Stomach contents with seeds in avian fossils from the latest early/earliest middle Eocene Messel oil shale (Germany) are surveyed. 20 bird specimens belonging to 10 species with seeds produced by at least 13 different plant species are reported. The fossils provide the earliest direct evidence for avian frugivory and suggest that seed dispersal by neornithine (crown group) birds occurred earlier and was more extensive than currently thought. For the first time, we report seeds in the stomach content of stem group Trogoniformes, which today are important seed dispersers in the New World tropics. Other birds belong to the Galliformes, Gruiformes (Messelornithidae), Coliiformes, Coraciiformes, and the extinct taxa Halcyornithidae and Zygodactylidae. Extant Coraciiformes are predominantly carnivorous, whereas some Galliformes and Gruiformes as well as the Coliiformes today also consume fruits. All reasonably well-preserved seeds appear to be from angiosperms, including specimens identified as Rutaceae, Mastixiaceae, and Vitaceae. Unidentified seeds represent various other plant groups. Several of the arboreal birds ingested seeds of the Vitaceae. This plant family already evolved in the Late Cretaceous, whereas arboreal Neornithes did not radiate before the early Cenozoic. As such, and at least concerning arboreal birds, these fossils provide evidence for the "recruitment hypothesis", which suggests that early Cenozoic seed dispersers exploited an existing diversity of edible fruits.
Idiopathic scoliosis is a common 3D spinal deformity with a global prevalence of 2% to 3% in adolescents. Early detection is crucial for timely intervention and preventing curve progression. Although standing full-spine radiography with Cobb angle measurement remains the diagnostic gold standard, its time-consuming nature limits its utility for large-scale screening. Safe, rapid, and noninvasive screening methods are urgently needed to identify high-risk individuals while reserving x-rays for definitive diagnosis. This study aimed to evaluate the diagnostic accuracy of a custom-developed millimeter-wave imaging system in patients with suspected scoliosis, with radiographic Cobb angle measurement serving as the reference standard, and explore its potential as a first-line screening tool. This prospective diagnostic accuracy study enrolled consecutive outpatients with suspected scoliosis. All participants underwent rapid millimeter-wave imaging scanning (Ka band, 29-40 GHz with no undressing required) followed by standard standing full-spine radiography. Scoliosis was defined as a Cobb angle of 10° or higher. Millimeter-wave images were evaluated using four morphological indicators: (1) shoulder height asymmetry (≥2 cm), (2) trunk lateral shift (≥2 cm), (3) waistline contour asymmetry (≥5°), and (4) lower-limb height difference (≥1 cm). A multiparameter integration strategy classified screening as positive if more than 2 indicators exceeded threshold values. Cobb angle measurements were performed independently by 2 experienced orthopedic surgeons blinded to millimeter-wave image results and each other's assessments. Diagnostic performance metrics (sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy) were calculated according to the STARD (Standards for Reporting of Diagnostic Accuracy Studies) guidelines. A multivariate logistic regression model incorporating the 4 morphological parameters was constructed for receiver operating characteristic curve analysis. Ultimately, 132 participants were included. Radiographic evaluation confirmed 98 (74.2%) cases with scoliosis (Cobb angle≥10°) and 34 (25.8%) negative cases. Millimeter-wave imaging achieved an overall accuracy of 86.4% (114/132; 95% CI 76.5%-94.7%), sensitivity of 85.7% (84/98; 95% CI 75.1%-96.5%), specificity of 88.2% (30/34; 95% CI 70.7%-97.6%), positive predictive value of 95.5%, and negative predictive value of 68.2%. Receiver operating characteristic curve analysis of the multivariate logistic regression model exhibited an area under the curve of 0.862 (95% CI 0.802-0.922), with a sensitivity of 92.9% (91/98) and specificity of 38.2% (13/34). Notably, sensitivity was lower for mild curves (Cobb angle=10°-20°) than for moderate or severe curves (≥20°). Millimeter-wave imaging represents a feasible, rapid, and non-ionizing radiation screening method for scoliosis with good diagnostic accuracy (accuracy=114/132, 86.4%; sensitivity=84/98, 85.7%; specificity=30/34, 88.2%). Its capability to penetrate clothing and rapid scanning time (approximately 2 seconds) make it suitable for large-scale screening applications. As a first-line screening tool, this method identifies high-risk individuals for targeted referral and definitive radiography. It follows the "as low as reasonably achievable" principle, optimizing scoliosis screening and reducing unnecessary radiation exposure.
To address the difficulty of quantifying risks in current automotive styling-design task management, this study proposes a risk identification method for automotive styling design tasks based on an improved FAHP-VIKOR approach. First, the work breakdown structure (WBS) is constructed based on the principle of task modularity, and the risk breakdown structure (RBS) is established through the analysis of factors influencing risk, thereby forming the WBS-RBS coupling matrix for automotive styling design. Then, the improved fuzzy analytic hierarchy process (FAHP) is employed to determine the weights of risk factors such as technical, schedule, and cost risks, while the VlseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method is applied to perform comprehensive ranking that adapts to the multidimensional and dynamic characteristics of styling design risks, thereby enabling quantitative risk assessment and identification. Finally, the design tasks involved in the exterior styling concept-design phase of a certain sport utility vehicle (SUV) model are taken as a case study and compared with the single FAHP method, the FAHP-TOPSIS method and the FAHP-VIKOR method. The results indicate that the proposed approach can classify the 27 core design tasks into high, medium and low risks, and can effectively identifies high-risk nodes such as the front bumper surface, lidar surface, and rear bumper surface. Compared with the other methods, the proposed method produces more stable and reasonable risk identification results and can provide decision-making support for risk management and optimal resource allocation in automotive styling design projects.
To assess the risk of stroke/TIA and progression to atrial fibrillation (AF) in Indian patients with device-detected atrial high-rate episodes (AHRE) lasting less than 24 h. In this single-centre prospective matched cohort study, 109 patients with AHRE < 24 h matched to 109 controls without AHRE on age (+/-5 years), sex, device type, device indication, and CHA2DS2-VASc score. Followed for a minimum of 12 months (mean 18.4 months). The CHA2DS2-VASc score was near-perfectly matched between groups (mean 3.26 vs. 3.29, score distribution chi-square p = 1.00). A stroke or TIA occurred in 7 patients with AHRE versus 1 control (annual rate 4.28% vs. 0.61%; OR 7.41, 95% CI 0.90-61.3; p = 0.020; HR 7.19, 95% CI 0.89-58.48; log-rank p = 0.031). Progression to clinical AF, AHRE ≥ 24 h, atrial flutter, or atrial tachycardia happened in 32 AHRE patients versus 2 controls (annual rate 19.7% vs. 1.2%; OR 22.2, 95% CI 5.17-95.6; HR 19.55, 95% CI 4.6-81.71; log rank p < 0.001). Stroke risk increased with CHA2DS2-VASc score: 2.15% (score 3), 4.16% (score 4), 6.66% (score 5), and 9.5% (score ≥ 6). In this hypothesis-generating study, device-detected AF lasting less than 24 h is associated with a significantly higher risk of stroke/TIA and progression to clinical AF in Indian patients. It requires confirmation in larger studies. Region-specific absolute risks must be considered when applying international anticoagulation guidelines.
Obesity-related type 2 diabetes (DM) is increasing rapidly and at present reaching epidemic proportions in some Worldwide populations. The aim of this study was to provide new knowledge on the interplay between genetic and lifestyle obesity-related risk factors in populations with the highest incidence of obesity-related diabetes could provide an important tool to help prevent or delay diabetes onset in high-risk groups. Community free-living individuals visiting primary health centers were recruited to the study following informed written consent. Demographic and clinical characteristics, physical activity, dietary intake and biological markers of DM were measured at baseline and follow up. Validated questionnaires were used to assess physical activity and dietary intakes. A Cox proportional hazards analysis was used to examine the risk of developing diabetes diagnosed using the WHO cut-of-points criterion of HbA1c ≥ 6.5% at follow after adjusting for known clinical risk indicators. A total of 375 Community free-living locals UAE citizens subjects, 348 (93%) of them females and 253 non-locals' expatriates [187 (73%)] females were recruited and followed up for a period of 427 ± 223 days. Using WHO cut-of-points for diagnosing DM (HbA1c ≥ 6.5%), 31 (6%) subjects out of 545 followed up developed DM. Overall local United Arab Emirates (UAE) citizens reported significantly lower levels of physical activity in comparison to non-local expatriates. The Cox proportional hazard model analysis revealed that being obese, UAE national and physically inactive is associated with a significantly increased risk of DM after adjusting for other prognostic indicators [non-UAE national: Odd ratio (95% CI): 0.13 (0.04, 0.47); p=0.002; physically active: 0.31 (0.11, 0.90); p=0.002]. The Kaplan Meier figures show the significantly increased risk of developing DM in physically inactive local UAE citizens compared with expatriates' residents (p<0.05). In contrast risk of developing DM was no different between physically very active UAE nationals compared to non-nationals at follow up (P>0.5). Our finding suggests that physical inactivity in high-risk groups is the most important risk factor for developing DM. Urgent actions are needed to increase physical activity in this high-risk group coupled with further research to understand the reasons for this striking indigenous population variability.
Primary malignant tumors of the mobile spine are rare but aggressive, and treatment decisions must balance oncologic control against neurologic risk, perioperative morbidity, and reconstruction durability. Because en bloc resection is technically demanding and associated with substantial morbidity, clinically important unanswered questions include which factors are associated with death and local recurrence after surgery, how prior procedure or local recurrence affects outcomes, and how often complications and revision for mechanical instrumentation problems occur. (1) What were the overall survival outcomes after en bloc resection, and which factors were associated with death? (2) What were the local recurrence-free survival outcomes after en bloc resection, and which factors-particularly margin status and prior procedure or local recurrence-were associated with local recurrence? (3) What were the proportions and patterns of perioperative complications, postoperative neurologic deterioration, and revision for mechanical instrumentation problems? We performed a retrospective comparative study using a longitudinally maintained institutional registry at a tertiary referral musculoskeletal tumor center. The study end date was set at December 2023; two patients who underwent surgery after that date were excluded because they no longer met the temporal inclusion criteria. Between August 2007 and December 2023, we included 70 patients with primary malignant tumors of the mobile spine who underwent planned en bloc resection when an oncologically appropriate margin was judged technically feasible and durable local control was expected to provide clinical benefit. Among these 70 patients, 84% (59 of 70) achieved at least 2 years of surveillance, 13% (9 of 70) died within 2 years, and 3% (2 of 70) were lost to follow-up before 2 years for reasons other than death. In addition, 14% (10 of 70) had not been seen within the last 5 years, although 9 of those 10 had already died. The mean ± SD age was 36 ± 17 years, 66% (46 of 70) were male, and chondrosarcoma was the most common histologic subtype, accounting for 33% (23 of 70) of patients. Tumors were staged using the Enneking and Weinstein-Boriani-Biagini systems. Overall survival and local recurrence-free survival were estimated using Kaplan-Meier methods, and factors associated with these outcomes were evaluated using Cox regression. Factors associated with perioperative complications were evaluated using multivariable logistic regression. Overall survival after en bloc resection was 67.0% at 5 years (95% confidence interval [CI] 54.3% to 79.7%). In the multivariable Cox model, high-grade tumor (HR 8.9 [95% CI 1.1 to 70.3]; p = 0.04), marginal margin (HR 4.4 [95% CI 1.1 to 17.5]; p = 0.04), and intralesional margin (HR 11.3 [95% CI 2.8 to 46.1]; p = 0.001) were associated with a higher hazard of death. Local recurrence-free survival was 67.5% at 5 years (95% CI 55.0% to 80.0%), and local recurrence developed in 31% (22 of 70) of patients. In the multivariable Cox model, prior intralesional procedure, open biopsy, or local recurrence (HR 2.9 [95% CI 1.2 to 7.1]; p = 0.02), marginal margin (HR 4.6 [95% CI 1.2 to 17.8]; p = 0.03), and intralesional margin (HR 9.7 [95% CI 2.6 to 36.5]; p = 0.001) were associated with a higher hazard of local recurrence. Perioperative complications occurred in 50% (35 of 70) of patients, including 18 major complication events. Postoperative neurologic deterioration occurred in 17% (12 of 70) of patients and was more frequent in patients with prior procedure or local recurrence than in those with no prior procedure other than core needle biopsy (31% [8 of 26] versus 9% [4 of 44], OR 4.4 [95% CI 1.2 to 16.7]; p = 0.02). Revision for mechanical instrumentation problems occurred in 6% (4 of 70) of patients; all four revisions were performed for posterior rod fracture. Although revision was more frequent in patients reconstructed with titanium mesh cages than in those reconstructed with three-dimensionally-printed vertebral body prostheses (30% [3 of 10] versus 2% [1 of 52], OR 21.9 [95% CI 2.0 to 240.2]; p = 0.01), no anterior column construct failed or required revision. For selected patients with primary malignant tumors of the mobile spine, en bloc resection can provide durable local control, but the likelihood of benefit depends on achieving an oncologically appropriate margin and avoiding unplanned intralesional procedures or open biopsy before referral. These findings support early referral to specialized centers, image-guided biopsy rather than unplanned open procedures, and multidisciplinary planning before definitive surgery. Future multicenter studies should incorporate tumor-specific analyses and longitudinal functional outcomes to better guide patient selection and counseling. Level III, therapeutic study.
To evaluate visual and anatomical outcomes after switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD), and to assess outcomes according to the clinical indication for switching. Multicentre retrospective observational study including 300 eyes with nAMD previously treated with anti-vascular endothelial growth factor therapy and switched to aflibercept 8 mg for non-response (n:74, 24.7%), suboptimal response (n:159, 53.0%), or durability-driven reasons (n:67, 22.3%). Longitudinal data from the 6 months preceding the switch and post-switch visits at 3 and 6 months were analyzed. The primary outcome was change in best-corrected visual acuity (BCVA, ETDRS letters) from the switch visit to the 3-month post-switch visit. Secondary outcomes included changes in central subfield thickness (CST) and retinal fluid status. During the pre-switch period, mean BCVA declined by - 1.9 ± 8.2 letters and CST increased. At 3 months after switching, BCVA improved by + 2.0 ± 9.2 letters (95% CI, + 0.8 to + 3.2; p < 0.01), with greater gains in eyes switched for non-response (+ 2.8 ± 12.6 letters). Mean CST decreased by - 45.3 ± 79.8 µm (95% CI, - 55.4 to - 35.2; p < 0.001), with corresponding reductions in retinal fluid. Anatomical improvements were more pronounced in eyes switched for non-response, whereas more modest but consistent changes were observed in suboptimal and durability-driven groups. Visual and anatomical outcomes were maintained at 6 months. In previously treated nAMD eyes, switching to aflibercept 8 mg was associated with reversal of pre-switch anatomical worsening, reduction in retinal fluid, and modest visual gains. Greater responses were observed in eyes with inadequate pre-switch disease control, supporting its role as a treatment escalation strategy in clinical practice.
Ebeye Hospital is a 60-bed acute care and district hospital in the Republic of the Marshall Islands (RMI). In October 2022, the hospital's Infection Prevention and Control (IPC) Program initiated health care-associated infection and antimicrobial resistance surveillance, along with efforts to promote appropriate antimicrobial use. New National IPC Guidelines call for the institution of appropriate infection control measures (based on the organism identified and site of infection) and adjustment, when needed, of patients' antibiotic regimen within 24 hours of release of multidrug-resistant organism culture results. A descriptive cohort study was conducted on hospital inpatients who tested positive for multidrug-resistant organisms, using program data from October 25, 2022, to December 31, 2023. Each case (n=58) was reviewed to assess: a) the timeliness of initiating infection control measures, and b) the timeliness and appropriateness of antibiotic selection, as guided by the RMI National Antimicrobial Guidelines. Multidrug-resistant organism cases involved a variety of organisms and occurred across all clinical wards. Of these, 35 cases (60%) met IPC standards. The primary reasons for not meeting IPC standards were lack of isolation rooms (n=10, 44%) and failure to meet the IPC initiation criterion per the working definition (n=13, 56%). Only 8 cases (14%) adhered to antibiotic usage guidelines. The most common reasons for non-adherence were prolonged antibiotic duration (n=19, 38%) and shorter-than-recommended duration (n=16, 32%). Management of a substantial proportion of multidrug-resistant cases at Ebeye Hospital failed to meet IPC standards. These findings highlight several areas for improvement.
Hormonal contraceptive (HC) use is common among servicewomen and has been discussed in relation to health, performance, and operational readiness. No systematic data exist on HC prevalence among German servicewomen. This study analyzes contraceptive practices and motivations for contraceptive choice in German servicewomen. A nationwide, cross-sectional online survey was conducted among female members of the German Armed Forces. Recruitment occurred via military institutions and a digital flyer. The anonymous questionnaire (40 items, 10-15 min) assessed demographic characteristics and contraceptive use. Data were cleaned and analyzed using R. Inferential analyses comprised pairwise adjacent comparisons using Fisher's exact test with Holm correction. A total of 2818 servicewomen completed the survey (response rate 11.2%; mean age 33.9 years). Overall, 38.1% reported current HC use. Combined oral contraceptive pills (COCP) were the most common method (18.5%), followed by hormonal intrauterine devices (8.9%) and progestin-only pills (8.4%). HC use declined with increasing age, primarily due to decreasing pill use, although 8% of women ≥40 years still reported COCP use. Systemic long-acting reversible contraceptives (LARC) (implants and injections) were virtually absent. Contraceptive use differed significantly across age- and length-of-service categories, but not BMI categories. Pregnancy prevention was the primary reason for HC use (82%), followed by management of menstrual pain and bleeding. A small proportion reported HC use for performance-related cycle control (13%) or masking of amenorrhea (2%). Deployment-related switching to HC was uncommon. HC use among German servicewomen appears low compared with reports from British and U.S. militaries. Given evidence linking certain systemic LARC formulations to potential effects on bone metabolism, the low prevalence warrants further investigation in the context on musculoskeletal health and injury risk in a population exposed to high mechanical loading. Preventive efforts in the German military should consider a broader range of modifiable risk factors, including nutrition and training load. The findings may indicate potential gaps in military-specific education and counseling regarding informed contraceptive choice, occupational implications of different methods, and age-related hormonal management. The response rate and the limited scope of certain questionnaire items should be considered when interpreting the results.
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Biologic therapies for patients with inflammatory bowel disease (IBD) were approved via large randomized controlled trials (RCTs) with strict criteria for patient enrollment. As newer IBD medications are approved, ongoing assessment is necessary to determine whether RCT eligibility criteria are too restrictive or adequately reflect real-world practice. Here, we investigate the trial-eligibility and clinical outcomes of patients with ulcerative colitis (UC) started on vedolizumab (VDZ) and ustekinumab (UST) therapy. This single-center retrospective cohort study at a large academic IBD referral center included patients with UC who received a new prescription for UST or VDZ between January 2020 and June 2023. The primary outcome assessed whether patients met trial eligibility using the inclusion and exclusion criteria from the UNIFI and GEMINI-1 RCTs. We also assessed treatment failure between the trial-eligible and ineligible groups. Only 19/168 (11.3%) of patients with UC (n = 85 receiving VDZ; n = 83 receiving UST) were trial-eligible. The most common reasons for ineligibility were prior biologics and inadequate wash-out periods, the use of topical therapy, medical comorbidities and ongoing treatment with high doses of prednisone. Treatment failure was numerically higher in trial-ineligible compared to trial-eligible patients, though this difference was not statistically significant. Most patients initiated on UST or VDZ would not have qualified for inclusion in their respective RCTs, largely due to current treatments. Revising trial eligibility criteria may be warranted to improve external validity and enable recruitment of a more diverse study population representative of real-world patients.
Perihilar cholangiocarcinoma (pCCA) is a highly aggressive malignancy that persists even after curative resection. Although serum gamma-glutamyl transferase (GGT) is associated with cancer prognosis, most studies have evaluated its prognostic role only at a single time point. However, the prognostic value of perioperative dynamic trajectories remains unclear. To evaluate perioperative GGT trajectories as prognostic markers in patients with pCCA undergoing radical resection. This retrospective multicentre study included 765 patients with pCCA who underwent curative resection at two centres. Perioperative GGT trajectories were modelled using latent class mixed models. Patients were categorised according to trajectory patterns, and associations with overall survival (OS) were evaluated using multivariate Cox regression with clinical covariates. Model discrimination was assessed using time-dependent receiver operating characteristic analysis. Two distinct perioperative GGT trajectories were identified: flat and V-shaped. The model showed an adequate fit (Bayesian Information Criterion (BIC) = 35818.61) and good classification quality (entropy = 0.69). The two classes accounted for 48.32% and 51.68% of the patients, respectively. Patients in the flat trajectory group had significantly longer OS (HR = 0.603, 95% CI: 0.450-0.808, p < 0.001), independent of other factors. The model yielded AUCs of 0.729 (0.658-0.801) and 0.805 (0.721-0.881) for 3- and 5-year OS, respectively. Perioperative GGT trajectories independently predicted pCCA prognosis. Monitoring GGT dynamics may offer a simple and practical tool for postoperative risk stratification. Changes in a routine blood test around surgery may help predict survival after surgery for perihilar cholangiocarcinoma Perihilar cholangiocarcinoma is a rare and aggressive cancer of the bile ducts. Surgery is currently the only treatment that can offer long-term survival, but outcomes vary widely between patients. For this reason, doctors are interested in simple ways to estimate a patient’s risk after surgery. Gamma-glutamyl transferase (GGT) is a routine blood test related to liver function and is commonly measured before and after surgery. Most previous studies have examined GGT at a single time point. In clinical practice, however, GGT levels often change during the perioperative period, and it is uncertain whether these changes are related to patient survival. In this retrospective multicentre study, we analysed data from 765 patients who underwent curative surgery for perihilar cholangiocarcinoma at two hospitals. We examined how GGT levels changed from before surgery to the early postoperative period and grouped patients according to similar patterns over time. We then assessed whether these patterns were associated with overall survival, taking other clinical factors into account. Two main patterns of GGT change were identified. One group showed relatively stable GGT levels, while the other showed a V-shaped pattern, with levels decreasing and then rising after surgery. Patients with stable GGT levels generally survived longer after surgery, even after adjustment for other factors. The model showed reasonable performance in predicting survival at three and five years. These findings suggest that changes in GGT over time may provide useful information beyond a single measurement. Because GGT testing is simple and widely available, monitoring perioperative GGT trends may help support postoperative risk assessment in patients with this disease.
Worldwide, pull through is uncommon in patients with cloacal exstrophy due to heterogeneous outcomes, however it is frequently performed at our center. We characterized this population and their longitudinal outcomes. A review of a prospectively maintained database (1981-present) of patients with cloacal exstrophy was conducted, noting demographics, associated anomalies, surgical history, and outcomes at most recent follow up. There were 91 patients with cloacal exstrophy (67 classic, 24 covered). Pull through, offered based on trial of bowel management through the stoma, was performed in 58 patients (63.7%) at median age 2.46 years (IQR 1.44, 5.08). The most frequent reasons to not undergo pull through were failed stoma bowel management (39.4%) and patient/family preference (33.3%). Outcomes, assessed at median 4.84 years post pull through, were reported in 40/58 patients, among which 36 were clean for stool or continent and 4 patients underwent reversal. With preservation of colon and incorporation into the gastrointestinal tract at initial operation, followed by successful bowel management through the stoma, a pull through was performed in 63.7% of patients. Candidacy for pull through should be assessed, ideally prior to, or concurrent with, bladder reconstruction.
To develop and validate a nomogram using routine admission indicators to predict total bilirubin on day 7 (TBil-Day7) in hepatitis B virus-related liver cirrhosis (HBV-LC) patients, enabling early identification of inadequate short-term TBil response and providing a reference for intensive treatment. We retrospectively enrolled 284 HBV-LC patients, randomly assigned 7:3 to training (n=198) and internal validation (n=86) cohorts. Candidate variables were clinical and laboratory parameters available within 24 hours of admission, with TBil-Day7 as the outcome. Predictors were selected via least absolute shrinkage and selection operator (LASSO) regression, and a multiple linear regression model was built and visualized as a nomogram. Model performance was evaluated using the coefficient of determination (R2), root mean square error (RMSE), mean absolute error (MAE), and the proportion of predicted values falling within ±20 μmol/L of the observed TBil-Day7 values. LASSO regression identified four predictors: admission TBil, direct bilirubin (DBil), aspartate aminotransferase (AST), and international normalized ratio (INR). The prediction equation was: TBil-Day7 (μmol/L) = -23.0159 + 0.5721×TBil + 0.5847×DBil + 0.0601×AST + 14.0707×INR. The training cohort had an R2 of 0.932. In the internal validation cohort, R2=0.75, RMSE=38.06 μmol/L, MAE=21.27 μmol/L, and 74.4% of predictions were within ±20 μmol/L of actual values. The calibration curve showed good agreement between predicted and observed TBil-Day7. This nomogram, incorporating four routine admission indicators (TBil, DBil, AST, INR), can predict TBil-Day7 in HBV-LC patients with reasonable accuracy. It facilitates early identification of high-risk patients with insufficient TBil decline and allows estimation of short-term treatment response at admission.
Sports and race betting are high-risk gambling activities used by young adults, yet limited research has examined how motives relate to outcomes assessed separately for each betting activity. This online survey examined associations between sports- and race-specific betting motives (enhancement, financial, social, coping) and betting expenditure, problem severity, and harm among young Australian adults. The sample comprised 188 participants aged 18-30 years (84.6% male; Mage= 24.11), including 185 sports betting participants and 127 race betting participants (defined as ≥2 bets in the past month and in a typical month over the past year). Separate linear regressions showed that financial motives were positively associated with sports betting expenditure (β = .16, p = .006), with no associations for race betting expenditure. Financial and coping motives were independently, positively associated with sports and race betting problem severity (sports: financial β = .34; coping β = .39; race: financial β = .19; coping β = .46) and harm (sports: financial β = .23; coping β = .47; race: financial β =.22; coping β = .49) in multivariable models (all p ≤ .004), demonstrating small-to-moderate associations for financial motives and moderate associations for coping motives. At the univariable level, social motives were positively associated with sports betting problem severity (β = .19, p= .007), and enhancement motives were positively associated with race betting problem severity (β = .32, p= .001). Findings highlight financial and coping motives as potential targets for early identification and prevention of harmful betting among young adults.
Cannabis use is increasing, even during pregnancy. The purpose of this study was to investigate how women of childbearing age perceive the safety of cannabis use during pregnancy compared to alcohol and tobacco use. Cloud Research recruited a national U.S. cohort of women of childbearing age (N = 622) to complete an anonymous online survey assessing cannabis, alcohol, and tobacco use during pregnancy. Validated tools measured perceptions of safety and risks to fetal, birth, and infant development. Data analyses included descriptive statistics, McNemar's tests, and repeated-measures ANOVA with post-hoc comparisons. The average age was 29.47 years (SD = 6.83, range: 18-42). Participants self-identified as White (65.9%, n = 410), Black or African American 28.1% (n = 175), Asian 5.9% (n = 37), American Indian or Alaska Native 3.9% (n = 24), or Other 4.7% (n = 29); 17.7% (n = 110) identified as Hispanic or Latino. Most participants identified as heterosexual (82.0%, n = 510). Among participants who had been pregnant (N = 351), 25.9% reported cannabis use during pregnancy, compared with 23.6% for tobacco and 8.2% for alcohol. The median frequency of prenatal cannabis use was twice weekly, with joints and blunts being the most common methods. Reported reasons for use included relief of nausea, anxiety, sleep disturbance, and pain. We used a five-point Likert scale to determine whether they thought cannabis, alcohol, and tobacco were safe to use during pregnancy, where 1 = not at all safe, and 5 = completely safe. Prenatal cannabis use was rated as safer (M = 3.85, SD = 1.46) than alcohol. (M = 4.86, SD = 0.54, p < .001) or tobacco (M = 4.79, SD = 0.63, p < .001). Findings indicate that women of childbearing age perceive cannabis as relatively safe during pregnancy, particularly for symptom management. These perceptions underscore the need for targeted education, accurate messaging, and consideration of the social, cultural, and emotional factors that influence substance use during pregnancy to safeguard maternal and fetal health.
Does direct warming preserve embryonic developmental competence and molecular integrity as well as conventional multi-step warming in vitrified human and mouse cleavage-stage embryos? Direct warming yielded comparable developmental and molecular outcomes to conventional warming in both mouse and human cleavage-stage embryos. Conventional embryo warming uses stepwise cryoprotectant dilution to minimize toxicity and osmotic shock. Direct warming methods have been proposed, but their impact on post-warming development and the molecular comparison remains unclear. This is a controlled experimental study conducted over 18 months. A total of 490 vitrified mouse embryos and 15 donated human embryos were tested either in direct or conventional warming group. A subset underwent embryo transfer and follow-up. Parallel transcriptomic and DNA methylation profiling was performed on mouse and donated human embryos. Mouse cleavage-stage embryos (C57BL/6J) were vitrified and randomly assigned to direct (n = 265) or conventional (n = 225) warming. Post-warming survival and blastocyst formation were assessed in vitro. A subset (n = 211) underwent embryo transfer to evaluate implantation, live birth, and postnatal development to Day 21. For molecular analysis, pooled mouse embryos from fresh, conventional, and direct groups were analyzed by bulk RNA-seq and bisulfite sequencing. Ten vitrified human embryos (n = 5 per group) were analyzed individually by scRNA-seq and scBS-seq. All procedures were conducted under standard IVF lab conditions with ethical approval. Direct warming in mouse achieved comparable survival (95.8% vs 93.8%), blastocyst formation (88.6% vs 88.2%), implantation (82.5% vs 83.0%), and live birth rates (69.6% vs 71.1%) to conventional warming (all P > 0.05). Offspring showed similar growth, developmental milestones, and organ histology. Mouse transcriptome and methylome profiles revealed minimal differences and no significant pathway enrichment. In human embryos, ion channel-related gene variability was observed but without coordinated pathway disruption. Global methylation levels remained within expected developmental ranges. N/A. While the mouse model enables in vivo validation, species-specific differences in embryo size, membrane properties, and development may limit generalizability. As all embryos were cultured under optimized conditions, caution is advised when extrapolating to diverse clinical settings. To our knowledge, this is the first study to provide multi-level evidence supporting the safety and efficacy of direct warming as an alternative to conventional multi-step embryo warming protocols. By incorporating in vivo reproductive outcomes, postnatal development, and molecular profiling, it strengthens current evidence on the feasibility of this approach. The absence of pathway-level disruptions in transcriptome and methylome datasets suggests that direct warming does not impair essential developmental programs. These findings may support the clinical use of simplified warming procedures, especially for cleavage-stage embryo transfer or in resource-limited settings. However, further clinical studies are warranted to confirm long-term safety in humans. This work was supported by Collaborative Research Fund (CRF-C4007-24E), and Early Career Scheme (ECS-26103623) from the University Grants Committee (UGC), and Health and Medical Research Fund (HMRF 12230736) from the Hong Kong Government. The authors report no competing interests. N/A.
Hemorrhagic shock (HS) remains a leading cause of trauma-related mortality, primarily due to severe hypovolemia and systemic hypoperfusion. These pathophysiological changes may profoundly affect the pharmacokinetics of fentanyl, an opioid widely used for analgesia in trauma care. Previous studies, predominantly based on fixed-pressure shock models, may not adequately reflect clinically relevant hemodynamic conditions. Therefore, we employed a fixed-volume HS model as an alternative approach to reflect hypovolemia-associated perfusion deficits influencing fentanyl disposition. This study aimed to evaluate the pharmacokinetics of fentanyl and its primary metabolite, norfentanyl, in an experimental model of fixed-volume HS. Male Wistar rats were randomly divided into two groups: a control group (C; n = 6) and a fixed-volume hemorrhagic shock group (HS; n = 6). In the HS group, hemorrhage was induced by withdrawal of 30% of the estimated blood volume (EBV) following vascular cannulation. Fentanyl (10 µg/kg) was administered intravenously, and serial blood samples were collected over 60 min. The concentrations of plasma fentanyl and norfentanyl were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Pharmacokinetic parameters were calculated using Phoenix WinNonlin software. Non-compartmental analysis demonstrated significantly increased systemic exposure to fentanyl in the HS group, reflected by higher area under the concentration-time curve (AUC0-∞ and AUC0-t) values, accompanied by a marked reduction in systemic clearance (CL). Mean residence time (MRT) and terminal elimination half-life (t½λz) were significantly prolonged. Compartmental analysis confirmed a more than two-fold increase in fentanyl exposure, driven primarily by reduced clearance and prolonged elimination. In contrast, peak plasma concentrations (Cmax) showed only a borderline increase, and no statistically significant differences were detected in distribution-related parameters. These findings suggest that the major detectable pharmacokinetic changes associated with HS were primarily related to impaired fentanyl elimination. The metabolic conversion ratio (MCR), defined as the ratio of norfentanyl AUC0-t to fentanyl AUC0-t, was lower in the HS group (0.117) compared with controls (0.197). HS significantly alters fentanyl pharmacokinetics in rats by reducing clearance and increasing systemic exposure. The lower norfentanyl-to-fentanyl AUC0-t ratio suggests that HS may also affect metabolite formation or disposition.
Contact lens (CL) wear may induce changes to the tear film, leading to sensations of ocular dryness and CL discomfort, key reasons for CL discontinuation. CL care solutions can help address underlying mechanisms of CL discomfort, improving wear experience. We report outcomes of an in-home use test of Biotrue® Hydration Plus Multi-Purpose Solution (BHP MPS; Bausch + Lomb, Rochester, NY, USA), which is formulated to maintain ocular surface homeostasis and improve CL comfort. In this IRB-approved, real-world survey study, adult soft CL users used BHP MPS for 7 days before completing a survey rating their experience (agreement/disagreement for attributes including CL cleanliness, comfort [including during extended screen use], prevention of CL dryness, perception of CL hydration, gentleness on eyes, and likelihood to recommend to others). A power analysis estimated sample size for 80% statistical power. Responses were analyzed with 2-sided exact binomial tests for agreement in >50% of responses (significance level α=0.05). Participants (N=435) were demographically balanced (mean age 42.5 years; 52.9% female). Over 60% of participants reported baseline CL dryness and tired eyes; 8.0% were likely to discontinue CL wear. At the end of the trial period, 98.9% were satisfied with how their CLs felt. Individual responses were significantly >50% for all attributes (p<0.05), including 91.7% agreeing that BHP MPS positively impacted CL comfort (and helped to keep CLs feeling clean [96.8%], keep CLs comfortable so that eyes do not feel tired [93.1%], maintain CL comfort [94.7%], prevent CL dryness [93.6%], maintain comfort with extended screen use [92.0%], and maintain hydration [94.7%] while being gentle on eyes [96.6%]); 94.0% would recommend BHP MPS to other CL wearers. No adverse events were reported. BHP MPS demonstrated strong performance across all key criteria evaluated in this real-world cohort of soft CL wearers for improved CL wear experience. Comfort is important to keep people wearing their contact lenses, but some people stop wearing them because their eyes feel uncomfortable and dry over time. For reusable contact lenses especially, the choice of lens cleaning and care solution is important to help keep lenses feeling comfortable. Biotrue® Hydration Plus Multi-Purpose Solution (BHP MPS; Bausch + Lomb, Rochester, NY, USA) is a unique contact lens solution with ingredients that help clean and remove spots off the lenses, which may help keep the eye healthy and help the contact lenses feel more comfortable. The BHP MPS ingredients were chosen based on scientific research and advice from experts. This study looked at how using BHP MPS in daily life made people feel. The study included 435 people who regularly wore reusable contact lenses. Overall, these people agreed that BHP MPS helped keep their contact lenses clean and comfortable, was gentle on their eyes, and stopped their lenses from feeling dry, even if they were using a screen, like a computer, for a long time. Nearly everyone in the study agreed they would recommend BHP MPS to others who wear contact lenses. This study showed that BHP MPS can help reusable contact lens wearers, improving the way people’s eyes feel. This real-life study is important because it builds on what we already know about BHP MPS from other studies and helps people who wear contact lenses and their eye care doctors choose the right contact lens solution to use.
What is the current good practice in the IVF laboratory, based on the best available evidence in the literature, if available, and the expertise of the working group? The updated ESHRE Recommendations on Good Practice in the IVF laboratory provides recommendations on all activities in the IVF laboratory. A previous version of the Good Practice in the IVF laboratory guideline was published in 2015. The adoption of new techniques, the increasing complexity of procedures, and the introduction of a revised European legislation on the quality and safety of tissues and cells for human application pertinent to assisted reproduction together necessitated an update of the document. This document was developed according to a predefined methodology for ESHRE Good Practice recommendations. The working group reviewed the document of 2015, and based on this assessment, each group member updated one or more sections. Recommendations are supported by data from the literature, if available, and the expertise of the working group and were discussed until consensus was reached within the working group. The working group included 10 members representing the ESHRE Special Interest Groups for Embryology, Safety and Quality, and Andrology, with different areas of expertise and representing different European countries and settings. Based on the available evidence and the expertise of the working group, recommendations were formulated. Following stakeholder review of the initial draft, the final version was approved by the working group and ultimately by the ESHRE Executive Committee. The ESHRE IVF labs working group updated the recommendations on the general organization of an IVF laboratory (staffing and direction, quality management, and laboratory safety) and on the specific aspects of the procedures performed in IVF laboratories (identification of patients and traceability of their reproductive cells, consumables, handling of biological material, oocyte retrieval, sperm preparation, insemination of oocytes, scoring for fertilization, embryo culture and transfer, embryo biopsy for pre-implantation genetic testing, cryopreservation, and emergency procedures). The section on embryo culture and transfer was split up, the section on sperm preparation was expanded to cover all general andrological procedures, and a new section on biopsy procedure was introduced. Not all recommendations are supported by evidence. Other recommendations, published in legal documents, relevant and recent documents, manuals, and consensus papers, were taken into account when formulating the recommendations. The guideline group is confident that this document will be helpful to directors and managers involved in the management and organization of IVF laboratories and also to embryologists and laboratory technicians performing daily tasks. The guideline was developed by ESHRE, which funded the guideline meetings, literature searches, and dissemination of the guideline. The guideline group members did not receive any financial incentives; all work was provided voluntarily. G.C. reports consulting fees from Gedeon Richter and Cooper Surgical and was part of the working group of the 'Guide to the quality and safety of tissues and cells for human application' of the European Directorate for the Quality of Medicines and Healthcare, on behalf of the Council of Europe. T.E. reports consulting fees from Nexpring Health and Esco Medical and speaker's fees from Nexpring Health and Esco Medical. J.K.-B. reports research grants from Gates Foundation and NIHR, consulting fees from Bayer, speakers fees from Merck, IBSA, Ferring and Cooper Surgical, and travel support from Merck, IBSA, Ferring, and Cooper Surgical. I.S. reports speaker's fees from Vitrolife and Cooper Surgical. I.S. also declares being a member of ARCS Scientific Committee. The other authors disclosed no conflicts of interest. This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (full disclaimer available at www.eshre.eu/guidelines).