Category: Statistics

J Biopharm Stat. 2023 Dec 22:1-20. doi: 10.1080/10543406.2023.2292209. Online ahead of print.

ABSTRACT

The goal of phase II clinical trials is to evaluate the therapeutic efficacy of a new drug. Some investigators want to use the time-to-event endpoint as the primary endpoint of the phase II study to see the improvement of the therapeutic efficacy of a new drug in median survival time. Recently, median event time test (METT) has been proposed to provide a simple and straightforward rule which compares the observed median survival time with the prespecified threshold. However, median survival time would not be observed during the trial if the drug performs well and indeed cures most patients or if the accrual rate is so fast. To address the issues in clinical practice, we first propose a percentile event time test (PETT), which generalizes METT to any percentile of the survival time, and develop data-driven monitoring for phase II clinical trial designs based on PETT. We evaluate the performance of the method through simulations and illustrate the proposed method with a trial example.

PMID:38131110 | DOI:10.1080/10543406.2023.2292209

J Dev Econ. 2024 Mar;167:103215. doi: 10.1016/j.jdeveco.2023.103215. Epub 2023 Nov 27.

ABSTRACT

We study how human capital and economic conditions causally affect the choice of religious denomination. We utilize a longitudinal dataset monitoring the religious history of more than 5,000 Kenyans over twenty years, in tandem with a randomized experiment (deworming) that has exogenously boosted education and living standards. The main finding is that the program reduces the likelihood of membership in a Pentecostal denomination up to 20 years later when respondents are in their mid-thirties, while there is a comparable increase in membership in traditional Christian denominations. The effect is concentrated and statistically significant among a sub-group of participants who benefited most from the program in terms of increased education and income. The effects are unlikely due to increased secularization, because the program does not reduce measures of religiosity. The results help explain why the global growth of the Pentecostal movement, sometimes described a “New Reformation”, is centered in low-income communities.

PMID:38131098 | PMC:PMC10732350 | DOI:10.1016/j.jdeveco.2023.103215

Chem Sci. 2023 Dec 6;15(1):250-258. doi: 10.1039/d3sc04861f. eCollection 2023 Dec 20.

ABSTRACT

Using a highly active permethylindenyl-phenoxy (PHENI*) titanium catalyst, high to ultra-high molecular weight ethylene-linear-α-olefin (E/LAO) copolymers are prepared in high yields under mild conditions (2 bar, 30-90 °C). Controllable, efficient, and predictable comonomer enchainment provides access to a continuum of copolymer compositions and a vast range of material properties using a single monomer-agnostic catalyst. Multivariate statistical tools are employed that combine the tuneability of this system with the analytical and predictive power of data-derived models, this enables the targeting of polyolefins with designer properties directly through predictive alteration of reaction conditions.

PMID:38131091 | PMC:PMC10731910 | DOI:10.1039/d3sc04861f

Chem Sci. 2023 Nov 29;15(1):389-398. doi: 10.1039/d3sc03685e. eCollection 2023 Dec 20.

ABSTRACT

Supramolecular dimers are elementary units allowing the build-up of multi-molecule architectures. New among these are cyanostar-stabilized dimers of phosphate and phosphonate anions. While the anion dimerization at the heart of these assemblies is reliable, the covalent synthesis leading to this class of designer anions serves as a bottleneck in the pathway to supramolecular assemblies. Herein, we demonstrate the reliable synthesis of 14 diverse anionic monomers by Heck coupling between vinyl phosphonic acid and aryl bromide compounds. When this synthesis is combined with reliable anion dimerization, we show formation of supramolecular dimers and polymers by co-assembly with cyanostar macrocycles. The removal of the covalent bottleneck opened up a seamless synthetic route to iterate through three monomers affording the solubility needed to characterize the mechanism of supramolecular polymerization. We also test the idea that the small size of these vinyl phosphonates provide identical dimer stabilities across the library by showing how mixtures of anions undergo statistical (social) self-sorting. We exploit this property by preparing soluble copolymers from the mixing of different monomers. This multi-anion assembly shows the utility of a library for programming properties.

PMID:38131081 | PMC:PMC10732014 | DOI:10.1039/d3sc03685e

Clin Oral Investig. 2023 Dec 22;28(1):13. doi: 10.1007/s00784-023-05421-4.

ABSTRACT

OBJECTIVES: Statistics on the rate of unconventional lymph node metastases (ULNM) at the time of one-stage radical surgery in tongue cancer patients. To assess whether an extended neck dissection group with additional removal of ULNs has a lower rate of neck recurrence compared to the traditional neck dissection group.

MATERIALS AND METHODS: A total of 336 patients with TSCC who underwent radical surgery were recruited and underwent traditional or extended neck dissection. Compared to traditional neck dissection, the aim of extended neck dissection is designed to additional resect ULNs.

RESULTS: In total, 180 patients underwent extended neck dissection, while 156 underwent traditional neck dissection. The incidence of ULNM was 11.67% (21/180) in patients treated with extended neck dissection. The incidence of ipsilateral neck recurrence was 9.49% and 0.56% in patients who underwent traditional and extended neck dissection, respectively (p = 0.0001).

CONCLUSIONS: Extended neck dissection is effective for preventing neck recurrence in TSCC patients with ULNs.

CLINICAL RELEVANCE: ULNM may be the main cause of neck recurrence after neck dissection in patients with tongue cancer. A better prognosis may be achieved by additional resection of ULNs on the basis of traditional neck dissection.

PMID:38129547 | DOI:10.1007/s00784-023-05421-4

Sci Rep. 2023 Dec 21;13(1):22919. doi: 10.1038/s41598-023-50128-x.

ABSTRACT

Health professionals need a strong prediction system to reach appropriate disease diagnosis, particularly for under-five child with health problems like anemia. Diagnosis and treatment delay can potentially lead to devastating disease complications resulting in childhood mortality. However, the application of machine learning techniques using a large data set provides scientifically sounded information to solve such palpable critical health and health-related problems. Therefore, this study aimed to determine the predictors of anemia among under-5 year’s age children in Ethiopia using a machine learning approach. A cross-sectional study design was done using the Ethiopian Demographic and Health Survey 2016 data set. A two-stage stratified cluster sampling technique was employed to select the samples. The data analysis was conducted using Statistical Package for Social Sciences/SPSS version 25 and R-software. Data were derived from Ethiopian Demographic and Health Survey. Boruta algorism was applied to select the features and determine the predictors of anemia among under-5 years-old children in Ethiopia. The machine learning algorism showed that number of children, distance to health facilities, health insurance coverage, youngest child’s stool disposal, residence, mothers’ wealth index, type of cooking fuel, number of family members, mothers’ educational status and receiving rotavirus vaccine were the top ten important predictors for anemia among under-five children. Machine-learning algorithm was applied to determine the predictors of anemia among under- 5 year’s age children in Ethiopia. We have identified the determinant factors by conducting a feature importance analysis with the Boruta algorithm. The most significant predictors were number of children, distance to health facility, health insurance coverage, youngest child’s stool disposal, residence, mothers’ wealth index, and type of cooking fuel. Machine learning model plays a paramount role for policy and intervention strategies related to anemia prevention and control among under-five children.

PMID:38129535 | DOI:10.1038/s41598-023-50128-x

Br J Cancer. 2023 Dec 21. doi: 10.1038/s41416-023-02542-1. Online ahead of print.

ABSTRACT

BACKGROUND: Berzosertib (M6620) is a highly potent (IC50 = 19 nM) and selective, first-in-class ataxia telangiectasia-mutated and Rad3-related protein kinase (ATR) inhibitor. This trial assessed the safety, preliminary efficacy, and tolerance of berzosertib in oesophageal cancer (A1 cohort) with RT and advanced solid tumours (A2 cohort) with cisplatin and capecitabine.

METHODS: Single-arm, open-label dose-escalation (Time-to-Event Continual Reassessment Method) trial with 16 patients in A1 and 18 in A2. A1 tested six dose levels of berzosertib with RT (35 Gy over 15 fractions in 3 weeks).

RESULTS: No dose-limiting toxicities (DLTs) in A1. Eight grade 3 treatment-related AEs occurred in five patients, with rash being the most common. The highest dose (240 mg/m²) was determined as the recommended phase II dose (RP2D) for A1. Seven DLTs in two patients in A2. The RP2D of berzosertib was 140 mg/m² once weekly. The most common grade ≥3 treatment-related AEs were neutropenia and thrombocytopenia. No treatment-related deaths were reported.

CONCLUSIONS: Berzosertib combined with RT is feasible and well tolerated in oesophageal cancer patients at high palliative doses. Berzosertib with cisplatin and capecitabine was well tolerated in advanced cancer. Further investigation is warranted in a phase 2 setting.

CLINICAL TRIALS IDENTIFIER: EU Clinical Trials Register (EudraCT) – 2015-003965-27 ClinicalTrials.gov – NCT03641547.

PMID:38129525 | DOI:10.1038/s41416-023-02542-1

Sci Rep. 2023 Dec 21;13(1):22891. doi: 10.1038/s41598-023-49784-w.

ABSTRACT

The Escherichia coli chemotaxis network, by which bacteria modulate their random run/tumble swimming pattern to navigate their environment, must cope with unavoidable number fluctuations (“noise”) in its molecular constituents like other signaling networks. The probability of clockwise (CW) flagellar rotation, or CW bias, is a measure of the chemotaxis network’s output, and its temporal fluctuations provide a proxy for network noise. Here we quantify fluctuations in the chemotaxis signaling network from the switching statistics of flagella, observed using time-resolved fluorescence microscopy of individual optically trapped E. coli cells. This approach allows noise to be quantified across the dynamic range of the network. Large CW bias fluctuations are revealed at steady state, which may play a critical role in driving flagellar switching and cell tumbling. When the network is stimulated chemically to higher activity, fluctuations dramatically decrease. A stochastic theoretical model, inspired by work on gene expression noise, points to CheY activation occurring in bursts, driving CW bias fluctuations. This model also shows that an intrinsic kinetic ceiling on network activity places an upper limit on activated CheY and CW bias, which when encountered suppresses network fluctuations. This limit may also prevent cells from tumbling unproductively in steep gradients.

PMID:38129516 | DOI:10.1038/s41598-023-49784-w

Commun Med (Lond). 2023 Dec 21;3(1):193. doi: 10.1038/s43856-023-00377-8.

ABSTRACT

INTRODUCTION: Public perception of the seriousness of the COVID-19 pandemic compared to six other major public health problems (alcoholism and drug use, HIV/AIDS, malaria, tuberculosis, lung cancer and respiratory diseases caused by air pollution and smoking, and water-borne diseases like diarrhea) is unclear. We designed a survey to examine this issue using YouGov’s internet panels in seven middle-income countries in Africa, Asia, and Latin America in early 2022.

METHODS: Respondents rank ordered the seriousness of the seven health problems using a repeated best-worst question format. Rank-ordered logit models allow comparisons within and across countries and assessment of covariates.

RESULTS: In six of the seven countries, respondents perceived other respiratory illnesses to be a more serious problem than COVID-19. Only in Vietnam was COVID-19 ranked above other respiratory illnesses. Alcoholism and drug use was ranked the second most serious problem in the African countries. HIV/AIDS ranked relatively high in all countries. Covariates, particularly a COVID-19 knowledge scale, explained differences within countries; statistics about the pandemic were highly correlated with differences in COVID-19’s perceived seriousness.

CONCLUSIONS: People in the seven middle-income countries perceived COVID-19 to be serious (on par with HIV/AIDS) but not as serious as other respiratory illnesses. In the African countries, respondents perceived alcoholism and drug use as more serious than COVID-19. Our survey-based approach can be used to quickly understand how the threat of a newly emergent disease, like COVID-19, fits into the larger context of public perceptions of the seriousness of health problems.

PMID:38129511 | DOI:10.1038/s43856-023-00377-8

Sci Rep. 2023 Dec 21;13(1):22888. doi: 10.1038/s41598-023-49782-y.

ABSTRACT

The aim is to study the intraocular pressure (IOP)-lowering effects of additional administration of ripasudil in open-angle glaucoma (OAG) patients including high myopia (HM) and pathological myopia (PM). Study design is retrospective cohort study. We assessed the changes in the mean IOP between the HM eyes (axial length ≧ 26.5 mm 33 eyes) and the non-HM eyes (axial length < 26.5 mm 29 eyes) at 4 and 12 weeks from baseline. We also assessed the IOP changes between the PM eyes (21 eyes) and the non-PM eyes (41 eyes). The significant IOP reduction by the ripasudil administration was observed at 4 weeks in the non-HM eyes and at 12 weeks in HM and non-HM eyes. And the IOP reduction in the HM eyes was significantly less than the non-HM eyes at 4 and 12 weeks. IOP reduction by ripasudil had statistically significant association with the baseline IOP and presence of PM. Furthermore, significant IOP reduction by the ripasudil administration was observed at 4 and 12 weeks in the non-PM eyes, but not in the PM eyes. The additional administration of ripasudil was effective in the HM eyes, but less than non-HM eyes. And the PM may negatively contribute to reducing the IOP by ripasudil.

PMID:38129467 | DOI:10.1038/s41598-023-49782-y