Substantial gains in bias reduction from matching with a variable number of controls

In observational studies that match several controls to each treated subject, substantially greater bias reduction is possible if the number of controls is not fixed but rather is allowed to vary from one matched set to another. In certain cases, matching with a fixed number of controls may remove only 50% of the bias in a covariate, whereas matching with a variable number of controls may remove 90% of the bias, even though both control groups have the same number of controls in total. An example of matching in a study of surgical mortality is discussed in detail.     

Oxidative balance score and oxidative stress biomarkers in a study of Whites,African Americans,and African immigrants

Abstract

Context: Oxidative balance score (OBS) is a composite measure of multiple pro- and antioxidant exposures.

Objective: To investigate associations of OBS with F2-isoprostanes (FIP), mitochondrial DNA copy number (mtDNA), and fluorescent oxidative products (FOP), and assess inter-relationships among the biomarkers.

Methods: In a cross-sectional study, associations of a thirteen-component OBS with biomarker levels were assessed using multivariable regression models.

Results: Association of OBS with FIP, but not with FOP, was in the hypothesized direction. The results for mtDNA were unstable and analysis-dependent. The three biomarkers were not inter-correlated.

Conclusions: Different biomarkers of oxidative stress may reflect different biological processes.     

Song matching in a long-lived,sedentary bird with a low song rate: The importance of song type,song duration and intrusion

Territorial songbirds often match the song features or singing patterns of rivals, commonly as an aggressive signal. Most studies of song matching have been on Northern Hemisphere species with short lifespans and high song rates, but vocal matching is predicted to be affected both by longevity and territorial stability. We studied song matching in males of the white-browed scrubwren, Sericornis frontalis, a long-lived, sedentary, territorial Australian songbird. We quantified natural song rate and diversity, and then conducted three playback experiments to test: (a) whether males match by song type; (b) how they respond physically and vocally to territorial intrusion; and (c) whether they match by song length, and use it as an agonistic signal. Males naturally had very low song rates, singing on average less than three times per hour, and moderate repertoires, with an estimated mean of 17.5 song types for individual males. Males did not engage in extended counter-singing bouts. The first experiment showed that males matched the song type of immediate neighbours almost 90% of the time, if that type was in their repertoire. The remaining experiments revealed that song-type matching was an aggressive signal; males responded more aggressively to, and were more likely to match, playback simulating a neighbour's territorial intrusion than song from their shared boundary. Males did not match songs by length, but they produced longer songs after simulated intrusion. Males also responded more aggressively to playback of longer songs that simulated intrusion, but less aggressively to longer songs from the territory boundary. Overall, we show that sedentary, long-lived songbirds with low song rates, can use song-type matching as an aggressive signal to communicate with neighbours and intruders. Song length had a different role in communication, possibly related to individual quality or territory ownership.     

Long-acting beta-agonists reduce mortality of patients with severe and very severe chronic obstructive pulmonary disease: a propensity score matching study

Background

Long-acting beta-agonists were one of the first-choice bronchodilator agents for stable chronic obstructive pulmonary disease. But the impact of long-acting beta-agonists on mortality was not well investigated.

Methods

National Emphysema Treatment Trial provided the data. Severe and very severe stable chronic obstructive pulmonary disease patients who were eligible for volume reduction surgery were recruited at 17 clinical centers in United States during 1988–2002. We used the 6–10 year follow-up data of patients randomized to non-surgery treatment. Hazard ratios for death by long-acting beta-agonists were estimated by three models using Cox proportional hazard analysis and propensity score matching were measured.

Results

The pre-matching cohort was comprised of 591 patients (50.6% were administered long-acting beta-agonists. Age: 66.6 ± 5.3 year old. Female: 35.4%. Forced expiratory volume in one second (%predicted): 26.7 ± 7.1%. Mortality during follow-up: 70.2%). Hazard ratio using a multivariate Cox model in the pre-matching cohort was 0.77 (P = 0.010). Propensity score matching was conducted (C-statics: 0.62. No parameter differed between cohorts). The propensity-matched cohort was comprised of 492 patients (50.0% were administered long-acting beta-agonists. Age: 66.8 ± 5.1 year old. Female: 34.8%. Forced expiratory volume in one second (%predicted) 26.5 ± 6.8%. Mortality during follow-up: 69.1%). Hazard ratio using a univariate Cox model in the propensity-matched cohort was 0.77 (P = 0.017). Hazard ratio using a multivariate Cox model in the propensity-matched cohort was 0.76 (P = 0.011).

Conclusions

Long-acting beta-agonists reduce mortality of severe and very severe chronic obstructive pulmonary disease patients.     

Effect of niacin supplementation on digestibility,nitrogen utilisation and milk and blood variables in lactating dairy cows fed a diet with a negative rumen nitrogen balance

The aim of the present experiment was to determine if a niacin supplementation of 6 g/d to lactating dairy cow diets can compensate negative effects of a rumen nitrogen balance (RNB) deficit. A total of nine ruminally and duodenally fistulated lactating multiparous German Holstein cows were successively assigned to one of three diets consisting of 10 kg maize silage (dry matter [DM] basis) and7 kg DM concentrate: Diet RNB– (n = 6) with energy and utilisable crude protein at the duodenum (uCP) according to the average requirement of the animals but with a negative RNB (–0.41 g N/MJ metabolisable energy [ME]); Diet RNB0 (n = 7) with energy, uCP and a RNB (0.08 g N/MJ ME) according to the average requirement of the animals and, finally, Diet NA (n = 5), which was the same diet as RNB–, but supplemented with 6 g niacin/d. Samples of milk were taken on two consecutive days, blood samples were taken on one day pre- and post-feeding and faeces and urine were collected completely over five consecutive days. The negative RNB reduced milk and blood urea content and apparent total tract digestibility of DM, organic matter (OM) and neutral detergent fibre (NDF). Also N excretion with urine, the total N excreted with urine and faeces and the N balance were reduced when the RNB was negative. Supplementation of niacin elevated plasma glucose concentration after feeding and the N balance increased. Supplementing the diet with a negative RNB with niacin led to a more efficient use of dietary N thereby avoiding the negative effects of the negative RNB on the digestibility of DM, OM and NDF.     

Effects of a core stability exercise program on balance and coordination in children with cerebellar ataxic cerebral palsy

Objective:To evaluate the effects of a core stability exercise program on balance, coordination, and severity of ataxia in children with cerebellar ataxic cerebral palsy (CP).Methods:Forty children with cerebellar ataxic CP (mean age: 6.75±1.35 years) were randomly assigned to a control group and an intervention group for 2 months of follow-up. The control group received a standard physical therapy program three times weekly (1 h per session), while the intervention group received a core stability program for 30 min, in addition to the selected physical therapy program. Both groups were evaluated pre-treatment and post-treatment using the Scale for the Assessment and Rating of Ataxia, the Balance Error Scoring Systems scale, Bruininks-Oseretsky tests of motor proficiency, and HUMAC balance system scores.Results:We found statistically significant reductions in the severity of ataxia, as well as improved balance and coordination in both groups, with stronger effects observed in the intervention group (P<0.05).Conclusion:The core stability program can improve balance and coordination in children with cerebellar ataxic CP when incorporated with a standard physical therapy program.     

Effect of tree leaves with or without urea as a feed supplement on nutrient digestion and nitrogen balance in sheep

Two nitrogen balance experiments in a 4 × 4 Latin square design were conducted to compare leaves of Grewia oppositifolia and Ziziphus mauritiana containing condensed tannins (CT) 0.08 g and 34.7 g per kg DM, respectively as supplement on feed intake, nutrients digestibility and nitrogen (N) retention in adult wethers and to examine the benefits of adding urea to Z. mauritiana leaves containing higher level of CT on N utilization in the animals. In experiment 1, the basal diet of oat hay was fed to sheep either un-supplemented or supplemented with 320 g dried leaves of Z. mauritiana or 320 g dried leaves of G. oppositifolia or 160 g dried leaves each of Z. mauritiana and G. oppositifolia. In vivo dry matter (DM) digestibility was not different among the four diets while N digestibility remained significantly lower (P<0.05) in Z. mauritiana supplemented diets. Daily intake of oat hay reduced (P<0.05) and that of total diet DM increased (P<0.001) with feeding of the leave supplements. Mean N retention on control diet was 4.39 g/d and increased to 7.51 g/d with inclusion of G. oppositifolia leaves but did not change with the other two supplements. In experiment 2, a basal diet of sorghum hay was fed ad libitum without any supplement (control diet) and the other three diets were supplemented with 320 g dried leaves of Z. mauritiana with no urea, 5 g urea/d or 10 g urea/d. Daily intake (g/d) of sorghum hay or total DM intake did not respond to inclusion of urea in the diets. Supplementation of Z. mauritiana with or without urea did not affect digestibility of DM, organic matter and acid detergent fiber. Nitrogen retention increased (P<0.05) from 0.57 g/d on control diet to 3.72 g/d with supplementation of Z. mauritiana leaves. Addition of urea 5 g/d did not further increase the N retention (4.78 g/d) but was significantly increased to 7.16 g/d in response to 10 g urea/d in the diet. It was concluded that response to urea feeding in the presence of tannin rich Z. mauritiana leaves was dose-dependant and that feeding 10 g urea/d increased the capacity of sheep to consume more feed and retain more N in the body.     

A complete energy balance from photons to new biomass reveals a light- and nutrient-dependent variability in the metabolic costs of carbon assimilation

The energy balance of Phaeodactylum tricornutum cells from photon to biomass have been analysed under nutrient-replete and N-limiting conditions in combination with fluctuating (FL) and non-fluctuating (SL) dynamic light. For this purpose, the amount of photons absorbed has been related to electrons transported by photosystem II, to gas exchange rates, and to the newly formed biomass differentially resolved into carbohydrates, proteins, and lipids measured by means of Fourier transform infrared (FTIR) spectroscopy. Under high nutrient conditions, the quantum efficiency of carbon-related biomass production (Phi(C)) and the metabolic costs of carbon (C) production were found to be strongly controlled by the light climate. Under N-limited conditions, the light climate was less important for the efficieny of primary production. Thus, the largest range of Phi(C) dependent on the nutrient status of the cells was observed under non-fluctuating light conditions which are comparable with stratified conditions in the natural environment. It is evident that N limitation induced pronounced changes in the composition of macromolecular compounds and, thus, influenced the degree of reduction of the biomass as well as the metabolic costs of C production. However, Phi(C) and the metabolic costs are not predictable from the photosynthesis rates. In consequence, the results clearly show that bio-optical methods as well as gas exchange measurements during the light phase can severely mismatch the true energy storage in the biomass especially under high nutrient in combination with non-fluctuating light conditions.     

Bioconversion of starches into maltotetraose using Pseudomonas stutzeri maltotetraohydrolase in a membrane recycle bioreactor: Effect of multiple enzyme systems and mass balance study

A simplified single-step method involving simultaneous production and purification of maltotetraose (G₄) by employing ultrafiltration (UF) membranes was previously proposed. The addition of a pretreatment step using pullulanase and then the G₄-amylase was expected to increase the yield of G₄. The single-enzyme system, however, showed 0.42 g higher total product output than the successive dual-enzyme system throughout 6 h reaction. The G₄ yield using the successive dual-enzyme system could be improved after removing the unwanted side product with UF. Experiments were conducted with membranes of larger pore size, but this did not significantly increase the total product output. The membrane unit with a molecular weight cutoff of 1,000 was the most appropriate membrane pore size for the G₄-exo--amylase membrane recycle bioreactor system. The total amount of substrate fouled in the membrane during a 6-h reaction was estimated as 69 mg glucose equivalent when substrate concentration was 0.25% (w/v). The mass balance equation indicated that the percent conversion of soluble starch to G₄ at steady state was 65%.     

Bias, precision and accuracy in the estimation of cuticular and respiratory water loss: a case study from a highly variable cockroach, Perisphaeria sp

We compared the precision, bias and accuracy of two techniques that were recently proposed to estimate the contributions of cuticular and respiratory water loss to total water loss in insects. We performed measurements of VCO2 and VH2O in normoxia, hyperoxia and anoxia using flow through respirometry on single individuals of the highly variable cockroach Perisphaeria sp. to compare estimates of cuticular and respiratory water loss (CWL and RWL) obtained by the VH2O-VCO2 y-intercept method with those obtained by the hyperoxic switch method. Precision was determined by assessing the repeatability of values obtained whereas bias was assessed by comparing the methods' results to each other and to values for other species found in the literature. We found that CWL was highly repeatable by both methods (R0.88) and resulted in similar values to measures of CWL determined during the closed-phase of discontinuous gas exchange (DGE). Repeatability of RWL was much lower (R=0.40) and significant only in the case of the hyperoxic method. RWL derived from the hyperoxic method is higher (by 0.044 micromol min(-1)) than that obtained from the method traditionally used for measuring water loss during the closed-phase of DGE, suggesting that in the past RWL may have been underestimated. The very low cuticular permeability of this species (3.88 microg cm(-2) h(-1) Torr(-1)) is reasonable given the seasonally hot and dry habitat where it lives. We also tested the hygric hypothesis proposed to account for the evolution of discontinuous gas exchange cycles and found no effect of respiratory pattern on RWL, although the ratio of mean VH2O to VCO2 was higher for continuous patterns compared with discontinuous ones.     

EMBalance - validation of a decision support system in the early diagnostic evaluation and management plan formulation of balance disorders in primary care: study protocol of a feasibility randomised controlled trial

BackgroundBalance problems are caused by multiple factors and often lead to falls and related fractures, bringing large socio-economic costs. The complexity of balance control mechanisms, the lack of medical expertise, and the absence of specialised equipment contribute to the delayed or incorrect diagnosis and management ofthese patients. Advances in computer science have allowed the development of computer systems that support clinical diagnosis and treatment decisions based on individualised patient data. The aim of the EMBalance decision support system (DSS) is to support doctors facing this clinical challenge, to make a definitive diagnosis and implement an effective management plan. The EMBalance study will determine the accuracy of this supportive tool when used by non-specialist doctors. This study is funded by the European Union’s Seventh Framework Programme.Methods/designEMBalance is a proof-of-concept study designed as a non-commercial, international, multi-centre, single-blind, parallel-group randomised controlled trial to be carried out at four clinical sites in the United Kingdom, Germany, Greece and Belgium. The study is comprised of three stages: internal pilot, phase I (diagnosis) and stage II (management). For this purpose, 200 patients presenting with persistent dizziness (>3 months’ duration) to primary care services will be randomised to either the intervention group (diagnostic assessment with the DSS) or a control group (diagnostic assessment without the DSS). Patients allocated to the intervention group will be assessed by a doctor with the support of the EMBalance DSS, while patients allocated to the control group will receive a visit as per standard practice. Ultimately, all patients’ diagnoses and management plans will be certified by a consultant in neuro-otology.DiscussionEMBalance is the first trial to test the accuracy of a DSS in both the diagnosis of and the management plan for vestibular disorders across the healthcare systems of four different countries. The EMBalance study is the result of a combined effort of engineers and physicians to develop an accurate tool to support non-specialist doctors, with no risk for the patient. This trial will provide reliable information about the benefits of implementing DSSs in primary care while supporting the feasibility of testing the EMBalance algorithms in further research.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02704819","term_id":"NCT02704819"}}NCT02704819. Registered 29 February 2016.

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1568-x) contains supplementary material, which is available to authorized users.     

A description of the findings from bull breeding soundness evaluations and their association with pregnancy outcomes in a study of western Canadian beef herds

The primary objectives were to describe beef bulls considered for use and those reported as used in 205 beef herds in western Canada, and to determine whether factors typically assessed during breeding soundness evaluations were associated with reproductive success. More than 100 veterinary clinics reported 2990 breeding soundness evaluations for bulls considered for natural service in client's herds. Differences among clinics explained 5.2% of the variation in scrotal circumference (SC) and 6.9% of the variation in percentage of morphologically normal sperm of all bulls considered for use (after accounting for age, breed, body condition, significant physical abnormalities, month, and year). The percentage of morphologically normal sperm was lower in bulls with an SC ≤34 versus >34 cm (P < 0.006). This study included data from 1384 and 1370 bulls used for breeding in 2001 and 2002, respectively. Most (80%) of the bulls used were Simmental, Black Angus, Charolais, Red Angus, or Hereford, and 80% were ≤4 y of age. Before the breeding season, a veterinarian evaluated 89.5% of all bulls used in these herds. Of the bulls subjected to a breeding soundness evaluation and subsequently used, 93.1% were satisfactory. In 2001 and 2002, injuries were reported in 2.5 and 2.1% of bulls and in 16.6 and 11.4% of herds, and necrobacillosis of the foot was reported in 2.5 and 1.2% of bulls and 11.2 and 6.5% of the herds. The average number of cows exposed to each bull was 26 (both years). Cows exposed to bulls with a smaller SC were less likely to be diagnosed pregnant (P < 0.047) and had a longer median interval from first bull exposure to calving (P < 0.016) than bulls with a larger SC. In conclusion, our findings emphasized the value of breeding soundness evaluations, including measurements of SC, in fertility management of beef cattle.     

Coupling satellite data with in situ measurements and numerical modeling to study fine suspended-sediment transport: a study for the lagoon of New Caledonia

This paper investigates the potential of remotely sensed data to map turbidity in a coral reef lagoon and to calibrate a numerical model of fine suspended-sediment transport. Simultaneous measurements of turbidity depth-profile and above-water spectral reflectance integrated according Landsat 7 ETM+ band 2 spectral sensitivity provide a linear regression relationship for the southwest lagoon of New Caledonia (r²=0.95, n=40). This relationship is applied to an empirically atmospherically corrected Landsat ETM+ image of the lagoon acquired on October 23, 2002. A comparison between Landsat estimates of turbidity and concurrent measurements at 14 stations indicates that the mean standard error in the satellite-estimated turbidity is 17.5%. The numerical model introduced in Douillet et al. (2001) is used to simulate the transport of fine suspended sediments in the lagoon in October 2002. A calibration of the erosion rate coefficient required by the model is proposed using in situ turbidity profiles and the remotely sensed turbidity field. In situ data are used to tune locally the erosion rate coefficient, while satellite data are used to determine its spatial zonation. We discuss necessary improvements in coupled studies of fine-sediment transport in coastal zones, namely relationships between turbidity and sediment concentration, integration of wave influence in the model, and correction of bottom reflection in satellite data processing.     

Pharmacokinetic data of propranolol enantiomers in a comparative human study with (S)- and (R,S)-propranolol

The pharmacokinetics of (S)-propranolol were compared after the oral administration of a 40 mg dose of the pure enantiomer and an 80 mg dose of a racemic mixture of (R,S)-propranolol. The results of this study indicate that the bioavailability of (S)-propranolol, as expressed by the mean area under the concentration-time curve (AUC) and maximum serum concentration, is lower after 40 mg of the optically pure drug than after the racemic drug.     

Effect of intensive lifestyle intervention on C-reactive protein in subjects with impaired glucose tolerance and obesity. Results from a randomized controlled trial with 5-year follow-up

C-reactive protein (CRP) is a marker of metabolic and cardiovascular disease. To study the effects of lifestyle on CRP in a high-risk population we conducted a randomized controlled trial on 200 obese subjects (BMI > 27 kg m^?2) with impaired glucose tolerance recruited from primary care settings. They were randomized to either a 1-month stay at a wellness centre focusing on diet, exercise and stress management (intervention group) or 30–60 min of oral and written information on lifestyle intervention (control group). A significant reduction of CRP was observed after 1 month and 1 year in the intervention group. They reduced their CRP levels more than the control group 1 year after intervention (p=0.004). In conclusion lifestyle intervention can decrease CRP in obese individuals with impaired glucose tolerance for up to 1 year. Further research is needed to evaluate whether the CRP level reduction translates into a decreased risk for cardiovascular morbidity.     

Modification of the Computational Procedure in Parker and Bregman's Method of Calculating Sample Size from Matched Case–Control Studies with a Dichotomous Exposure

Summary .   Several authors have addressed the problem of calculating sample size for a matched case–control study with a dichotomous exposure. The approach of Parker and Bregman (1986, Biometrics 42, 919–926) is, in our view, one of the most satisfactory, since it requires specification of quantities that are often easily available to the investigator. However, its recommended implementation involves a computational approximation. We show here that the approximation performs poorly in extreme situations and can be easily replaced with a more exact calculation.     

参苓白术散结合双歧杆菌四联活菌片对肥胖症患者代谢状况和脂肪因子及肠道菌群平衡影响的前瞻性研究

通过前瞻性研究探讨参苓白术散联合双歧杆菌四联活菌片对肥胖症患者代谢状况、脂肪因子及肠道菌群平衡的影响, 为临床干预方案的制定提供参考。

选取2018年10月至2020年10月我院112例肥胖症患者行前瞻性研究, 应用随机数字表法分为观察组(n=56)和对照组(n=56)。对照组患者予以饮食、运动等常规干预, 观察组患者在对照组基础上予以参苓白术散联合双歧杆菌四联活菌片治疗。两组患者均干预3个月。比较两组患者临床疗效、干预前和干预3个月后肥胖相关指标[体质量、体质量指数(BMI)、体脂百分率、肥胖度]、糖脂代谢指标[空腹血糖(FBG)、空腹胰岛素(FINS)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、脂肪因子[脂联素(APN)、抵抗素(resistin)、瘦素(LP)]、炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)]水平和肠道菌群(双歧杆菌、乳杆菌、拟杆菌、肠杆菌、肠球菌)数量。

(1) 干预3个月后, 观察组患者总有效率为85.71%(48/56), 高于对照组的69.64%(39/56), 而体质量、BMI、体脂百分率、肥胖度水平均低于对照组(均P < 0.05)。(2)与干预前比较, 干预3个月后两组患者FBG、FINS、TC、TG、LDL-C、HDL-C水平均降低, 同时观察组低于对照组(均P < 0.05)。(3)干预3个月后, 两组患者血清APN水平高于干预前, resistin、LP水平低于干预前, 同时观察组均优于对照组(均P < 0.05)。(4)与干预前比较, 干预3个月后两组患者血清TNF-α、IL-6、IL-1β水平均呈降低趋势, 同时观察组降低幅度大于对照组(均P < 0.05)。(5)观察组患者干预3个月后肠道双歧杆菌、乳杆菌、拟杆菌数量均高于对照组, 而肠杆菌、肠球菌数量均低于对照组(均P < 0.05)。

参苓白术散、双歧杆菌四联活菌片联合干预方案在肥胖症患者中的应用效果理想, 可有效控制肥胖, 促进患者体质量降低, 同时对机体糖脂代谢、脂肪因子、炎症因子水平及肠道菌群均有良好调节作用, 临床应用价值较高。