Category: Statistics

Hum Reprod. 2024 Apr 9:deae070. doi: 10.1093/humrep/deae070. Online ahead of print.

ABSTRACT

STUDY QUESTION: Can the application of the theory of planned behavior (TPB) help predict heterosexual parents’ disclosure of donor conception to their children?

SUMMARY ANSWER: Parents with a stronger will to act in accordance with social norms favoring disclosure were more likely to start the disclosure process within the next 5-9 years.

WHAT IS KNOWN ALREADY: In contrast to single mothers by choice and same-sex couples, heterosexual couples need to make an active decision to disclose their use of donor conception to their child. While disclosure at an early age is encouraged by international guidelines, many heterosexual-couple parents struggle with this. A previous study has found an association between parental scores of TPB factors and disclosure intention, but so far, no study has applied the TPB to predict parents’ disclosure behavior.

STUDY DESIGN, SIZE, DURATION: The present study is based on the fourth and fifth waves of data collection (T4 and T5) in a nation-wide longitudinal study. Participating parents had conceived through identity-release oocyte donation (n = 68, response rate 65%) and sperm donation (n = 62, response rate 56%) as part of a heterosexual couple.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The present study is part of the prospective longitudinal Swedish Study on Gamete Donation (SSGD). Consecutive recruitment of couples starting oocyte or sperm donation treatment was conducted at all seven fertility clinics providing gamete donation in Sweden during a 3-year period (2005-2008). Participants were requested to complete postal surveys at five time points. The present study includes heterosexual-couple parents following oocyte or sperm donation who participated at the two latest time points when their children were 7-8 years old (T4), and 13-17 years old (T5). At T4, participants completed the study-specific TPB Disclosure Questionnaire (TPB-DQ) measuring attitudes and intentions to disclose the donor conception to the child, and disclosure behavior was assessed at both T4 and T5. Data from those participants who had not yet disclosed at T4 were analyzed using survival analysis with Cox regressions.

MAIN RESULTS AND THE ROLE OF CHANCE: Forty participants had not disclosed the donor conception to their children at T4 and, out of these, 13 had still not disclosed at T5. We found a significant association between scores of the TPB factor Subjective norms at T4 and their subsequent disclosure behavior at T5 (HR = 2.019; 95% CI: 1.36-3.01). None of the other factors were significantly associated with disclosure behavior.

LIMITATIONS, REASONS FOR CAUTION: The present study concerns heterosexual-couple parents with children conceived following treatment with gametes from open-identity donors, which limits the generalizability of our findings to other groups and contexts. Other limitations include the risk of systematic attrition due to the longitudinal study design and decreased statistical power due to few participants.

WIDER IMPLICATIONS OF THE FINDINGS: Our findings highlight the importance of perceived subjective norms for parents’ disclosure behavior and indicate that the co-parent’s opinion about disclosure is of particular relevance in this regard. Counselors should focus on supporting prospective parents to initiate and maintain a healthy and open dialogue about concerns around building a family with donor conception.

STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Swedish Research Council. The authors have no competing interests to declare.

TRIAL REGISTRATION NUMBER: N/A.

PMID:38593421 | DOI:10.1093/humrep/deae070

Folia Primatol (Basel). 2023 Feb 28;94(4-6):173-206. doi: 10.1163/14219980-bja10010.

ABSTRACT

In order to achieve a better understanding of the factors that might have led our hominin ancestors to transition to a more terrestrial niche, including sleeping on the ground, we have conducted a study on the ground nesting behavior of chimpanzees (Pan troglodytes). Chimpanzees, like all other species of great apes, build nests in which to sleep each night, but little is known about regional differences in their nesting habits. Previously, nesting on the ground was considered typical of gorillas, but rare in most populations of chimpanzees. Using data acquired during our extensive chimpanzee nesting survey conducted between 2004 and 2013 across a > 50 000 km2 region in northern Democratic Republic of the Congo, we report a distinctive ground nesting behaviour of eastern chimpanzees (P. t. schweinfurthii). We have mapped the geographical distribution of ground nesting and compared its frequency at 20 survey areas on both sides of a large river, the Uele. We found that ground nests made up more than 1% of total nests at 15 of the 20 survey regions. For a subset of 16 of these regions, we utilized statistical models to investigate whether forest type and structure, as well as the abundance of carnivores and large herbivores, and the activities of humans impacted the frequency of ground nesting and nest height. We predicted that higher encounter rates of human and dangerous animal signs would be associated with lower rates of ground nesting as well as increased nest height. Overall, 10.4% of the Bili-Uéré chimpanzee nests were terrestrial, but the frequency of ground nesting varied extensively between the survey areas (0-29% of nests). The occurrence of ground nests was positively associated with denser forests (p = 0.004), herb patches (p < 0.001), and light gaps (p < 0.001). Light gaps (p < 0.001), herb patches (p = 0.044), and vine tangles (p = 0.016) also had a strong negative effect on nest height. Hunting by humans had a negative effect on the probability of the occurrence of ground nests (p = 0.001) and a positive one on nest height (p = 0.013), with a similar but likely marginal effect of large herbivores on nest height (p = 0.023). In addition, the chimpanzees nested at significantly lower heights with increasing distance from roads and settlements (p < 0.001). Carnivore encounter rates, however, had no significant impact on ground nest frequency or nest height. Our results indicate that ground nesting can no longer be considered a rare and patchily-occurring phenomenon in Pan troglodytes, but is instead a major component of the chimpanzee behavioural repertoire across a considerable fraction of the range of the Eastern subspecies. Our study highlights that neither the large body size of gorillas nor the taming of fire are necessary conditions for hominids to sleep overnight on the ground, even in areas inhabited by multiple species of large carnivore. Human hunting, however, appears to reduce the probability of ground nesting, or eliminate the behavior altogether.

PMID:38593407 | DOI:10.1163/14219980-bja10010

Diabetes Care. 2024 Apr 9:dc232336. doi: 10.2337/dc23-2336. Online ahead of print.

ABSTRACT

OBJECTIVE: Whether genetic susceptibility to disease and dietary cholesterol (DC) absorption contribute to inconsistent associations of DC consumption with diabetes and cardiovascular disease (CVD) remains unclear.

RESEARCH DESIGN AND METHODS: DC consumption was assessed by repeated 24-h dietary recalls in the UK Biobank. A polygenetic risk score (PRS) for DC absorption was constructed using genetic variants in the Niemann-Pick C1-Like 1 and ATP Binding Cassettes G5 and G8 genes. PRSs for diabetes, coronary artery disease, and stroke were also created. The associations of DC consumption with incident diabetes (n = 96,826) and CVD (n = 94,536) in the overall sample and by PRS subgroups were evaluated using adjusted Cox models.

RESULTS: Each additional 300 mg/day of DC consumption was associated with incident diabetes (hazard ratio [HR], 1.17 [95% CI, 1.07-1.27]) and CVD (HR, 1.09 [95% CI, 1.03-1.17]), but further adjusting for BMI nullified these associations (HR for diabetes, 0.99 [95% CI, 0.90-1.09]; HR for CVD, 1.04 [95% CI, 0.98-1.12]). Genetic susceptibility to the diseases did not modify these associations (P for interaction ≥0.06). The DC-CVD association appeared to be stronger in people with greater genetic susceptibility to cholesterol absorption assessed by the non-high-density lipoprotein cholesterol-related PRS (P for interaction = 0.04), but the stratum-level association estimates were not statistically significant.

CONCLUSIONS: DC consumption was not associated with incident diabetes and CVD, after adjusting for BMI, in the overall sample and in subgroups stratified by genetic predisposition to cholesterol absorption and the diseases. Nevertheless, whether genetic predisposition to cholesterol absorption modifies the DC-CVD association requires further investigation.

PMID:38593324 | DOI:10.2337/dc23-2336

Clin Pharmacol Drug Dev. 2024 Apr 9. doi: 10.1002/cpdd.1399. Online ahead of print.

ABSTRACT

Fixed-dose combination (FDC) therapies can enhance patient convenience and adherence to prescribed treatment regimens. Elagolix is a novel oral gonadotropin-releasing hormone receptor antagonist approved for management of moderate to severe pain associated with endometriosis and heavy menstrual bleeding associated with uterine fibroids. Hormonal add-back therapy can attenuate the reversible hypoestrogenic effects of elagolix. An FDC formulation containing elagolix/estradiol (E2)/norethindrone acetate (NETA) 300/1/0.5 mg as the morning dose and an elagolix 300 mg capsule as the evening dose, were evaluated in 2 bioequivalence studies including the effects of food. Study 1 in premenopausal women assessed the bioavailability of the elagolix 300-mg capsule relative to the commercially available elagolix 300-mg tablet. Study 2 in postmenopausal women, elagolix/E2/NETA (300 mg/1 mg/0.5 mg) FDC capsule was assessed relative to the elagolix 300-mg tablet coadministered with E2/NETA 1-mg/0.5-mg tablet, the regimen that was studied in Phase 3 uterine fibroid studies. Under fasting conditions, the test elagolix 300-mg capsule was bioequivalent to the reference elagolix 300-mg tablet. Under fasting conditions, the elagolix/E2/NETA FDC capsule was bioequivalent to the coadministered elagolix 300-mg tablet and E2/NETA 1/0.5-mg tablet. Following administration of elagolix/E2/NETA FDC capsule after a high-fat breakfast, elagolix mean maximum concentration (C_max) and area under the plasma concentration-time curve (AUC) were 38% and 28% lower, relative to fasting conditions. NETA mean C_max was 51% lower and AUC from time 0 to infinity was 20% higher, while baseline-adjusted total estrone mean C_max and AUC were 46% and 14% lower, respectively. No safety concerns were identified. These results enabled bridging the elagolix/E2/NETA FDC capsule.

PMID:38593267 | DOI:10.1002/cpdd.1399

J Magn Reson Imaging. 2024 Apr 9. doi: 10.1002/jmri.29368. Online ahead of print.

ABSTRACT

BACKGROUND: Improved characterization of healthy muscle aging is needed to establish early biomarkers in age-related diseases.

PURPOSE: To quantify age-related changes on multiple MRI and clinical variables evaluated in the same cohort and identify correlations among them.

STUDY TYPE: Prospective.

POPULATION: 70 healthy subjects (30 men) from 20 to 81 years old.

FIELD STRENGTH/SEQUENCE: 3T/water T₂ (multiecho SE, multi-TE STEAM), water T₁ (GRE MR Fingerprinting), fat-fraction (multiecho GRE, multi-TE STEAM), carnosine (PRESS), multicomponent water T₂ (ISIS-CPMG SE train), and ³¹P pulse-acquire spectroscopy.

ASSESSMENT: Age- and sex-related changes on: Imaging: fat-fraction (FF_MRI), water T₁ (T_1-H2O), and T₂ (T_2-H2O-MRI) and their heterogeneities ΔT_1-H2O and ΔT_2-H2O-MRI in the posterior compartment (PC) and anterior compartment (AC) of the leg. ¹H spectroscopy: Carnosine concentration, pH, water T₂ components (T_2-H2O-CPMG), fat-fraction (FF_MRS), and water T₂ (T_2-H2O-MRS) in the gastrocnemius medialis. ³¹P spectroscopy: Phosphodiesters (PDE), phosphomonoesters, inorganic phosphates (Pi), and phosphocreatine (PCr) normalized to adenosine triphosphate (ATP) and pH in the calf. Clinical evaluation: Body-mass index (BMI), gait speed (GS), plantar flexion strength, handgrip strength (HS), HS normalized to wrist circumference (HS_norm), physical activity assessment.

STATISTICAL TESTS: Multilinear regressions with sex and age as fixed factors. Spearman correlations calculated between variables. Benjamini-Hochberg procedure for false positives reduction (5% rate). A P < 0.05 significance level was used.

RESULTS: Significant age-related increases were found for BMI (ρ_Age = 0.04), HS_norm (ρ_Age = -0.01), PDE/ATP (ρ_Age = 2.8 × 10^-3), Pi/ATP (ρ_Age = 2.0 × 10^-3), Pi/PCr (ρ_Age = 0.3 × 10^-3), T_2-H2O-MRS (ρ_Age = 0.051 msec), FF_MRS (ρ_Age = 0.036) the intermediate T_2-H2O-CPMG component time (ρ_Age = 0.112 msec), and fraction (ρ_Age = -0.3 × 10^-3); and in both compartments for FF_MRI (ρ_Age = 0.06, PC; ρ_Age = 0.06, AC), T_2-H2O-MRI (ρ_Age = 0.05, PC; ρ_Age = 0.05, AC; msec), ΔT_2-H2O-MRI (ρ_Age = 0.02, PC; ρ_Age = 0.02, AC; msec), T_1-H2O (ρ_Age = 1.08, PC; ρ_Age = 1.06, AC; msec), and ΔT_1-H2O (ρ_Age = 0.22, PC; ρ_Age = 0.37, AC; msec). The best age predictors, accounting for sex-related differences, were HS_norm (R² = 0.52) and PDE/ATP (R² = 0.44). In both leg compartments, the imaging measures and HS_norm were intercorrelated. In PC, T_2-H2O-MRS and FF_MRS also showed numerous correlations to the imaging measures. PDE/ATP correlated to T_1-H2O, T_2-H2O-MRI, ΔT_2-H2O-MRI, FF_MRI, FF_MRS, the intermediate T_2-H2O-CPMG, BMI, Pi/PCr, and HS_norm.

DATA CONCLUSION: Our multiparametric MRI approach provided an integrative view of age-related changes in the leg and revealed multiple correlations between these parameters and the normalized HS.

LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

PMID:38593265 | DOI:10.1002/jmri.29368

J Refract Surg. 2024 Apr;40(4):e260-e269. doi: 10.3928/1081597X-20240311-07. Epub 2024 Apr 1.

ABSTRACT

PURPOSE: To compare the parameters of three different topographic devices (Pentacam HR, Oculus Optikgeräte GmbH; Sirius, Costruzione Strumenti Oftalmici; and Cassini, i-Optics) in grading the severity of keratoconus in cross-linked and non-cross-linked eyes.

METHODS: This was a prospective comparative interventional study done in a tertiary eye care center, wherein 114 eyes of 68 patients with keratoconus were divided into two groups: 62 eyes that were observed and 52 eyes that were cross-linked. All eyes were evaluated on all three topographers at baseline, 3-month follow-up, and 6-month follow-up.

RESULTS: The Sirius showed significantly lower values of mean flat keratometry in comparison to the Pentacam HR (limits of agreement [LoA]: 1.75 to 3.51%) and Cassini (LoA: 1.75 to 3.51%). The mean steep keratometry values were higher for the Cassini in comparison to the Pentacam HR (LoA: 4.39 to 7.02%) and Sirius (LoA: 3.51 to 6.14%). The mean steep keratometry values of the Sirius were significantly lower than those of the Pentacam HR and in both the cross-linked and observation groups (LoA: 3.51 to 6.14%). The mean keratometry values were significantly higher in the Cassini compared to the Pentacam HR (LoA: 3.51 to 8.77%) and significantly lower in the Sirius in comparison to the Pentacam HR (LoA: 3.51 to 6.14%). The mean difference in astigmatism was also statistically significant between the three tomographers in both groups, with the Cassini showing higher values (LoA: 3.51 to 5.26%) and the Sirius lower values than the Pentacam HR (LoA: 5.26 to 6.14%).

CONCLUSIONS: The authors conclude the three devices cannot be used interchangeably. The Cassini showed better agreement and correlation with the Pentacam HR in the staging of keratoconus, whereas the Sirius tended to underdiagnose and under-stage the disease. [J Refract Surg. 2024;40(4):e260-e269.].

PMID:38593263 | DOI:10.3928/1081597X-20240311-07

J Refract Surg. 2024 Apr;40(4):e199-e207. doi: 10.3928/1081597X-20240214-01. Epub 2024 Apr 1.

ABSTRACT

PURPOSE: To investigate the efficacy of incorporating Generative Adversarial Network (GAN) and synthetic images in enhancing the performance of a convolutional neural network (CNN) for automated estimation of Implantable Collamer Lens (ICL) vault using anterior segment optical coherence tomography (AS-OCT).

METHODS: This study was a retrospective evaluation using synthetic data and real patient images in a deep learning framework. Synthetic ICL AS-OCT scans were generated using GANs and a secondary image editing algorithm, creating approximately 100,000 synthetic images. These were used alongside real patient scans to train a CNN for estimating ICL vault distance. The model’s performance was evaluated using statistical metrics such as mean absolute percentage error (MAPE), mean absolute error (MAE), root mean squared error (RMSE), and coefficient of determination (R²) for the estimation of ICL vault distance.

RESULTS: The study analyzed 4,557 AS-OCT B-scans from 138 eyes of 103 patients for training. An independent, retrospectively collected dataset of 2,454 AS-OCT images from 88 eyes of 56 patients, used prospectively for evaluation, served as the test set. When trained solely on real images, the CNN achieved a MAPE of 15.31%, MAE of 44.68 µm, and RMSE of 63.3 µm. However, with the inclusion of GAN-generated and algorithmically edited synthetic images, the performance significantly improved, achieving a MAPE of 8.09%, MAE of 24.83 µm, and RMSE of 32.26 µm. The R² value was +0.98, indicating a strong positive correlation between actual and predicted ICL vault distances (P < .01). No statistically significant difference was observed between measured and predicted vault values (P = .58).

CONCLUSIONS: The integration of GAN-generated and edited synthetic images substantially enhanced ICL vault estimation, demonstrating the efficacy of GANs and synthetic data in enhancing OCT image analysis accuracy. This model not only shows potential for assisting postoperative ICL evaluations, but also for improving OCT automation when data paucity is an issue. [J Refract Surg. 2024;40(4):e199-e207.].

PMID:38593258 | DOI:10.3928/1081597X-20240214-01

J Refract Surg. 2024 Apr;40(4):e218-e228. doi: 10.3928/1081597X-20240311-02. Epub 2024 Apr 1.

ABSTRACT

PURPOSE: To assess agreement between a new aberrometer (Osiris-T; CSO) employing pyramid wavefront sensor technique and Scheiner-Smirnov aberrometer (OPD-Scan III; Nidek) on measuring ocular, corneal, and internal aberrations in healthy participants.

METHODS: The measurements were conducted three times consecutively by an experienced examiner. The total root mean square (RMS) aberrations, higher order aberration RMS, coma Z₃^±1, trefoil Z₃^±3, spherical aberration Z₄⁰_, and astigmatism II Z₄^±2 up to 7th order were exported in both 4-and 6-mm pupil zones. The parameters between the two devices were statistically compared using the paired t-test, and the differences assessed with Bland-Altman plots and 95% limits of agreement.

RESULTS: This prospective study included 70 right eyes of 70 healthy participants with an average age of 25.94 ± 6.59 years (range: 18 to 47 years). The mean difference in the two devices ranged from 0.01 µm for astigmatism II Z₄^±2 to 0.63 µm for total RMS in 4 mm and from 0.01 to 1.41 µm in 6-mm pupil size. The Bland-Altman analysis of ocular, corneal, and internal aberrations indicated high agreement between the two devices and the maximum absolute values for 95% limits of agreement ranged from 0.03 to 1.06 µm for 4-mm pupil diameters and 0.12 to 1.13 µm for 6-mm pupil diameters.

CONCLUSIONS: The newly developed pyramid wavefront sensor technique aberrometer demonstrated a high agreement with a Scheiner-Smirnov aberrometer when measuring ocular, corneal, and internal aberrations in healthy participants. Thus, the two aberrometers may be considered interchangeable for clinical applications. [J Refract Surg. 2024;40(4):e218-e228.].

PMID:38593257 | DOI:10.3928/1081597X-20240311-02

Cancer Discov. 2024 Apr 9. doi: 10.1158/2159-8290.CD-23-1441. Online ahead of print.

ABSTRACT

Childhood cancer survivorship studies generate comprehensive datasets comprising demographic, diagnosis, treatment, outcome, and genomic data from survivors. To broadly share this data, we created the St. Jude Survivorship Portal (https://survivorship.stjude.cloud), the first data portal for sharing, analyzing, and visualizing pediatric cancer survivorship data. Over 1,600 phenotypic variables and 400 million genetic variants from over 7,700 childhood cancer survivors can be explored on this free, open-access portal. Summary statistics of variables are computed on-the-fly and visualized through interactive and customizable charts. Survivor cohorts can be customized and/or divided into groups for comparative analysis. Users can also seamlessly perform cumulative incidence and regression analyses on the stored survivorship data. Using the portal, we explored the ototoxic effects of platinum-based chemotherapy, uncovered a novel association between mental health, age, and limb amputation, and discovered a novel haplotype in MAGI3 strongly associated with cardiomyopathy specifically in survivors of African ancestry.

PMID:38593228 | DOI:10.1158/2159-8290.CD-23-1441

Blood Adv. 2024 Apr 9:bloodadvances.2023011388. doi: 10.1182/bloodadvances.2023011388. Online ahead of print.

ABSTRACT

Inhibitor development is the most severe complication of hemophilia A care, and is associated with increased morbidity and mortality. The aim of this study was to use a novel IgG epitope mapping method to explore the factor VIII (FVIII)-specific epitope profile in the SIPPET cohort population and to develop an epitope-mapping based inhibitor prediction model. The population consisted of 122 previously untreated patients with severe hemophilia A that were followed-up for 50 days of exposure to FVIII or 3 years, whichever occurred first. Sampling was performed before FVIII treatment and at the end of the follow-up. The outcome was inhibitor development. The FVIII epitope repertoire was assessed by means of a novel random peptide phage-display assay. A LASSO regression model and a random forest model were fitted on post-treatment sample data and validated in pre-treatment sample data. The predictive performance of these models was assessed by the C-statistic and a calibration plot. We identified 27,775 peptides putatively directed against FVIII, which were used as input for the statistical models. The C-statistic of the LASSO and random forest models were good at 0.78 (95%CI: 0.69-0.86) and 0.80 (95%CI: 0.72-0.89). Model calibration of both models was moderately good. Two statistical models, developed on data from a novel random peptide phage display assay, were used to predict inhibitor development before exposure to exogenous FVIII. These models can be used to set up diagnostic tests that predict the risk of inhibitor development before starting treatment with FVIII.

PMID:38593222 | DOI:10.1182/bloodadvances.2023011388