The Coordinating Center

BackgroundTecovirimat is approved for smallpox treatment under the Food and Drug Administration Animal Rule on the basis of efficacy in nonhuman primate models of mpox (previously known as monkeypox). However, the clinical efficacy of tecovirimat against human clade II mpox is unclear.MethodsIn a phase 3, international, double-blind, randomized, placebo-controlled trial, we evaluated the efficacy of oral tecovirimat in adults with laboratory-confirmed clade II mpox. Participants were randomly assigned in a 2:1 ratio to receive tecovirimat or placebo for 14 days. The primary outcome was clinical resolution, assessed in a time-to-event analysis in participants with active skin or mucosal lesions. Secondary outcomes included reduction in pain, assessed in all participants with laboratory-confirmed mpox and in those with severe pain at baseline (pain score, 7 to 10; scale, 0 [no pain] to 10 [worst pain imaginable]); complete lesion healing (assessed in a time-to-event analysis); viral DNA clearance; and safety.ResultsOf 412 participants who underwent randomization (275 to tecovirimat and 137 to placebo), 344 had laboratory-confirmed mpox, and 336 had active skin or mucosal lesions and were included in the primary analysis. By day 29, the estimated cumulative incidence of clinical resolution was 83% with tecovirimat and 84% with placebo; the competing-risks hazard ratio for clinical resolution was 0.98 (95% confidence interval [CI], 0.74 to 1.31; P=0.89). No substantial between-group differences were seen in pain reduction among participants with severe pain (difference, 0.1 point; 95% CI, −0.8 to 1.0), in complete lesion healing (competing-risks hazard ratio, 0.97; 95% CI, 0.75 to 1.26), or in viral DNA clearance. The incidence of adverse events of grade 3 or higher was similar in the two groups (4% with tecovirimat and 3% with placebo).ConclusionsThis trial showed no evidence that tecovirimat therapy shortened the time to clinical resolution, reduced pain, or increased viral clearance among adults with clade II mpox. (Funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; STOMP/A5418 ClinicalTrials.gov number, NCT05534984.)

Background: Multiple studies demonstrate that the Alvarado Score is less effective than other studies in predicting the incidence of patients with suspected acute appendicitis. It does not distinguish between ages and does not suggest a clinical stage of the disease. However, its use is still current in our unit and in most hospitals in our country. General Objective: To identify the utility of the Alvarado Score in patients with suspected acute appendicitis in relation to imaging results. Materials and Methods: Descriptive, observational, cross-sectional, retrospective study, which was carried out with 62 records of patients with suspected acute appendicitis and who were requested imaging studies at the Regional General Hospital 1 of Orizaba, Veracruz with the suspected diagnosis of Acute Appendicitis during the period from December 1, 2017 to November 30, 2022. Patients of any age group and both sexes who came to the emergency service with pain in the right iliac fossa and classified with the Alvarado scale that met the selection criteria were included. This study was conducted from March 1 to September 30, 2023. Data analysis included descriptive statistics for qualitative variables using frequencies and percentages, as well as measures of dispersion. For quantitative variables, such as mean and standard deviation, the Fisher exact test was used between variables with two categories based on the nature of the categorical variables. SPSS 23 and GraphPad Prism 8 software were used. Resources and infrastructure: those of the institution, the patients, and the researcher. Group experience: There is a master's degree in science and a radiologist with experience in ultrasound and CT interpretation. A resident physician who will carry out the activities of the research project. Results: The female sex predominated with a frequency of 40 patients (56.33%) with a mean age of 28.80 years, standard deviation +/- 19.36 (95% CI 22.61-34.99), of the male sex a frequency of 31 patients (43.66%) was observed with a mean age of 28.16 years, standard deviation +/- 17.69, the time of onset of symptoms: 35 patients (49.3%) began with symptoms at 24 hours, followed by 15 patients (21.1%) at 12 hours, 11 patients (15.5%) at 72 hours, 7 patients reported onset of symptoms at 48 hours (9.9%). The relationship between the Alvarado scale and imaging studies was identified using Fisher's exact test. The P value was 0.8791, which is considered statistically insignificant. Conclusion: The Alvarado score has proven to be a useful, simple, noninvasive, and rapid tool for guiding the diagnosis of acute appendicitis. However, due to its low specificity, the use of imaging studies is always recommended to confirm suspected diagnoses.

Background: Inherited retinal dystrophies are a heterogeneous group of progressive disorders impacting photoreceptor function, often limiting the usefulness of standard electroretinography in advanced cases. Full-field stimulus test (FST) testing has become a sensitive psychophysical technique for detecting residual visual function when traditional electrophysiology is non-recordable. This study evaluated the ability of chromatic FST to differentiate rod-cone from cone photoreceptor dysfunction in patients with genetically confirmed inherited retinal dystrophies. Methods: Cross-sectional FST data were analyzed from 39 patients (mean age 45.7 ± 20.0 years) with genetically confirmed inherited retinal dystrophies at a tertiary academic center. All participants underwent standardized FST testing using white, red, and blue stimuli. Patients were classified into rod-cone dystrophy (n = 27) or cone dystrophy (n = 12) groups based on genetic and clinical criteria. Group comparisons focused on FST thresholds and especially blue-red threshold differences as markers of photoreceptor-mediated function. Bonferroni correction was applied to adjust for multiple comparisons across four primary FST parameters. Additional analyses by genotype were performed with nonparametric tests. Results: Eight different genetic mutations were represented, including Phosphodiesterase 6A (PDE6A) (n = 10), Rhodopsin (RHO) (n = 7), Phosphodiesterase 6B (PDE6B) (n = 6), Cyclic Nucleotide-Gated Channel Beta 1 (CNGB1) (n = 4), Cyclic Nucleotide-Gated Channel Alpha 3 (CNGA3) (n = 4), Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3) (n = 4), Guanylate Cyclase 2D (GUCY2D) (n = 2), and Cyclic Nucleotide-Gated Channel Beta 3 (CNGB3) (n = 2). Blue-red FST threshold differences exhibited moderate group discrimination in uncorrected analysis, with rod-cone dystrophies averaging -8.35 ± 10.37 dB and cone dystrophies -11.20 ± 14.60 dB. The area under the receiver operating characteristic curve for blue-red difference was 0.74 (95% CI: 0.59-0.90), with 75% sensitivity and 70.4% specificity at a -10 dB cutoff. However, no chromatic FST parameter maintained statistical significance between groups after Bonferroni correction. Inter-eye FST correlation was high (r = 0.758, p < 0.001), supporting test reliability. Conclusions: Chromatic FST testing provides a practical and sensitive means to assess photoreceptor function in advanced inherited retinal dystrophies, particularly when standard electrophysiologic methods are uninformative. Although the blue-red threshold difference offers moderate discrimination between rod-cone and cone dystrophies in uncorrected analysis, no chromatic parameter reached statistical significance after adjustment for multiple testing. Chromatic FST should be considered a supplementary approach for clinical monitoring and therapeutic studies in advanced retinal dystrophies, with further validation needed in larger cohorts.

Background/Objectives: Prediction models are implemented frequently, yet, compared with other study designs, their incorporation of clinical measurements (CMs; i.e., vital signs and laboratory results) is rather underdeveloped. The purpose is to describe methods used and illustrate clinical utility in parameters systematically derived from CMs; as a case study, we use the risk of all-cause mortality following coronavirus disease 2019 (COVID-19) as the basis for prognosis. Methods: We identified cases through the Department of Veterans Affairs COVID-19 Shared Data Resource, utilizing data from the first visit until 14 days before testing positive. Thirteen parameters were derived from each of the 11 CMs, capturing departures from normality considering variability and time. The 143 candidate predictors were used to generate the main logistic regression model. The area under the receiver operating characteristic curve (AUROC) analysis was performed to assess discrimination between those who lived and died for subset and main regressions; for comparison, this was performed for an age-only model and the Charlson Comorbidity and Elixhauser Indices. Results: There were 329,491 patients. The main model's AUROC (0.785 ± 0.002) was similar to the age-only model (0.783 ± 0.002; p > 0.05) and significantly greater than the comorbidity indices' (range: 0.675 ± 0.002 to 0.729 ± 0.002; p < 0.001 each). Conclusions: The study found several parameters were significant determinants of mortality following COVID-19, highlighting the importance of a systematic approach for multivariate modeling to obtain informative insights into underlying pathophysiology. The main model outperforms common comorbidity indices as a summary metric for pre-existing conditions in this case study. If validated, this approach could revolutionize the way CMs are handled in multivariate models.

The substantial damage to homes and infrastructure in Australia rekindles the push for improved governance frameworks and adaptive policy measures. Coordinating efforts across federal, state, and local governments has proven challenging due to policy fragmentation, delayed responses, overlapping roles, and disparities in resource allocation. This study examines the strengths and weaknesses of Australia’s flood risk management (FRM) policies through a qualitative document analysis approach, comparing governance structures with international best practices from countries such as Japan, the Netherlands, and the United States. The findings highlight Australia’s strengths in collaborative governance, targeted funding mechanisms, and advanced technical resources such as flood mapping and real-time monitoring systems. However, key weaknesses include governance fragmentation, inconsistent policy implementation, and insufficient support for rural and regional councils. The study proposes a more integrated and adaptive governance framework incorporating cross-jurisdictional coordination, enhanced stakeholder engagement, and sustainable investment strategies. The results contribute to policy discussions on flood risk governance by offering recommendations for strengthening institutional resilience and improving disaster preparedness. By addressing governance inefficiencies and adopting international best practices, Australia can develop a more cohesive and adaptive FRM system to mitigate future flood risks.

The production of green and economically attractive cyclic carbonates from CO2 as an alternative to the highly toxic and expensive method of phosgene gas is a well-established synthetic route in green chemistry. It is also consistent with achieving net-zero emissions and promoting 100% atom economy. This study presents the preparation and characterization of reusable ZnO@BD-g-C3N4 nanoplate catalysts (1–9), which feature abundant active sites and a dynamic oscillating active architecture and demonstrate a catalytic role in enhancing the fixation of CO2 to cyclic carbonates under ambient pressure conditions. The structure of the most active ZnO@BD-g-C3N4 nanoplate catalyst (1) was characterized by using FTIR spectroscopy, UV–DR spectroscopy, XRD, SEM-EDS, TEM, XPS, and BET techniques. The ZnO@BD-g-C3N4 nanoplate catalyst (1) showed the best catalytic activity with 98% conversion for epichlorohydrin (ECH) and 99% selectivity toward epichlorohydrin carbonate (ECHC) under appropriate conditions (ambient pressure, 100 °C, 4 h) without the need for any solvent. The ZnO@BD-g-C3N4 nanoplate catalyst (1) has been successfully tested with various terminal and internal epoxides under the same reaction conditions. Additionally, the synergic effect of Lewis acidic active centers resulted in an efficiency of over 93% and a selectivity of about 99% without a significant decrease in catalytic activity during five consecutive reaction cycles in the recyclability test for the ZnO@BD-g-C3N4/PPNCl catalytic system. In addition, kinetic studies of this cycloaddition reaction revealed that the reaction was pseudo-first-order under similar conditions. The rate constant at 100 °C was 0.8684 h 1, and the activation energy was 45.16 ± 2 kJ/mol.

Multiparental populations have been produced for quantitative trait loci (QTL) mapping in many crops, where next-generation sequencing has become a cost-effective tool for genotyping. Previously, we have developed a hidden Markov framework denoted by MagicImpute_mma for genotype imputation in a multiparental population, which was implemented in Mathematica. However, its computational time increases quickly with the number of parents. In this work, we extend MagicImpute_mma into MagicImpute for increasing computational efficiency and robustness to various types of errors. Particularly, it has the following novel features: (1) allowing for multiple multiparental populations that may be connected by sharing parents, (2) allowing for many missing parents that are not available for sequencing, (3) accounting for allelic bias and overdispersion in next generation sequencing data, (4) inferring marker-specific error rates and filtering for markers with low error rates, and (5) being implemented in the high performance Julia language. Besides extensive simulation studies, we evaluate MagicImpute by three real datasets: the rice F2 population with sequence depth being low, the apple F1 population with parents being outbred, and the sorghum multi-parent advanced generation inter-cross (MAGIC) population with 10 male sterile lines (out of 29 parents) being missing. The results have shown that MagicImpute is accurate for genotype imputation in connected bi- or multi-parental populations with various types of sequence errors and it opens up new opportunities for QTL mapping after imputing many missing parents.