Higher Confidence Interval Research Articles

Meta-analysis of prevalence of paratuberculosis in cattle using published estimates under serum and milk ELISA

Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP), poses significant challenges to the global livestock industry, particularly affecting bovine populations. To better understand the prevalence of paratuberculosis and its diagnostic nuances, a comprehensive meta-analysis was conducted. This analysis encompassed 21 studies involving 632,767 cows for milk enzyme-linked immunosorbent assay (ELISA) and 51 studies involving 256,409 cows for serum ELISA. The pooled prevalence estimate for paratuberculosis on a cow-basis was found to be 16% (95% CI: 14%; 18%) for milk ELISA and 8% (95% CI: 7%; 8%) for serum ELISA. Notably, higher confidence intervals (CI) were observed in milk ELISA, the Europe and Asia groups, suggesting variability in prevalence estimates within these regions. Conversely, lower CIs were noted in the USA and Canada groups, indicating greater consistency in prevalence estimates within these countries. However, serum ELISA exhibited high CI values across all regions, underscoring potential variability in diagnostic performance. These findings provide valuable insights for veterinarians, researchers, policymakers, and livestock producers in optimizing paratuberculosis detection and control strategies to mitigate its impact on bovine health and agricultural productivity.

Towards accurate indel calling for oncopanel sequencing through an international pipeline competition at precisionFDA

Accurately calling indels with next-generation sequencing (NGS) data is critical for clinical application. The precisionFDA team collaborated with the U.S. Food and Drug Administration’s (FDA’s) National Center for Toxicological Research (NCTR) and successfully completed the NCTR Indel Calling from Oncopanel Sequencing Data Challenge, to evaluate the performance of indel calling pipelines. Top performers were selected based on precision, recall, and F1-score. The performance of many other pipelines was close to the top performers, which produced a top cluster of performers. The performance was significantly higher in high confidence regions and coding regions, and significantly lower in low complexity regions. Oncopanel capture and other issues may have occurred that affected the recall rate. Indels with higher variant allele frequency (VAF) may generally be called with higher confidence. Many of the indel calling pipelines had good performance. Some of them performed generally well across all three oncopanels, while others were better for a specific oncopanel. The performance of indel calling can further be improved by restricting the calls within high confidence intervals (HCIs) and coding regions, and by excluding low complexity regions (LCR) regions. Certain VAF cut-offs could be applied according to the applications.

Medical management of early pregnancy loss is cost-effective compared with office uterine aspiration

Early pregnancy loss, also referred to as miscarriage, is common, affecting approximately 1 million people in the United States annually. Early pregnancy loss can be treated with expectant management, medications, or surgical procedures-strategies that differ in patient experience, effectiveness, and cost. One of the medications used for early pregnancy loss treatment, mifepristone, is uniquely regulated by the Food and Drug Administration. This study aimed to compare the cost-effectiveness from the healthcare sector perspective of medical management of early pregnancy loss, using the standard of care medication regimen of mifepristone and misoprostol, with that of office uterine aspiration. We developed a decision analytical model to compare the cost-effectiveness of early pregnancy loss treatment with medical management with that of office uterine aspiration. Data on medical management came from the Pregnancy Failure Regimens randomized clinical trial, and data on uterine aspiration came from the published literature. The analysis was from the healthcare sector perspective with a 30-day time horizon. Costs were in 2018 US dollars. Effectiveness was measured in quality-adjust life-years gained and the rate of complete gestational sac expulsion with no additional interventions. Our primary outcome was the incremental cost per quality-adjust life-year gained. Sensitivity analysis was performed to identify the key uncertainties. Mean per-person costs were higher for uterine aspiration than for medical management ($828 [95% confidence interval, $789-$868] vs $661 [95% confidence interval, $556-$766]; P=.004). Uterine aspiration more frequently led to complete gestational sac expulsion than medical management (97.3% vs 83.8%; P=.0001); however, estimated quality-adjust life-years were higher for medical management than for uterine aspiration (0.082 [95% confidence interval, 0.8148-0.08248] vs 0.079 [95% confidence interval, 0.0789-0.0791]; P<.0001). Medical management dominated uterine aspiration, with lower costs and higher confidence interval. The probability that medical management is cost-effective relative to uterine aspiration is 97.5% for all willingness-to-pay values of ≥$5600/quality-adjust life-year. Sensitivity analysis did not identify any thresholds that would substantially change outcomes. Although office-based uterine aspiration more often results in treatment completion without further intervention, medical management with mifepristone pretreatment costs less and yields similar quality-adjust life-years, making it an attractive alternative. Our findings provided evidence that increasing access to mifepristone and eliminating unnecessary restrictions will improve early pregnancy care.

A permutation-based approach for heterogeneous meta-analyses of rare events.

The increasingly widespread use of meta-analysis has led to growing interest in meta-analytic methods for rare events and sparse data. Conventional approaches tend to perform very poorly in such settings. Recent work in this area has provided options for sparse data, but these are still often hampered when heterogeneity across the available studies differs based on treatment group. We propose a permutation-based approach based on conditional logistic regression that accommodates this common contingency, providing more reliable statistical tests when such patterns of heterogeneity are observed. We find that commonly used methods can yield highly inflated Type I error rates, low confidence interval coverage, and bias when events are rare and non-negligible heterogeneity is present. Our method often produces much lower Type I error rates and higher confidence interval coverage than traditional methods in these circumstances. We illustrate the utility of our method by comparing it to several other methods via a simulation study and analyzing an example data set, which assess the use of antibiotics to prevent acute rheumatic fever.

Evaluating the diagnostic accuracy of gene xpert analysis in pediatric pulmonary tuberculosis: a prospective clinical study in North-Western India

Background: The diagnosis of tuberculosis (TB) by microbiological tests is a major challenge particularly in children. The use of Xpert analysis, a rapid genetic testing modality is not widely reported in our locality. The aim of the study to evaluate the diagnostic accuracy of Gene xpert analysis in diagnosis of pediatric Pulmonary TB.Methods: A prospective hospital-based study was conducted among 140 participants with symptomatology pertaining to pulmonary TB as per Revised national tuberculosis control program (RNTCP, India) criteria. The Xpert testing (GXT) was performed as per standards and was compared with erythrocyte sedimentation rate (ESR), tuberculin test (TT) and chest X-rays (CXR). The obtained results were reported in terms of Sensitivity %, Specificity %, Positive Predictive Value % (PPV) and Negative Predictive Value % (NPV) for comparisons. The receiver operating curve (ROC) analysis was employed to evaluate the accuracy of diagnosis.Results: The GXT was positive (10.71 %) in suspected TB patients. TT has significantly (10 %) with a73.33% sensitivity, 93.60% specificity and a PPV of 57.89 % when compared with xpert. The ESR showed a sensitivity of 53.33% and a specificity of 56%. The CXR showed sensitivity of 93.33%. The ROC analysis showed that TT had a higher confidence interval (0.699-0.970) t5`han other methods. The Rifampicin resistance was found 7.5% (n=2) of 15 GXT positive cases.Conclusions: The xpert based diagnosis of gastric lavage samples after a tuberculin test (TT) had high sensitivity and specificity, followed by chest X ray while the ESR had lower clinical accuracy. The ‘gene xpert analysis’ is highly useful rapid tool for diagnosis of children with TB.

Can multitrophic interactions shape morphometry, allometry, and fluctuating asymmetry of seed-feeding insects?

Body size is commonly associated with biological features such as reproductive capacity, competition, and resource acquisition. Many studies have tried to understand how these isolated factors can affect the body pattern of individuals. However, little is known about how interactions among species in multitrophic communities determine the body shape of individuals exploiting the same resource. Here, we evaluate the effect of fruit infestation, parasitism rate, and seed biomass on size, allometric and asymmetric patterns of morphological structures of insects that exploit the same resource. To test it, we measured 750 individuals associated with the plant Senegalia tenuifolia (Fabaceae), previously collected over three consecutive years. Negative allometry was maintained for all species, suggesting that with increasing body size the body structure did not grow proportionally. Despite this, some variations in allometric slopes suggest that interactions in a multitrophic food web can shape the development of these species. Also, we observed a higher confidence interval at higher categories of infestation and parasitism rate, suggesting a great variability in the allometric scaling. We did not observe fluctuating asymmetry for any category or species, but we found some changes in morphological structures, depending on the variables tested. These findings show that both allometry and morphological trait measurements are the most indicated in studies focused on interactions and morphometry. Finally, we show that, except for the fluctuating asymmetry, each species and morphological structure respond differently to interactions, even if the individuals play the same functional role within the food web.

Downside risk and the energy hedger's horizon

In this paper, we explore the impact of investor time-horizon on an optimal downside hedged energy portfolio. The optimal heating oil hedge ratio is first calculated for a variety of downside risk objective functions at different time-horizons using the wavelet transform. Next, associated hedging effectiveness is contrasted for a range of risk metrics, with all metrics showing increasing hedging effectiveness at longer horizons. Moreover, decreased hedging effectiveness is demonstrated for increased levels of uncertainty at higher confidence intervals. While small differences in effectiveness are found across the different hedging objectives, time-horizon effects are found to dominate confirming the importance of the hedging horizon. The findings suggest that while downside risk measures are useful in determining an optimal futures hedge encompassing negative returns, hedging horizon and confidence intervals should also be given careful consideration by the energy hedger.

Downside Risk and the Energy Hedger's Horizon

In this paper, we explore the impact of investor time-horizon on an optimal downside hedged energy portfolio. Previous studies have shown that minimum-variance hedging effectiveness improves for longer horizons using variance as the performance metric. This paper investigates whether this result holds for different hedging objectives and effectiveness measures. A wavelet transform is applied to calculate the optimal heating oil hedge ratio using a variety of downside objective functions at different time-horizons. We demonstrate decreased hedging effectiveness for increased levels of uncertainty at higher confidence intervals. Moreover, for each of the different hedging objectives and effectiveness measures studied, we also demonstrate increasing hedging effectiveness at longer horizons. While small differences in effectiveness are found across the different hedging objectives, time-horizon effects are found to dominate confirming the importance of considering the hedgers horizon. The findings suggest that while downside risk measures are useful in the computation of an optimal hedge ratio that accounts for unwanted negative returns, hedging horizon and confidence intervals should also be given careful consideration by the energy hedger.

Interpreting SuperPAVE PG test results with confidence intervals

The innovative method to interpret SuperPAVE PG test results using regression analysis and confidence intervals is evaluated in this research. Till now, most of researches and conclusions in the field of bitumen rheological aspects are based on the mean values of test results. Using the mean values does not show the reliability of the test results and in many cases two bitumen with the same PG show different performances, due to different data variances. In this study the confidence intervals method is implemented to interpret the results of SuperPAVE PG tests and notify that the mean values of the variables are occasionally misleading and always some uncertainty exists when using bitumen. This study presents a new formulation that quantifies the uncertainties in bitumen behavior to obtain the true temperature grade of the bitumen with different confidence levels (75% and 95%). Two samples of bitumen with same PG were evaluated with this formulation and the interesting results were found. The behavior of these samples with same PG was significantly different regarding the higher confidence intervals.

Clinical Significance of CEA and CA19-9 in Postoperative Follow-up of Colorectal Cancer

We evaluated the efficiency of CEA and CA19-9 as tools for diagnosing recurrence in the postoperative surveillance of colorectal cancer. A total of 227 patients who underwent curative resection for colorectal cancer between 1999 and 2003 at our hospital received complete follow-up according to the schedule determined prospectively. Using receiver operating characteristic (ROC) analysis, performance of postoperative values of CEA or CA19-9 for detecting recurrence was assessed. The sensitivity (1.000) and specificity (0.978) of the postoperative values of CEA in the high preoperative CEA group were very high. Even in the normal preoperative CEA group, the area under the curve (AUC) of the ROC curve of CEA (0.740, 95% confidence interval [95% CI], 0.628-0.852) was significantly larger than 0.5 (P < 0.001). The postoperative values of CA19-9 showed high sensitivity (0.833) and specificity (0.900) in the high preoperative CA19-9 group, while the AUC of the ROC curve of the normal preoperative group was as small as 0.510 (95% CI, 0.376-0.644). In the high preoperative CA19-9 group, however, there was no significant difference between the AUC of CA19-9 (0.904, 95% CI, 0.786-1.000) and that of CEA (0.869, 95% CI, 0.744-0.994) (P = 0.334). The measurement of CEA is an efficient way to detect recurrence. The efficiency of measuring CA19-9 for the purpose of detecting recurrence is low, especially in patients with a normal level of preoperative CA19-9. Even in patients with a high preoperative level of CA19-9, CEA might be able to fill the role of CA19-9.

Industry-sponsored economic studies in oncology vs studies sponsored by nonprofit organisations.

The purpose of this analysis of health economic studies in the field of oncology was to investigate among sponsored studies whether any relationship could be established between the type of sponsorship and (1) type of economic analysis, (2) health technology assessed, (3) sensitivity analysis performed, (4) publication status, and (5) qualitative conclusions about costs. The Health Economic Evaluations Database (HEED, version 1995–2000) was searched on the basis of oncological ICD-9 codes, sponsorship, and comparative studies. This search yielded a total of 150 eligible articles. Their evaluations were prepared independently by two investigators, on the basis of specific criteria. When evaluators disagreed, a third investigator provided a deciding evaluation. There was no statistically significant relationship between the type of sponsorship and sensitivity analysis performed (P=0.29) or publication status (P=0.08). However, we found a significant relationship between the types of sponsorship and of economic analysis (P=0.004), the health technology assessed (P<0.0001), and qualitative cost assessment (P=0.002). Studies with industrial sponsorship were 2.56 (99% lower confidence interval (CI)=1.28) times more likely to involve cost-minimisation analyses, were 0.04 (99% higher CI=0.39) times less likely to investigate diagnostic screening methods, and were 1.86 (99% lower CI=1.21) times more likely to reach positive qualitative conclusions about costs than studies supported by nonprofit organisations. In conclusion, our results suggest that there is a greater probability that industry-sponsored economic studies in the field of oncology tend to be cost-minimisation analyses, to investigate less likely diagnostic screening methods, and to draw positive qualitative conclusions about costs, as compared to studies supported by nonprofit organisations.

IS simulation for the waiting time of ATM burst cell traffic

AbstractInvestigations of cell delay characteristics for various kinds of traffic are necessary for the design of buffer sizes in ATM converters. The purpose of this research is to obtain the cell delay characteristics, particularly the cell delay α value, using simulations. However, using the prior method, the Monte Carlo (MC) method, requires considerable design time and imposes limits on the precision of the pseudo‐random numbers. As a result, cell delay characteristics for a very small α cannot be obtained. Therefore, the purpose of this research is to apply Importance Sampling (IS) and obtain cell delay characteristics quickly at a precision below 10−9. In particular, the IS method is applied to the waiting time characteristics in the steady state for Geo/D/1, a queue model for random cell traffic, and to the two‐state MMGP/D/1 queue for burst cell traffic. An approximate optimal simulation distribution is obtained based on large deviation theory. Then an actual IS simulation is performed using the obtained simulation distribution. Compared to the MC simulation, the IS simulation is shown to have superior speed and a higher confidence interval. In addition, the IS estimated values are shown to be more precise compared to theoretical values or approximate values. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 85(11): 97–105, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.1142