Secondary Response Variables Research Articles

Large‐scale breeding applications of unoccupied aircraft systems enabled genomic prediction

AbstractBreeding for improved, reliable cultivars despite growing environmental irregularity can be challenging. Unoccupied aircraft systems (UAS) are a popular high‐throughput phenotyping technology that has been shown to help interpret the mechanisms associated with crop productivity and environmental response, creating potential for improved breeding strategies. Spectral reflectance indices (SRIs), encompassing both vegetation and water indices like normalized difference vegetation index (NDVI), normalized difference red‐edge index, and normalized water index, were employed to assess 4094 winter wheat genotypes across 11,593 breeding plots at Washington State University from 2019 through 2022. SRIs were then used with genomic data in univariate models as covariates and multivariate models as secondary response variables for predictions of grain yield. The prediction accuracy of models was evaluated using a leave‐one‐year‐out validation strategy against a base genomic prediction method. Including SRI data as fixed effects in univariate genomic prediction models can improve prediction accuracy over the control but is unreliable across years. When used in multivariate models, SRIs improve prediction performance across years but require high‐performance computational resources that could limit feasibility. In univariate models, when test year NDVI data were available and used to calculate breeding values, prediction performance was at least 16% better than the control, ranging in prediction accuracy from 0.54 in 2019 to 0.93 in 2020. This study highlights the limited reliability of SRI use in genomic prediction of untested environments and locations. However, a significant application for the technology can be found in early‐season UAS data collection to aid accurate predictions in late season, a helpful tool in tight turnaround times commonly experienced in winter crop breeding programs.

Factors Associated With Severity of Cubital Tunnel Syndrome at Presentation.

The outcomes of cubital tunnel syndrome surgery are affected by preoperative disease severity. The aim of this study was to identify factors associated with clinical and electrodiagnostic severity of cubital tunnel syndrome at presentation. We retrospectively identified 213 patients with electrodiagnostically confirmed cubital tunnel syndrome who underwent cubital tunnel surgery from July 2008 to June 2013. Our primary response variable was clinical cubital tunnel syndrome severity assessed by the McGowan grade. Our secondary response variables were sensory nerve action potential (SNAP) recordability, presence of fibrillations, and motor nerve conduction velocities (CVs) in the abductor digiti minimi (ADM) and first dorsal interosseous (FDI). Bivariate analysis was used to screen for factors associated with disease severity; significant variables were selected for multivariable regression analysis. Older age was associated with higher McGowan grade and diabetes mellitus was associated with unrecordable SNAPs on bivariate analysis. No other variables met inclusion criteria for multivariable regression analysis for McGowan grade or unrecordable SNAPs. Multivariable regression analysis showed older age and higher Distressed Communities Index (DCI) to be associated with decreased motor nerve CVs in ADM. Multivariable regression analysis showed higher body mass index (BMI) and higher DCI to be associated with decreased motor nerve CVs in FDI. No variable was associated with the presence of fibrillations. A subset of patients with cubital tunnel syndrome may benefit from earlier referral for hand surgery evaluation and earlier surgery. Older patients, with higher BMI, with diabetes mellitus, and with economic distress are at higher risk for presentation with more severe disease.

Local knowledge and attitude towards the Vulnerable Bhutan takin Budorcas whitei among residents living within its seasonal range

AbstractWe assessed local knowledge of and attitudes towards a large, endemic bovid, the Bhutan takin Budorcas whitei, within its seasonal range in Jigme Dorji National Park, Bhutan. Using semi-structured questionnaires, data were collected in March 2015 from interviews with 169 park residents. A conditional inference tree analysis was used to explore associations between demography, locality, and secondary response variables through questions relating to respondents’ knowledge of the takin's status as a protected species, a Vulnerable species, and as the national animal. Most respondents knew the takin was Bhutan's national animal, and of those, a significantly high proportion also knew of its protected status. Significantly more respondents residing in the species’ summer, rather than winter, range were aware of the takin's Vulnerable status. Most respondents expressed positive feelings towards the takin and supported its protection. This strong positive attitude, in conjunction with awareness-raising efforts, could be valuable for promoting the takin as a montane flagship species.

Organosolv delignification of agricultural residues (date palm fronds, Phoenix dactylifera L.) of the United Arab Emirates

Date palm fronds (primary agricultural residue of the United Arab Emirates) were used as a feedstock in an ethanol–water organosolv delignification process to generate organosolv lignin (OSL) and enzymatically digestible cellulose-rich pulp. Conditions of the treatment (temperature, catalyst concentration and amount of ethanol in the digesting solvent mixture) were screened and preliminarily optimized for OSL recovery and digestibility of the cellulose-rich pulp as primary and secondary response variables, respectively. OSL recovery was positively influenced only by temperature (140–200°C), while the digestibility of the cellulose pulp was positively influenced by temperature and negatively influenced by ethanol content in the digesting solvent. Maximum production of 12.93g lignin/100g RM (raw material) and 21.38g glucose/100g RM was achieved. Xylan losses reached up to 70%, increasing with temperature. Addition of the catalyst (sulfuric acid) was found to have no significant influence on any of the responses investigated.

Prediction Accuracy in Multivariate Repeated-Measures Bayesian Forecasting Models with Examples Drawn from Research on Sleep and Circadian Rhythms.

In study designs with repeated measures for multiple subjects, population models capturing within- and between-subjects variances enable efficient individualized prediction of outcome measures (response variables) by incorporating individuals response data through Bayesian forecasting. When measurement constraints preclude reasonable levels of prediction accuracy, additional (secondary) response variables measured alongside the primary response may help to increase prediction accuracy. We investigate this for the case of substantial between-subjects correlation between primary and secondary response variables, assuming negligible within-subjects correlation. We show how to determine the accuracy of primary response predictions as a function of secondary response observations. Given measurement costs for primary and secondary variables, we determine the number of observations that produces, with minimal cost, a fixed average prediction accuracy for a model of subject means. We illustrate this with estimation of subject-specific sleep parameters using polysomnography and wrist actigraphy. We also consider prediction accuracy in an example time-dependent, linear model and derive equations for the optimal timing of measurements to achieve, on average, the best prediction accuracy. Finally, we examine an example involving a circadian rhythm model and show numerically that secondary variables can improve individualized predictions in this time-dependent nonlinear model as well.

Phase II, Randomized Trial to Compare Anastrozole Combined with Gefitinib or Placebo in Postmenopausal Women with Hormone Receptor–Positive Metastatic Breast Cancer

This phase II randomized trial evaluated the efficacy and tolerability of anastrozole combined with gefitinib or anastrozole with placebo in women with hormone receptor-positive metastatic breast cancer (MBC). Postmenopausal women with hormone receptor-positive measurable or evaluable MBC who had not received prior endocrine therapy for this disease stage or who developed metastatic disease during/after adjuvant tamoxifen were eligible. The primary response variable was progression-free survival (PFS) and secondary response variables included clinical benefit rate, objective response rate, overall survival, safety and tolerability, and pharmacokinetics. Tumor biomarker evaluation was an exploratory objective. Forty-three patients were randomized to anastrozole plus gefitinib and 50 patients were randomized to anastrozole plus placebo of a planned total of 174 patients (enrollment was prematurely discontinued due to slow recruitment). PFS for patients receiving the combination of anastrozole and gefitinib was longer than for patients receiving anastrozole plus placebo [hazard ratio (gefitinib/placebo), 0.55; 95% confidence interval, 0.32-0.94; median PFS, 14.7 versus 8.4 months]. The clinical benefit rate was 49% versus 34%, and the objective response rate was 2% versus 12% with anastrozole plus gefitinib and anastrozole plus placebo, respectively. No evidence of interaction between baseline biomarker levels and relative treatment effect was found. No unexpected adverse events were observed. This small randomized study showed that anastrozole in combination with gefitinib is associated with a marked advantage in PFS compared with anastrozole plus placebo, and that the combination was tolerated in postmenopausal women with hormone receptor-positive MBC. Further investigation of epidermal growth factor receptor inhibition in combination with endocrine therapy may be warranted.

Secondary endpoints can be validly analyzed, even if the primary endpoint does not provide clear statistical significance

Response variables from clinical trials are often divided into those considered primary and those considered secondary to the purposes of the study. If the difference between treatment groups on primary outcomes is not significant, the interpretation of significant differences in secondary response variables may be difficult because of multiple comparisons. It is proposed that the comparison on the primary outcome use a significance level of α and that the secondary endpoints be evaluated using a significance level α ( k + 1) , where k is the number of secondary outcomes to be evaluated. Examples from recently completed clinical trials illustrate the use of this rule.

Issues in the evaluation of clinical trials of periodontitis: a clinical perspective.

The goals of clinical trials designed to establish claims for equivalency or superiority of treatment for periodontitis must be clearly stated and defined in terms of measurable and meaningful response variables. It is suggested that these clinical trials use designs that compare new treatment methods to basic periodontal therapy which consists of thorough scaling and root planing, oral hygiene instruction, and regular maintenance care. The primary response variable should be clinical attachment level. It is important to document changes in probing depth since this is a meaningful measure to many clinicians. Gingival inflammation and bleeding should be used as secondary response variables because these are not necessarily indicative of progressive periodontal destruction. Radiographic measures of disease may be useful as primary response variables if safe, reproducible and valid methods of measuring change are utilized. Microbiological monitoring should be a secondary response variable because of numerous questions concerning sampling methodology, quantitative expression of data, and meaningful interpretation in terms of relevance to disease activity. The length of periodontitis trials should be set at a minimum of 9 months if claims of superiority or equivalency are made compared to basic periodontal therapy. Calibration trials should be included and measurement error should be expressed in terms that are meaningful to the clinician while retaining statistical validity. Statistical methods for determining change should take into account site and subject heterogeneity, bursts of change and gradual change over time. It is important that statistical techniques be used that detect change as early as possible and that appropriate consideration be given to the clinical implications of the type, magnitude and duration of change in outcome variables.

Primary and secondary stress responses of striped bass (Morone saxatilis) exposed to benzene

Striped bass (Morone .sfi.~uri/i.s) were collected from the San Francisco Bay-Delta estuary in 1982. from areas distant from pollution sources. After acclimatization. plasma cortisol concentration (primary response) and blood biochemicals indicative of energy mobilization (secondary responses) were followed in individuals exposed to sublethal levels of benzene for up to 21 d. Despite the persistence of benzene in blood and liver tissues for the exposure duration. stress responses were moderate and returned to control values within the initial 7 d. Blood and liver rapidly accumulated benzene to approximately 20 times the exposure concentrations (0.1 and 1.0 ppni). Concentrations of cortisol and secondary response varia bles were not proportional to benzene exposure or to accumulation levels. however. Plasma cortisol concentrations increased two- to three-fold at 8 h and returned to control levels prior to 48 h exposure. Glucose. lactate. H’. protein and triglyceride concentrations were elevated during the initial 4 h to 7 d. with protein and triglyceride returning to normal levels prior to the other secondary response variables. From the perspective of the general adaptation syndrome (GAS), benzene activated the hypothalamopituitary-interrenal axis. resulting in clinical stress responses characteristic of an alarm reaction. The timecourses and amplitudes of primary and secondary responses to benzene suggest the sensory perception of a noxious agent eliciting mild. acute stress followed by adaptation.