Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.

Objective: Relative to the vast literature that employs measures of decision-making (DM), rigorous examination of their psychometric properties is sparse. This study aimed to determine whether three measures of DM assess the same construct, and to measure invariance of this construct across relevant covariates. Method: Participants were 372 adolescents at risk of escalation in cannabis use. DM was assessed via four indices from the Cups Task, Game of Dice Task (GDT), and Iowa Gambling Task (IGT). We used confirmatory factor analysis to assess unidimensionality of the DM construct, and moderated nonlinear factor analysis (MNLFA) to examine its measurement invariance. Results: The unidimensional model of DM demonstrated good fit. MNLFA results revealed that sex influenced mean DM scores, such that boys had lower risk-taking behaviors. There was evidence of differential item functioning (DIF), such that IQ and age moderated the IGT intercept and GDT factor loading, respectively. Significant effects were retained in the final model, which produced participant-specific DM factor scores. These scores showed moderate stability over time. Conclusions: Indices from three DM tasks loaded significantly onto a single factor, suggesting that these DM tasks assess a single underlying construct. We suggest that this construct represents the ability to make optimal choices that maximize rewards in the presence of risk. Our final DM factor accounts for DIF caused by covariates, making it comparable across adolescents with different characteristics. (JINS, 2019, 25, 661–667)

The disease caused by the influenza virus is a global public health problem due to its high rates of morbidity and mortality. Thus, analysis of the information generated by epidemiological surveillance systems has vital importance for health decision making. A retrospective analysis was performed using data generated by the four molecular diagnostic laboratories of the Mexican Social Security Institute between 2010 and 2016. Demographics, influenza positivity, seasonality, treatment choices and vaccination status analyses were performed for the vaccine according to its composition for each season. In all cases, both the different influenza subtypes and different age groups were considered separately. The circulation of A/H1N1pdm09 (48.7%), influenza A/H3N2 (21.1%), influenza B (12.6%), influenza A not subtyped (11%) and influenza A/H1N1 (6.6%) exhibited well-defined annual seasonality between November and March, and there were significant increases in the number of cases every 2 years. An inadequate use of oseltamivir was determined in 38% of cases, and the vaccination status in general varied between 12.1 and 18.5% depending on the season. Our results provide current information about influenza in Mexico and demonstrate the need to update both operational case definitions and medical practice guidelines to reduce the inappropriate use of antibiotics and antivirals.

Filamentary structures can form within the beam of protons accelerated during the interaction of an intense laser pulse with an ultrathin foil target. Such behaviour is shown to be dependent upon the formation time of quasi-static magnetic field structures throughout the target volume and the extent of the rear surface proton expansion over the same period. This is observed via both numerical and experimental investigations. By controlling the intensity profile of the laser drive, via the use of two temporally separated pulses, both the initial rear surface proton expansion and magnetic field formation time can be varied, resulting in modification to the degree of filamentary structure present within the laser-driven proton beam.

The black rat Rattus rattus and the house mouse Mus musculus are two commensal rodent species that harbour and shed zoonotic pathogens, including helminths. The aim of this survey was to study the helminth community and the patterns of infections in R. rattus and M. musculus from two Mayan communities in Mexico. Gastrointestinal helminths were isolated from 322 M. musculus and 124 R. rattus, including Gongylonema neoplasticum, Hassalstrongylus aduncus, Hassalstrongylus musculi, Hydatigera taeniaeformis metacestode, Hymenolepis diminuta, Nippostrongylus brasiliensis, Oligacanthorhynchidae gen. sp., Syphacia muris, Syphacia obvelata, Rodentolepis microstoma and Trichuris muris. The overall richness of helminths was seven in R. rattus and six in M. musculus. The results of generalized linear models showed that juvenile rodents had lower probabilities of being infected with G. neoplasticum, H. taeniaeformis and H. musculi than adult rodents. A positive association between the prevalence of S. muris and rat abundance was found. The intensity of infection with S. muris was higher in the rainy season than in the dry season; the opposite result was found for H. musculi infection. Male R. rattus harboured more S. muris specimens. The intensity of infection with T. muris was inversely associated with mouse abundance. The presence of the zoonotic H. diminuta, as well as H. taeniaeformis and R. microstoma in rodent populations indicates that there is risk of transmission, and that their entire life cycle occurs in the study area.

Breeding for resilience requires a better understanding of intra-flock variability and the related mechanisms responsible for robustness traits. Among such traits, the animals’ ability to cope with feed fluctuations by mobilizing or restoring body reserves (BR) is a key mechanism in ruminants. The objective of this work was to characterize individual variability in BR dynamics in productive Romane ewes reared in extensive conditions. The BR dynamics profiles were characterized by combining individual longitudinal measurements of BW and body condition scores (BCS) over several production cycles. Historical data, including up to 2628 records per trait distributed in 1146 ewes, underwent cluster analysis. Two to four trajectories were observed for BW depending on the cycle, while three trajectories were found for BCS, whatever the cycle. Most trajectories suggested that BR dynamics were similar but the level of BR may differ between ewes. Nevertheless, some trajectories suggested that both BR dynamics and levels were different for a proportion of ewes. Clustering on BW and BCS profiles adjusted for individual level trends, resulted in differences only in the level of BW or BCS, rather than differences in trajectories. Thus, the overall shape of trajectories was not changed considering or not the individual level trend across cycles. In addition to individual variability, the ewe’s age at first lambing and litter size contributed to the distribution of the ewes between the trajectories. Regarding the entire productive life, three trajectories were observed for BW and BCS changes over three productive cycles. Increase in BW at each cycle suggested that ewes kept growing up until 3 to 4 years old in our conditions. Similar alternation of BCS gains and losses across cycles suggested BR dynamics might be repeatable. Many individual trajectories remained the same throughout a ewe’s life, whatever the age at first lambing, parity or litter size. Our results demonstrate the relevance of using BW and BCS changes for characterizing the diversity of BR mobilization–accretion profiles in sheep in a long timespan perspective.

With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.

Hookworms of the genus Uncinaria parasitize pinniped pups in various locations worldwide. Four species have been described, two of which parasitize pinniped pups in the southern hemisphere: Uncinaria hamiltoni parasitizes Otaria flavescens and Arctocephalus australis from the South American coast, and Uncinaria sanguinis parasitizes Neophoca cinerea from the Australian coast. However, their geographical ranges and host specificity are unknown. Uncinaria spp. are morphologically similar, but molecular analyses have allowed the recognition of new species in the genus Uncinaria. We used nuclear genetic markers (internal transcribed spacer (ITS) and large subunit (LSU) rDNA) and a mitochondrial genetic marker (cytochrome c oxidase subunit I (COI)) to evaluate the phylogenetic relationships of Uncinaria spp. parasitizing A. australis and O. flavescens from South American coasts (Atlantic and Pacific coasts). We compared our sequences with published Uncinaria sequences. A Generalized Mixed Yule Coalescent (GMYC) analysis was also used to delimit species, and principal component analysis was used to compare morphometry among Uncinaria specimens. Parasites were sampled from A. australis from Peru (12°S), southern Chile (42°S), and the Uruguayan coast, and from O. flavescens from northern Chile (24°S) and the Uruguayan coast. Morphometric differences were observed between Uncinaria specimens from both South American coasts and between Uncinaria specimens from A. australis in Peru and southern Chile. Phylogenetic and GMYC analyses suggest that south-eastern Pacific otariid species harbour U. hamiltoni and an undescribed putative species of Uncinaria. However, more samples from A. australis and O. flavescens are necessary to understand the phylogenetic patterns of Uncinaria spp. across the South Pacific.

A raw clay from Uruguay was modified with aluminium to obtain an aluminium pillared clay (Al-PILC). The solids were characterized by scanning electron microscopy, X-ray diffraction and nitrogen adsorption-desorption isotherms. The Al-PILC retained the typical laminar structure of montmorillonite. The specific surface area and the microporous volume of the Al-PILC, 235 m2 g-1 and 0.096 cm3 g-1, respectively, were much higher than those of the clay. The phosphate adsorption capacity of the Al-PILC was higher than those of the clay. The phosphate adsorption kinetic followed the pseudo-first-order model for both, the clay and the Al-PILC, and the phosphate adsorption isotherm for the Al-PILC fit the Freundlich model.

This study investigated the in vitro culture of bovine follicles included in ovarian tissue for 2 or 6 days (D2 or D6), with the addition of different concentrations of follicle-stimulating hormone (FSH) (0, 10, 50, 100 or 200 ng/ml). Data were compared for follicular development, morphological integrity and diameter of follicles and oocytes. Ovaries (n = 10) from Nelore cows (n = 5) were divided into fragments (n = 11 per ovary) and were immediately fixed in Bouin’s solution (D0) or were individually cultured for 2 or 6 days in one of the described concentrations of FSH and then processed for histology. Compared with the rates of follicular development at D2 for minimal essential medium (MEM) (75.0%) and 50 ng/ml of FSH (71.1%), the best rates of follicular development at D2 were obtained with 10 (84.7%), 100 (87.5%) and 200 ng/ml of FSH (85.0%; P<0.05). After 6 days of cultivation, there were no differences among treatments regarding follicular growth. The morphological integrity of preantral follicles was better maintained by 100 ng/ml FSH for 2 and 6 days of cultivation (51.2 and 40.4%, respectively; P<0.05) than that for MEM (D2: 30.9%, D6: 20.8%), 10 (D2: 39.2%, D6: 22.8%), 50 (D2: 30.4%, D6: 28.8%) and 200 ng/ml FSH (D2: 45.2%, D6: 36.8%). FSH at 100 ng/ml provided the highest mean diameter averages: 34.5±10.8 µm at D2 and 33.2±12.5 µm at D6 (P<0.05). We concluded that the medium supplemented with 100 ng/ml FSH during in vitro culture provided appropriate conditions for the development and morphological integrity of preantral follicles in cattle.

El objetivo de este trabajo es discutir la relevancia de la localidad arqueológica Laguna de los Pampas en el estudio de las ocupaciones humanas del Campo de Dunas del Centro Pampeano (subregión Pampa Húmeda) durante el Holoceno. Un hallazgo relevante lo constituyen tres huevos de ñandú enteros y semienterrados, con perforaciones que sugieren su utilización como contenedor de líquido. Si bien la laguna fue habitada a lo largo del todo el Holoceno, las dataciones radiocarbónicas del sector excavado ubican a las ocupaciones humanas en el Holoceno medio (entre ca. 7000 y 5800 aP). Para este lapso se determinó que la explotación faunística estuvo orientada al consumo del guanaco, pero con un fuerte complemento de otros taxones como ñandú, venado de las Pampas y especies de menor tamaño. Se registró una tecnología ósea estandarizada sobre huesos de guanaco. Las rocas proceden principalmente del sistema serrano de Tandilia, aunque se identifican materias primas de otras áreas como el oeste pampeano. Las similitudes en las estrategias de producción y usos de los instrumentos con otros sitios de la subregión Pampa Húmeda sugieren el empleo de una misma concepción tecnológica a escala regional durante el Holoceno medio y la interacción con grupos cazadores-recolectores que ocupaban los pastizales pampeanos.