Linear Treatment Effect Research Articles

Doses of orange (Citrus sinensis) essential oil for Nellore steers fed with a forage-based diet

The aim was to evaluate whether the doses of orange essential oil supplementation impact on dry matter intake (DMI), ruminal fermentation parameters, apparent nutrient digestibility, and methane production in Nellore steers fed with forage-based diet. A total of 32 rumen-cannulated Nellore steers (initial BW= 335±25 kg; age= 20±1 month) were assigned to individual pens in a randomized complete block design. Within block, steers were randomly assigned to treatments: CON= diet without orange essential oil (EO); 100EO= CON diet plus 100 mg orange EO/kg DM diet; 200EO= CON diet plus 200 mg orange EO/kg DM diet; and 500EO= CON diet plus 500 mg orange EO/kg DM diet. The main active compounds of the orange EO used were limonene (88.0 %) and myrcene (5.79 %). The experimental period lasted 28d, with 22d for adaptation and 6d for sample collection. From d23 to 27, samples of haylage, concentrate, and total fecal production were collected to determine the total tract apparent nutrient digestibility. Ruminal fluid was obtained from d28 at 0, 6, and 12 h after feeding to determine ruminal fermentation parameters and methane production. The difference was considered significant when P ≤ 0.05. No treatment effects were detected (P>0.05) to DMI or specific nutrient intake. The increasing levels of EO did not affect (P>0.05) the total apparent nutrient digestibility. No treatment effects were detected (P>0.05) for ruminal fermentation parameters in vivo. In ex situ, there was a treatment effect for acetate, total short-chain fatty acids (SCFA), methane, and relative energy loss (REL). For acetate, an increasing linear effect was observed for treatments that received EO for the variables production (g/kg) (P = 0.002) and gross energy (MJ/kg) (P = 0.002), with a higher concentration for the 500EO. For the total production of SCFA, there was an increasing linear effect of treatment with a higher concentration for 500EO for the variables production (g/kg) (P = 0.001) and gross energy (MJ/kg) (P = 0.001). For methane, a quadratic treatment effect was observed for the variables production (g/kg) (P = 0.045) and gross energy (MJ/kg) (P = 0.046), with lower concentrations for the 200EO. There was a decreasing linear treatment effect for REL(%) (P<0.001). The results for the use of orange EO as a manipulator of ruminal fermentation were promising and the dose of 500 mg/kg of DM showed a greater capacity to increase the energy efficiency of fermentation, with greater production of acids and lower production of methane, without affecting the voluntary intake of steers.

Multiplicity-adjusted semiparametric benefiting subgroup identification in clinical trials.

Background A recent focus in the health sciences has been the development of personalized medicine, which includes determining the population for which a given treatment is effective. Due to limited data, identifying the true benefiting population is a challenging task. To tackle this difficulty, the credible subgroups approach provides a pair of bounding subgroups for the true benefiting subgroup, constructed so that one is contained by the benefiting subgroup while the other contains the benefiting subgroup with high probability. However, the method has so far only been developed for parametric linear models. Methods In this article, we develop the details required to follow the credible subgroups approach in more realistic settings by considering nonlinear and semiparametric regression models, supported for regulatory science by conditional power simulations. We also present an improved multiple testing approach using a step-down procedure. We evaluate our approach via simulations and apply it to data from four trials of Alzheimer's disease treatments carried out by AbbVie. Results Semiparametric modeling yields credible subgroups that are more robust to violations of linear treatment effect assumptions, and careful choice of the population of interest as well as the step-down multiple testing procedure result in a higher rate of detection of benefiting types of patients. The approach allows us to identify types of patients that benefit from treatment in the Alzheimer's disease trials. Conclusion Attempts to identify benefiting subgroups of patients in clinical trials are often met with skepticism due to a lack of multiplicity control and unrealistically restrictive assumptions. Our proposed approach merges two techniques, credible subgroups, and semiparametric regression, which avoids these problems and makes benefiting subgroup identification practical and reliable.

Effects of clay after a grain challenge on milk composition and on ruminal, blood, and fecal pH in Holstein cows

Oral supplementation of clay has been reported to function as buffer in dairy cows. However, its effects on rumen, blood, and fecal pH have varied among studies. Our objective was to determine the effects of 3 concentrations of dietary clay supplementation after a grain challenge. Ten multiparous rumen-cannulated Holstein cows [body weight (mean ± standard deviation)=648±12kg] with 142±130 (60 to 502) days in milk were assigned to 1 of 5 treatments in a replicated 5×5 Latin square design balanced to measure carryover effects. Periods (21d) were divided into an adaptation phase (d 1 to 18, with regular total mixed ration fed ad libitum) and a measurement phase (d 19 to 21). Feed was restricted on d 18 to 75% of the average of the total mixed ration fed from d 15 to 17 (dry matter basis), and on d 19 cows received a grain challenge. The challenge consisted of 20% finely ground wheat administered into the rumen via a rumen cannula, based on the average dry matter intake obtained on d 15 to 17. Treatments were POS (no clay plus a grain challenge), 3different concentrations of clay (0.5, 1, or 2% of dietary dry matter intake), and control (C; no clay and no grain challenge). Statistical analysis was performed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC). Contrasts 1 (POS vs. C) and 2 (POS vs. the average of 0.5, 1, or 2%) were compared, along with linear and quadratic treatment effects. Rumen, fecal, and blood pH, along with blood metabolites, were measured at 0, 4, 8, 12, 16, 20, 24, 36, and 48h relative to the grain challenge. Cows fed POS had lower rumen pH [(mean ± standard error) 6.03±0.06] than cows fed C (6.20±0.06). Cow fed POS had lower fecal pH (6.14±0.04) than cows fed C (6.38±0.04). We observed a linear treatment effect for rumen pH and fecal pH. Fecal pH (6.22±0.04) was higher for cows fed clay (contrast 2) then for cows fed POS (6.14±0.04). We also observed a treatment difference (contrast 2) for negative incremental area under the curve, pH below 5.6 × h/d, (0.5% clay=7.93±0.83, 1% clay=8.56±0.83, and 2% clay=7.79±0.83) compared with POS (11.0±0.83). Cows fed clay tended to have higher milk yield (0.5% clay=28.8±3.4kg, 1% clay=30.2±3.4kg, and 2% clay=29.1±3.4kg, contrast 2), and had higher 3.5% fat-corrected milk (0.5% clay=29.9±3.5kg, 1% clay=34.1±3.5kg, and 2% clay=33.1±3.4kg), and higher energy-corrected milk (0.5% clay=29.1±3.3kg, 1% clay=32.8±3.4kg, and 2% clay=31.6±3.3kg) than cows fed POS (27.7±3.4kg, 28.0±3.4kg, 27.7±3.3kg, respectively). In conclusion, cows fed clay had higher rumen pH, energy-corrected milk, fat-corrected milk, and a trend for milk yield than cows fed POS.

The Efficacy of Cooling with Phase Change Material for the Treatment of Exercise-Induced Muscle Damage

PURPOSE: The limited efficacy of cold-water immersion in diminishing muscle damage may be due to inadequate treatment duration. Phase Change Material (PCM) can provide prolonged cooling. The purpose of this study was to examine the efficacy of post-exercise PCM cooling on strength loss and pain after eccentric exercise. METHODS: Four men and 2 women (39±13 yo) performed isometric quadriceps strength tests at 30°, 50° and 70° knee flexion, then performed 120 eccentric quadriceps contractions (Biodex System 2, Shirley NY) at 90% MVC. The protocol was repeated on the contralateral leg. PCM packs were then placed inside compression shorts over the quadriceps. PCM at 15°C were applied to the first leg, and PCM at room temperature were applied to the second leg. The 15°C packs were replaced after 3 hr (6 hr total). Quadriceps skin temperature was recorded continually. Strength and pain (VAS 0-10 scale) were assessed for 4 days. The protocol was repeated 5 mo later (room temperature PCM on both legs). Since cooling one leg might have a systemic effect on the contralateral leg, the effect of cooling was assessed by Treatment by Time ANOVA with treatments defined as Direct Cooling (leg with 15°C packs), Systemic Cooling (leg with room temperature packs contralateral to the 15°C packs), and Control (legs tested 5 mo later). RESULTS: Skin temperature averaged 21±1° C for Direct Cooling versus 31±2°C for Systemic Cooling and Control (P<0.01). Strength (% of baseline) across 4 days post-exercise was 101±9% for Direct Cooling, 94±16% for Systemic Cooling, and 91±7% for Control (Linear Treatment effect P<0.05). Peak strength loss occurred 1 day post exercise: Direct Cooling, 93±13%, Systemic Cooling, 92±16%, Control 83±10% (Linear Treatment effect P<0.01). Pain across 4 days post exercise was 0.9±1.0 for Direct Cooling, 1.6±1.4 for Systemic Cooling, and 2.5±2.4 for Control (Linear Treatment effect P<0.05). Peak pain occurred 2 days post exercise: Direct Cooling, 1.7±1.9, Systemic Cooling, 2.7±2.3, Control 4.0±0.7 (Linear Treatment effect P<0.05). CONCLUSIONS: Prolonged post-exercise muscle cooling using PCM resulted in minimal strength loss and pain compared to control (with a possible systemic effect also evident). This study demonstrates the potential utility of a cooling garment for accelerating recovery from damaging exercise.

Effect of a grain challenge on ruminal, urine, and fecal pH, apparent total-tract starch digestibility, and milk composition of Holstein and Jersey cows

The effects of a grain challenge on ruminal, urine, and fecal pH, apparent total-tract starch digestibility, and milk composition were determined. Six Holstein cows, 6 rumen-cannulated Holstein cows, and 6 Jersey cows were used in a replicated 3×3 Latin square design balanced to measure carryover effects. Periods (10 d) were divided into 4 stages (S): S1, d 1 to 3, served as baseline with regular total mixed ration ad libitum; S2, d 4, served as restricted feeding, with cows offered 50% of the total mixed ration fed on S1 (dry matter basis); S3, d 5, a grain challenge was performed, in which cows were fed total mixed ration ad libitum and not fed (CON) or fed an addition of 10% (MG) or 20% (HG) pellet wheat-barley (1:1) top-dressed onto the total mixed ration, based on dry matter intake obtained in S1; S4, d 6 to 10, served as recovery stage with regular total mixed ration fed ad libitum. Overall, cows had a quadratic treatment effect for milk yield where CON (22.6kg/d) and HG (23.5kg/d) had lower milk yield than cows in MG (23.7kg/d). Jersey cows had a quadratic treatment effect for dry matter intake where cows in CON (13.2kg/d) and HG (12.4kg/d) had lower dry matter intake than cows in MG (14kg/d). Holstein cows had a linear treatment effect for dry matter intake (17.7, 18.4, and 18.6kg/d for CON, MG, and HG, respectively). Rumen pH for the rumen-cannulated cows had a linear treatment effect (6.45, 6.35, and 6.24 for CON, MG, and HG, respectively). Cows in HG spent more time with rumen pH below 5.8 (4.33 h) than MG (2 h) or CON (2.17 h) as shown by the quadratic treatment effect. Holstein cows in HG (8.46) had lower urine pH than MG (8.51) or CON (8.54) as showed by the linear treatment effect for urine pH. Apparent total-tract starch digestibility had a tendency for a linear treatment effect on S3 (97.62±1.5, 97.47±1.5, and 91.84±1.6%, for CON, MG, and HG, respectively). Fecal pH was associated with rumen pH depression as early as 15 h after feeding for Holstein cows. In conclusion, a grain challenge reduced urine pH in Holstein cows but not in Jersey cows. Holstein cows’ health were not affected when rumen pH was depressed. A potentially useful link between rumen pH and systemic (urine) pH within 2 h after feeding was quantified in Holstein cows.

Corn silage from corn treated with foliar fungicide and performance of Holstein cows

Foliar fungicide application to corn plants is used in corn aimed for corn silage in the dairy industry, but questions regarding frequency of application and its effect on corn silage quality and feed conversion when fed to dairy cows remain prevalent. The objective of this study was to evaluate the effects of various foliar fungicide applications to corn on dry matter intake (DMI), milk production, and milk composition when fed to dairy cows. Sixty-four Holstein cows with parity 2.5±1.5, 653±80kg of body weight, and 161±51d in milk were blocked and randomly assigned to 1 of 4 corn silage treatments (total mixed ration with 35% of the dry matter as corn silage). Treatments were as follows: control (CON), corn silage with no applications of foliar fungicide; treatment 1 (1X), corn silage from corn that received 1 application of pyraclostrobin (PYR) foliar fungicide (Headline; BASF Corp.) at corn vegetative stage 5; treatment 2 (2X), corn silage from corn that received the same application as 1X plus another application of a mixture of PYR and metconazole (Headline AMP; BASF Corp.) at corn reproductive stage 1 (“silking”); and treatment 3 (3X), corn silage from corn that received the same applications as 2X as well as a third application of PYR and metconazole at reproductive stage 3 (“milky kernel”). Corn was harvested at about 32% dry matter and 3/4 milk line stage of kernel development and ensiled for 200d. Treatments were fed to cows for 5wk, with the last week being used for statistical inferences. Week –1 was used as a covariate in the statistical analysis. Dry matter intake tended to be lower for cows fed corn silage treated with fungicide than CON (23.8, 23.0, 19.5, and 21.3kg for CON, 1X, 2X, and 3X, respectively). A linear treatment effect for DMI was observed, with DMI decreasing as foliar fungicide applications increased. Treatments CON, 1X, 2X, and 3X did not differ for milk yield (34.5, 34.5, 34.2, and 34.4kg/d, respectively); however, a trend for increased feed conversion represented by fat-corrected milk/DMI (1.65 vs. 1.47) and energy-corrected milk/DMI (1.60 vs. 1.43) was noted for cows fed corn silage with fungicide compared with CON. In conclusion, cows receiving corn silage treated with foliar fungicide had better conversion of feed dry matter to milk than those receiving CON silage.

Níveis de fitase sobre o desempenho, parâmetros ósseos e bioquímicos de suínos alimentados com ração de origem vegetal sem inclusão de fosfato bicálcico

Este estudo foi conduzido com o objetivo de avaliar os níveis de fitase em rações para suínos em crescimento selecionados para deposição de carne. Foram utilizados 64 suínos mestiços (32 machos castrados e 32 fêmeas), híbridos comerciais, com peso médio inicial de 23,311±2,254 kg, distribuídos em delineamento de blocos casualizados, com quatro tratamentos, oito repetições e dois animais (um macho e uma fêmea) por unidade experimental. Os tratamentos foram constituídos por uma ração controle de origem vegetal, sem inclusão de fosfato bicálcico e fitase, contendo 0,100% de fósforo disponível; e de outras três rações obtidas pela inclusão de 300, 600 e 1200 unidades de fitase (UFT kg-1) à ração controle. Os níveis de fitase influenciaram de forma linear o ganho de peso diário e consumo de ração, aumentando até o nível de 293 e 307 UFT kg-1 de ração, respectivamente, a partir do qual permaneceram em um platô. A conversão alimentar diminuiu até 255 UFT kg-1 de ração, a qual permaneceu em um platô. Os níveis de fitase não influenciaram os teores de cinzas e fósforo no metacarpo dos animais. Houve efeito linear decrescente dos tratamentos sobre o resultado bioquímico de fosfatase alcalina. Os melhores resultados de ganho de peso, consumo de ração e conversão alimentar foram obtidos, respectivamente, com os níveis de 293, 307 e 255 UFT kg-1 de ração, em suínos de alto potencial genético para deposição de carne na fase dos 55 aos 90 dias de idade.

The Effect of a Compulsory Schooling Reform on Disability Pensioning – Evidence from the Danish Registers

A growing literature is examining the effects of compulsory schooling reforms on various measures of health later in life (SRH, hospitalization, mortality, BMI, health behaviors and self-reported work disability). However, few studies explore spillover effects of education on disability, and even fewer allow for heterogeneous treatment effects by gender. Yet, disability pensions constitute a large share of health care spending and have implications for health care utilization. Using comprehensive register data from Denmark providing administrative data on both health and disability on the entire Danish population coupled with a major compulsory schooling reform from 1958 that substantially lowered the costs of education and enhanced its quality in rural areas, we estimate Probit, OLS and linear treatment effects models which show that both men and women in rural born cohorts subject to the reform have a lower rate of disability pensioning and fewer medical diagnoses for chronic illnesses later in life compared to urban born counterparts and pre-reform cohorts from both regions. Furthermore, we find that an important channel of transmission of education to disability and health for both men and women is through higher income. A possible explanation for the symmetric effects of education on male and female disability in this setting could be that women in older cohorts in Denmark are more active on the labour market compared to other countries.

Características agronômicas do trigo em função de Azospirillum brasilense, ácidos húmicos e nitrogênio em casa de vegetação

Objetivou-se, neste estudo, verificar o efeito do uso combinado de Azospirillum brasilense, ácidos húmicos e diferentes doses de nitrogênio nas características agronômicas do trigo. Os experimentos foram instalados no dia 21 de maio de 2011 e a colheita foi procedida no dia 13 de setembro de 2011. O delineamento experimental adotado foi o de blocos casualizados em esquema fatorial 4 x 4, com quatro repetições. O primeiro fator se refere à combinação da estirpe Ab-V5 de A. brasilense com os ácidos húmicos, sendo utilizados os seguintes tratamentos: controle; Ab-V5; ácido húmico e Ab-V5+ácido húmico e o segundo fator se refere às doses de nitrogênio (0, 30, 60 e 90 kg ha-1 N). A maioria das variáveis em análise apresentou efeito linear positivo dos tratamentos em função da adubação nitrogenada sendo que apenas para a variável massa de cem grãos este efeito foi linear negativo. Não houve diferença significativa entre as variâncias, na produção de grãos. Pôde-se concluir que o uso combinado de Ab-V5 + ácido húmico promove principalmente a produção de matéria seca de folhas e não é responsivo à adubação nitrogenada para os demais componentes produtivos em estudo nem para a produtividade dos grãos.

The performance of different propensity score methods for estimating marginal hazard ratios

Propensity score methods are increasingly being used to reduce or minimize the effects of confounding when estimating the effects of treatments, exposures, or interventions when using observational or non-randomized data. Under the assumption of no unmeasured confounders, previous research has shown that propensity score methods allow for unbiased estimation of linear treatment effects (e.g., differences in means or proportions). However, in biomedical research, time-to-event outcomes occur frequently. There is a paucity of research into the performance of different propensity score methods for estimating the effect of treatment on time-to-event outcomes. Furthermore, propensity score methods allow for the estimation of marginal or population-average treatment effects. We conducted an extensive series of Monte Carlo simulations to examine the performance of propensity score matching (1:1 greedy nearest-neighbor matching within propensity score calipers), stratification on the propensity score, inverse probability of treatment weighting (IPTW) using the propensity score, and covariate adjustment using the propensity score to estimate marginal hazard ratios. We found that both propensity score matching and IPTW using the propensity score allow for the estimation of marginal hazard ratios with minimal bias. Of these two approaches, IPTW using the propensity score resulted in estimates with lower mean squared error when estimating the effect of treatment in the treated. Stratification on the propensity score and covariate adjustment using the propensity score result in biased estimation of both marginal and conditional hazard ratios. Applied researchers are encouraged to use propensity score matching and IPTW using the propensity score when estimating the relative effect of treatment on time-to-event outcomes. Copyright © 2012 John Wiley & Sons, Ltd.

Concentração de nitrogênio na solução nutritiva, na produtividade e na qualidade de frutos de melão cultivado em substrato

Este experimento foi conduzido em ambiente protegido, na UFSM, entre agosto de 2004 e janeiro de 2005, com o híbrido "Magelan". As mudas foram plantadas em sacolas de polietileno contendo 4,5dm3 do substrato Plantmax PXT®, na densidade de 3,3 plantas m-2. As plantas foram conduzidas verticalmente em haste única, com até dois frutos por planta, e despontadas ao atingir a altura de 2m. Os tratamentos foram constituídos por concentrações de nitrogênio na solução nutritiva de 8 (T1), 11 (T2), 14 (T3), 17 (T4) e 20 (T5) mmol L-1. Os demais nutrientes foram fornecidos nas concentrações, em mmol L-1, de 0,9 de H2PO4-; 2,25 de SO4--; 10,0 de Ca++; 6,0 de K+ e 5,0 de Mg++, e, em mg L-1, 0,42 de Mn; 0,26 de Zn; 0,05 de Cu; 0,50 de B; 0,04 de Mo e 4,82 de quelato de Fe. A solução nutritiva foi fornecida várias vezes ao dia, de acordo com a demanda hídrica da cultura, com um coeficiente de drenagem diário não inferior a 30%. O delineamento experimental foi inteiramente casualizado, com cinco tratamentos e quatro repetições. Foi observada resposta linear dos tratamentos na matéria seca vegetativa e de frutos, na área foliar, no número de frutos e na produtividade. Quanto às características qualitativas dos frutos, somente a acidez titulável apresentou diferença significativa, decrescendo com o aumento da concentração de N. A concentração de até 20mmol L-1 de N pode ser empregada na fertirrigação de lavouras comerciais dessa cultura em substrato.

Níveis de energia metabolizável mantendo a relação lisina digestível: caloria em rações para suínos machos castrados em terminação

Foram utilizados 40 suínos machos castrados, híbridos comerciais com peso inicial de 60,1 ± 1,3 kg, em um estudo para avaliar os efeitos de diferentes níveis de EM, mantendo-se a relação lisina digestível:caloria sobre o desempenho e as características de carcaça. Foi utilizado o delineamento experimental de blocos ao acaso, com quatro tratamentos, cinco repetições e dois animais por unidade experimental. Os tratamentos corresponderam a quatro níveis de EM (3.100, 3.230, 3.370 e 3.500 kcal/kg de ração), nos quais foi mantida a relação de 2,41 g de lisina digestível/Mcal de EM. As rações foram fornecidas à vontade até o fim do período experimental, quando os animais atingiram 95,46 ± 2,89 kg. Os níveis de energia metabolizável influenciaram o consumo diário de ração, que reduziu linearmente. A conversão alimentar melhorou linearmente com o aumento dos níveis de energia metabolizável. Não houve efeito dos tratamentos sobre o consumo de energia, o ganho de peso diário, a eficiência de utilização da EM para ganho de peso, o rendimento de carcaça, a espessura de toucinho e o rendimento de carne magra. Níveis crescentes de energia metabolizável (3.100 a 3.500 kcal/kg), mantendo-se a relação lisina digestível:caloria na ração de suínos machos castrados, promovem melhora na conversão alimentar e redução no consumo de ração, sem alterar os valores do ganho de peso e das características de carcaça.

Should we take measurements at an intermediate design point?

It is well known that, for estimating a linear treatment effect with constant variance, the optimal design divides the units equally between the two extremes of the design space. If the dose-response relation may be nonlinear, however, intermediate measurements may be useful in order to estimate the effects of partial treatments. We consider the decision of whether to gather data at an intermediate design point: do the gains from learning about nonlinearity outweigh the loss in efficiency in estimating the linear effect? Under reasonable assumptions about nonlinearity, we find that, unless sample size is very large, the design with no interior measurements is best, because with moderate total sample sizes, any nonlinearity in the dose-response will be difficult to detect. We discuss in the context of a simplified version of the problem that motivated this work-a study of pest-control treatments intended to reduce asthma symptoms in children.