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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.
Dirofilariosis caused by Dirofilaria immitis (heartworm) is a zoonosis, considered an endemic disease of dogs and cats in several countries of Western Europe, including Portugal. This study assesses the levels of D. immitis exposure in humans from Northern Portugal, to which end, 668 inhabitants of several districts belonging to two different climate areas (Csa: Bragança, Vila Real and Csb: Aveiro, Braga, Porto, Viseu) were tested for anti-D. immitis and anti-Wolbachia surface proteins (WSP) antibodies. The overall prevalence of seropositivity to both anti-D. immitis and WSP antibodies was 6.1%, which demonstrated the risk of infection with D. immitis in humans living in Northern Portugal. This study, carried out in a Western European country, contributes to the characterisation of the risk of infection with D. immitis among human population in this region of the continent. From a One Health point of view, the results of the current work also support the close relationship between dogs and people as a risk factor for human infection
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.
The dietary inclusion of feed additives to improve the carcass characteristics of the final product is of great importance for the pork production chain. The aim of our study was to evaluate the effects of the association of ractopamine (RAC) and conjugated linoleic acid (CLA) on the performance traits of finishing pigs during the last 26 days prior to slaughter. In total, 810 commercial hybrid barrows were used. Animals were distributed among treatments according to a randomised block design in a 3 × 3 factorial arrangement, with three RAC levels (0, 5 or 10 ppm) and three CLA levels (0, 0.3 or 0.6%). Pigs fed the diet with 5 ppm RAC had higher average daily feed intake (ADFI) (2.83 kg; P < 0.05) when compared with those fed 10 ppm RAC and the control diet (2.75 and 2.74 kg, respectively). Lower ADFI values (P < 0.01) were observed with the diets containing CLA compared with the control diet with no CLA (2.73 and 2.75 v. 2.85 kg/day, respectively). The average daily weight gain of pigs fed 5 and 10 ppm RAC was +148 and +173 g/dayhigher (P < 0.001), respectively, than those fed the control diet. Dietary RAC levels influenced (P < 0.001) feed conversion ratio (FCR), which was reduced as RAC levels increased, with the pigs fed 10, 5 and 0 ppm RAC presenting FCR values of 2.57, 2.71 and 3.05, respectively. FCR also improved (P < 0.05) with the inclusion of 0.6% CLA relative to the control diet (2.70 v. 2.84, respectively). There was a significant interaction between CLA × RAC levels (P < 0.01) for final BW, loin eye area (LEA) (P < 0.05) and backfat thickness (BT) (P < 0.05). The treatments containing 10 ppm RAC + 0.6% or 0.3% CLA increased LEA and reduced BT. In conclusion, the level of 10 ppm inclusion of RAC increased the overall performance parameters of pigs and therefore improved production efficiency. The combined use of RAC and CLA promoted a lower feed conversion ratio as well as better quantitative carcass traits, as demonstrated by the higher LEA and lower BT. The dietary inclusion of CLA at 0.3% improved feed efficiency, however, without affecting LEA or BT yields.
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.
We establish the general form of a geometric comparison principle for n-fold convolutions of certain singular measures in ℝd which holds for arbitrary n and d. This translates into a pointwise inequality between the convolutions of projection measure on the paraboloid and a perturbation thereof, and we use it to establish a new sharp Fourier extension inequality on a general convex perturbation of a parabola. Further applications of the comparison principle to sharp Fourier restriction theory are discussed in the companion paper .
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.
Widespread and repeated use of glyphosate resulted in an increase in glyphosate-resistant (GR) weeds. This led to an urgent need for diversification of weed control programs and use of PRE herbicides with alternative sites of action. Field experiments were conducted over a 4-yr period (2015 to 2018) across three locations in Nebraska to evaluate the effects of PRE-applied herbicides on critical time for weed removal (CTWR) in GR soybean. The studies were laid out in a split-plot arrangement with herbicide regime as the main plot and weed removal timing as the subplot. The herbicide regimes used were either no PRE or premix of either sulfentrazone plus imazethapyr (350 + 70 g ai ha−1) or saflufenacil plus imazethapyr plus pyroxasulfone (26 + 70 + 120 g ai ha−1). The weed removal timings were at V1, V3, V6, R2, and R5 soybean stages, with weed-free and weedy season-long checks. Weeds were removed by application of glyphosate (1,400 g ae ha−1) or by hoeing. The results across all years and locations suggested that the use of PRE herbicides delayed CTWR in soybean. In particular, the CTWR without PRE herbicides was determined to be around the V1 to V2 (14 to 21 d after emergence [DAE]) growth stage, depending on the location and weed pressure. The use of PRE-applied herbicides delayed CTWR from about the V4 (28 DAE) stage up to the R5 (66 DAE) stage. These results suggest that the use of PRE herbicides in GR soybean could delay the need for POST application of glyphosate by 2 to 5 wk, thereby reducing the need for multiple applications of glyphosate during the growing season. Additionally, the use of PRE herbicides could provide additional modes of action needed to manage GR weeds in GR soybean.
Perinatal maternal high-fat diet (HFD) increases susceptibility to obesity and fatty liver diseases in adult offspring, which can be attenuated by the potent hypolipidaemic action of fish oil (FO), an n-3 PUFA source, during adult life. Previously, we described that adolescent HFD offspring showed resistance to FO hypolipidaemic effects, although FO promoted hepatic molecular changes suggestive of reduced lipid accumulation. Here, we investigated whether this FO intervention only during the adolescence period could affect offspring metabolism in adulthood. Then, female Wistar rats received isoenergetic, standard (STD: 9 % fat) or high-fat (HFD: 28·6 % fat) diet before mating, and throughout pregnancy and lactation. After weaning, male offspring received the standard diet; and from 25 to 45 d old they received oral administration of soyabean oil or FO. At 150 d old, serum and hepatic metabolic parameters were evaluated. Maternal HFD adult offspring showed increased body weight, visceral adiposity, hyperleptinaemia and decreased hepatic pSTAT3/STAT3 ratio, suggestive of hepatic leptin resistance. FO intake only during the adolescence period reduced visceral adiposity and serum leptin, regardless of maternal diet. Maternal HFD promoted dyslipidaemia and hepatic TAG accumulation, which was correlated with reduced hepatic carnitine palmitoyl transferase-1a content, suggesting lipid oxidation impairment. FO intake did not change serum lipids; however, it restored hepatic TAG content and hepatic markers of lipid oxidation to STD offspring levels. Therefore, we concluded that FO intake exclusively during adolescence programmed STD offspring and reprogrammed HFD offspring male rats to a healthier metabolic phenotype in adult life, reducing visceral adiposity, serum leptin and hepatic TAG content in offspring adulthood.
To assess iodine status and its effects on maternal thyroid function throughout pregnancy.
In the present prospective cohort study, three urinary samples were requested for urinary iodine concentration (UIC) determinations in both the first and third gestational trimesters. Serum thyrotropin (TSH) and free thyroxine (FT4) were analysed in both trimesters and thyroid antibodies were assessed once.
Rio de Janeiro, Brazil.
First-trimester pregnant women (n 243), of whom 100 were re-evaluated during the third trimester.
Iodine sufficiency was found in the studied population (median UIC=216·7 µg/l). The first- and third-trimester median UIC was 221·0 and 208·0 µg/l, respectively. TSH levels (mean (sd)) were higher in the third trimester (1·08 (0·67) v. 1·67 (0·86) mIU/l; P<0·001), while FT4 levels decreased significantly (1·18 (0·16) v. 0·88 (0·12) ng/dl; P<0·001), regardless the presence of iodine deficiency (UIC<150 µg/l) or circulating thyroid antibodies. UIC correlated (β; 95% CI) independently and negatively with age (–0·43; –0·71, –0·17) and positively with multiparity (0·15; 0·02, 0·28) and BMI (0·25; 0·00, 0·50). Furthermore, median UIC per pregnant woman tended to correlate positively with TSH (0·07; –0·01, 0·14). Women with median UIC≥250 µg/l and at least one sample ≥500 µg/l throughout pregnancy had a higher risk of subclinical hypothyroidism (OR=6·6; 95% CI 1·2, 37·4).
In this cohort with adequate iodine status during pregnancy, excessive UIC was associated with an increased risk of subclinical hypothyroidism.
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.
Urbanization and intense vessel traffic in coastal areas are obstacles for right whales when selecting breeding and calving grounds. Human activities might be the main cause for the recently observed drop in right whale sightings along the south-eastern coast of Brazil. Information concerning the biology and the activities that can potentially affect the presence of individuals along the coast are essential for management purposes, as well as for the recovery of the species stocks after a period of whaling pressure. This study correlated the occurrence of right whales in the northern limit of the breeding ground in the South-western Atlantic Ocean with local geomorphology, degree of urbanization and oceanographic features to better identify suitable areas for use by these whales. The study area was divided into 14 sub-areas based on local coastal geomorphology and discharge of large rivers. The following five ranking criteria were applied to each sub-area: presence of whaling stations and whaling activity in the past; presence and activity of ports; protection from swell, coastal slope and composition of the bottom substrate. The sub-areas that offered conditions conducive to the presence of right whales received higher scores. The proposed criteria were validated by overlapping the ranking scores with the records of right whales sighted in each sub-area. In south-eastern Brazil, protected areas with sandy bottom and gentle slope were associated with more sightings of female-calf pairs. The criteria can be used as a primary diagnostic indicating suitable sub-areas for right whales in poorly known breeding grounds.
Glyphosate-resistant (GR) goosegrass [Eleusine indica (L.) Gaertn.] was recently identified in Brazil, but its resistance mechanism was unknown. This study elucidated the resistance mechanism in this species and developed a molecular marker for rapid detection of this target-site resistance trait. The resistance factor for the resistant biotype was 4.4-fold compared with the glyphosate-susceptible (GS) in greenhouse dose–response experiments. This was accompanied by a similar (4-fold) difference in the levels of in vitro and in planta shikimate accumulation in these biotypes. However, there was no difference in uptake, translocation, or metabolism of glyphosate between the GS and GR biotypes. Moreover, both biotypes showed similar values for 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) copy number and transcription. Sequencing of a 330-bp fragment of the EPSPS gene identified a single-nucleotide polymorphism that led to a Pro-106-Ser amino acid substitution in the enzyme from the GR biotype. This mutation imparted a 3.8-fold increase in the amount of glyphosate required to inhibit 50% of EPSPS activity, confirming the role of this amino acid substitution in resistance to glyphosate. A quantitative PCR–based genotyping assay was developed for the rapid detection of resistant plants containing this Pro-106-Ser mutation.
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.
Like many other medieval and Renaissance works, the Lusíadas by Luis de Camões can be profitably interpreted as a work of rhetorical persuasion. Although rhetoric was a primary feature of the educational curriculum of the time, this line of reasoning has been missing from the critical studies of the poem, most of which are committed instead to historical, biographical, and ideological approaches. In each narrative surface of the Lusíadas, a royal audience is cajoled, admonished, guided, or taught by an eloquent petitioner who may lack the credentials of power but manifestly possesses those of experience, wisdom, virtue, and love. Finally, this petitioner, whether in the form of a historical or mythological personage, Vasco da Gama the protagonist, or some projection of the inspired poet-orator, accesses a wide range of rhetorical strategies, among them the popular and efficacious Aristotelian categories of ethos, pathos, and logos, in order more effectively to move and persuade.
Mullets inhabit a wide range of habitats from tropical to temperate regions and play a critical role in their ecosystems. This commercially important fish group constitutes a significant source of food in several geographic regions, and the production of some species for consumption is an increasing trend. About 64 myxosporean species have been reported in mullets, some of which are cryptic, as is the case of Myxobolus exiguus, and M. muelleri. This paper provides, for the first time, a detailed and critical revision of the data available for myxobolids reported in mullets, determining the species that have bona fide mugiliform fish hosts, in accordance with the original species descriptions, the available molecular data and the currently accepted taxonomic and phylogenetic criteria. Phylogenetic analyses using Bayesian inference and maximum-likelihood methodologies suggest that the evolutionary history of myxobolids with bona fide mugiliform fish hosts reflects that of its vertebrate hosts, while reinforcing known evolutionary factors and old systematic issues of the clade of myxobolids. A comprehensive morphological, ultrastructural and molecular redescription is also provided for the cryptic species M. exiguus, from infections in the visceral peritoneum of the thinlip-grey mullet Chelon ramada in the River Minho, Portugal.
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.