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Consideration of ethical, legal, and social issues plus patient values (ELSI+) in health technology assessment (HTA) is challenging because of a lack of conceptual clarity and the multi-disciplinary nature of ELSI+. We used concept mapping to identify key concepts and inter-relationships in the ELSI+ domain and provide a conceptual framework for consideration of ELSI+ in HTA.
We conducted a scoping review (Medline and EMBASE, 2000–2016) to identify ELSI+ issues in the HTA literature. Items from the scoping review and an expert brainstorming session were consolidated into eighty ELSI+-related statements, which were entered into Concept Systems® Global MAX™ software. Participants (N = 38; 36 percent worked as researchers, 21 percent as academics; 42 percent self-identified as HTA experts) sorted the statements into thematic groups, and rated them on importance in making decisions about adopting technologies in Canada, from 1 (not at all important) to 5 (extremely important). We used Concept Systems® Global MAX™ software to create and analyze concept maps with four to sixteen clusters.
Our final ELSI+ map consisted of five clusters, with each cluster representing a different concept and the statements within each cluster representing the same concept. Based on the concepts, we named these clusters: patient preferences/experiences, patient quality of life/function, patient burden/harm, fairness, and organizational. The highest mean importance ratings were for the statements in the patient burden/harm (3.82) and organizational (3.92) clusters.
This study suggests an alternative approach to ELSI+, based on conceptual coherence rather than academic disciplines. This will provide a foundation for incorporating ELSI+ into HTA.
Traditional designs for functional languages (such as Haskell or ML) have separate sorts of syntax for terms and types. In contrast, many dependently typed languages use a unified syntax that accounts for both terms and types. Unified syntax has some interesting advantages over separate syntax, including less duplication of concepts, and added expressiveness. However, integrating unrestricted general recursion in calculi with unified syntax is challenging when some level of type-level computation is present, since properties such as decidable type-checking are easily lost. This paper presents a family of calculi called pure iso-type systems (PITSs), which employs unified syntax, supports general recursion and preserves decidable type-checking. PITS is comparable in simplicity to pure type systems (PTSs), and is useful to serve as a foundation for functional languages that stand in-between traditional ML-like languages and fully blown dependently typed languages. In PITS, recursion and recursive types are completely unrestricted and type equality is simply based on alpha-equality, just like traditional ML-style languages. However, like most dependently typed languages, PITS uses unified syntax, naturally supporting many advanced type system features. Instead of implicit type conversion, PITS provides a generalization of iso-recursive types called iso-types. Iso-types replace the conversion rule typically used in dependently typed calculus and make every type-level computation explicit via cast operators. Iso-types avoid the complexity of explicit equality proofs employed in other approaches with casts. We study three variants of PITS that differ on the reduction strategy employed by the cast operators: call-by-name, call-by-value and parallel reduction. One key finding is that while using call-by-value or call-by-name reduction in casts loses some expressive power, it allows those variants of PITS to have simple and direct operational semantics and proofs. In contrast, the variant of PITS with parallel reduction retains the expressive power of PTS conversion, at the cost of a more complex metatheory.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
A completely randomized experiment was designed to evaluate the effects of α-amylase (AMY) and glucoamylase (GLU) on total losses, fermentative profile, chemical composition and amylolytic activity of rehydrated maize. Eighty-four experimental silos of rehydrated maize [0.33 litres/kg ground maize, 4-mm theoretical particle size, and 625 g/kg dry matter (DM)] were assigned to the following treatments: (1) control (CON), no enzyme addition; (2) GLU added at 300 µl/kg of ground maize (as-fed); and (3) AMY added at 300 µl/kg of ground maize. Seven silos from each treatment were opened after 7, 14, 21 and 28 days. Differences among treatments were evaluated through orthogonal contrasts (CON v. enzymes, and AMY v. GLU). Time effects were decomposed using polynomial regression. Glucoamylase silage exhibited greater total losses than AMY. Enzymes increased acetate and lactic acid concentrations and decreased ethanol concentration. Regardless of treatment, gas, effluent and total fermentative losses linearly increased, whereas DM recovery linearly decreased with higher storage length. Glucoamylase silage had lower ammonia nitrogen and higher lactic acid concentrations than AMY. Enzyme treatments decreased silage neutral detergent fibre content and increased in vitro DM degradation. Glucoamylase silage exhibited a more moderate starch content and greater in vitro DM degradation than AMY. Storage time linearly decreased DM, starch and fibre content of rehydrated maize. In vitro degradation of DM linearly increased as the storage length increased. This study showed evidence that enzymes with amylolytic activity, particularly GLU, improve the fermentative profile and DM degradation of rehydrated maize silage.
Chagas Disease is a zoonosis caused by the parasite Trypanosoma cruzi. Several high-resolution markers have subdivided T. cruzi taxon into at least seven lineages or Discrete Typing Units (DTUs) (TcI-TcVI and TcBat). Trypanosoma cruzi I is the most diverse and geographically widespread DTU. Recently a TcI genotype related to domestic cycles was proposed and named as TcIDOM. Herein, we combined traditional markers and housekeeping genes and applied a Multispecies Coalescent method to explore intra-TcI relationships, lineage boundaries and genetic diversity in a random set of isolates and DNA sequences retrieved from Genbank from different countries in the Americas. We found further evidence supporting TcIDOM as an independent and emerging genotype of TcI at least in Colombia and Venezuela. We also found evidence of high phylogenetic incongruence between parasite's gene trees (including introgression) and embedded species trees, and a lack of genetic structure among geography and hosts, illustrating the complex dynamics and epidemiology of TcI across the Americas. These findings provide novel insights into T. cruzi systematics and epidemiology and support the need to assess parasite diversity and lineage boundaries through hypothesis testing using different approaches to those traditionally employed, including the Bayesian Multispecies coalescent method.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
Graded exercises tests are performed in adult populations; nonetheless, the use of this type of assessment is greatly understudied in overweight and obese adolescents.
To investigate heart rate autonomic responses to submaximal aerobic exercise in obese and overweight adolescents.
We recruited 40 adolescents divided into two groups: (1) overweight group comprising 10 boys and 10 girls between Z-score +1 and +2 and (2) obese group comprising 10 boys and 10 girls above Z-score >+2. Heart rate variability was analysed before (T1) and after exercise (T2–T4) on treadmill at a slope of 0%, with 70% of the maximal estimated heart rate (220 – age) for 20 minutes.
Heart rate in the overweight group was: 93.2±10.52 bpm versus 120.8±13.49 bpm versus 94.6±11.65 bpm versus 93.0±9.23 bpm, and in the obese group was: 92.0±15.41 bpm versus 117.6±16.31 bpm versus 92.1±12.9 bpm versus 91.8±14.33 bpm. High frequency in the overweight group was: 640±633.1 ms2 versus 84±174.66 ms2 versus 603.5±655.31 ms2 versus 762.6±807.21 ms2, and in the obese group was: 628.4±779.81 ms2 versus 65.4±119.34 ms2 versus 506.2±482.70 ms2 versus 677.9±939.05 ms2; and root mean square of successive differences in the overweight group was: 37.9±18.81 ms versus 10.9±8.41 ms versus 32.8±24.07 ms versus 36.7±21.86 ms, and in the obese group was: 38.7±23.17 ms versus 11.5±8.62 ms versus 32.3±16.74 ms versus 37.3±24.21 ms. These values significantly changed during exercise compared with resting values in overweight and obese groups. Moreover, we also reported no significant difference of resting parasympathetic control of heart rate between obese and overweight adolescents.
There was no significant difference of autonomic responses elicited by submaximal aerobic exercise between overweight and obese adolescents.
The effects of growing pinto peanut mixed with elephant grass-based pastures are still little known. The aim of the current research was to evaluate the performance of herbage yield, nutritive value of forage and animal responses to levels of pinto peanut forage mass mixed with elephant grass in low-input systems. Three grazing systems were evaluated: (i) elephant grass-based (control); (ii) pinto peanut, low-density forage yield (63 g/kg of dry matter – DM) + elephant grass; and (iii) pinto peanut, high-density dry matter forage yield (206 g/kg DM) + elephant grass. The experimental design was completely randomized with the three treatments (grazing systems) and three replicates (paddocks) in split-plot grazing cycles. Forage samples were collected to evaluate the pasture and animal responses. Leaf blades of elephant grass and the other companion grasses of pinto peanut were collected to analyse the crude protein, in vitro digestible organic matter and total digestible nutrients. The pinto peanut, high-density dry matter forage yield + elephant grass treatment was found to give the best results in terms of herbage yield, forage intake and stocking rate, as well as having higher crude protein contents for both elephant grass and the other grasses, followed by pinto peanut with low-density forage yield + elephant grass and finally elephant grass alone. Better results were found with the grass–legume system for pasture and animal responses.
Non-decorticated sunflower meal (SFM) is a potential protein source for dairy cows with high-fibre content but high ruminal degradability. The effect of replacement of soybean meal (SBM) and wheat middlings (WM) with SFM on the intake, digestibility, microbial protein synthesis, nitrogen utilization and milk production of dairy cows was evaluated. Twelve Holstein cows were blocked by days in milk and distributed in three 4 × 4 Latin squares. Diets were formulated to be isonitrogenous and contained 550 g maize silage/kg dry matter (DM). Treatment diets were no SFM (CON) or 70, 140 and 210 g/kg DM of SFM replacing fixed mixture of SBM and WM (536 and 464 g/kg of the mixture, respectively). The inclusion of SFM in diet did not affect DM intake, but intake of rumen degradable protein increased linearly. Inclusion of SFM reduced or tended to reduce total-tract digestibility of non-fibre carbohydrate, total digestible nutrients and excretion of purine derivatives. Milk production, milk protein content and efficiency of nitrogen use for lactation were reduced with increasing levels of SFM in the diet. The use of non-decorticated SFM as a replacement for SBM–WM mixture in diet reduces performance and efficiency of nutrient use in lactating dairy cows. The outcome of the current study is attributed to reduced fibre digestibility in SFM hulls. Therefore, future studies should evaluate the use of decorticated SFM.
Differences in forage nutritive value between morning and afternoon are related to patterns of dehydration and carbohydrate accumulation throughout the day. In this way, management strategies that maximize grazing time during the afternoon could increase forage nutritive value and consequently nutrient intake. The aim of the current experiment was to evaluate the effect of the time of day (06.00 h [designated AM] or 15.00 h [PM]) that cattle are moved to a new paddock on forage nutritive value, grazing behaviour and animal performance of beef cattle on rotationally stocked Marandu palisadegrass (Brachiaria brizantha cv. Marandu Syn. Urochloa brizantha cv. Marandu) pastures. A spring and summer study was conducted in Pirassununga, SP, Brazil from October 2012 to March 2013 (182 days). Treatments were distributed in a randomized complete block design with three replications. Herbage mass, morphological composition, herbage allowance and stocking rates were similar between treatments during spring and summer. Moving animals to a new paddock, regardless of the time of day – 06.00 h (AM) or 15.00 h (PM) – stimulated grazing, modifying the distribution of meals throughout the day. However, compensatory mechanisms among grazing time, bite rate and forage nutritive value throughout the day operated in order to generate similar performance between animals offered a new paddock in the morning or in the afternoon.
An experiment was conducted to evaluate whether dietary reduction and sex class affect nutrient intake, digestibility, purine derivative (PD) excretion and heat tolerance coefficient in lambs. Thirty-five hair lambs (14.5 ± 0.89 kg initial body weight (BW), 2 months old) were used in a completely randomized study with a 3 × 3 factorial arrangement, three sex classes (11 intact males, 12 castrated males and 12 females) and three levels of feeding (ad libitum, 300 and 600 g/kg/dry matter (DM) feed restriction) for 120 days. Intact and castrated males showed higher intakes of DM and neutral detergent fibre corrected for ash and protein (NDFap) than females. At 300 g/kg/DM feed restriction, NDFap digestibility was lower in intact males than in other classes; however, no differences were found between classes when subjected to ad libitum feeding or 600 g/kg/DM. The basal endogenous nitrogen and endogenous urinary losses were highest in intact males. Allantoin, uric acid and PD excretion, as well as PD absorption and microbial protein production were lowest in the animals subjected to 600 g/kg/DM feed restriction. Microbial protein synthesis (MPS) was highest in animals subjected to 600 g/kg/DM feed restriction. The lowest temperatures were observed in animals subjected to 600 g/kg/DM feed restriction. The heat tolerance coefficient was highest in animals subjected to 600 g/kg/DM feed restriction. In conclusion, feed restriction reduced the time spent on feeding and rumination but increased the digestibility of DM. The restriction level of 600 g/kg/DM maximized MPS and infrared thermography indicated an elevated heat tolerance coefficient.
The aim of this study was to evaluate the effect of incubating semen for different periods (90, 270 or 450 min) with or without Trolox® (100 or 150 µM) on the quality of sperm from Saimiri collinsi. Sperm motility, vigour, and plasma membrane integrity (PMI) were evaluated in both fresh semen and semen incubated for different time periods, i.e. 90, 270 or 450 min of incubation. Supplementation of semen extender with Trolox® 100 µM improved sperm motility, vigour and PMI for up to 270 min of incubation.
Giant electromagnetic pulses (EMP) generated during the interaction of high-power lasers with solid targets can seriously degrade electrical measurements and equipment. EMP emission is caused by the acceleration of hot electrons inside the target, which produce radiation across a wide band from DC to terahertz frequencies. Improved understanding and control of EMP is vital as we enter a new era of high repetition rate, high intensity lasers (e.g. the Extreme Light Infrastructure). We present recent data from the VULCAN laser facility that demonstrates how EMP can be readily and effectively reduced. Characterization of the EMP was achieved using B-dot and D-dot probes that took measurements for a range of different target and laser parameters. We demonstrate that target stalk geometry, material composition, geodesic path length and foil surface area can all play a significant role in the reduction of EMP. A combination of electromagnetic wave and 3D particle-in-cell simulations is used to inform our conclusions about the effects of stalk geometry on EMP, providing an opportunity for comparison with existing charge separation models.
Considering the impact of coastal dynamics on the radiocarbon (14C) marine reservoir effect (MRE), upwelling has the potential of enhancing marine influence, usually 14C depleted. Freshwater input can contribute either to increased reservoir offsets, when dead carbon from rock weathering is available, but also towards an atmospheric 14C signal, when the presence of terrestrial organic matter from catchment prevails. An overview of the MRE studies based on shellmounds on the coast of Rio de Janeiro reveals a pattern of negative local corrections for Saquarema and Rio das Ostras but positive values for Cabo Frio island, suggesting the presence of cold upwelling waters in Cabo Frio at 1.6–1.2 cal kBP. New results for a shellmound on the Ilha Grande island, in the western portion of the Rio de Janeiro coast, revealed a negative value at about 3 ka. We discuss distribution of MRE values and temporal variability in the region and their relation to ocean dynamics, continental input and the choice of marine organisms used for ∆R determination. A comparison of local reservoir offsets for the Saquarema region obtained from fish otolith and mollusk shells revealed similar ΔR distributions, showing that both materials can be equally used.
This study systematised and synthesised the results of observational studies that were aimed at supporting the association between dietary patterns and cardiometabolic risk (CMR) factors among adolescents. Relevant scientific articles were searched in PUBMED, EMBASE, SCIENCE DIRECT, LILACS, WEB OF SCIENCE and SCOPUS. Observational studies that included the measurement of any CMR factor in healthy adolescents and dietary patterns were included. The search strategy retained nineteen articles for qualitative analysis. Among retained articles, the effects of dietary pattern on the means of BMI (n 18), waist circumference (WC) (n 9), systolic blood pressure (n 7), diastolic blood pressure (n 6), blood glucose (n 5) and lipid profile (n 5) were examined. Systematised evidence showed that an unhealthy dietary pattern appears to be associated with poor mean values of CMR factors among adolescents. However, evidence of a protective effect of healthier dietary patterns in this group remains unclear. Considering the number of studies with available information, a meta-analysis of anthropometric measures showed that dietary patterns characterised by the highest intake of unhealthy foods resulted in a higher mean BMI (0·57 kg/m²; 95 % CI 0·51, 0·63) and WC (0·57 cm; 95 % CI 0·47, 0·67) compared with low intake of unhealthy foods. Controversially, patterns characterised by a low intake of healthy foods were associated with a lower mean BMI (−0·41 kg/m²; 95 % CI −0·46,−0·36) and WC (−0·43 cm; 95 % CI −0·52,−0·33). An unhealthy dietary pattern may influence markers of CMR among adolescents, but considering the small number and limitations of the studies included, further studies are warranted to strengthen the evidence of this relation.
Forage is the primary feed source for livestock in tropical regions and energy is one of the most important nutrients for ruminant nutrition. The effects of harvest management of Marandu palisade grass (Brachiaria brizantha cv. Marandu Syn. Urochloa brizantha cv. Marandu) on non-structural carbohydrate (NSC) concentrations were evaluated. A plot (Experiment 1) and a greenhouse study (Experiment 2) were conducted in 2013–14. In Experiment 1, treatments were the factorial arrangement of two harvest times and two vertical canopy layers (upper and intermediate), distributed in a completely randomized design with five replicates. In Experiment 2, treatments were the factorial arrangement of six harvest times and two morphological fractions (leaf blade and pseudostem). In both experiments, NSC concentration increased during the day. Upper and intermediate canopy layers had greater NSC concentration at 15.00 than 06.00 h during spring and summer. In addition, the magnitude of NSC increase was greater in the upper than intermediate canopy layer and in spring than summer. Marandu palisade grass shows greater digestibility in the afternoon than morning, representing an opportunity to optimize energy concentration through harvest management.
In the traditional silvo–pastoral system, Alentejano pigs are fattened with acorns and pasture. Although this production system (“Montanheira”) has been characterised, there is a lack of knowledge on intake and digestibility of the diet, mainly due to the absence of tested methodologies in pigs. The n–alkane technique, extensively used in ruminants to estimate diet intake and digestibilitiy, has had less use in pigs. The objective of this experiment was to validate the n–alkane technique in Alentejano pigs. Faecal recoveries of natural and dosed n-alkanes, the diurnal variation of faecal n–alkane concentration, and the time span required to reach a steady state excretion of dosed alkanes were determined. Eight male Alentejano pigs (54.4±9.8 kg LW) were randomly allocated to two groups and placed in metabolic cages. They were fed 0.7 kg of pasture and 0.7kg of ground acorns daily as two meals. Pigs in Group-1 were given once daily artificial C32 (40mg/d) and C36 (40 mg/d) and those in Group-2 the same alkanes as two daily doses of 20 mg. Steady state excretion of both alkanes was reached 3 days after first dosing. Although no difference (P>0.05) was observed between treatments, the coefficient of variation of feacal alkane concentration when dosed twice daily was generally lower than when dosed once daily. Mean faecal recoveries of n–alkanes increased with increasing carbon-chain length (C25 to C36) from 38 to 69%, but were not significantly different from C29, C32, C33 and C36 (mean 0.694 SEM 0.067). Faecal nalkanes in samples collected every four hours for three days showed no diurnal variation in patterns of excretion apart from a higher concentration of C32 4 hours after dosing once daily. However variation between animals was lower when artificial alkanes were dosed twice daily than when once daily. The results indicate that the n–alkane techique may be used to estimate intake and digestibility under “Montanheira”, although further validation work needs to be done.
Although a national programme for control of visceral leishmaniosis (VL) is being run in Brazil, the disease continues to spread. This programme is essentially based on culling infected dogs from endemic regions. Thus, there is an urgent need to develop other control measures against VL to deter its advance. Here, a subunit vaccine, a recombinant vaccine, an insecticide-impregnated collar and the associations between these measures were evaluated for reducing the incidence of Leishmania infection in dogs. This was through a cohort study conducted in an endemic region of Brazil, considering the incidence and time of total exposure over a period of 1 year. The incidence of VL was estimated by means of serological and molecular diagnostic tests, 180 and 360 days after the application of the control measures. The estimates of the effectiveness (EF) were not significant in any cohort. The EF of the subunit vaccine, the recombinant vaccine and the collar were 26.4%, 32.8% and 57.7% and the upper limit of the 95% confidence interval for EF were 63.7%, 67.9% and 82.5%, respectively. In conclusion, under the conditions of this study, none of the immunogens for VL control was sufficiently effective to protect dogs against infection. On the other hand, use of collars impregnated with insecticide seems to constitute a method with better prognosis, corroborating other studies in this field.
The objective of the current research was to evaluate the fermentative characteristics of silage made with the upper third section of cassava (Manihot esculenta) plants with added condensed tannin levels of 0, 25, 50 and 75 g/kg dry matter (DM). The experimental design was a complete randomized design, with treatments arranged in a 4 × 7 factorial (tannin addition levels × days of ensiling). The loss of gas and the presence of moulds observed in the opening days had increased linearly. Fermentative characteristics were decreased by the addition of tannin. Acetic acid content showed a linear increase. Tannin levels had a quadratic effect on gas production at 28 days of ensiling. After 56 days, however, tannin levels had no significant effect on silage gas production. After 28 days of ensiling, the degradability of potentially degradable fraction ‘b’ demonstrated quadratic effect. The same occurred with the fractions ‘a’, ‘b’ which were undegradable after 56 days of ensiling. The addition of condensed tannin lengthened the fermentative stage and caused the silage to stabilize after 56 days of ensiling.