, and often these water bodies are used as waste disposal in many regions of the world. The consequences of this are often studied with regard to bacterial and viral infections, but rarely for parasitic infections. In this study the authors examined a rural community settled along a river in Brazil, and found that the concentration of fecal bacteria in water accumulates as the river runs downstream. Molecular methods were able to show that most of these fecal bacteria were of human origin rather than from local livestock or other domestic animals. To assess the impact of fecal contamination of surface waters, the authors investigated its association with schistosomiasis, a parasitic infection transmitted by snails exposed to water contaminated by human feces. Similar to the distribution of fecal contamination, the proportion of people with schistosomiasis was higher in areas located downstream. A model combining concentration of human fecal bacteria in water and Geographic Information Systems (GIS) analysis of schistosomiasis prevalence showed that areas of increased concentration of human feces correlated with areas in the village at higher risk for schistosomiasis. This research provides insight into the dynamics of fecal contamination of rivers and its spatial impact on a human parasitic disease.

Cosmology is a data intensive field that will become more so in the coming years. In this scenario, GPU-computing is becoming very relevant for analysing large catalogs within a reasonable amount of time. In this work, we investigate the acceleration of the analysis by using a hybrid MPI-CUDA implementation.

Karstic springs are characterized by their unsteady behaviour of quantitative and qualitative parameters. The irregular and unpredictable increases of turbidity, natural organic matter (NOM), particles and solutes require a flexible and reliable treatment to ensure save drinking water quality at any time. In this study, results of a microfiltration (MF) and an ultrafiltration (UF) pilot plant are presented based on 15 and 12 months on-site experience. The investigations were focused on the optimization of the operation conditions of the membranes (maximum flux, dead-end mode, cross-flow mode) in order to guarantee drinking water production at any raw water quality. The results strongly support that MF performance is mainly influenced by submicron particles contained in the raw water suspension at higher turbidity peaks and that UF membrane permeability is affected by NOM during storm weather events. Additional quality problems in some springs caused by the presence of micropollutants (trichlorethene, tetrachlorethene, atrazine) gave rise to experimentally assess the combination of powdered activated carbon (PAC) with membrane filtration. The adsorption characteristics of the solutes on different PACs were tested in laboratory and pilot scale. In the on-site experiments, removal rates of 80–90% could be achieved by adopting the necessary contact time to the previously determined kinetic data. Additionally, NOM adsorption by PAC addition could substantially improve UF performance.

This paper presents a novel approach for the problem of detecting and extracting the QRS complex of electrocardiogram signals for different kinds of arrhythmias. First, an autocorrelation function is used in order to obtain the period of an electrocardiagram signal and then the Hilbert transform is applied to obtain R-peaks and beats. Twenty three different records extracted from the MIT-BIH arrhythmia database were used to validate the proposed approach. In this testing has been observed a 99.9 % of accuracy in detecting the QRS complexity, being a positive result in comparison with other recent researches.

Untreated sewage discharges and limited agricultural manure management practices contribute to fecal pollution in rural Brazilian waterways. Most microbial source tracking studies have focused on Bacteroidales, and few have tested host-specific indicators in underdeveloped regions. Sequencing of sewage and human and animal feces with Illumina HiSeq revealed Prevotellaceae as the most abundant family in humans, with Lachnospiraceae and Ruminococcaceae also comprising a large proportion of the microbiome. These same families were also dominant in animals. Bacteroides, the genus containing the most commonly utilized human-specific marker in the United States was present in very low abundance. We used oligotyping to identify Prevotella and Blautia sequences that can distinguish human fecal contamination. Thirty-five of 61 Blautia oligotypes and 13 of 108 Prevotella oligotypes in humans were host-specific or highly abundant (i.e. host-preferred) compared to pig, dog, horse and cow sources. Certain human Prevotella and Blautia oligotypes increased more than an order of magnitude along a polluted river transect in rural Brazil, but traditional fecal indicator levels followed a steady or even decreasing trend. While both Prevotella and Blautia oligotypes distinguished human and animal fecal pollution in Brazil surface waters, Blautia appears to contain more discriminatory and globally applicable markers for tracking sources of fecal pollution.

For patients undergoing transrectal ultrasound-guided biopsy of the prostate (TRUBP), use of rectal screening culture results to guide antimicrobial prophylaxis was effective for prevention of fluoro-quinolone-resistant Escherichia coli infections. In practice, elimination of infections after TRUBP required the rectal screening protocol and addition of gentamicin for patients missing prior screening.

This paper presents a method for modeling and identification of electrocardiogram signals; the proposed method consists of two phases; the first one is focused on obtaining the period of an ECG signal using a procedure of autocorrelation. The second phase obtains R-peaks using the Hilbert transform. Finally, an Artificial Neural Network using a retraining technique is applied for the prediction stage; this has been validated using the record 100 from the MIT-BIH arrhythmia database. Results confirm that the presented approach for detection of the ECG complex obtains 100% accuracy. The performance of the prediction method is promising due to the root mean squared errors of the prediction are of 0.029, 0.04, and 0.059 of the ECG amplitude, for 1, 2, and 3 steps ahead, respectively.

Nonclinical to clinical correlations of biotherapeutics generally support the utility of nonclinical studies for predicting adverse clinical responses, if the fidelity of the pharmacodynamics of human biotherapeutics is maintained in nonclinical models. However, toxicities associated with immunomodulation—opportunistic infections, cytokine release syndrome, and other indirect outcomes of immunomodulation—are less likely to be predicted by routine nonclinical studies. Predicting adverse reactions to biotherapeutics is further complicated by the rapidly expanding array of modalities. Predicting adverse reactions to biotherapeutics is further complicated by the rapidly expanding array of modalities. In this chapter, we discuss safety considerations for establishing the safety profiles for various modalities of biotherapeutics in early nonclinical development and provide examples of adverse events, with special emphasis on immunotoxicity. Special approaches to predicting immunotoxicity due to on-target and off-target toxicities to ensure the well-being of healthy volunteers as well as patients are also discussed. Novel and scientifically appropriate additional nonclinical studies are necessary to make informed drug development decisions in addition to information gathered from routine nonclinical studies.

Em regiões de clima quente e úmido, com elevados valores de temperatura e umidade e altos níveis de radiação solar, recomenda-se o emprego de materiais leves, de superfícies com baixa absortância e, principalmente, o sombreamento das superfícies externas, além da permeabilidade das edificações ao vento. Contudo, observa-se nos novos edifícios, o emprego de materiais com alta inércia térmica e alta absortância, acompanhadas pela redução da vegetação e o adensamento inadequado das áreas construídas, características opostas às recomendações bioclimáticas de projeto. O presente artigo teve início com o desenvolvimento de um projeto de pesquisa PIBIC-EM, que teve por objetivo investigar a influência das cores de revestimentos cerâmicos no ganho térmico do edifício através de registros realizados por termômetro infravermelho e câmera termográfica, demonstrando a necessidade da observação criteriosa da especificação de tal característica no processo de concepção de projeto, e sua consequente contribuição no conforto térmico dos usuários e na eficiência energética do edifício.

O processo de autoconstrução é característico das áreas urbanas e rurais de baixa renda. Sem acesso aos serviços de engenharia e arquitetura e sem o conhecimento das normas técnicas vigentes, esse processo resulta na concepção de ambientes desconfortáveis, subdimensionados e, até mesmo, insalubres. Além disso, a ausência do projeto de arquitetura acarreta maior desperdício de materiais, gastos desnecessários e aumento do tempo de execução da obra. No ambiente rural, estas dificuldades são potencializadas devido à dificuldade de acesso à informação, aos profissionais capacitados, aos recursos financeiros e aos materiais de construção adequados. Neste sentido, o presente artigo relata a experiência de um projeto de extensão, vinculado ao núcleo de extensão Campo Solar, que atua como um escritório modelo de arquitetura social no Campus Cajazeiras do IFPB, atendendo os assentamentos localizados na região do Alto Sertão da Paraíba. No primeiro período do projeto, trabalhou-se com as demandas de alguns espaços coletivos que visam produzir lucro a toda comunidade, promovendo a melhoria da qualidade de vida dos moradores.

The Physics of the Accelerating Universe (PAU) is a project whose main goal is the study of dark energy. For this purpose, a new large field of view camera (the PAU Camera, PAUCam) is being built. PAUCam is designed to carry out a wide area imaging survey with narrow and broad band filters spanning the optical wavelength range. The PAU Camera is now at an advance stage of construction. PAUCam will be mounted at the prime focus of the William Herschel Telescope. With the current WHT corrector, it will cover a 1 degree diameter field of view. PAUCam mounts eighteen 2k×4k Hamamatsu fully depleted CCDs, with high quantum efficiency up to 1 μm. Filter trays are placed in front of the CCDs with a technologically challenging system of moving filter trays inside the cryostat. The PAU Camera will use a new set of 42 narrow band filters ranging from ~4400 to ~8600 angstroms complemented with six standard broad-band filters, ugrizY. With PAUCam at the WHT we will carry out a cosmological imaging survey in both narrow and broad band filters that will perform as a low resolution spectroscopic survey. With the current survey strategy, we will obtain accurate photometric redshifts for galaxies down to i AB ~22.5 detecting also galaxies down to i AB ~24 with less precision in redshift. With this data set we will obtain competitive constraints in cosmological parameters using both weak lensing and galaxy clustering as main observational probes.

Interleukin-21 (IL-21), a pleiotropic immunostimulatory type I cytokine, has anticancer effects in animal models. Preclinical studies designed to assess the safety of recombinant human IL-21 (rIL-21) for use in phase I oncology studies are described. The rIL-21 (≤3.0 mg/kg per dose) was given intravenously to cynomolgus monkeys ( Macaca fascicularis) once daily for 5 days, followed by 9 nondosing days (1 cycle) for ≤4 cycles. The rIL-21 pharmacokinetics was dose-dependent. Accumulation was not observed after repeated dosing, consistent with the short elimination half-life ( t1/2,λz; 0.4-0.8 hours). Safety findings included cyclical anemia and thrombocytopenia, clinical pathology changes consistent with acute-phase response, leukocyte infiltrates in hepatic sinusoids, and sporadic serum transaminase elevations (typically

The urban spaces environmental quality is determined by the interaction between the natural elements and the man-made changes to adapt the environment to their physical, social and economic needs. In this context, is inserted the urban climate, result of the dialogic relationship between the morphology of the city, the human activities and the various local and global climate factors. The climate change, characteristic of urban space, causes several damages to most cities by increasing the rigors of local climate. In this sense, the study of urban space, in particular, the research about urban climatology, become fundamental to the search for environmental quality, as well as to achieve the energy efficiency in urban areas. In the city, the use of vegetation is an important strategy for mitigation of the local climate, however, is still unknown the potential of this contribution, requiring studies to evaluate the best ways of its application, in accordance with the morphology of the green space and urban space and the local climatic characteristics. The present study analyzed the extent and the magnitude of the influence of the Buraquinho s Forest, in João Pessoa/ PB, in the climatic characteristics of their surroundings by monitoring the temperature and the air s humidity in winter and summer periods, arranged in three transects in downwind of the forest, total of thirteen points of data collection, one of them located in forest interior. It was observed that among the points considered, in the summer, the averages air temperatures were in general 3°C higher than the winter and the relative humidity 15% lower. The temperature differences between points with higher and lower temperatures were similar in both periods, it was observed the main difference at 13h: 3° C in the winter and 2,8 °C in the summer. It was also discovered that the lowest temperatures were obtained in points located on the edge of the forest, whereas the higher temperatures were found in the farthest points, however, it wasn t possible to identify a linear tendency of temperature increase associated to the increased distance from the forest. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES A qualidade ambiental do espaço urbano é determinada pela interação entre os elementos naturais e as transformações artificiais produzidas pelo homem na adaptação do meio às suas necessidades físicas, sociais e econômicas. Neste contexto, insere-se o clima urbano, fruto da relação dialógica entre a morfologia da cidade, as atividades humanas e os diversos fatores climáticos locais e globais. Por sua vez, a alteração climática no espaço urbano ocasiona diversos malefícios para grande parte das cidades ao intensificar os rigores climáticos locais. Neste sentido, o estudo do espaço urbano e, em especial, as pesquisas sobre climatologia urbana, tornam-se fundamentais para a busca da qualidade ambiental, assim como para o alcance da eficiência energética urbana. Na cidade, o uso de vegetação configura-se em uma importante estratégia para amenização climática local, porém, ainda é desconhecido o potencial dessa contribuição, necessitando-se de estudos que avaliem as melhores formas de sua aplicação, de acordo com a morfologia do espaço verde e do espaço urbano e as características climáticas locais. O presente estudo analisou o alcance e magnitude da influência da Mata do Buraquinho, em João Pessoa/ PB, nas características climáticas do seu entorno ao monitorar a temperatura e umidade do ar nos períodos de inverno e verão, em três transectos dispostos a sotavento da mata, totalizando treze pontos de coleta, sendo um deles localizado em seu interior. Observou-se que entre os pontos analisados, no período de verão, as temperaturas médias do ar foram em geral 3ºC superiores as de inverno e a umidade relativa do ar 15% inferior. As diferenças de temperatura entre pontos com maior e menor temperatura foram semelhantes nos dois períodos, observando-se a maior divergência às 13h, sendo 3°C no inverno e 2,8°C no verão. Constatou-se também, que as menores temperaturas foram obtidas nos pontos localizados na borda da mata, enquanto as maiores temperaturas foram encontradas nos pontos mais afastados, porém não foi possível identificar uma tendência linear de aumento de temperatura relacionada ao aumento do distanciamento da mata.

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) S9 is the first international regulatory guidance document devoted to a specific therapeutic area, highlighting its importance in harmonizing regulatory expectations for the nonclinical development of therapeutics designed to treat advanced cancer. ICH S9 successfully outlines the core requirements for the nonclinical development of novel oncology therapeutics, and the unique risk-benefit considerations for expediting drug development to treat these most grievous diseases. However, development companies and regulatory agencies have had limited opportunity to apply this guidance, so our collective experience in developing therapeutics under the guidance is limited. Discussed here are several key areas of ambiguity in the guidance, including identification of the patient population, selection of the initial safe dose for first-in-human trials, and requirements for nonclinical recovery data.

An important safety consideration for developing new therapeutics is assessing the potential that the therapy will increase the risk of cancer. For biotherapeutics, traditional two-year rodent bioassays are often not scientifically applicable or feasible. This paper is a collaborative effort of industry toxicologists to review past and current practice regarding carcinogenicity assessments of biotherapeutics and to provide recommendations. Publicly available information on eighty marketed protein biotherapeutics was reviewed. In this review, no assessments related to carcinogenicity or tumor growth promotion were identified for fifty-one of the eighty molecules. For the twenty-nine biotherapeutics in which assessments related to carcinogenicity were identified, various experimental approaches were employed. This review also discusses several key principles to aid in the assessment of carcinogenic potential, including (1) careful consideration of mechanism of action to identify theoretical risks, (2) careful investigation of existing data for indications of proliferative or immunosuppressive potential, and (3) characterization of any proliferative or immunosuppressive signals detected. Traditional two-year carcinogenicity assays should not be considered as the default method for assessing the carcinogenicity potential of biotherapeutics. If experimentation is considered warranted, it should be hypothesis driven and may include a variety of experimental models. Ultimately, it is important that preclinical data provide useful guidance in product labeling.

Information retrieval for geo-locatable places and services must be provided with the most according and personalized content to a user’s information request, based this on his or her spatio-temporal situation. One initiative that describes a set of geo-locable services is the Chefmoz project, in which different restaurants from the entire world are semantically described; in this paper is presented an approach that takes advantage of the information contained in Chefmoz in order to apply semantic Web technologies for the contextual and personalized query of services. In order to this, a extended version for the FOAF vocabulary which describes the personal context of a user was used. The precision and recall results for an experimental case are presented. Finally the conclusions and future work is mentioned.

In Mexico the computer science security is growing, but not therefore the initiatives of law nor the standards in the matter of computer science security, although they exist international standard of computer science security the recommendations are not adopted due to infrastructure differences and that contain there, and that cannot be adopted by the Mexican companies. The main idea to propose a methodology and architecture for the small and medium companies is with the purpose of providing a tool that allows the companies to count on basic a computer science security system that allows diminishing the security problems.

Publisher Summary Biotechnology-derived therapeutic products represent a diverse class of agents that are categorized by their method of manufacture, typically based on recombinant DNA technology. These products include recombinant proteins and nucleotides as gene therapies, anti-sense therapies, cytokines, monoclonal antibodies, growth factors, soluble receptors, fusion proteins, vaccines, and coagulation factors. Therapeutic targets of these products include genetic deficiency; neurological, cardiovascular, autoimmune and inflammatory disorders; cancer; metabolic disorders; and other conditions. Given that these molecules are typically derived and produced to mimic endogenous nucleotides and proteins, their toxicity tends to be related to that associated with over-stimulation or suppression of the targeted biological pathways. In addition, unlike potentially active metabolites associated with small molecule therapies, the metabolic by-products of biotechnology-derived therapeutics are generally inactive amino acid and nucleotide fragments.

Los isangos (Trombicula autumnalis) son conocidos popularmente en la selva peruana pero no se ha documentado su frecuencia. Se realizó un estudio transversal en un caserío de Lamas, región San Martín, se evaluó a 18 menores de cinco años los cuales todos tenían lesiones producidas por isangos, estos ejemplares fueron remitidos al Instituto Nacional de Salud los cuales fueron identificados como T. autumnalis. Se evaluó también a escolares y población adulta de esa localidad encontrando que 56/70 niños y 85/130 adultos tenían lesiones compatibles por infestación con T. autumnalis. Las zonas más afectadas fueron las piernas, ingle y nalg Isangos (Trombicula autumnalis) are popularly known in the Peruvian jungle has not been documented their frequency. We performed a cross-sectional study in a village of Lamas, San Martín region, 18 children under five years were evaluated who all had injuries due isangos, these specimens were sent to the National Institute of Health (Lima, Peru) which were identified as T. autumnalis. It also assessed school students and adult population of this village found that 56/70 children and 85/130 adults had lesions compatible with infestation by T. autumnalis. The zones most affected were the legs, groin and buttocks.

Talimogene laherparepvec is an investigational oncolytic immunotherapy based on a modified herpes simplex virus type-1 (HSV-1) designed to selectively replicate in tumors and to initiate a systemic immune response to target cancer cells that have metastasized. Intralesional administration of talimogene laherparepvec is intended to result in oncolysis within injected tumors. Iterative viral replication of virus within permissive tumor tissue results in lytic cell destruction and local release of progeny virus and tumor derived antigens. GM-CSF, a product of the viral transgene, is also produced locally such that it can recruit and stimulate antigen presenting cells which, in addition to relevant tumor-derived antigens, are required for the initiation of a systemic antitumor immune response. Recently, in a retrospective analysis of a Phase III melanoma trial investigators found that about two-thirds of the lesions injected with talimogene laherparepvec shrank 50% or more. And the same effect was seen in about a third of all uninjected tumors in the skin and lymph nodes and about a sixth of uninjected visceral lesions providing an indication that the treatment is triggering the desired immune system effect. Ongoing clinical trials are investigating T-VEC in combination with the immune checkpoint inhibiting antibodies ipilimumab and pembrolizumab in advanced melanoma. We sought to determine if the combination of intratumoral injection of talimogene laherparepvec and the systemic delivery of the checkpoint anti-PD1 antibody could increase the anti-tumor efficacy in a preclinical syngeneic contralateral tumor model. Using established MC-38 colon carcinoma tumors in C57Bl/6 mice, we delivered three intratumoral injections three days apart of the talimogene laherparepvec surrogate OncoVEXmuGM-CSF and twice weekly systemic injections of an antagonistic anti-PD-1 antibody. Either OncoVEXmuGM-CSF or anti-PD-1 alone induced modest tumor growth inhibition/tumor regressions of contralateral tumors. In combination, the OncoVEXmuGM-CSF injected tumor displayed 8/10 complete regressions and the distant tumors had 2/10 complete regressions. Peripheral blood was analyzed at 4 days and 10 days post the initial OncoVEXmuGM-CSF and anti-PD-1 antibody injections. OncoVEXmuGM-CSF increased the percent of PD-L1+ CD4 and CD8 T cells and the combination increased the percent of activated CD8+ T cells. Our findings demonstrate that localized therapy with talimogene laherparepvec augments the systemic anti-tumor immune response seen with anti-PD-1 therapy, providing a strong rationale for continued investigation of such combinations in the clinic. Citation Format: Julia Piasecki, Tiep le, Rafael Ponce, Courtney Beers. Talilmogene laherparepvec increases the anti-tumor efficacy of the anti-PD-1 immune checkpoint blockade. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 258. doi:10.1158/1538-7445.AM2015-258

Talimogene laherparepvec is an investigational oncolytic immunotherapy based on a modified herpes simplex virus type-1 (HSV-1) immunotherapy designed to selectively replicate in tumors and to initiate an anti-tumor immune response. Intralesional administration of talimogene laherparepvec is intended to result in oncolysis within injected tumors. Iterative replication of virus within permissive tumor tissue results in lytic cell destruction and local release of progeny virus and tumor derived antigens. GM-CSF, a product of the viral transgene, is also produced locally such that it can recruit and stimulate antigen presenting cells which, in addition to relevant tumor-derived antigens, are required for the initiation of a systemic antitumor immune response. The talimogene laherparepvec-induced immune mediated mechanism of action in both the virus-injected and distant tumors have yet to be fully understood therefore, we evaluated viral replication, tumor cell lysis, and the changes in immune cell populations in both the injected and distant tumors using syngeneic contralateral tumor models. Animals received a single intratumoral dose of the murine surrogate of talimogene laherparepvec (OncoVEXmuGM-CSF), which induced regression in the majority of virus-injected tumors and tumor growth inhibition/regression in the contralateral (uninjected) tumors. HSV-1 antigen was only detected by IHC in the virus-injected tumor and not the contralateral tumor (and no other tissues). Virally-mediated tumor destruction (oncolysis) was also localized to only the virus-injected tumor. In preliminary experiments, morphometric analysis of the tumor tissue revealed that the percent area of CD3+ and CD8+ lymphocytes were significantly increased in both the virus-injected and contralateral tumors compared to the formulation control mice. In addition, the percent area occupied by CD103+ cells (a marker found on potent cytotoxic T cell stimulating dendritic cells) was increased in the virus-injected tumor compared to the contralateral tumor and the tumors in the control animals. Although cellular infiltration was increased in both virus-injected and contralateral tumors and was inversely correlated with tumor volume, the decreased volume of injected tumors was attributed to viral oncolysis. Taken together these data supports that talimogene laheparepvec activates a systemic T cell mediated anti-tumor immune response. Citation Format: Julia Piasecki, Jim Rottman, Tiep Le, Rafael Ponce, Courtney Beers. Talimogene laherparepvec activates systemic T-cell-mediated anti-tumor immunity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4287. doi:10.1158/1538-7445.AM2015-4287

Dietary factors influence the development of cardiovascular disease (CVD). The diet of Alaskan Eskimos differs from that of other populations. We surveyed Eskimo adults in Northwest Alaska to document their usual dietary intakes, differences based on gender and age, and sources of selected nutrients, and to generate appropriate dietary advice to reduce CVD. Interviewers surveyed 850 men and women 17-92 y old, using a quantitative food-frequency instrument. We observed many significant (chi(2) analysis P0.05) differences in nutrient intakes among 3 age-groups. Energy intake from carbohydrate was negatively related to participant age-group (Por = 0.01). Energy intake from all fats (P0.001) and polyunsaturated fat (Por = 0.01) was positively related to age-group among both men and women in contrast to other studies in which age differences were either not observed or decreased with age. Native foods were major sources of monounsaturated and polyunsaturated fats, including 56% of (n-3) fatty acids primarily from seal oil and salmon. However, Native foods contributed significantly less to the diets of young adults than to those of elders, especially among women. Store-bought foods were the main sources of energy, carbohydrate, fat, saturated fat, and fiber for all adults. Based on their nutrient density and potential to inhibit CVD, continued consumption of traditional foods is recommended. Variations in intake by age may portend changing eating patterns that will influence CVD as participants age. These data will contribute to understanding dietary risk factors for cardiovascular disease in this population.

This paper presents a novel approach for QRS complex detection and extraction of electrocardiogram signals for different types of arrhythmias. Firstly, the ECG signal is filtered by a band pass filter, and then it is differentiated. After that, the Hilbert transform and the adaptive threshold technique are applied for QRS detection. Finally, the Principal Component Analysis is implemented to extract features from the ECG signal. Nineteen different records from the MIT-BIH arrhythmia database have been used to test the proposed method. A 96.28% of sensitivity and a 99.71% of positive predictivity are reported in this testing for QRS complexity detection, being a positive result in comparison with recent researches. All Rights Reserved © 2015 Universidad Nacional Autonoma de Mexico, Centro de Ciencias Aplicadas y Desarrollo Tecnologico. This is an open access item distributed under the Creative Commons CC License BY-NC-ND 4.0.

In this paper the effect of weak lensing magnification on galaxy number counts is studied by cross-correlating the positions of two galaxy samples, separated by redshift, using data from the Dark Energy Survey Science Verification dataset. The analysis is carried out for two photometrically-selected galaxy samples, with mean photometric redshifts in the $0.2 < z < 0.4$ and $0.7 < z < 1.0$ ranges, in the riz bands. A signal is detected with a $3.5��$ significance level in each of the bands tested, and is compatible with the magnification predicted by the $��$CDM model. After an extensive analysis, it cannot be attributed to any known systematic effect. The detection of the magnification signal is robust to estimated uncertainties in the outlier rate of the pho- tometric redshifts, but this will be an important issue for use of photometric redshifts in magnification mesurements from larger samples. In addition to the detection of the magnification signal, a method to select the sample with the maximum signal-to-noise is proposed and validated with data., 18 pages, 16 figures, submitted to MNRAS