Category: Nevin Manimala

Stat Med. 2023 Dec 18. doi: 10.1002/sim.9972. Online ahead of print.

ABSTRACT

We focus on Bayesian inference for survival probabilities in a prime-boost vaccination regime in the development of an Ebola vaccine. We are interested in the heterologous prime-boost regimen (unmatched vaccine deliverys using the same antigen) due to its demonstrated durable immunity, well-tolerated safety profile, and suitability as a population vaccination strategy. Our research is motivated by the need to estimate the survival probability given the administered dosage. To do so, we establish two key relationships. Firstly, we model the connection between the designed dose concentration and the induced antibody count using a Bayesian response surface model. Secondly, we model the association between the antibody count and the probability of survival when experimental subjects are exposed to the Ebola virus in a controlled setting using a Bayesian probability of survival model. Finally, we employ a combination of the two models with dose concentration as the predictor of the survival probability for a future vaccinated population. We implement our two-level Bayesian model in Stan, and illustrate its use with simulated and real-world data. Performance of this model is evaluated via simulation. Our work offers a new application of drug synergy models to examine prime-boost vaccine efficacy, and does so using a hierarchical Bayesian framework that allows us to use dose concentration to predict survival probability.

PMID:38109707 | DOI:10.1002/sim.9972

J Urol. 2023 Dec 18:101097JU0000000000003825. doi: 10.1097/JU.0000000000003825. Online ahead of print.

ABSTRACT

PURPOSE: To examine the association of extraprostatic extension (EPE) with biochemical recurrence (BCR) separately in men with grade group 1 (GG1) and GG2 prostate cancer (PCa) treated with radical prostatectomy.

MATERIALS AND METHODS: We reviewed our institutional database of patients who underwent radical prostatectomy for PCa between 2005 and 2022 and identified patients with GG1 and GG2 disease on final pathology. Fine-Gray competing risk models with an interaction between EPE (yes vs no) and grade group (GG1 vs GG2) were used to examine the relationship between disease group and BCR-free survival.

RESULTS: The cohort consisted of 6309 men, of whom 169/2740 (6.2%) with GG1 disease had EPE while 1013/3569 (28.4%) with GG2 disease had EPE. Median follow up was 4 years. BCR occurred in 400/6309 (6.3%) patients. For men with GG1, there was no statistically significant difference in BCR-free survival for men with vs without EPE (subdistribution hazard ratio [SHR] = 0.88; 95% CI: 0.37-2.09). However, for GG2 patients BCR-free survival was significantly worse for those with vs without EPE (SHR = 1.97, 95% CI: 1.54-2.52).

CONCLUSION: Although there are a subset of GG1 PCa’s capable of invading through the prostatic capsule, patients with GG1 PCa and EPE at prostatectomy experience similar biochemical recurrence and survival outcomes compared to GG1 patients without EPE. However, among men with GG2 EPE connotes a worse prognosis.

PMID:38109699 | DOI:10.1097/JU.0000000000003825

J Clin Oncol. 2023 Dec 18:JCO2301586. doi: 10.1200/JCO.23.01586. Online ahead of print.

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The LYMA trial demonstrated the benefit of rituximab maintenance (RM) in first-line young patients with mantle-cell lymphoma. In this prolonged follow-up of 7.5 years (95% CI, 7.4 to 7.7) from inclusion, the median progression-free survival (PFS) and overall survival (OS) for the full population were not reached (NR) with a 7-year PFS of 55.5% (95% CI, 49.5 to 61) and OS of 69.5% (95% CI, 63.8 to 74.5). The EFS remained statistically superior in favor of RM (median NR v 5.8 years, P < .0001; HR, 0.39 [95% CI, 0.52 to 0.6] and 7-year estimate, 76.2% versus 46% for RM and observation, respectively). Similarly, RM prolonged PFS (estimated PFS at 7 years, 78.5% v 47.4% and HR, 0.36 [95% CI, 0.23 to 0.56] for RM and observation, respectively, P < .0001). The 7-year OS estimate was 83.2% versus 72.2%, respectively (P = .088, HR, 0.63 [95% CI, 0.37 to 1.08]). Cause of death was not significantly distinct between the two groups, with lymphoma being the leading cause with a very low rate of infection-related death. Overall, the PFS benefit of RM after autologous stem cell transplantation remains after 7-year follow-up, and RM was not associated with an increase in infection-related mortality, making this strategy a safe standard of care with long-term follow-up.

PMID:38109684 | DOI:10.1200/JCO.23.01586

Anesthesiology. 2023 Dec 18. doi: 10.1097/ALN.0000000000004879. Online ahead of print.

ABSTRACT

BACKGROUND: Mechanical power (MP), the rate of mechanical energy (ME) delivery, is a recently introduced unifying ventilator parameter consisting of tidal volume, airway pressures, and respiratory rates, which predicts pulmonary complications in several clinical contexts. However, ME has not been previously studied in the perioperative context and neither parameter has been studied in the context of thoracic surgery utilizing one lung ventilation.

METHODS: The relationships between mechanical energy variables and postoperative pulmonary complications were evaluated in this post hoc analysis of data from a multicenter randomized clinical trial of lung resection surgery conducted between 2020 and 2021 (n=1,170). Time-weighted average MP (MPTWA) and ME (the area under the MP time curve) were obtained for individual patients. The primary analysis was the association of MPTWA and ME with pulmonary complications within 7 postoperative days. Multivariable logistic regression was performed to examine the relationships between energy variables and the primary outcome.

RESULTS: In 1,055 patients analyzed, pulmonary complications occurred in 41% (431/1055). The median (interquartile ranges) ME and MPTWA in patients who developed postoperative pulmonary complications (PPC) vs those who did not were 1,146 (811‒1530) J vs 924 (730‒1240) J (P<0.001), and 6.9 (5.5‒8.7) J/min vs 6.7 (5.2‒8.5) J/min (P=0.091), respectively. ME was independently associated with PPCs (ORadj 1.44 [95%CI 1.16‒1.80], P=0.001). However, the association between MPTWA and PPCs was time dependent and MPTWA was significantly associated with PPCs in cases utilizing longer periods of mechanical ventilation (≥210 minutes; ORadj 1.46 [95%CI 1.11‒1.93], P=0.007). Normalization of ME and MPTWA to either predicted body weight or to respiratory system compliance did not alter these associations.

CONCLUSIONS: ME and, in cases requiring longer periods of mechanical ventilation, MP were independently associated with PPC in thoracic surgery.

PMID:38109657 | DOI:10.1097/ALN.0000000000004879

J Vis. 2023 Dec 1;23(15):56. doi: 10.1167/jov.23.15.56.

ABSTRACT

When we enter a dark place like a tunnel from a bright exterior, our visual sensitivities take some time to adapt to the lower light level. However, there have been few reports about how quickly our sensitivities of luminance and chromaticity discrimination recover in this situation. This study aimed to quantify the time course of discrimination sensitivity for luminance and chromaticity directions after an abrupt decrease in background luminance. In each trial, the background luminance dropped from 100 cd/m² to 1 cd/m². Then, one target and three reference stimuli with different colors were presented under four stimulus onset asynchrony (SOA) conditions. The observer was asked to discriminate the target stimulus from the reference stimuli. The results showed that discrimination sensitivity was lowest right after the background luminance change and gradually improved with SOAs. However, sensitivity recovery differed across color directions, with the most improvement in luminance, followed by S, and negligible change in L-M. There was a statistically significant difference between +S and ±(L-M) sensitivities, indicating that the sensitivity recovery after the sudden background luminance change differed between chromaticity directions. Based on the comparison with previous studies, we speculate that both adaptation and masking may contribute to the temporal change of discrimination sensitivities.

PMID:38109592 | DOI:10.1167/jov.23.15.56

J Vis. 2023 Dec 1;23(15):80. doi: 10.1167/jov.23.15.80.

ABSTRACT

When a person views a color sample, they can usually provide a color term for it. But will that color term allow someone else to understand which sample was named? We examined color understanding using a Color Communication Game, in which one person (the “sender”) names 30 color samples as in any color-naming study, then another person (the “receiver”) chooses the sample they think the sender intended to communicate. The receiver cannot always guess the right sample, and no choice strategy will do better than randomly choosing among the samples the receiver called by that term. When 70 English-speaking dyads and 63 Somali-speaking dyads played the game, receivers did not perform randomly. Instead, they systematically chose “focal” samples near the centers of their color term distributions. When the senders’ named samples were compared directly to the receivers’ chosen samples, the systematic distribution of receiver choices revealed color categories, which appeared without any statistical analysis of the players’ terms. Simulation of receiver choices based on senders’ color names showed that both Somali-speaking and English-speaking participants knew more color terms than the ones they used in color-naming. Our Color Communication Game showed that color-naming experiments underestimate color understanding: people understand colors categorically, but they express colors using multiple synonymous color terms that are well-understood by others.

PMID:38109568 | DOI:10.1167/jov.23.15.80

Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2304404120. doi: 10.1073/pnas.2304404120. Epub 2023 Dec 18.

ABSTRACT

The dominant paradigm for assessing ecological responses to climate change assumes that future states of individuals and populations can be predicted by current, species-wide performance variation across spatial climatic gradients. However, if the fates of ecological systems are better predicted by past responses to in situ climatic variation through time, this current analytical paradigm may be severely misleading. Empirically testing whether spatial or temporal climate responses better predict how species respond to climate change has been elusive, largely due to restrictive data requirements. Here, we leverage a newly collected network of ponderosa pine tree-ring time series to test whether statistically inferred responses to spatial versus temporal climatic variation better predict how trees have responded to recent climate change. When compared to observed tree growth responses to climate change since 1980, predictions derived from spatial climatic variation were wrong in both magnitude and direction. This was not the case for predictions derived from climatic variation through time, which were able to replicate observed responses well. Future climate scenarios through the end of the 21st century exacerbated these disparities. These results suggest that the currently dominant paradigm of forecasting the ecological impacts of climate change based on spatial climatic variation may be severely misleading over decadal to centennial timescales.

PMID:38109562 | DOI:10.1073/pnas.2304404120

Eur J Cardiothorac Surg. 2023 Dec 18:ezad412. doi: 10.1093/ejcts/ezad412. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate employing the German Registry of Acute Aortic Dissection Type A (GERAADA) score to predict 30-day mortality in an aortic center in the United States.

METHODS: Between January 2010 and June 2021, 689 consecutive patients underwent surgery for acute type A dissection at a single institution. Excluded were patients with missing clinical data (N = 4). The GERAADA risk score was retrospectively calculated via a web-based application. Model discrimination power was calculated with c-statistics from logistic regression and reported as the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CIs). The calibration was measured by calculating the observed versus estimated mortality (O/E) ratio. The Brier score was used for the overall model evaluation.

RESULTS: Included were 685 patients [mean age 60.6 years (SD: 13.5), 64.8% male] who underwent surgery for acute Type A aortic dissection. The 30-day mortality rate was 12.0%. The GERAADA score demonstrated very good discrimination power with an AUC of 0.762 (95% CI 0.703-0.821). The entire cohort’s O/E ratio was 0.543 (0.439-0.648), indicating an overestimation of the model-calculated risk. The Brier score was 0.010, thus revealing the model’s acceptable overall performance.

CONCLUSIONS: The GERAADA score is a practical and easily accessible tool for reliably estimating the 30-day mortality risk of patients undergoing surgery for acute Type A aortic dissection. This model may naturally overestimate risk in patients undergoing surgery in experienced aortic centers.

PMID:38109506 | DOI:10.1093/ejcts/ezad412

Plant Physiol. 2023 Dec 18:kiad672. doi: 10.1093/plphys/kiad672. Online ahead of print.

ABSTRACT

Desiccation is typically fatal, but a small number of land plants have evolved vegetative desiccation tolerance (VDT), allowing them to dry without dying through a process called anhydrobiosis. Advances in sequencing technologies have enabled the investigation of genomes for desiccation-tolerant plants over the past decade. However, a dedicated and integrated database for these valuable genomic resources has been lacking. Our prolonged interest in VDT plant genomes motivated us to create the “Drying without Dying” database, which contains a total of 16 VDT-related plant genomes (including ten mosses) and incorporates 10 genomes that are closely related to VDT plants. The database features bioinformatic tools, such as blast and homologous cluster search, sequence retrieval, GO term and metabolic pathway enrichment statistics, expression profiling, co-expression network extraction, and JBrowser exploration for each genome. To demonstrate its utility we conducted tailored PFAM family statistical analyses, and we discovered that the drought-responsive ABA transporter AWPM-19 family is significantly tandemly duplicated in all bryophytes but rarely so in tracheophytes. Transcriptomic investigations also revealed that response patterns following desiccation diverged between bryophytes and angiosperms. Combined, the analyses provided genomic and transcriptomic evidence supporting a possible divergence and lineage-specific evolution of VDT in plants. The database can be accessed at http://desiccation.novogene.com. We expect this initial release of the “Drying without Dying” plant genome database will facilitate future discovery of VDT genetic resources.

PMID:38109500 | DOI:10.1093/plphys/kiad672

J Low Genit Tract Dis. 2023 Dec 18. doi: 10.1097/LGT.0000000000000793. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the characteristics and screening history of vaginal intraepithelial neoplasia (VaIN) or vaginal cancer and compare the sensitivity of cytology and human papillomavirus (HPV) tests on the cervix against vaginal and cervical high-grade squamous intraepithelial lesion or cancer.

METHODS: This study included patients who underwent colposcopy-directed biopsy and were diagnosed with VaIN or vaginal cancer from February 2013 to November 2022. Clinical information was obtained from the medical records of the department. Statistical analysis was performed on SPSS 26.0 (IBM Corp, Armonk, NY) using t test, chi-square, and Fisher exact tests.

RESULTS: A total of 1,166 patients were included in this study. The median age of VaIN2+ patients was 50.5 years, whereas VaIN1 reported a median age of 42.1 years old, p < .001. This study reported that VaIN was significantly and positively correlated with cervical lesions (r = 0.244). The high-risk HPV (hr-HPV) detection rate was 88.2% (858/973) in VaIN and 95.2% in VaIN2+. Human papillomavirus 16 was the most prevalent HPV type in VaIN2+, which accounted for 54.9%, followed by HPV58 (19.5%), HPV52 (15.2%), HPV51 (12.2%), and HPV18 (11.0%). The sensitivity of hr-HPV and cytology tests on the cervix for detecting VaIN2+ was 94.7% and 83.4%, respectively. Both tests were not significantly different from detecting cervical intraepithelial neoplasia 2+.

CONCLUSIONS: Human papillomavirus 16 is the dominant HPV type in vaginal precancer lesions. Cervical cancer screening has similar sensitivity for VaIN2+ as for cervical intraepithelial neoplasia 2+, with hr-HPV testing showing higher sensitivity than cytology.

PMID:38109483 | DOI:10.1097/LGT.0000000000000793