Application of Geostatistical Tools to the Geochemical Characterization of the Peloritani Mts (Sicily, Italy) Aquifers

Sources of groundwater contaminants in inhabited areas, located in complex geo-tectonic contexts, are often deeply interlocked, thus, making the discrimination between anthropic and natural origins difficult. In this study, we investigate the Peloritani Mountain aquifers (Sicily, Italy), using the combination of probability plots with concentration contour maps to retrieve an overall view of the groundwater geo-chemistry with a special focus on the flux of heavy metals. In particular, we present a methodology for integrating spatial data with very different levels of precision, acquired before and during the “geomatic era”. Our results depict a complex geochemical layout driven by a geo-puzzle of rocks with very different lithological natures, hydraulically connected by a dense tectonic network that is also responsible for the mixing of deep hydrothermal fluids with the meteoric recharge. Moreover, a double source, geogenic or anthropogenic, was individuated for many chemicals delivered to groundwater bodies. The concentration contour maps, based on the different data groups identified by the probability plots, fit the coherency and congruency criteria with the distribution of both rock matrices and anthropogenic sources for chemicals, indicating the success of our geostatistical approach.

Differences and similarities in clinical and functional responses among patients receiving tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate: a post hoc analysis of data from ORAL Strategy

Background This post hoc analysis assessed clinical and functional responses to tofacitinib monotherapy, tofacitinib + methotrexate (MTX), and adalimumab + MTX, in patients with rheumatoid arthritis enrolled in the ORAL Strategy study, including evaluation of patient-level data using cumulative probability plots. Methods In the 12-month, phase IIIb/IV ORAL Strategy study, patients with rheumatoid arthritis and an inadequate response to MTX were randomized to receive tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID + MTX, or adalimumab 40 mg every other week + MTX. In this post hoc analysis, cumulative probability plots were generated for mean percent change from baseline (%∆) in the Clinical Disease Activity Index (CDAI; clinical response) and mean change from baseline (∆) in the Health Assessment Questionnaire-Disability Index (HAQ-DI; functional response) at month 12. Median C-reactive protein (CRP) levels by time period were summarized by CDAI remission (≤ 2.8) status at months 6 and 12. Results Data for 1146 patients were analyzed. At month 12, cumulative probability plots for %∆CDAI and ∆HAQ-DI were similar across treatments in patients with greater response. At lower levels of response, patients receiving tofacitinib monotherapy did not respond as well as those receiving combination therapies. With tofacitinib + MTX, numerically higher baseline CRP levels and numerically larger post-baseline CRP reductions were seen in patients achieving CDAI remission at months 6 and 12 vs those who did not. Conclusions These results suggest that patients with a greater response did well, irrespective of which therapy they received. Patients with lesser response had better outcomes with combination therapies vs tofacitinib monotherapy, suggesting they benefitted from MTX. High pre-treatment CRP levels may be associated with better response to tofacitinib + MTX. Trial registration ClinicalTrials.gov, NCT02187055. Registered on 08 July 2014.

Comparison of the SITA Faster–a new visual field strategy with SITA Fast strategy

AIM: To compare visual field defects using the Swedish Interactive Thresholding Algorithm (SITA) Fast strategy with SITA Faster strategy, a newly developed time-saving threshold visual field strategy. METHODS: Ninety-three participants (60 glaucoma patients and 33 normal controls) were enrolled. One eye from each participant was selected randomly for the study. SITA Fast and SITA Faster were performed using the 24-2 default mode for each test. The differences of visual field defects between the two strategies were compared using the test duration, false-positive response errors, mean deviation (MD), visual field index (VFI) and the numbers of depressed test points at the significant levels of P<5%, <2%, <1%, and <0.5% in probability plots. The correlation between strategies was analyzed. The agreement between strategies was acquired by Bland-Altman analysis. RESULTS: Mean test durations were 246.0±60.9s for SITA Fast, and 156.3±46.3s for SITA Faster (P<0.001). The test duration of SITA Faster was 36.5% shorter than SITA Fast. The MD, VFI and numbers of depressed points at P<5%, <2%, <1%, and <0.5% in probability plots showed no statistically significant difference between two strategies (P>0.05). Correlation analysis showed a high correlation for MD (r=0.986, P<0.001) and VFI (r=0.986, P<0.001) between the two strategies. Bland-Altman analysis showed great agreement between the two strategies. CONCLUSION: SITA Faster, which saves considerable test time, has a great test quality comparing to SITA Fast, but may be not directly interchangeable.

The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study

Background The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery. Methods In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery. Results Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2–5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1–0.7) or in OT (HR = 0.1, 95% CI = 0.0–0.8) treated with tocilizumab. Conclusion To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.

Supplemental Material: ‘Taters versus Sliders: Evidence for a Long-Lived History of Strike-Slip Displacement along the Canadian Arctic Transform System (CATS)

Probability plots, Shepard plot, and sources of U/Pb data in Figure 2A.

Supplemental Material: ‘Taters versus Sliders: Evidence for a Long-Lived History of Strike-Slip Displacement along the Canadian Arctic Transform System (CATS)

Probability plots, Shepard plot, and sources of U/Pb data in Figure 2A.

Differences and Similarities in Clinical and Functional Responses Among Patients Receiving Tofacitinib Monotherapy, Tofacitinib Plus Methotrexate, and Adalimumab Plus Methotrexate: A Post-hoc Analysis of Data From Oral Strategy

BackgroundThis post-hoc analysis assessed clinical and functional responses to tofacitinib monotherapy, tofacitinib + methotrexate (MTX), and adalimumab + MTX, in patients with rheumatoid arthritis enrolled in the ORAL Strategy study, including evaluation of patient-level data using cumulative probability plots.MethodsIn the 12-month, phase IIIb/IV ORAL Strategy study, patients with rheumatoid arthritis and an inadequate response to MTX were randomized to receive tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID + MTX, or adalimumab 40 mg every other week + MTX. In this post-hoc analysis, cumulative probability plots were generated for mean percent change from baseline (%∆) in Clinical Disease Activity Index (CDAI; clinical response) and mean change from baseline (∆) in Health Assessment Questionnaire-Disability Index (HAQ-DI; functional response) at month 12. Median C-reactive protein (CRP) levels by time period were summarized by CDAI remission (≤2.8) status at months 6 and 12. ResultsData for 1146 patients were analyzed. At month 12, cumulative probability plots for %∆CDAI and ∆HAQ-DI were similar across treatments in patients with greater response. At lower levels of response, patients receiving tofacitinib monotherapy did not respond as well as those receiving combination therapies. With tofacitinib + MTX, numerically higher baseline CRP levels and numerically larger post-baseline CRP reductions were seen in patients achieving CDAI remission at months 6 and 12 vs those who did not.ConclusionsThese results suggest that patients with a greater response did well, irrespective of which therapy they received. Patients with lesser response had better outcomes with combination therapies vs tofacitinib monotherapy, suggesting they benefitted from MTX. High pre‑treatment CRP levels may be associated with better response to tofacitinib + MTX. Trial registrationClinicalTrials.gov, NCT02187055. Registered 08 July 2014, https://clinicaltrials.gov/ct2/show/NCT02187055?term=NCT02187055&draw=2&rank=1

Bivariate confidence probability plots as a method to test the accuracy and variability of microbiological measures

IntroductionIn an interlaboratory calibration analysis to validate a methodology that will be proposed as a European standard for domestic laundry disinfection, tests were carried out to detect if there are different behaviors in the measurements regarding accuracies and variabilities. Interlaboratory tests using different doses of disinfectant and microorganisms were carried out. ISO 5725-2 and ISO 13528 form the basis of validations of quantitative methods, providing validation specifications for interlaboratory studies. However, a need for a simple graphical method to detect interlaboratory differences in accuracy and variability was observed.ObjectivesThe general goal of this work is to present a new exploratory methodology, graphical and easy to interpret, that can determine the accuracy and variability (precision) of a variable, and compare it to the methodology applied in ISO 5725-2 and ISO 13528.MethodsWe used confidence probability plots of the multivariate Student’s t-distribution to observe the accuracy and variability of microbiological measures carried out by different laboratories during a ring trial exercise. A function in R was built for this purpose: Miriam.analysis.ellipse(Y, factor_a, eel.plot = “ t-Student”). The different observations of accuracy and variability are represented in the ellipses. If any of the points are outside the ellipse with 95% confidence, we can assume a deviation in accuracy and / or variability.ResultsTwo examples are provided with real microbiological data (logarithmic unit reductions (LR) for Pseudomonas aeruginosa, Escherichia coli, Staphilococcus aureus, Enterococcus hirae, Candida albicans and microbial counts in water (WW)). The proposed new method allowed us to detect possible deviations in the WWMEA variable and we believe it has future application for the rapid control of microbiological measures.

Joint analysis of duration of ventilation, length of intensive care, and mortality of COVID-19 patients: a multistate approach

Background The clinical progress of patients hospitalized due to COVID-19 is often associated with severe pneumonia which may require intensive care, invasive ventilation, or extracorporeal membrane oxygenation (ECMO). The length of intensive care and the duration of these supportive therapies are clinically relevant outcomes. From the statistical perspective, these quantities are challenging to estimate due to episodes being time-dependent and potentially multiple, as well as being determined by the competing, terminal events of discharge alive and death. Methods We used multistate models to study COVID-19 patients’ time-dependent progress and provide a statistical framework to estimate hazard rates and transition probabilities. These estimates can then be used to quantify average sojourn times of clinically important states such as intensive care and invasive ventilation. We have made two real data sets of COVID-19 patients (n = 24* and n = 53**) and the corresponding statistical code publically available. Results The expected lengths of intensive care unit (ICU) stay at day 28 for the two cohorts were 15.05* and 19.62** days, while expected durations of mechanical ventilation were 7.97* and 9.85** days. Predicted mortality stood at 51%* and 15%**. Patients mechanically ventilated at the start of the example studies had a longer expected duration of ventilation (12.25*, 14.57** days) compared to patients non-ventilated (4.34*, 1.41** days) after 28 days. Furthermore, initially ventilated patients had a higher risk of death (54%* and 20%** vs. 48%* and 6%**) after 4 weeks. These results are further illustrated in stacked probability plots for the two groups from time zero, as well as for the entire cohort which depicts the predicted proportions of the patients in each state over follow-up. Conclusions The multistate approach gives important insights into the progress of COVID-19 patients in terms of ventilation duration, length of ICU stay, and mortality. In addition to avoiding frequent pitfalls in survival analysis, the methodology enables active cases to be analyzed by allowing for censoring. The stacked probability plots provide extensive information in a concise manner that can be easily conveyed to decision makers regarding healthcare capacities. Furthermore, clear comparisons can be made among different baseline characteristics.