Category: Statistics

JCO Oncol Pract. 2024 Jan 8:OP2300126. doi: 10.1200/OP.23.00126. Online ahead of print.

ABSTRACT

PURPOSE: National Cancer Institute (NCI) and nonprofit organization (NPO) funding is critical for research and advocacy but may not be equitable across cancers.

METHODS: This study evaluated funding from the NCI and NPOs supporting lung, breast, colorectal, pancreatic, hepatobiliary, prostate, ovarian, cervical and endometrial cancers, leukemia, lymphoma, and melanoma from 2015 to 2018. The primary objectives were to assess for funding disparities across different cancers compared with their incidence and mortality and across racial groups. We also determined if underfunding correlates with fewer clinical trials. Correlations between funding for each cancer and its incidence, mortality, and number of clinical trials were analyzed using descriptive statistics and Pearson correlation coefficients (CCs).

RESULTS: Diseases with the largest combined NCI and NPO funding were breast cancer ($3.75 billion in US dollars [USD]) and leukemia ($1.99 billion USD). Those with the least funding were endometrial ($94 million USD), cervical ($292 million USD), and hepatobiliary cancers ($348 million USD). Disease-specific funding correlated well with incidence but correlated poorly with mortality (Pearson CCs, 0.74; P = .006 and .30, P = .346, respectively). Breast cancer, leukemia, and lymphoma were well-funded while colorectal, lung, hepatobiliary and uterine cancers were underfunded. Higher incidence among Black patients correlated with underfunding. The amount of funding for a particular cancer correlated strongly with the number of clinical trials for that disease (Pearson CC, 0.91; P < .0001).

CONCLUSION: Many cancers with high incidence and mortality rates are underfunded. Cancers that affect Black patients at higher rates are also underfunded. Underfunding strongly correlates with fewer clinical trials, which could impede future advances in underfunded cancers.

PMID:38190584 | DOI:10.1200/OP.23.00126

JCO Precis Oncol. 2024 Jan;8:e2300317. doi: 10.1200/PO.23.00317.

ABSTRACT

Advances in genomics have enabled anticancer therapies to be tailored to target specific genomic alterations. Single-arm trials (SATs), including those incorporated within umbrella, basket, and platform trials, are widely adopted when it is not feasible to conduct randomized controlled trials in rare biomarker-defined subpopulations. External controls (ECs), defined as control arm data derived outside the clinical trial, have gained renewed interest as a strategy to supplement evidence generated from SATs to allow comparative analysis. There are increasing examples demonstrating the application of EC in precision oncology trials. The prospective application of EC in conducting comparative studies is associated with distinct methodological challenges, the specific considerations for EC use in biomarker-defined subpopulations have not been adequately discussed, and a formal framework is yet to be established. In this review, we present a framework for conducting a prospective comparative analysis using EC. Key steps are (1) defining the purpose of using EC to address the study question, (2) determining if the external data are fit for purpose, (3) developing a transparent study protocol and a statistical analysis plan, and (iv) interpreting results and drawing conclusions on the basis of a prespecified hypothesis. We specify the considerations required for the biomarker-defined subpopulations, which include (1) specifying the comparator and biomarker status of the comparator group, (2) defining lines of treatment, (3) assessment of the biomarker testing panels used, and (4) assessment of cohort stratification in tumor-agnostic studies. We further discuss novel clinical trial designs and statistical techniques leveraging EC to propose future directions to advance evidence generation and facilitate drug development in precision oncology.

PMID:38190581 | DOI:10.1200/PO.23.00317

J Refract Surg. 2024 Jan;40(1):e20-e29. doi: 10.3928/1081597X-20231212-02. Epub 2024 Jan 1.

ABSTRACT

PURPOSE: To evaluate the efficacy of paired opposite clear corneal incisions (OCCIs) in Implantable Collamer Lens (ICL; STAAR Surgical) implantation surgery for correcting preexisting low-to-moderate astigmatism and observe their influence on corneal aberration.

METHODS: This prospective controlled randomized study included 123 eyes: 73 eyes in the ICL surgery group (control group) and 50 eyes in the ICL combined with OCCI group (OCCI group). All patients had corneal astigmatism between 0.50 and 3.00 D. Parameters considered included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refraction, keratometry, slit-lamp biomicroscopy, indirect ophthalmoscopy, corneal topography, and higher order aberrations (HOAs). The Alpins method was used to analyze the correction of astigmatism. The follow-up period lasted for 12 months.

RESULTS: Both groups showed a statistically significant improvement in mean UDVA and CDVA after surgery. At 1 and 12 months, the OCCI group had statistically better UDVA than the control group (P = .021 and .01). The OCCI group showed a significant reduction in mean refractive astigmatism from -0.835 ± 0.274 to -0.535 ± 0.353 and -0.450 ± 0.346 D postoperatively (P < .05) after 1 and 12 months. No significant change was observed in the control group (P > .05). The average magnitude of surgically induced astigmatism (SIA) was 0.911 ± 0.442 and 0.811 ± 0.397 D at 1 and 12 months postoperatively, respectively, in the OCCI group, which was slightly lower than the target induced astigmatism. The difference in SIA between the OCCI and control groups was significant by the end of 1 and 12 months postoperatively (P < .0001). The mean correction index was below 1, suggesting an undercorrection effect caused by clear corneal incisions in the opposite direction. HOAs increased in both the control and OCCI groups after surgery (t = 5.668, P < .0001, t = 3.773, P = .0003, respectively), with oblique trefoil only significantly increasing in the OCCI group.

CONCLUSIONS: This study demonstrated that OCCIs represent a secure, efficient, reliable, and long-term technique for reducing preexisting low-to-moderate corneal astigmatism during ICL surgery. However, OCCIs did not show any advantageous impact in terms of wavefront aberrations when compared to the traditional single-incision method. The presence of oblique trefoil may be the main contributor to the alteration of HOAs during OCCI surgery. [J Refract Surg. 2024;40(1):e20-e29.].

PMID:38190562 | DOI:10.3928/1081597X-20231212-02

J Refract Surg. 2024 Jan;40(1):e1-e9. doi: 10.3928/1081597X-20231204-02. Epub 2024 Jan 1.

ABSTRACT

PURPOSE: To determine the visual outcomes and safety 12 months after implantation of the Presbia Flexivue Microlens refractive corneal inlay.

METHODS: In this prospective, non-randomized trial, 22 patients with a mean age of 52.54 ± 2.86 years were implanted with the Flexivue Microlens refractive corneal inlay in the non-dominant eye at the Department of Ophthalmology, Goethe University, Frankfurt, Germany. Corrected near, intermediate, and distance (CNVA, CIVA, and CDVA) visual acuity and uncorrected near, intermediate, and distance (UNVA, UIVA, and UDVA) visual acuity, manifest refraction, subjective quality of vision, endothelial cell count, and contrast sensitivity were measured 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively.

RESULTS: For binocular CDVA, no patient lost two or more lines and 30% lost only one line at the 12-month visit. In the eye that had surgery, 85% of the patients lost two or more lines of UDVA, which was statistically significant. Sixty-five percent of the patients gained one or more lines in binocular UIVA, and 80% achieved 20/40 or better in DCIVA. UNVA showed a statistically significant improvement, with 90% of the patients achieving 20/40 or better 12 months after implantation. A total of 85% gained two or more lines in binocular UNVA.

CONCLUSIONS: This refractive corneal inlay showed an improvement in binocular UNVA, UIVA, CNVA, and CIVA, whereas binocular CDVA and UDVA were not statistically affected. [J Refract Surg. 2024;40(1):e1-e9.].

PMID:38190559 | DOI:10.3928/1081597X-20231204-02

Proc Natl Acad Sci U S A. 2024 Jan 16;121(3):e2309825120. doi: 10.1073/pnas.2309825120. Epub 2024 Jan 8.

ABSTRACT

The impact of sexual selection on the evolution of birds has been widely acknowledged. Although sexual selection has been hypothesized as a driving force in the occurrences of numerous morphological features across theropod evolution, this hypothesis has yet to be comprehensively tested due to challenges in identifying the sex of fossils and by the limited sample size. Confuciusornis sanctus is arguably the best-known early avialan and is represented by thousands of well-preserved specimens from the Early Cretaceous Jehol lagerstätte, which provides us with a chance to decipher the strength of sexual selection on extinct vertebrates. Herein, we present a morphometric study of C. sanctus based on the largest sample size of this taxon collected up to now. Our results indicate that the characteristic elongated paired rectrices is a sexually dimorphic trait and statistically robust inferences of the sexual dimorphism in size, shape, and allometry that have been established, providing the earliest known sexual dimorphism in avian evolution. Our findings suggest that sexual selection, in conjunction with natural selection, does act upon body size and limb length ratio in early birds, thereby promoting a deeper understanding of the role of sexual selection in large-scale phylogenetic evolution.

PMID:38190528 | DOI:10.1073/pnas.2309825120

Proc Natl Acad Sci U S A. 2024 Jan 16;121(3):e2315857121. doi: 10.1073/pnas.2315857121. Epub 2024 Jan 8.

ABSTRACT

Epstein-Barr virus (EBV) infection has long been associated with multiple sclerosis (MS), but the role of EBV in the pathogenesis of MS is not clear. Our hypothesis is that a major fraction of the expanded clones of T lymphocytes in the cerebrospinal fluid (CSF) are specific for autologous EBV-infected B cells. We obtained blood and CSF samples from eight relapsing-remitting patients in the process of diagnosis. We stimulated cells from the blood with autologous EBV-infected lymphoblastoid cell lines (LCL), EBV, varicella zoster virus, influenza, and candida and sorted the responding cells with flow cytometry after 6 d. We sequenced the RNA for T cell receptors (TCR) from CSF, unselected blood cells, and the antigen-specific cells. We used the TCR Vβ CDR3 sequences from the antigen-specific cells to assign antigen specificity to the sequences from the CSF and blood. LCL-specific cells comprised 13.0 ± 4.3% (mean ± SD) of the total reads present in CSF and 13.3 ± 7.5% of the reads present in blood. The next most abundant antigen specificity was flu, which was 4.7 ± 1.7% of the reads in the CSF and 9.3 ± 6.6% in the blood. The prominence of LCL-specific reads was even more marked in the top 1% most abundant CSF clones with statistically significant 47% mean overlap with LCL. We conclude that LCL-specific sequences form a major portion of the TCR repertoire in both CSF and blood and that expanded clones specific for LCL are present in MS CSF. This has important implications for the pathogenesis of MS.

PMID:38190525 | DOI:10.1073/pnas.2315857121

Proc Natl Acad Sci U S A. 2024 Jan 23;121(4):e2309881120. doi: 10.1073/pnas.2309881120. Epub 2024 Jan 8.

ABSTRACT

Climate change is increasing the frequency and severity of short-term (~1 y) drought events-the most common duration of drought-globally. Yet the impact of this intensification of drought on ecosystem functioning remains poorly resolved. This is due in part to the widely disparate approaches ecologists have employed to study drought, variation in the severity and duration of drought studied, and differences among ecosystems in vegetation, edaphic and climatic attributes that can mediate drought impacts. To overcome these problems and better identify the factors that modulate drought responses, we used a coordinated distributed experiment to quantify the impact of short-term drought on grassland and shrubland ecosystems. With a standardized approach, we imposed ~a single year of drought at 100 sites on six continents. Here we show that loss of a foundational ecosystem function-aboveground net primary production (ANPP)-was 60% greater at sites that experienced statistically extreme drought (1-in-100-y event) vs. those sites where drought was nominal (historically more common) in magnitude (35% vs. 21%, respectively). This reduction in a key carbon cycle process with a single year of extreme drought greatly exceeds previously reported losses for grasslands and shrublands. Our global experiment also revealed high variability in drought response but that relative reductions in ANPP were greater in drier ecosystems and those with fewer plant species. Overall, our results demonstrate with unprecedented rigor that the global impacts of projected increases in drought severity have been significantly underestimated and that drier and less diverse sites are likely to be most vulnerable to extreme drought.

PMID:38190514 | DOI:10.1073/pnas.2309881120

Med Phys. 2024 Jan 8. doi: 10.1002/mp.16905. Online ahead of print.

ABSTRACT

BACKGROUND: Delta radiomics is a high-throughput computational technique used to describe quantitative changes in serial, time-series imaging by considering the relative change in radiomic features of images extracted at two distinct time points. Recent work has demonstrated a lack of prognostic signal of radiomic features extracted using this technique. We hypothesize that this lack of signal is due to the fundamental assumptions made when extracting features via delta radiomics, and that other methods should be investigated.

PURPOSE: The purpose of this work was to show a proof-of-concept of a new radiomics paradigm for sparse, time-series imaging data, where features are extracted from a spatial-temporal manifold modeling the time evolution between images, and to assess the prognostic value on patients with oropharyngeal cancer (OPC).

METHODS: To accomplish this, we developed an algorithm to mathematically describe the relationship between two images acquired at time $t=0$ and $t>0$ . These images serve as boundary conditions of a partial differential equation describing the transition from one image to the other. To solve this equation, we propagate the position and momentum of each voxel according to Fokker-Planck dynamics (i.e., a technique common in statistical mechanics). This transformation is driven by an underlying potential force uniquely determined by the equilibrium image. The solution generates a spatial-temporal manifold (3 spatial dimensions + time) from which we define dynamic radiomic features. First, our approach was numerically verified by stochastically sampling dynamic Gaussian processes of monotonically decreasing noise. The transformation from high to low noise was compared between our Fokker-Planck estimation and simulated ground-truth. To demonstrate feasibility and clinical impact, we applied our approach to ¹⁸ F-FDG-PET images to estimate early metabolic response of patients (n = 57) undergoing definitive (chemo)radiation for OPC. Images were acquired pre-treatment and 2-weeks intra-treatment (after 20 Gy). Dynamic radiomic features capturing changes in texture and morphology were then extracted. Patients were partitioned into two groups based on similar dynamic radiomic feature expression via k-means clustering and compared by Kaplan-Meier analyses with log-rank tests (p < 0.05). These results were compared to conventional delta radiomics to test the added value of our approach.

RESULTS: Numerical results confirmed our technique can recover image noise characteristics given sparse input data as boundary conditions. Our technique was able to model tumor shrinkage and metabolic response. While no delta radiomics features proved prognostic, Kaplan-Meier analyses identified nine significant dynamic radiomic features. The most significant feature was Gray-Level-Size-Zone-Matrix gray-level variance (p = 0.011), which demonstrated prognostic improvement over its corresponding delta radiomic feature (p = 0.722).

CONCLUSIONS: We developed, verified, and demonstrated the prognostic value of a novel, physics-based radiomics approach over conventional delta radiomics via data assimilation of quantitative imaging and differential equations.

PMID:38190505 | DOI:10.1002/mp.16905

Adv Mater. 2024 Jan 8:e2310282. doi: 10.1002/adma.202310282. Online ahead of print.

ABSTRACT

Acquisition of defect-free transition metal dichalcogenides (TMDs) channels with clean heterojunctions has been a critical issue in production of TMD-based functional electronic devices. Conventional approaches have synthesized high quality TMDs and transferred them onto a target substrate, and then applied the typical device fabrication processes. Unfortunately, those processes cause physical defects and chemical contamination in the TMD channels. Here, we propose a novel synthetic process of TMD thin films, named confined interfacial chalcogenization (CIC). In the proposed synthesis, a uniform TMD layer is created at the Au/transition metal (TM) interface by diffusion of chalcogen through the grain boundaries of the Au layer and reaction of chalcogen with the underlying TM. CIC allows for ultraclean heterojunctions with the metals, rapid synthesis of homo- and hetero-structured TMDs, and in-situ TMD channel formation in the last stage of device fabrication. We reveal the mechanism of TMD growth by the TM-accelerated chalcogen diffusion, epitaxial growth of TMD on Au(111), and dependence of the growth rate on material species of chalcogen and TM. We demonstrate a 100% production yield of TMD-based vertical memristors which exhibit excellent statistical concordance in device performance enabled by the ultraclean heterojunctions and superior uniformity in thickness and chemical composition. CIC proposed in this study represents a breakthrough in the synthesis of TMD thin films and also in the TMD-based electronic device fabrication, marking a substantial step towards practical next-generation integrated electronics. This article is protected by copyright. All rights reserved.

PMID:38190458 | DOI:10.1002/adma.202310282

PLoS Genet. 2024 Jan 8;20(1):e1010155. doi: 10.1371/journal.pgen.1010155. Online ahead of print.

ABSTRACT

Introgression is a common evolutionary phenomenon that results in shared genetic material across non-sister taxa. Existing statistical methods such as Patterson’s D statistic can detect introgression by measuring an excess of shared derived alleles between populations. The D statistic is effective to detect genome-wide patterns of introgression but can give spurious inferences of introgression when applied to local regions. We propose a new statistic, D+, that leverages both shared ancestral and derived alleles to infer local introgressed regions. Incorporating both shared derived and ancestral alleles increases the number of informative sites per region, improving our ability to identify local introgression. We use a coalescent framework to derive the expected value of this statistic as a function of different demographic parameters under an instantaneous admixture model and use coalescent simulations to compute the power and precision of D+. While the power of D and D+ is comparable, D+ has better precision than D. We apply D+ to empirical data from the 1000 Genome Project and Heliconius butterflies to infer local targets of introgression in humans and in butterflies.

PMID:38190420 | DOI:10.1371/journal.pgen.1010155