Optimal two-stage spatial sampling design for estimating critical parameters of SARS-CoV-2 epidemic: Efficiency versus feasibility.

The COVID-19 pandemic presents an unprecedented clinical and healthcare challenge for the many medical researchers who are attempting to prevent its worldwide spread. It also presents a challenge for statisticians involved in designing appropriate sampling plans to estimate the crucial parameters of the pandemic. These plans are necessary for monitoring and surveillance of the phenomenon and evaluating health policies. In this respect, we can use spatial information and aggregate data regarding the number of verified infections (either hospitalized or in compulsory quarantine) to improve the standard two-stage sampling design broadly adopted for studying human populations. We present an optimal spatial sampling design based on spatially balanced sampling techniques. We prove its relative performance analytically in comparison to other competing sampling plans, and we also study its properties through a series of Monte Carlo experiments. Considering the optimal theoretical properties of the proposed sampling plan and its feasibility, we discuss suboptimal designs that approximate well optimality and are more readily applicable.

Topics and trends in Mountain Livestock Farming research: a text mining approach.

Pasture-based and small-scale livestock farming systems are the main source of livelihood in the mountain primary sector, ensuring socioeconomic sustainability and biodiversity in rural communities throughout Europe and beyond. Mountain livestock farming (MLF) has attracted substantial research efforts from a wide variety of scientific communities worldwide. In this study, the use of text mining and topic modelling analysis drew a detailed picture of the main research topics dealing with MLF and their trends over the last four decades. The final data corpus used for the analysis counted 2 679 documents, of which 92% were peer-reviewed scientific publications. The number of scientific outputs in MLF doubled every 10 years since 1980. Text mining found that milk, goat and sheep were the terms with the highest weighed frequency in the data corpus. Ten meaningful topics were identified by topic analysis: T1-Livestock management and vegetation dynamics; T2-Animal health and epidemiology; T3-Methodological studies on cattle; T4-Production system and sustainability; T5-Methodological studies; T6-Wildlife and conservation studies; T7-Reproduction and performance; T8-Dairy/meat production and quality; T9-Land use and its change and T10-Genetic/genomic studies. A hierarchical clustering analysis was performed to explore the interrelationships among topics, and three main clusters were identified: the first focused on sustainability, conservation and socioeconomic aspects (T4; T6 and T9), the second was related to food production and quality (T7 and T8) and the last one considered methodological studies on mountain flora and fauna (T1; T2; T3; T5 and T10). The 10 topics identified represent a useful and a starting source of information for further and more detailed analysis (e.g. systematic review) of specific research or geographical areas. A truly holistic and interdisciplinary research approach is needed to identify drivers of change and to understand current and future challenges faced by livestock farming in mountain areas.

Introducing FDG PET/CT-guided chemoradiotherapy for stage III NSCLC in low- and middle-income countries: preliminary results from the IAEA PERTAIN trial.

PURPOSE: Patients with stage III non-small-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) in low- and middle-income countries (LMIC) continue to have a poor prognosis. It is known that FDG PET/CT improves staging, treatment selection and target volume delineation (TVD), and although its use has grown rapidly, it is still not widely available in LMIC. CRT is often used as sequential treatment, but is known to be more effective when given concurrently. The aim of the PERTAIN study was to assess the impact of introducing FDG PET/CT-guided concurrent CRT, supported by training and quality control (QC), on the overall survival (OS) and progression-free survival (PFS) of patients with stage III NSCLC. METHODS: The study included patients with stage III NSCLC from nine medical centres in seven countries. A retrospective cohort was managed according to local practices between January 2010 and July 2014, which involved only optional diagnostic FDG PET/CT for staging (not for TVD), followed by sequential or concurrent CRT. A prospective cohort between August 2015 and October 2018 was treated according to the study protocol including FDG PET/CT in treatment position for staging and multimodal TVD followed by concurrent CRT by specialists trained in protocol-specific TVD and with TVD QC. Kaplan-Meier analysis was used to assess OS and PFS in the retrospective and prospective cohorts. RESULTS: Guidelines for FDG PET/CT image acquisition and TVD were developed and published. All specialists involved in the PERTAIN study received training between June 2014 and May 2016. The PET/CT scanners used received EARL accreditation. In November 2018 a planned interim analysis was performed including 230 patients in the retrospective cohort with a median follow-up of 14 months and 128 patients in the prospective cohort, of whom 69 had a follow-up of at least 1 year. Using the Kaplan-Meier method, OS was significantly longer in the prospective cohort than in the retrospective cohort (23 vs. 14 months, p = 0.012). In addition, median PFS was significantly longer in the prospective cohort than in the retrospective cohort (17 vs. 11 months, p = 0.012). CONCLUSION: In the PERTAIN study, the preliminary results indicate that introducing FDG PET/CT-guided concurrent CRT for patients with stage III NSCLC in LMIC resulted in a significant improvement in OS and PFS. The final study results based on complete data are expected in 2020.

A survey of selected animal-based measures of dairy cattle welfare in the Eastern Alps: Toward context-based thresholds.

In the Alps, traditional dairy farms are small-scale operations where vertical transhumance from valley indoor housing systems to highland pasture-based systems is still practiced in summer. Vertical transhumance implies a substantial change of environment, available resources, and management practices from one season to another. In such systems, animal-based welfare measures need to be monitored throughout the year to capture the variation of welfare outcomes, based on which targeted welfare management plans can be implemented. Because the Welfare Quality assessment approach has been tailored to indoor housing and intensive farming systems, the European Food Safety Authority recently developed a welfare assessment protocol for small-scale dairy cattle farms adapted after the Welfare Quality framework. The aim of this study was to assess nonbehavioral animal-based measures as defined by this protocol at different time points for transhumant systems in the Alps. In total, 18 animal-based measures were assessed before, during, and after the mountain pasture period in a sample of 67 small-scale dairy cattle farms practicing vertical transhumance in neighboring provinces of Austria, Italy, and Slovenia. Significant differences between assessments were identified for dirtiness of legs and teats, hairless patches, lesions and swellings, claw condition, ocular discharge, and diarrhea whereas BCS, lameness/severe lameness, vulvar discharge, nasal discharge, and hampered respiration were unchanged between seasons. In addition, a benchmarking exercise was carried out to identify relative boundaries (worst quartile thresholds) for each animal-based measure and to contribute to the discussion about achievable welfare outcomes for the 2 husbandry conditions that characterize a transhumant system. Worst quartile thresholds indicated a high prevalence of dirtiness (>80%) when cows were kept indoors, high prevalence of hairless patches (65%) before pasture turnout, and high prevalence of very lean cows (>13%) throughout the assessments. On the other hand, the best quartile thresholds for most clinical conditions suggested that high welfare standards (zero prevalence) are widely achievable in mountain farms practicing vertical transhumance during all assessments. The thresholds identified through benchmarking should serve as the basis for an effective context-based welfare management strategy promoting continuous welfare improvement on-farm.

Borromean three-body FRET in frozen Rydberg gases.

Controlling the interactions between ultracold atoms is crucial for quantum simulation and computation purposes. Highly excited Rydberg atoms are considered in this prospect for their strong and controllable interactions known in the dipole-dipole case to induce non-radiative energy transfers between atom pairs, similarly to fluorescence resonance energy transfer (FRET) in biological systems. Here we predict few-body FRET processes in Rydberg atoms and observe the first three-body resonance energy transfer in cold Rydberg atoms using cold caesium atoms. In these resonances, additional relay atoms carry away an energy excess preventing the two-body resonance, leading thus to a Borromean type of energy transfer. These few-body processes present strong similarities with multistep FRET between chromophores sometimes called donor-bridge-acceptor or superexchange. Most importantly, they generalize to any Rydberg atom and could lead to new implementations of few-body quantum gates or entanglement.

La participación: determinante social en la construcción de políticas públicas / Participation: social determinant in the development of public policy

En este artículo se presentan los resultados de una investigación realizada durante 2009 y 2010 con actores políticos, técnicos y sociales, quienes participaron en la Política Pública de Mejoramiento Alimentario y Nutricional de Antioquia (MANA) de la Gobernación de Antioquia, como un modelo de construcción participativa que promueve la salud y el bienestar. OBJETIVO: comprender el proceso de participación de los diferentes actores en el diseño de la Ordenanza No 17 que fija la Política Pública de Mejoramiento Alimentario y Nutricional de Antioquia (MANA). MÉTODOS:utilizando un enfoque cualitativo se hizo un estudio de caso, de tipo interpretativo instrumental. La información obtenida con entrevistas a los actores y revisión documental fue sometida a un análisis de carácter heurístico. RESULTADOS :el proceso fue una participación activa donde los actores, tanto políticos, como técnico-metodológicos y sociales, hacen variados aportes en los diferentes momentos de la construcción de la Política Pública de Mejoramiento Alimentario y Nutricional de Antioquia. CONCLUSIONES:el Plan y la Política se convirtieron en un referente para la construcción de otras políticas, planes o programas similares, fue trascendental por su transformación comunitaria y legitimidad, y aunque tuvo dificultades en el proceso, demostró la importancia del trabajo intersectorial y de una mirada integral frente a problemas sociales tan complejos.

This paper presents the results of a research carried out in 2009 and 2010 with individuals from the political, technical and social fields who participated in the Public Policy for Food and Nutritional Improvement created by the Government of Antioquia. This program was conceived as a model of participatory construction that promotes health and welfare. OBJECTIVE:to understand the participation process of different people in the design of Ordinance 17, which establishes the Food and Nutritional Improvement Public Policy. METHODOLOGY: an interpretive instrumental case study was conducted using a qualitative approach. The information obtained from interviews with the participants and from the literature review was heuristically analyzed. RESULTS:individuals from political, technical-methodological and social areas participated actively in this project. Likewise, they made several contributions at different moments of the construction of the Food and Nutritional Improvement Public Policy for Antioquia. CONCLUSION: The Plan and The Policy became a referent for the construction of other policies, plans or similar programs. They were significant because it transformed the community and was legitimate; even though there were difficulties during the process, they proved the importance of having intersectoral work and an integral view of such complex social problems.

Reconocimiento del niño con síndrome de Down como un sujeto de crianza / Recognizing a child with Down's syndrome as a subject of parenting

OBJETIVOS:Describir el reconocimiento del niño con síndrome de Down como sujeto de crianza y de acompañamiento por parte de la madre. METODOLOGIA:investigación etnográfica con participación de 20 madres de niños con síndrome de Down, mediante entrevistas semiestructuradas y observaciones de campo, con análisis categorial y revisión documental. RESULTADOS las madres experimentan tristeza y ansiedad frente al encuentro de un niño con síndrome de Down, dadas las concepciones culturales y sociales, pero en la convivencia y en el vínculo madre-hijo surge un sujeto posible de crianza igual a otro sin síndrome. DISCUSION: el niño se transforma en sujeto social para su madre cuando logra metas en su crecimiento y desarrollo y así ella lo percibe. CONCLUSION las madres de este estudio descubren en la convivencia con su hijo que emerge un sujeto social con la condición de síndrome de Down, con potencialidades de acompañarlo en su crianza y, por tanto, realizarse como madre.

OBJECTIVE: to describe how the children with Down`s syndrome are recognized by mothers as subjects of parenting and accompaniment. METHODOLOGY an ethnographic study whose participants were 20 mothers of children with Down's syndrome. Data were collected using semi-structured interviews and field observations. Similarly, this study included a categorical analysis and a literature review. RESULTS : given the cultural and social conceptions regarding this condition, mothers experience sadness and anxiety upon giving birth to a child with Down's syndrome. Despite this, and thanks to coexistence and to the mother-child bond, the child is later perceived as a subject of parenting who is equal to another person without the syndrome. DICUSSION: children become social subjects when they achieve their goals in growth and development, and mothers can perceive this. CONCLUSION: by living with their sons, the mothers participating in this study discovered that their sons emerge as social persons with Down's syndrome. The mothers also discovered that these individuals have their own potential and that it is possible to accompany them through parenting and therefore to realize themselves as mothers.

[Immunity related to allergic response at the beginning of life] / Imunidade relacionada à resposta alérgica no início da vida.

OBJECTIVE: Given that the most common allergic manifestations (asthma, rhinitis, dermatitis, food allergies) occur during childhood, because the immune system can be induced into sensitization rather than into allergenic tolerance at the beginning of life, we analyzed the main immunological aspects of fetuses and infant in terms of allergic sensitization and response. METHODS: Detailed bibliographic revision concerning nonspecific immune response (physical and chemical barriers, myeloid cells) and specific immune response (T and B lymphocytes, cytokines) of the fetus and infant, with special attention to studies carried out in the last fifteen years. RESULTS: Various compartments of the immune system in fetuses and infants are different from those present in older children and adults. Thus, developmental aspects of nonspecific and specific immunity may contribute to atopic disease. CONCLUSIONS: Atopic predisposition is determined at the beginning of life and seems to originate not only from genetic factors, but also from intrauterine environment and initial stage of childhood, inducing the immune system to increase the synthesis of IgE.

Long-term production and delivery of human growth hormone in vivo.

The application of somatic cell gene therapy to large patient populations will require the development of safe and practical approaches to the generation and characterization of genetically manipulated cells. Transkaryotic implantation is a gene therapy system based on the production of clonal strains of engineered primary and secondary cells, using non-viral methods. We demonstrate here that, on implantation, these clonal cell strains stably and reproducibly deliver pharmacologic quantities of protein for the lifetime of the experimental animals.

Isolation of bovine kidney leucine aminopeptidase cDNA: comparison with the lens enzyme and tissue-specific expression of two mRNAs.

Aminopeptidases catalyze the hydrolysis of amino acid residues from the amino terminus of peptide substrates. Leucine aminopeptidase (LAP) from bovine lens is the best characterized aminopeptidase and the only LAP for which the amino acid sequence was determined by protein sequencing. Using this sequence information, we isolated a bovine kidney LAP cDNA and compared its deduced amino acid sequence to the published amino acid sequence for bovine lens LAP. Overall, the sequences are highly conserved. However, several differences are observed. The kidney LAP cDNA indicates a 26 amino acid extension at the amino terminus which is not found in the mature purified lens LAP. The cDNA also indicates an additional octapeptide in the C-terminal region which was not indicated in the published lens LAP amino acid sequence but which was required for best fit of crystallographic data regarding bovine lens LAP. Several other single amino acid changes were also noted. Levels of LAP transcripts were examined in bovine lens and kidney tissue as well as in cultured lens cells. Lens epithelial tissue showed only one LAP transcript (2.4 kb) whereas two transcripts (2.0 and 2.4 kb) were observed in cultured lens cells derived from epithelial tissue and in kidney tissue. Using Northern blot analysis, we correlated LAP mRNA levels with previously determined changes of LAP activity in aging lens tissue and in progressively passaged lens epithelial cells which were used to simulate aging in vitro. No differences were found in LAP mRNA levels in epithelial tissue from old and young lenses.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of aging in vitro on intracellular proteolysis in cultured rabbit lens epithelial cells in the presence and absence of serum.

Alterations in proteolytic capabilities have been associated with abnormalities in the aged eye lens, but in vivo tests of this hypothesis have been difficult to pursue. To simulate aging, we cultured cells from an 8-yr-old rabbit to early (population-doubling level 20 to 30) and late (population-doubling level greater than 125) passage. Long-lived (t1/2 greater than 10 h) and short-lived (t1/2 less than 10 h) intracellular proteins were labeled with [3H]leucine, and the ability of the cells to mount a proteolytic response to the stress of serum withdrawal was determined. For early passage cells, the average t1/2 of long-lived proteins in the presence and absence of serum was 62 and 39 h, respectively. For late-passage cells, the average t1/2 of long-lived proteins in the presence and absence of serum was 58 and 43 h, respectively. The net increase in intracellular proteolysis in the absence of serum was 59 and 35% for early and late-passage cells, respectively. Thus, in vitro-aged rabbit lens epithelial cells amount only 60% the proteolytic response to serum removal shown in "younger" cells. The enhanced ability of early passage cells to respond to serum removal seems to involve lower homeostatic levels of proteolysis in the presence of serum and greater enhancement of proteolysis in the absence of serum. Less than 2% of the protein is in the pool of short-lived proteins. Rates of proteolysis of short-lived proteins in the presence and absence of serum were indistinguishable. With respect to basal proteolytic rates in the presence of serum and ability to mount a proteolytic response upon serum withdrawal, these rabbit lens epithelial cells are similar to bovine lens epithelial cells and fibroblasts.

Evidence for ATP and ubiquitin dependent degradation of proteins in cultured bovine lens epithelial cells.

Degradation of endogenous lens proteins has been difficult to show under physiological conditions using lens tissue preparations. In contrast, active proteolytic systems in cultured bovine lens epithelial (BLE) cells have been demonstrated previously. BLE cells also contain ubiquitin, a 76 amino-acid polypeptide which is conjugated to proteins in an ATP/Mg(2+)-dependent process prior to their cytosolic proteolysis. In this study, we show that histone H2A, alpha-crystallin, and actin are conjugated to ubiquitin, resulting in higher molecular mass species, which are detected by anti-ubiquitin antibodies. These proteins are also degraded in cell-free assays containing BLE cell supernatants under physiological conditions in an ATP/Mg(2+)-dependent manner. Observation of 125I-labeled proteolytic fragments was made after SDS polyacrylamide gel electrophoresis of the assays. Quantitation of trichloroacetic acid-soluble radiolabeled fragments generated in the presence of ATP/Mg2+ revealed that, with BLE cell supernatant, 25% of the histone H2A was degraded in 3 hr. Proteolysis of alpha-crystallin and actin amounted to 2.3% and 2.9%, respectively. The requirement of ATP/Mg2+ for proteolysis and the observation of ubiquitin conjugation to the same proteins is consistent with the presence of a ubiquitin-dependent proteolytic pathway in BLE cells. Additionally, in this study the BLE cell proteases were even more active on some substrates than the reticulocyte ubiquitin/ATP-dependent proteolytic system.

Moderate caloric restriction delays cataract formation in the Emory mouse.

Eye lens senile cataract is a major cause of blindness, affecting the elderly in particular. The etiology of the disorder has been elusive, and attempts to delay the onset of senile cataracts have been unsuccessful. The need for more information is underscored by epidemiologists who estimate that the ability to delay cataract formation in humans by only 10 years would eliminate the need for 50% of the cataract extractions performed annually in the United States. The Emory mouse provides the best model for human senile cataracts. Feeding Emory mice a diet that was restricted in calories by approximately 21% delayed the onset of cataracts. This is the first study that demonstrates in vivo the delay of senile-type cataracts. In these animals, aging and cataracts are associated with diverse changes in the proportion of various proteins (particularly 21, 22, 31-34 kDa) and with transformation of proteins from a soluble to an insoluble state. In advanced cataracts, there is a loss of total protein. Within a cataract grade, there is no difference between restricted and nonrestricted animals in relative proportion of specific lens proteins or in amounts of total or soluble proteins. The transition from a clear to cataractous lens appears when the soluble-to-total protein ratio falls below about 0.58. The exclusive use of gamma-crystallin as an indicator of lens viability is questioned. To the extent that cataract formation is due to lens protein oxidation and/or an inability to proteolytically remove damaged protein, it would appear that caloric restriction results in enhanced protection against lens oxidative stress or in prolonged proteolytic function.

Imunidade especifica em pacientes com carcinoma do pancreas. Estudo preliminar. / Specific immunity in patients with carcinoma of the pancreas.Preliminary report

No presente estudo, investigamos a imunidade especifica mediada por celulas em pacientes portadores de carcinoma do pancreas. Para tanto utilizamos o teste de inibicao da aderencia de leucocitos. Em nosso estudo o ensaio para inibicao da aderencia leucocitaria mostrou-se especifico para pacientes portadores de cancer de pancreas sendo negativo quando se utilizou antigeno derivado de tumor nao-pancreatico. A aplicacao clinica deste ensaio bem como a relativa facilidade de seus aspectos tecnicos permitem afirmar que a inibicao da aderencia de leucocitos venha a se tornar um ensaio util para avaliacao da imunidade tumoral, especialmente importante para neoplasias onde o diagnostico precoce e essencial, tais como o carcinoma do pancreas