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Stochastic field reconstruction is a crucial technique to improve the accuracy of modern rock simulation. It allows explicit modelling of field conditions, often employed in uncertainty quantification analysis and upsampling and upscaling procedures. This paper presents a case-study of a framework for the stochastic reconstruction of rock’s strain field using experimental data. The proposed framework is applied to a limestone outcrop in which the strain field is measured using Digital Image Correlation (DIC). Assuming that the strain fields of these rocks are well-represented by Gaussian random fields, we capitalize on the algorithms used for training Gaussian processes to estimate the correlation family and the parameters that best represent these fields. Although the spherical and exponential kernels often correspond to the best fit, our results depict that each field shall be analyzed separately and no general rule can be defined. We show that the method is versatile and can be employed in any measurable field reasonably represented by a Gaussian random field. Therefore, the present work aims to highlight the following topics: • A study-case of stochastic strain field reconstruction aims to contribute to uncertainty quantification of rock experimental procedures. • A stochastic minimization algorithm is presented to solve the maximum likelihood estimation to define the most suitable hyper-parameter: correlation length. • The calculated hyper-parameters of a set correlation functions are presented to best reproduce the strain fields of a rock sample.

Introdução: A variante Ômicron do vírus SARS-CoV-2 (B.1.1.529) foi designada uma variante preocupante (VOC) devido à alta transmissibilidade e capacidade de escapar da imunidade natural e induzida por vacina. Objetivo: Caracterizar a duração da infectividade da variante Ômicron em indivíduos vacinados com sintomas leves de COVID-19. Método: Estudo transversal com 30 indivíduos vacinados com COVID-19 para avaliar a duração da infectividade da Ômicron comparando o isolamento viral com o teste rápido de antígeno (RAT) e os valores de Ct da reação em cadeia da polimerase em tempo real (RT-PCR) de amostras respiratórias nos dias 5, 7, 10 e 14 a partir do início dos sintomas. Resultados: O crescimento viral foi observado em 46% (11/24) das amostras dos indivíduos vacinados no dia 5 dos sintomas e 20% (6/30) no dia 7, nenhuma amostra teve isolamento viral no dia 10. A carga de RNA viral permaneceu detectável em 97% (29/30) e 57% (17/30) dos participantes nos dias 10 e 14, respectivamente. Entre as amostras com isolamento viral, todas (n = 17) foram RAT e RT-PCR positivas. Por outro lado, amostras sem isolamento viral (n = 97) foram RAT e RT-PCR positivas em 36 (37%) e 83 (86%), respectivamente. RAT e RT-PCR evidenciaram sensibilidade global e valores preditivos negativos de 100%, porém, RAT apresentou 63% de especificidade global e 32% de valor preditivo positivo (VPP), enquanto RT-PCR evidenciou menor especificidade (14%) e VPP (17%) para predizer a infectividade. Conclusão: Indivíduos vacinados imunocompetentes com infecção por Ômicron ainda podem transmitir o vírus no 7° dia de sintomas, portanto, é altamente improvável que estejam transmitindo o vírus infeccioso no dia 10. Testes rápidos de antígeno podem ser usados para estimar a duração da infectividade dos casos de Ômicron. Ag. Financiadora: Instituto todos pela saúde do Banco Itaú.

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is used worldwide to test and trace the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). "Extraction-less" or "direct" real time-reverse transcription polymerase chain reaction (RT-PCR) is a transparent and accessible qualitative method for SARS-CoV-2 detection from nasopharyngeal or oral pharyngeal samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged 10 global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international interlaboratory ring trial. Participating laboratories were provided a common protocol, common reagents, aliquots of identical pooled clinical samples, and purified nucleic acids and used their existing in-house equipment. We observed 100% concordance across laboratories in the correct identification of all positive and negative samples, with highly similar cycle threshold values. The test also performed well when applied to locally collected patient nasopharyngeal samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that direct RT-PCR assay methods can be clearly translated across sites utilizing readily available equipment and expertise and are thus a feasible option for more efficient COVID-19 coronavirus disease testing as demanded by the continuing pandemic.

Peak load shaving using energy storage systems has been the preferred approach to smooth the electricity load curve of consumers from different sectors around the world. These systems store energy during off-peak hours, releasing it for usage during high consumption periods. Most of the current solutions use solar energy as a power source and chemical batteries as energy storage elements. Despite the clear benefits of this strategy, the service life of the battery energy storage system (BESS) is a driving factor for economic feasibility. The present research work proposes the use of storage systems based on actively connected batteries with power electronics support. The proposed scheme allows the individualized control of the power flow, enabling the use of batteries with different ages, technologies or degradation states in a same BESS. The presented results show that overcoming inherent limitations found in passively connected battery banks makes it possible to extend the system’s useful life and the total amount of dispatched energy by more than 50%. Experimental tests on a bench prototype with electronified batteries are carried out to proof the central concept of the proposed solution. Computational simulations using collected data from a photovoltaic plant support the conclusions and discussions on the achieved benefits.

This paper presents the Intertropical Convergence Zone (ITCZ) as the possible source mechanism of the medium-scale traveling ionospheric disturbances (MSTIDs) propagating to the southeast direction over the South American region. Using the data collected by the GNSS dual-frequency receivers network from January 2014 to December 2019, detrended TEC maps were generated to identify and characterize 144 MSTIDs propagating southeastward over the South American low-latitude and equatorial region. We also used images from the Geostationary Operational Environmental Satellite (GOES) 13 and 16 in the infrared (IR) and water vapor (WV) channel, and reanalisys data from the National Centers for Environmental Prediction (NCEP) of the National Oceanic and Atmospheric Administration (NOAA) to study the daily features and seasonal migration of ITCZ. In the winter, when ITCZ migrates to the northern hemisphere around 10–15° N, 20 MSTIDs propagated southeastward. During summer, when the ITCZ lies within the continent, around 0–5° S 80 MSTIDs were observed to propagate southeastward; in the equinoxes (spring and fall), 44 MSTIDs were observed. Again, the MSTIDs propagating southeastward showed a clear seasonality of their local time dependence; in summer, the MSTIDs occurred frequently in the evening hours, whereas those in winter occurred during the daytime. We also found for the first time that the day-to-day observation of ITCZ position and MSTIDs propagation directions were consistent. With regard to these new findings, we report that the MSTIDs propagating southeastward over the South American region are possibly induced by the atmospheric gravity waves, which are proposed as being generated by the ITCZ in the troposphere. The mean distribution of the horizontal wavelength, period, and phase velocity are 698 ± 124 km, 38 ± 8 min, and 299 ± 89 m s−1, respectively. For the first time, we were able to use MSTID propagation directions as a proxy to study the source region.

Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2-4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.

Background: SARS-CoV-2 quickly spreads in the worldwide population, imposing social restrictions to control the infection, being the massive testing another essential strategy to break the chain of transmission. Aim: To compare the performance of at-home self-collected samples – saliva and combined nasal-oropharyngeal swabs (NOP) – for SARS-CoV-2 detection in a telemedicine platform for COVID-19 surveillance. Material and methods: We analyzed 201 patients who met the criteria of suspected COVID-19. NOP sampling was combined (nostrils and oropharynx) and saliva collected using a cotton pad device. Detection of SARS-COV-2 was performed by using the Altona RealStar® SARS-CoV-2 RT-PCR Kit 1.0. Results: There was an overall significant agreement (κ coefficient value of 0.58) between saliva and NOP. Considering results in either sample, 70 patients positive for SARS-CoV-2 were identified, with 52/70 being positive in NOP and 55/70 in saliva. This corresponds to sensitivities of 74.2% (95% CI; 63.7% to 83.1%) for NOP and 78.6% (95% CI; 67.6% to 86.6%) for saliva. Conclusion: Our data show the feasibility of using at-home self-collected samples (especially saliva), as an adequate alternative for SARS-CoV-2 detection. This new approach of testing can be useful to develop strategies for COVID-19 surveillance and for guiding public health decisions.

We analyse the influence of spiral dislocation topology on the revival time for the harmonic oscillator, for a particle confined to one-dimensional quantum ring, and a two-dimensional quantum ring. We first investigate the effects of a cut-off point that stems from the topology of this defect on the harmonic oscillator. Then, we show that the influence of spiral dislocation topology on the harmonic oscillator gives rise to a non-null revival time related to the radial quantum number. In the case of the two-dimensional quantum ring, we show that the revival times related to the radial quantum number and the angular momentum quantum number are influenced by the spiral dislocation topology.

La equinococosis es una infección parasitaria provocada por Echinococcus granulosus, que, en su estado quístico, forma al denominado quiste hidatídico. Presenta morbilidad importante, con posibles secuelas relacionadas con la ubicación, y altos costos debido al tratamiento quirúrgico y farmacológico prolongado. El hígado y el pulmón son las ubicaciones anatómicas más usuales, mucho más raras son el riñón, bazo, cerebro y corazón, este último representa el 0,5 % a 2 % del total de casos. El Perú es un país endémico de esta antropozoonosis y principalmente registra casos procedentes de la sierra central (95 %). Se presenta el caso de una niña de diez años, con diagnóstico de esta entidad, clasificación ecográfica CE 1, grupo clínico 1 (confirmado por anatomía patológica) con posterior tratamiento quirúrgico y farmacológico específico (albendazol). La paciente se recuperó satisfactoriamente de la cirugía practicada, y fue dada de alta a los 16 días, sin complicaciones.

Using data collected by the GNSS dual-frequency receivers network, de-trended TEC maps were generated to identify and characterize the medium-scale traveling ionospheric disturbances (MSTIDs) over the South American equatorial region (latitude: 0∘ to 15∘ S and longitude: 30∘ to 55∘ W) during solar cycle 24 (from January 2014 to December 2019). A total of 712 MSTIDs were observed during quiet geomagnetic conditions. The Frequency of occurrence of MSTID is high during the solar maximum and low in the minimum phase. This might be due to the solar cycle dependence of gravity wave activity in the lower atmosphere and gravity wave propagation conditions in the thermosphere. The predominant daytime MSTIDs, representing 80% of the total observations, occurred in winter (June-August season in the southern hemisphere) with the secondary peak in the equinox; while the evening time MSTIDs, representing 18% of the entire events, occurred in summer (December to February season) and equinox (March to May and September to November), and the remaining 2% of the MSTIDs were observed during nighttime. The seasonal variation of the MSTID events was attributed to the source mechanisms generating them, the wind filtering and dissipation effects, and the local time dependency. The horizontal wavelengths of the MSTIDs were mostly concentrated between 500 and 800 km, with the mean value of 667 ± 131 km. The observed periods ranged from 30 to 45 min with the mean value of 36 ± 7 min. The observed horizontal phase speeds were distributed around 200 to 400 m/s, with the corresponding mean of 301 ± 75 m/s. The MSTIDs in the winter solstice and equinoctial months preferentially propagated northeastward and northwestward. Meanwhile, during the summer solstice, they propagated in all directions. The anisotropy of the propagation direction might be due to several reasons: the wind and dissipative filtering effects, ion drag effects, the primary source region, and the presence of the secondary or tertiary gravity waves in the thermosphere. Atmospheric gravity waves from strong convective sources might be the primary precursor for the observed equatorial MSTIDs. In all seasons, we noted that the MSTIDs propagating southeastward were probably excited by the likely gravity waves generated by the intertropical convergence zone (ITCZ).

Populations of Ocyurus chrysurus were compared genetically and morphometrically along the West Atlantic coast to test the null hypothesis of population homogeneity in the area. Brazilian populations were found to be differentiated in shape (canonical variates analysis; F[48,515] = 10.84, p < 0.0001). Analyses of mitochondrial DNA sequences (663 bp of the control region) did not show any differences between Brazilian populations but could detect differences between Brazilian and Caribbean (Belize) populations. The samples from Pernambuco differed significantly from the other Brazilian populations in allozyme frequencies (11 loci; F ST = 0.167; p < 0.05), but this may have resulted from the small number of samples analysed for that population. Sequence variation of Belize samples departed from neutral expectations (Fu's FS = -8.88; p < 0.001). A mismatch distribution analysis points to an ancient population expansion in that area. We conclude that the genetic data do not allow the rejection of the null hypothesis of panmixia for Brazilian yellowtail snapper populations which should be treated as a single genetic stock, with a latitudinal gradient on their morphology which probably results from phenotypic plasticity. On the other hand, there is a severe restriction to gene flow between O. chrysurus populations from the Caribbean and from the southwestern Atlantic.

Knowledge of the role of Neotropical montane landscapes in shaping genetic connectivity and local adaptation is essential for understanding the evolutionary processes that have shaped the extraordinary species diversity in these regions. In the present study, we examined the landscape genetics, estimated genetic diversity, and explored genetic relationships with morphological variability and reproductive strategies in seven natural populations of Cattleya liliputana (Orchidaceae). Nuclear microsatellite markers were used for genetic analyses. Spatial Bayesian clustering and population-based analyses revealed significant genetic structuring and high genetic diversity (He = 0.733 ± 0.03). Strong differentiation was found between populations over short spatial scales (FST = 0.138, p < 0.001), reflecting the landscape discontinuity and isolation. Monmonier´s maximum difference algorithm, Bayesian analysis on STRUCTURE and principal component analysis identified one major genetic discontinuity between populations. Divergent genetic groups showed phenotypic divergence in flower traits and reproductive strategies. Increased sexual reproductive effort was associated with rock outcrop type and may be a response to adverse conditions for growth and vegetative reproduction. Here we discuss the effect of restricted gene flow, local adaptation and phenotypic plasticity as drivers of population differentiation in Neotropical montane rock outcrops.

Avaliou-se o efeito da aeração no primeiro estágio do processo de compostagem em carcaças de aves mediante o monitoramento de parâmetros físicos (temperatura), químicos (reciclagem de nutrientes) e microbiológicos (coliformes fecais, totais, ausência ou presença de Salmonella sp). O processo de compostagem desenvolveu-se em dois estágios, o primeiro em composteiras com e sem aeração e o segundo no pátio de compostagem. A temperatura máxima atingida, considerando a média semanal, no primeiro estágio, foi de 56,1 ºC e 54,1 ºC (com e sem aeração) e 66,2 ºC e 61,9 ºC (com e sem aeração), respectivamente, para o primeiro e o segundo carregamentos realizados nos sistemas, enquanto no segundo estágio foi de 53,6 ºC e 61,1 ºC; 64,6 ºC e 66,3 ºC, respectivamente, para os sistemas com e sem aeração nos dois carregamentos realizados. Não houve diferença de temperatura entre os sistemas no primeiro estágio do processo a ponto de impedir o desenvolvimento de Salmonella sp ocorrido no primeiro carregamento, em ambos os sistemas. Entretanto, a redução de coliformes totais e fecais bem como a ausência de Salmonella sp nas amostras do composto pronto, em ambos os sistemas, permite inferir sobre a necessidade da realização de um segundo estágio tanto para garantir a biossegurança do processo como para a obtenção de um composto com melhores características agronômicas.The effects of aeration in the first stage of poultry carcasses composting through the monitoring of physics parameters (temperature), chemicals (nutrients recycling) and microbiologic (total and fecal coliforms and Salmonella sp absence or presence) were evaluated. The composting trial was carried out in two stages, the first at composters with or without aeration and the second at the composting area. The maximum temperature attained, considering weekly average, in the first stage was 56.1 ºC and 66.2 ºC (with and without aeration) and 54.1 ºC and 61.9 ºC (with and without aeration), respectively for the first and second loading system, while in the second stage was 53.6 ºC and 64.6 ºC; 61.1 ºC and 66.3 ºC, respectively for the systems with or without aeration in the two loading. The results obtained showed that didn't have any difference of temperature between treatments at the first stage of the process to impede the development of Salmonella sp occurred in the first loading in both systems. However, the decrease of total and fecal coliforms as well as the absence of Salmonella sp at the compost samples in both system allow to infer about the necessity to realize the second stage as much to guarantee the biosecurity of the process as to obtain a compost with better agronomic characteristics.

O processo de compostagem foi avaliado por meio do monitoramento diário da temperatura em leiras confeccionadas com o resíduo da indústria de desfibrilação de algodão e tipos de inóculo. Foram avaliadas seis leiras, divididas em dois sistemas: com aeração e sem aeração, sendo estudados, em cada sistema, três tipos de inóculo: esterco bovino diluído em água; esterco bovino, e conteúdo ruminal. Avaliou-se, também, a porcentagem de redução de volume nas leiras quando se intensificaram os revolvimentos, visando a obter informações para fins de dimensionamento do pátio de compostagem. Os compostos produzidos foram transferidos para minhocário e amostras do produto após a compostagem e após a vermicompostagem foram analisadas quimicamente com o objetivo de avaliar os teores de nutrientes. Os resultados obtidos demonstraram que o conteúdo ruminal utilizado como inóculo tende a apresentar valores mais altos de temperatura na fase inicial (fase ativa) e menores na fase final (maturação), embora, independentemente do tipo de inóculo utilizado, a estabilização praticamente tenha ocorrido no mesmo período; o sistema com aeração possibilitou, em todos os tratamentos, estabilização mais rápida do material, quando comparado ao sistema sem aeração; a intensificação dos revolvimentos possibilitou diminuição do tempo de retenção com redução de 46% no volume final, e a composição química dos vermicompostos apresentou-se enriquecida quando comparada aos compostos produzidos.The composting process performance was evaluated through diary temperature monitoring at piles made with the waste of cotton carding industry and kinds of inocule. Were evaluated six piles divided in two systems: with aeration and without aeration. In each system three kinds of inocule: cattle waste diluted in water; cattle waste and rumen were studied. In a second phase three piles with rumen intensifying the turnings aiming to evaluate the reduction of weight and volume in order to evaluate the dimension of a composting area were also conducted. All the composts produced were transferred to a earthworm creation area and samples of the product after the composting and after the vermicomposting were chemically analyzed aiming to evaluate the nutrients content. The results obtained showed that: the rumen as a inocule presents high values of temperatures in the initial phase (active phase) and low values in the final phase (maturity) although independently of the inocule the stabilization occurred at the same time; the system with aeration allowed in all treatments a faster material stabilization when compared to the system without aeration; the intensification of turnings in the second phase allowed the decreasing of the composting time and 46% of final volume reduction; the chemical composition of the vermicomposts showed enriched when compared with the composts produced.

The bacterial community and genes involved in geobiocycling of arsenic (As) from sediment impacted by long-term gold mining were characterized through culture-based analysis of As-transforming bacteria and metagenomic studies of the arsC, arrA, and aioA genes. Sediment was collected from the historically gold mining impacted Mina stream, located in one of the world's largest mining regions known as the "Iron Quadrangle". A total of 123 As-resistant bacteria were recovered from the enrichment cultures, which were phenotypically and genotypically characterized for As-transformation. A diverse As-resistant bacteria community was found through phylogenetic analyses of the 16S rRNA gene. Bacterial isolates were affiliated with Proteobacteria, Firmicutes, and Actinobacteria and were represented by 20 genera. Most were AsV-reducing (72%), whereas AsIII-oxidizing accounted for 20%. Bacteria harboring the arsC gene predominated (85%), followed by aioA (20%) and arrA (7%). Additionally, we identified two novel As-transforming genera, Thermomonas and Pannonibacter. Metagenomic analysis of arsC, aioA, and arrA sequences confirmed the presence of these genes, with arrA sequences being more closely related to uncultured organisms. Evolutionary analyses revealed high genetic similarity between some arsC and aioA sequences obtained from isolates and clone libraries, suggesting that those isolates may represent environmentally important bacteria acting in As speciation. In addition, our findings show that the diversity of arrA genes is wider than earlier described, once none arrA-OTUs were affiliated with known reference strains. Therefore, the molecular diversity of arrA genes is far from being fully explored deserving further attention.

OBJETIVO: Traçar o perfil dos pacientes de fisioterapia no pré e pós-operatório de cirurgias ortopédicas e traumatológicas na Santa Casa de Caridade do Município de Uruguaiana/RS. METODOLOGIA: Estudo retrospectivo com análise das fichas de avaliação dos pacientes atendidos no período de 11/03 à 11/05/2011. RESULTADOS: Neste período foram atendidos 22 pacientes, 68,2% eram do sexo masculino (média de idade de 50 anos) e 31,8% correspondiam ao sexo feminino (média de idade de 59 anos). As lesões em membros superiores equivaleram a 27,3% dos casos e membros inferiores a 59,1%. Das lesões por sexo, 57,1 % das mulheres e 60% dos homens apresentaram lesões por acidente de trânsito, com tempo médio de internação de 11,7 dias. Com estes resultados, podemos inferirque o elevado número de pacientes com fraturas relacionadas a acidentes de trânsito está possivelmente relacionado com o aumento da frota urbana de motocicletas, associado à imprudência de seus condutores.

Southeast Brazil is a neotropical region composed of a mosaic of different tropical habitats and mountain chains, which allowed for the formation of bird-rich communities with distinct ecological niches. Although this region has the potential to harbor a remarkable variety of avian parasites, there is a lack of information about the diversity of malarial parasites. We used molecular approaches to characterize the lineage diversity of Plasmodium and Haemoproteus in bird communities from three different habitats in southeast Brazil based on the prevalence, richness and composition of lineages. We observed an overall prevalence of 35.3%, with a local prevalence ranging from 17.2% to 54.8%. Moreover, no significant association between prevalence and habitat type could be verified (p>0.05). We identified 89 Plasmodium and 22 Haemoproteus lineages, with 86% of them described for the first time here, including an unusual infection of a non-columbiform host by a Haemoproteus (Haemoproteus) parasite. The composition analyses of the parasite communities showed that the lineage composition from Brazilian savannah and tropical dry forest was similar, but it was different from the lineage composition of Atlantic rainforest, reflecting the greater likeness of the former habitats with respect to seasonality and forest density. No significant effects of habitat type on lineage richness were observed based on GLM analyses. We also found that sites whose samples had a greater diversity of bird species showed a greater diversity of parasite lineages, providing evidence that areas with high bird richness also have high parasite richness. Our findings point to the importance of the neotropical region (southeast Brazil) as a major reservoir of new haemosporidian lineages.

Abstract With advances in information technology for health and wellness, Smart Home-based solution providers using Internet of Things (IoT) technologies, have increased in importance and become accepted as an alternative means of saving energy when based on Home Energy Management Systems (HEMS). This paper defines a modern architecture (SmartCoM), which is implemented to monitor and manage residential dwellings by using IoT technologies. This involves setting out the parameters that can make interoperability possible between measurement and management, and the layers of data communication, which are the features necessary for the hardware required for monitoring and measurement. In addition, an interface is defined by a middleware layer to integrate the management of external installations and the visualization of data by means of a cloud service. The SmartCoM end-to-end architecture is defined in detail from the standpoint of the consumer and optimization strategies are employed for both the end customer and the utility. The main advantages of using SmartCoM were confirmed by the numerical results obtained from the proposed architecture. This paper ends by showing the current position of SmartCoM as well as suggesting further stages for this line of research.

The eukaryotic translation initiation factor 4E (eIF4E) is a potent oncogene that is found to be dysregulated in 30% of human cancer, including colorectal carcinogenesis (CRC). ISIS 183750 is a second-generation antisense oligonucleotide (ASO) designed to inhibit the production of the eIF4E protein. In preclinical studies we found that EIF4e ASOs reduced expression of EIF4e mRNA and inhibited proliferation of colorectal carcinoma cells. An additive antiproliferative effect was observed in combination with irinotecan. We then performed a clinical trial evaluating this combination in patients with refractory cancer. No dose-limiting toxicities were seen but based on pharmacokinetic data and tolerability the dose of irinotecan was reduced to 160 mg/m(2) biweekly. Efficacy was evaluated in 15 patients with irinotecan-refractory colorectal cancer. The median time of disease control was 22.1 weeks. After ISIS 183750 treatment, peripheral blood levels of eIF4E mRNA were decreased in 13 of 19 patients. Matched pre- and posttreatment tumor biopsies showed decreased eIF4E mRNA levels in five of nine patients. In tumor tissue, the intracellular and stromal presence of ISIS 183750 was detected by IHC in all biopsied patients. Although there were no objective responses stable disease was seen in seven of 15 (47%) patients who were progressing before study entry, six of whom were stable at the time of the week 16 CT scan. We were also able to confirm through mandatory pre- and posttherapy tumor biopsies penetration of the ASO into the site of metastasis.

Based on recent political happenings, such as Brexit (UK) and the election of Donald Trump (USA), it has become clear that political marketing has been using 'Big Data' intensively. Information gathered from social media networks is organized into digital environments and has the power to determine the outcome of elections, plebiscites and popular consultations. New advertising and persuasion mechanisms have been created to undermine the reliability of traditional mass media communication that are familiar to the general audience. Consequently, 'fake news' and 'alternative facts' have emerged along with the notion of 'post-truth', which defines the state of affairs represented in public opinion that has been contaminated by these strategies. Based on the pragmatic-semiotic concepts developed by Peirce, such as belief, mental habits, controlled action, final opinion, truth, and reality, we argue that the 'global village', (McLuhan, 2008) may be at a dangerous fork in the road. This author's 'scientific method' was elaborated based on (1) the concatenation of hypotheses, (2) the deduction of its consequences, and (3) the design of experiences and aims to test our beliefs against our results which would be critically evaluated by communities of researchers. This fork in the road, which rapidly evolves as a dystopia built and reaffirmed by the spread of disinformation on social networks, points towards a 'post-reality' that can represent an illusory and brief comfort zone for those who live in it but may also represent a tragedy with no turning back for our entire civilization.

Background: A longitudinal cohort study was established to investigate the well‐being of children born with cleft lip and/or palate (CL/P) during the COVID‐19 pandemic, in Victoria, Australia. Materials and Methods: The Royal Children's Hospital cleft service database was used to identify children aged between 4 and 17 years old born with an isolated CL/P. Families of eligible children who consented to participate were asked to complete the Strengths and Difficulties Questionnaire (SDQ) between October and December 2020 and again 6‐month later. SDQ results from typically developing Australian children during the COVID‐19 pandemic were utilized from a previously published study. Results: 63 parents completed the baseline questionnaire, with 44 completing the 6‐month follow‐up. For participants at baseline, the mean age was 8.9 years, with 55% male. All outcome domains of the SDQ improved between baseline and timepoint 2, with the difference in total difficulties scores being statistically significant, indicating a reduction in total difficulties at timepoint 2, associated with the easing of COVID‐19 restrictions. When compared with the Australian population during the COVID‐19 pandemic, Victorian children born with CL/P had lower SDQ scores for all difficulties outcome domains, with statistically significant results for conduct problems, hyperactivity, peer problems and total difficulties, indicating fewer difficulties for children born with CL/P. Conclusions: Children born with CL/P experienced fewer difficulties when compared with the typically developing Australian population during the COVID‐19 pandemic. The level of restrictions imposed because of the pandemic also had little influence on the well‐being of these children. [ABSTRACT FROM AUTHOR]