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Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
The research has shown the interesting contributions of shearing in mid-gestation on the performance of lambs from birth to weaning. Other studies have reported that shearing at early pregnancy influences the development of the placenta and lamb live weight at birth. However, there was a lack of information on the effect of early-prepartum shearing on the behavior of the offspring from weaning onward. This study evaluated the effect of shearing ewes at 50 days of gestation on the growth, reproductive behavior and response to a gastrointestinal parasite challenge in the female offspring from weaning to 18 months old. Fifty-seven Polwarth female lambs were used, 22 being singles and 35 twins born to ewes either shorn at 50 days of pregnancy (PS, n = 23) or shorn at 62 days postpartum (U, control, n = 34) resulting in four subgroups: single lambs born to PS ewes (n = 8), born to U ewes (n = 14), twin lambs born to PS ewes (n = 15) or born to U ewes (n = 20). All progeny were managed together under improved pasture with a minimum forage allowance of 6% live weight on dry basis. Body weight, body condition score and fecal eggs count were recorded every 14 days from weaning to 18 months of age. Concentrations of progesterone were measured weekly (from 4 to 10 months of age and from 14 to 18 months of age) to establish the onset of puberty. Ovulation rate at an induced and a natural heat (545 ± 1.0 and 562 ± 1.0 day old) was recorded. Prepartum shearing did not affect the age at puberty or the ovulation rate of female offspring, but those born as singles were more precocious ( P = 0.03) and heavier ( P = 0.02) at puberty than twin born lambs. Both the average value of parasite egg count ( P = 0.0 7) and the Famacha index ( P = 0.02) for the entire study period were lower in lambs born to prepartum shorn ewes than those born to postpartum shorn ewes. In conclusion, shearing at 50 days of gestation did not affect the growth or the reproductive behavior of female offspring. However, female lambs born from ewe shorn during gestation showed a better response to the parasitic challenge, and further research is required to confirm this.
Social cognition has been associated with functional outcome in patients with first episode psychosis (FEP). Social cognition has also been associated with neurocognition and cognitive reserve. Although cognitive reserve, neurocognitive functioning, social cognition, and functional outcome are related, the direction of their associations is not clear. Therefore, the main aim of this study was to analyze the influence of social cognition as a mediator between cognitive reserve and cognitive domains on functioning in FEP both at baseline and at 2 years.
The sample of the study was composed of 282 FEP patients followed up for 2 years. To analyze whether social cognition mediates the influence of cognitive reserve and cognitive domains on functioning, a path analysis was performed. The statistical significance of any mediation effects was evaluated by bootstrap analysis.
At baseline, as neither cognitive reserve nor the cognitive domains studied were related to functioning, the conditions for mediation were not satisfied. Nevertheless, at 2 years of follow-up, social cognition acted as a mediator between cognitive reserve and functioning. Likewise, social cognition was a mediator between verbal memory and functional outcome. The results of the bootstrap analysis confirmed these significant mediations (95% bootstrapped CI (−10.215 to −0.337) and (−4.731 to −0.605) respectively).
Cognitive reserve and neurocognition are related to functioning, and social cognition mediates in this relationship.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
The aim of the present study is to use the syndemic framework to investigate the risk of contracting HIV in the US population. Cross-sectional analyses are from The National Health and Nutrition Examination Survey. We extracted and aggregated data on HIV antibody test, socio-demographic characteristics, alcohol use, drug use, depression, sexual behaviours and sexually transmitted diseases from cycle 2009–2010 to 2015–2016. We carried out weighted regression among young adults (20–39 years) and adults (40–59 years) separately. In total, 5230 men and 5794 women aged 20–59 years were included in the present analyses. In total, 0.8% men and 0.2% women were tested HIV-positive. Each increasing HIV risk behaviour was associated with elevated odds of being tested HIV-positive (1.15, 95% CI 1.15–1.15) among young adults and adults (1.61, 95% CI 1.61–1.61). Multi-faceted, community-based interventions are urgently required to reduce the incidence of HIV in the USA.
The authors prepared a micro-structured, thermosensitive hydrogel with N-isopropylacrylamide microgels with a lower critical solution temperature (LCST) of 32 °C dispersed on a matrix of N-isopropylacrylamide-co-dimethylacrylamide with an LCST at 40 °C. Incubation of the hydrogel at 33 °C in a solution of fluorescein-albumin induced loading of the protein. The protein was not loaded at a temperature below the LCST of the microgels (4 °C), suggesting that the shrinkage of the microgels followed by the formation of micropores within the hydrogel matrix is a prerequisite for protein loading. A sustained and complete release of the loaded protein was obtained at 37 °C.
Oilseed rape seed yield has increased in the last 40 years in most countries, but this yield gain has not been accompanied by greater yield stability. The current study aimed to quantify the genotype by environment (G × E) interaction on oilseed rape yield, identify genotypes with broad adaptability and the main environmental drivers related to seed yield. A weighted two-stage mixed-model analysis was applied to official multi-environment trials of nine spring genotypes (G), in three locations (L) during 6 years (Y) on central and southern Argentine Pampas under rainfed conditions. Best linear unbiased prediction of seed yield ranged from 0.37 to 3.73 kg/ha. Fixed effect L × Y was highly significant and G variability was estimated as 130 kg/ha of standard deviation. Contrasting genotypes were identified by Shukla's stability index and two of those showed the best yield performance in the wettest year. Factor analysis explained 0.75 of total variation and discriminated genotypes with broad and specific adaptability, as well as combined environments according to the similarities in seed yield of the evaluated genotypes. Environmental loadings of Factor 2 were linearly associated with cumulative rainfall in the post-flowering period (up to 230 mm). It is concluded that (i) a significant G × L × Y interaction underlies the high variability of seed yield, (ii) two genotypes (G6 and G7) with high yield stability were identified, and (iii) G × E effects are associated with post-flowering rainfall.
At a global level, dairy cow production systems (DCPS) are important sources of nourishment and profits, but they generate environmental impacts such as overexploitation of different resources including water, lands and fossil energy. Quantification of water and carbon footprint to define mitigation strategies and a more rational use of natural resources, is a reiterated claim. The aim of this study was to perform an economic evaluation of the environmental impact of the DCPS from the Comarca Lagunera, Mexico (24°N, 102°W, 220 mm, hot-semiarid climate) We contrasted the economic value (EV) generated by the DCPS with respect to the economic costs (EC) due to the greenhouse gas emissions (GHGE) and the water footprint (WFP) of this DCPS. While quantifications of GHGE considered those proposed by the Intergovernmental Panel on Climate Change, the WFP involved the use of blue, gray and green water by the DCPS and related activities. Quantification of the EC of WFP considered an international average price of water. In the year 2017, the Comarca Lagunera registered a dairy cow inventory of 493 144 heads, with 227 142 lactating cows, which produced 2386 million liters of milk per year with an annual average EV of €525.3 million. The EC (€, millions) generated by the GHGE and WFP were €311.8 and €11 980.7, respectively, with a total EC of € 12 292.5 million. When the EV of milk production and the total environmental EC are compared, the contrast demonstrates not only the noteworthy environmental impact but also the significant and senseless biological and EC. In addition, having a large dairy cow concentration creates pollution concerns and the DCPS transfers both nutrients and water resources from an ecologically vulnerable arid region. Therefore, some mitigation strategies such as, better cow genotype, feed and manure management combined with the production of forages and grains in a different geographical region are suggested to promote an optimum use of water in order to uphold the social, economic and biologic sustainability of the Comarca Lagunera, Mexico.
The present study investigated the adsorption of fluorides in natural zeolites clinoptilolite-type, sourced in Sonora, Mexico, and modified with Fe. Characterization of the material was carried out along with determination of kinetic parameters varying time and concentration of reagents to calculate maximum adsorption capacity. To determine thermodynamic parameters temperature was varied for accurate characterization of the adsorption process. It was found that the zeolite fixed Fe in its structure without model significant modification, likewise when put in contact with a fluoride solution (F-), it was capable of taking up these ions through adsorption due to the interaction between the sorbato and the pollutant. The kinetics best fit Pseudo-second-order model with Qmax=0.91 mgg-1, therefore it indicates that the process is reversible, spontaneous and endothermic what can favor the reuse of the material.
An initial mixture of raw materials (batch) typically used for the manufacture of conventional soda-lime float glass was subjected to a mechanical activation process for 30 or 60 minutes in a planetary ball mill. An intensification of the chemical reactivity of the batch, which was directly related with the increase in the milling time, was observed. This accelerated the chemical reactions that took place during the batch melting process between sodium, calcium and magnesium carbonates and other components of the mixture, which happened at significantly lower temperatures with respect to the batch without mechanical activation. The heat of fusion of the batch, estimated using a methodology previously reported in the literature, indicated that the mechanical activation given to the initial mixture of raw materials decreased the energy consumed during the batch melting. This was also evidenced by a decrease in the temperature at which the release of CO2 ended, which was considerably larger than that previously reported in the literature based solely on the decrease in the particle size of a batch of similar composition achieved by dry sieving.
CdSe nanoparticles were grown using a colloidal method, in which the pH was the main parameter that was varied (from 8 to 12) with the objective of knowing the morphological and structural effects after the synthesis process. The samples were characterized with X-ray diffraction and High-Resolution Transmission Electron Microscope to know their crystalline structure. We identified the formation of two crystalline phases in a single sample, as well as the different crystal direction of the material, the crystallites size was calculated from the X-ray diffraction pattern using the Debye- Scherrer equation. The distance between planes was also calculated using the Fast Fourier Transformation (FFT). The results and analysis of the experimental work are reported.
This work combines very detailed measurements from terrestrial laser scanner (TLS), ground-based interferometry radar (GB-SAR) and ground-penetrating radar (GPR) to diagnose current conditions and to analyse the recent evolution of the Monte Perdido Glacier in the Spanish Pyrenees from 2011 to 2017. Thus, this is currently one of the best monitored small glacier (<0.5 km2) worldwide. The evolution of the glacier surface was surveyed with a TLS evidencing an important decline of 6.1 ± 0.3 m on average, with ice losses mainly concentrated over 3 years (2012, 2015 and 2017). Ice loss is unevenly distributed throughout the study period, with 10–15 m thinning in some areas while unchanged areas in others. GB-SAR revealed that areas with higher ice losses are those that are currently with no or very low ice motion. In contrast, sectors located beneath the areas with less ice loss are those that still exhibit noticeable ice movement (average 2–4.5 cm d─1 in summer, and annual movement of 9.98 ma─1 from ablation stakes data). GPR informed that ice thickness was generally <30 m, though locally 30–50 m. Glacier thinning is still accelerating and will lead to extinction of the glacier over the next 50 years.
Recent approaches in the care of older people have led to a greater emphasis on good practices to prevent elder abuse. The instruments assessing good practices are very limited, and those focused on elder abuse have rarely considered subtle forms, especially in institutional settings. The aim of this study was to develop and assess the content validity of a good practices scale for professionals working in nursing homes. An extensive literature review of the tools assessing professionals’ good–bad practices towards older people was conducted. A preliminary scale based on Kayser-Jones’ (1990) [Old, Alone and Neglected: Care of the Aged in Scotland and the United States. Berkeley, CA: University of California Press] types of abuse was developed, including four subscales: Personalization, Humanization, Absence of Infantilization, and Absence of Victimization. Content validity was analyzed through a panel of eight experts. Rovinelli and Hambleton’s index of item-objective congruence was used to analyze the items’ inclusiveness in the assigned subscale to establish their representativeness. Items’ relevance and clarity were analyzed using the paired comparison method. The final version of the scale included 56 items, with appropriate levels of item objective-congruence, relevance, and clarity. This instrument will allow professionals to detect and develop awareness and intervention programs that aim to promote good practices in nursing homes.
Chagas disease, whose aetiological agent is the protozoan Trypanosoma cruzi, mainly occurs in Latin America. In order to know the epidemiology and the geographical distribution of this disease in Mexico, the present work analyses the national surveillance data (10 years) for Chagas disease issued by the General Directorate of Epidemiology (GDE). An ecological analysis of Chagas disease (2007–2016) was performed in the annual reports issued by the GDE in Mexico. The cases and incidence were classified by year, state, age group, gender and seasons. A national distribution map showing Chagas disease incidence was generated. An increase of new cases was identified throughout the country (rates from 0.37 to 0.81 per 100 000 inhabitants). Of the total cases accumulated (7388), the major cases were attributed to the states of Veracruz, Chiapas, Quintana Roo, Oaxaca, Morelos and Yucatán. The analysis per age groups and gender revealed that, in most age groups, the incidence was higher in the male population. The most number of cases was identified in spring and summer; a direct relationship between the environmental temperature increase and the number of new cases was identified. The analysis showed that the rate of Chagas disease increased presumably due to state programmes; the search for new cases has expanded and we speculate that the disease is associated with occupational activities. These results summarise and recall how important it is to implement the monitoring of Chagas disease mainly in south states of the Mexican Republic in order to implement strategies to control this disease.