Generalized Linear Models Research Articles

279 Effect of multiple feed additives on sow inflammatory status and reproductive performance during lactation

Abstract Low grade inflammation and insulin resistance were associated with increased gut permeability in lactating sows during the farrowing transition period. The objective of the present study is to investigate the effect of 4 feed additives including monolaurin, essential oil (Cinergy FIT 3S), phytogenic prototype 1 (PT1) and 2 (PT2) on sow inflammatory status and reproductive performance. It was hypothesized that the active components in these additives will reduce sow inflammation during lactation and lead to better sow reproductive performance. A randomized block design with 5 treatments was used in the study. A total of 550 gestating sows were enrolled with entry body weight of 240.1 ± 14.6 kg and allotted to one of the following five diets: Control; monolaurin; Cinergy; PT1 and PT2. Corn-soy based lactation diet was formulated with CP of 18%. All diets were formulated to be at similar net energy and standardized ileal digestible Lysine level. Experimental diets were fed beginning approximately 4 d before farrowing and throughout the entire lactation phase (21 d). Blood was collected from 16 sows per treatment before farrowing and within 5 d post farrowing to measure inflammatory cytokine concentrations. Performance data were analyzed using a general linear model in R (version 4.0.0). Count data were analyzed using a generalized linear model with a binomial distribution. Dietary treatments did not impact average daily feed intake. Dietary treatment did not affect probability of still born or number of weaned pigs, but diet supplemented with PT1 resulted in greater (P < 0.05) probability of born alive compared with the control (Table 1). There was a tendency (P < 0.10) in treatment effect on pre-weaning mortality, with sows received PT2 supplemented diet having lowest value numerically. The concentration of cytokines IL-1α (P < 0.05), IL-1β (P < 0.01), IL-4 (P < 0.01), IL-6 (P < 0.10) and IL-10 (P < 0.10) were reduced between pre and post farrowing to a greater extent in sows fed Cinergy supplemented diet compared with the control. In conclusion, Cinergy worked best in reducing multiple inflammatory cytokine concentrations post-farrowing. Sows received PT1 supplemented diet had greater born alive and those received PT2 supplemented diet had numerically least pre-weaning mortality.

Exploring Flexural Strength Variation in Polymeric Materials for Provisional Fixed Prosthetic Structures: Comparative Analysis with and without Reinforcement through Laboratory Experimentation and Statistical Evaluation

Provisional fixed partial dentures represent a critical phase in dental treatment, necessitating heightened mechanical durability, particularly in comprehensive and extended treatment plans. Strengthening these structures with various reinforcing materials offers a method to enhance their resilience. Utilizing a three-point testing methodology on standardized trial specimens allows for a comparative assessment of various materials and reinforcement techniques for pre-prosthetic applications. This study aims to validate and assess the significance of integrating different reinforcing materials into standardized test bodies. The study focuses on test specimens comprising three types of unreinforced laboratory and clinical polymers for provisional constructions (n = 6)—heat-cured PMMA (Superpont C+B, Spofa Dental, Czech Republic), CAD-CAM prefabricated PMMA (DD temp MED, Dental Direkt, Germany), CAD-CAM printing resin (Temporary CB Resin, FormLabs, USA), self-polymerizing PEMA (DENTALON plus, Kulzer, Germany), light-polymerizing composite (Revotek LC, GC, Japan), and dual-polymerizing composite (TempSpan, Pentron, USA). Additionally, laboratory polymers are evaluated in groups with five types of reinforcing filaments (n = 15)—Glass Fiber (Fiber Splint One-Layer, Polydentia, Switzerland), Polyethylene thread (Ribbond Regular 4.0 mm, Ribbond Inc., USA), triple-stranded chrome-cobalt wire for splinting 015″ (Leone S.p.a., Italy), Aesthetic ligature wire 012″ (Leone S.p.a., Italy), and Glass Fiber coated with light-cured composite 8.5 × 0.2 mm (Interlig, Angelus, Brazil). Analysis of the data using Generalized Linear Models (GLMs) reveals that the experimental bodies, produced via the subtractive digital method using PMMA (DD temp MED, Dental Direkt GmbH, Germany) as the polymer and glass filaments as the reinforcement, exhibit superior mechanical properties, particularly when pre-wetted with Interlig liquid composite (Angelus, Brazil).

PSVI-17 Inclusion of glutathione precursor to diet of sows from d 114of lactation through to weaning d 21 improves serum hormone concentrations and piglet performance

Abstract Glutathione (GSH) is a critical endogenous antioxidant found in all eukaryotic cells and has a critical role in maintaining redox homeostasis. Greater GSH concentrations protect cellular damage, tissue degeneration, and disease progression in various models but very limited study exists in swine model. Thus, we aimed to examine the effect of GSH supplementation on lactating sows and their suckling performance. From d 114 of lactation to 21 d of weaning, a total of 40 multiparous sows (Landrace x Yorkshire, parity 2.4) were assigned to one of four dietary treatments. The test treatments were: CON, a basal diet and a basal diet supplemented with 0.1%, 0.2%, and 0.3% GSH precursors. Experimental data (reproductive performance, growth performance, and blood profile) was analyzed by the general linear model (GLM) procedure with individual sow and their progenies as an experimental unit. Orthogonal polynomial regression was conducted to determine the linear and quadratic effects of 0.1%, 0.2%, and 0.3% GSH precursors in pigs. Piglets born to sows fed GSH precursors showed linearly increased body weight and total average daily gain (P < 0.05) at the end of weaning d 21. Moreover, dietary GSH showed linearly increased (P < 0.05) GSH and GSH/GSSG (oxidized glutathione) ratio in sow blood at the end of lactation d 14 and d 21. Whereas, at the end of weaning serum cortisol concentration of sows was significantly reduced by GSH precursor supplementation. In conclusion, adding 0.3% of GSH supplement to lactating sow diet would be beneficial to enhance the immune status and performance of both sows and their progenies respectively.

76 Effect of 0.79% top-dressed arginine supplementation at different gestation periods and seasons on the colostrum composition and productive performance of sows and piglets

Abstract This study aimed to evaluate the effect of supplementation with 0.79% top-dressed arginine (Arg) at different gestation periods and seasons on the productive performance and colostrum composition of sows. A total of 320 sows were divided into 4 feeding groups (80 sows/group) under 2 different seasons (summer and winter): a control group (CO) fed a standard diet and 3 groups supplemented with 0.79% Arg either for the first 35 d of gestation (TRT35), the last 45 d of gestation (TRT45), or the entire gestation period (TRTCOM). Colostrum was collected at farrowing from 12 sows per group per season. Productive performance and individual piglet body weight (BW) were recorded at birth (d 0), d 6 of age, weaning (d 28) and 14 d post-weaning (d 14p). Data were analyzed using a general linear mixed model including diet, season, their interaction, and parity class as fixed factors. At the end of the gestation, sows from the TRTCOM group had a greater BW (P = 0.003) and average daily gain (ADG; P = 0.009) than the CO group. The diet did not influence the number of total born and total born alive piglets. The stillborn % was less in the TRT35 group than CO and TRTCOM groups (P < 0.001). The TRTCOM group had a greater crushed % and hypo-vital % than CO group (P < 0.001). Colostral IgG was reduced in the Arg groups compared with the CO group (P < 0.001) while no differences were found for IgA and IgM between the groups. The BW of pilets at d 0, d 6, d 28 and d 14p and ADGs were not affected by the diet; however, the TRT35 had a reduced % of low-birth BW piglets than CO (P = 0.02). The TRT45 tended to have greater % in low-birth BW piglets than CO (P = 0.051) and greater % in high-birth BW piglets than the other groups (P < 0.001). The sows having the gestation in summer had decreased BW at the beginning of gestation, a greater final BW and ADG (P < 0.001), a lower number of total born (P = 0.003), mummified % but a greater crushed % (P < 0.01). Piglets BW at birth, d 28 and d 14p was greater in winter. Lactose (P = 0.001) and IgG (P < 0.001) were greater in the winter. In conclusion, 0.79% of on top-dressed Arg had a negative effect on the productive performance of the sows during the entire gestation period. Conversely, supplementing Arg during the first 35 d of gestation led to a decrease in the percentage of stillborn and low-birth BW piglets.

Surface water quality prediction in the lower Thoubal river watershed, India: A hyper-tuned machine learning approach and DNN-based sensitivity analysis

The accurate and efficient monitoring, assessment, and prediction of water resources is crucial for the sustenance of life and health of the environment. Traditional methods for assessing water quality can be laborious and time-consuming, but the use of machine learning algorithms can improve the speed and precision of these predictions. The study aimed to evaluate the quality of surface water in the lower Thoubal river using a comprehensive approach that analyzed 12 physico-chemical properties of the water samples collected from 16 different sites. Four machine learning algorithms namely, deep neural network (DNN), gradient boost model (GBM), generalized linear model (GLM), and random forest (RF) were applied and compared for the prediction efficiency of a water quality index (WQI). Sensitivity and uncertainty analysis of the parameters were carried out using a DNN-based model. The study incorporated model evaluation using learning curve along with five key performance assessors. The findings revealed marked variation in the WQI in the watershed. Of the samples tested, about 70 % were found to have good water quality, 18 % had excellent water quality, 11 % had poor water quality, 1 % had very poor water quality, and less than 1 % were deemed unsuitable. Turbidity, BOD, and COD were found to be the most influential parameter towards WQI prediction. The effectiveness of the predictive models ranked as GLM>DNN>RF>GBM, GLM>GBM>DNN>RF, and GLM>DNN>RF>GBM; based on testing, training and 5-fold cross-validation. The GLM model consistently showed superior performance with the lowest RMSEs of 0.14783 in training, 0.15936 in validation, and 0.26115 in 5-fold cross-validation. Conversely, during the training, RF displayed the worst RMSEs of 5.38354, 4.79754 by GBM in validation, and 7.04887 by GBM in 5-fold cross-validation. The analysis using the Taylor diagram and learning curve further supported that GLM was the most effective model for predicting surface water quality. Biological oxygen demand, chemical oxygen demand, electrical conductivity, turbidity and total hardness were found to be the key parameters influencing the water quality. Unregulated and illegal sand mining from the riverbed, garbage dumping into the water bodies, runoffs from agricultural fields have significantly deteriorated the water quality in the study area. The scalable approach of the study and its results can benefit the local water managers and water research community.

Development of algorithms for estimating the Child Health Utility 9D from Caregiver Priorities and Child Health Index of Life with Disability.

The primary aim was to determine Child Health Utility 9D (CHU9D) utilities from the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) for non-ambulatory children with cerebral palsy (CP). One hundred and eight surveys completed by Australian parents/caregivers of children with CP were analysed. Spearman's coefficients were used to investigate the correlations between the two instruments. Ordinary least square, robust MM-estimator, and generalised linear models (GLM) with four combinations of families and links were developed to estimate CHU9D utilities from either the CPCHILD total score or CPCHILD domains scores. Internal validation was performed using 5-fold cross-validation and random sampling validation. The best performing algorithms were identified based on mean absolute error (MAE), concordance correlation coefficient (CCC), and the difference between predicted and observed means of CHU9D. Moderate correlations (ρ 0.4-0.6) were observed between domains of the CHU9D and CPCHILD instruments. The best performing algorithm when considering the CPCHILD total score was a generalised linear regression (GLM) Gamma family and logit link (MAE=0.156, CCC=0.508). Additionally, the GLM Gamma family logit link using CPCHILD comfort and emotion, quality of life, and health domain scores also performed well (MAE=0.152, CCC=0.552). This study established algorithms for estimating CHU9D utilities from CPCHILD scores for non-ambulatory children with CP. The determined algorithms can be valuable for estimating quality-adjusted life years for cost-utility analysis when only the CPCHILD instrument is available. However, further studies with larger sample sizes and external validation are recommended to validate these findings.

Genome wide association analysis reveals the genetic sites of heat resistance in largemouth bass (Micropterus salmoides)

Largemouth bass (Micropterus salmoides) is an important commercially cultured freshwater fish. High temperature is a common challenge encountered in the summer cultivation of largemouth bass. In this study, we conducted a genome-wide association study using general linear models and linear mixed models to identify significant single nucleotide polymorphisms (SNPs) and candidate genes associated with loss of equilibrium (LOE) and weight gain (WG) during high temperature challenge. We collected fin tissue from 353 individuals of largemouth bass exposed to high water temperature (37.5 °C) and performed whole-genome resequencing. Through association analysis, we successfully identified 10 SNPs and 38 candidate genes that were significantly associated with LOE, and four SNPs and 19 candidate genes that were significantly associated with WG. Using quantitative PCR and Western blot, we tested the expression of eight genes related to LOE in heat-sensitive and heat-tolerant individuals, and identified significant differences in the expression of the following five genes: Tmub2, Ngfr, Hgf, Hdac6, and Sypl. For WG, we assessed the expression of three candidate genes, among which Mrc2l displayed significant differences in expression between the high WG group and low WG group. We discuss the functions and potential biological processes of candidate genes for LOE and WG. Our results provide basic genetic information for breeding largemouth bass with high temperature tolerance.

Sex and adrenal hormones in association with insecticide biomarkers among adolescents living in ecuadorian agricultural communities

BackgroundOrganophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. MethodsIn 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17β-estradiol, and cortisol. We used general linear models to assess linear (β = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (β2 = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. ResultsThe organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (βboys = 5.88% [1.21%, 10.78%], βgirls = 4.10% [-0.02%, 8.39%]), and cortisol (βboys = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (β2boys = −0.17 (−0.33, −0.003), p = 0.04) and DHEA (β2boys = −0.49 (−0.80, −0.19), p = 0.001) in boys. The neonicotinoid summary score (βboys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (βboys = 3.90% [1.28%, 6.58%]) were positively associated with 17β-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE. ConclusionsWe observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17β-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.

Anatomical Markers Associated With the Presence of Intracranial Aneurysms in Individuals Screened for Aneurysms

BACKGROUND Hemodynamic stress is linked to the development of intracranial aneurysms (IAs) and may be influenced by anatomic variation of intracranial arteries. We assessed diameters and bifurcation angles of intracranial arteries forming the circle of Willis in a cohort of individuals screened for the presence of IAs. METHODS Individuals with and without IAs identified at screening with magnetic resonance angiography were compared. Diameters and bifurcation angles of the following arteries were measured using semiautomatic methods: A1 and A2 segments of the anterior cerebral artery, M1 and M2 segments of the middle cerebral artery, P1 segments of the posterior cerebral artery, posterior communicating artery (Pcom), internal carotid artery, vertebral artery, and basilar artery. We employed univariate general linear models to assess group differences. This included subgroup comparisons between individuals with IAs at specific locations and matched controls, and comparisons on group level between individuals with and without IAs, corrected for age and sex. RESULTS In 94 of the 1049 individuals (9.0%) included, IAs were detected. Individuals with middle cerebral artery IAs had wider ipsilateral M2–M2 bifurcation angles compared with controls (121±25° versus 97±19°; P <0.01). Individuals with anterior communicating artery IAs showed smaller angles for the A1–A2 bifurcation (106±16° versus 120±17°; P = 0.02), while those with Pcom IAs had wider Pcom–C7 bifurcation angles (147±14° versus 127±17°; P = 0.02) and smaller diameters below the ipsilateral internal carotid artery top (2.86±0.36 mm versus 3.10±0.33 mm; P = 0.03) compared with controls. CONCLUSION We found associations between wider M2–M2 bifurcation angles or narrower A1–A2 bifurcation angles and IA presence, consistent with prior literature. Moreover, we uncovered previously unexplored associations, including wider Pcom–C7 bifurcation angles and smaller internal carotid artery diameters in individuals with Pcom IAs. Future research should explore the potential of these markers in predicting IAs in at‐risk populations during follow‐up screenings.

Accounting for spatio-temporal and sampling dependence in survey and CPUE biomass indices: simulation and Bayesian modeling framework

Abstract Estimating changes in the biomass of a fish stock is crucial for successful management. However, fishery assessment may be affected by the quality of the inputs used in stock assessment models. Survey biomass indices derived from fishery-independent and catch per unit effort (CPUE) biomass indices derived from fishery-dependent data are key inputs for model calibration. These indices have biases that could compromise the accuracy of the stock assessment models results. Therefore, there are plenty proposed methods to standardize survey or CPUE biomass data. From simpler models like generalized linear models (GLMs) to more complex models that take into account spatio-temporal correlation, like geostatistical models, and sampling dependence, like marked point processes. But many of them do not consider the underlying spatio-temporal or sampling dependence of these data. Hence, the goal of the study is to present a spatio-temporal simulation and Bayesian modeling framework to assess the impact of applying models that do not consider spatio-temporal and sampling dependence. Results indicate that geostatistical models and marked point processes achieve the lowest measures of error. Hence, to capture the underlying spatio-temporal process of the survey and CPUE biomass indices and data sampling preferentiality, it is essential to apply models that consider the spatio-temporal and sampling dependence.

Spatio-temporal dynamics and drivers of highly pathogenic avian influenza H5N1 in Chile.

Highly pathogenic avian influenza A H5N1 clade 2.3.4.4b (hereafter H5N1) is causing vast impacts on biodiversity and poultry around the globe. In Chile, lethal H5N1 cases have been reported in a wide range of wild bird species, marine mammals, backyard and industrial poultry, and humans. This study describes the spatio-temporal patterns of the current epizootic of H5N1 in Chile and test drivers that could be associated with outbreak occurrence. We used H5N1 cases reported by the Chilean National Animal Health Authority from 5 December 2022 to 5 April 2023. These included wild bird cases confirmed through an avian influenza-specific real-time reverse transcription PCR assay (RT-qPCR), obtained from passive and active surveillance. Data were analyzed to detect the presence of H5N1 clusters under space-time permutation probability modeling, the association of H5N1 with distance and days since the first outbreak through linear regression, and the correlation of H5N1 presence with a number of ecological and anthropogenic variables using general linear modeling. From 445 H5N1 identified outbreaks involving 613 individual cases in wild birds, a consistent wave-like spread of H5N1 from north to south was identified, which may help predict hotspots of outbreak risk. For instance, seven statistically significant clusters were identified in central and northern Chile, where poultry production and wildlife mortality are concentrated. The presence of outbreaks was correlated with landscape-scale variables, notably temperature range, bird richness, and human footprint. In less than a year, H5N1 has been associated with the unusual mortality of >100,000 individuals of wild animals in Chile, mainly coastal birds and marine mammals. It is urgent that scientists, the poultry sector, local communities, and national health authorities co-design and implement science-based measures from a One Health perspective to avoid further H5N1 spillover from wildlife to domestic animals and humans, including rapid removal and proper disposal of wild dead animals and the closure of public areas (e.g., beaches) reporting high wildlife mortalities.

Abstract PO4-03-11: Discerning the impact of ctDNA detection on patient decisions in early-stage breast cancer

Abstract Background: Detection of circulating tumor DNA (ctDNA) after neoadjuvant therapy for triple negative breast cancer (TNBC) is associated with increased risk of recurrence. Ongoing trials aim to determine whether knowledge of specific genomic mutations in ctDNA can inform targeted adjuvant therapy to improve prognosis. The impact of knowledge of ctDNA status on patient treatment decisions weighing benefit and toxicity is unknown. Methods: 401 women were recruited via the Research Advocacy Network from Young Survivors’ Coalition, Living Beyond Breast Cancer, and Pink-4-Ever Ending Disparities. Participants had to self-report a history of non-metastatic breast cancer and have received chemotherapy in the prior 6 months to 10 years to be eligible. Participants completed a 27 question Qualtrics survey detailing demographics and experience with prior chemotherapy. Based on estimations from prior data, participants were presented with scenarios mimicking residual TNBC and unknown, negative, or positive ctDNA status with corresponding risk of recurrence of 40%, 20%, or 55% respectively. Participants were then presented with 12 scenarios (in random order) combining various degrees of absolute risk reduction (5%, 15%, 35%) with established toxicity profiles of four possible post-neoadjuvant therapies (capecitabine, immunotherapy, PARP inhibitor, and PI3K inhibitor). Participants rated scenarios in terms of acceptability from 0-100. A general linear model with repeated measures (3 × 4) was used to determine the contributions of risk reduction and toxicity to acceptability. Models were also run with the addition of between subject factors: age group (< 40; >40), stage of cancer (Stage 1; Stage 2/3), and previous experience with toxicity (Yes; No), to examine whether any of these factors moderated the effects of risk reduction and toxicity. Effect sizes were determined by partial h2. Results: 286 eligible respondents completed the survey with evaluable responses. Average age was 41.2 (range 27-75). When the hypothetical risk of recurrence decreased from 40% (ctDNA-unknown) to 20% (ctDNA-negative), significantly less participants preferred adjuvant capecitabine vs. no therapy (95.1% versus 63.3%, p< 0.001). Across the 12 scenarios, both benefit (F=448.5, p< 0.001; preference for greater benefit) and toxicity (F=33.64, p< 0.001; preference for lower toxicity) significantly influenced acceptability, but benefit had a much larger effect size than toxicity (h2=0.76 and 0.26, respectively). There was no significant interaction effect, and the pattern of results was not moderated by age, stage of cancer, or prior experience with chemotherapy toxicity. The most preferred scenario (greatest benefit, lowest toxicity) had a mean rating of 87.8/100; however, even when presented with the scenario with the lowest benefit and highest toxicity, the mean rating was still 31.5/100, suggesting that this combination would be acceptable to some individuals. Conclusions: Knowledge of ctDNA-negative status significantly reduced the number of participants preferring adjuvant capecitabine over no further therapy. When faced with ctDNA-positive status, participants preferred maximum risk reduction regardless of toxicity profile. As genomic technology advances, it is imperative that researchers and treating physicians understand its impact on patient decision making. Citation Format: Tarah Ballinger, Gregory Zimet, Elda Railey, Mary Lou Smith, Bryan Schneider. Discerning the impact of ctDNA detection on patient decisions in early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-11.

Cost of disease progression among US patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.

Aim: The objectives were to investigate the differences in per patient per month (PPPM) healthcare resource utilization (HCRU) and costs among commercially insured and Medicare Advantage patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) who experience disease progression in 12months compared with those who don't investigate the impact of progression timing on cumulative healthcare costs. Patients & methods: This claims-based study included patients diagnosed with mBC between 1January 2013 and 30April 2020 and received HER2-targeted therapy. Patients were categorized as progressed or nonprogressed. For objective one, monthly HCRU and costs were assessed for up to two lines of therapy (LOTs). Data were summarized descriptively and compared using a generalized linear model (GLM). For objective two, patients with at least 6 months of follow-up were assessed and cumulative healthcare costs were estimated in the 3 years following the start of LOT1 or LOT2 using a GLM and Kaplan-Meier weighting. Results: Among the 4113 patients in the study sample, 3406 had at least 12 months of follow-up (or less if due to death). Compared with nonprogressed patients, progressed patients had higher mean PPPM healthcare costs (LOT1: $22,014 vs $18,372, p<0.001; LOT2: $19,643 vs $16,863, p=0.001), and HCRU, including number of emergency room visits and inpatient stays (both p<0.001) in the 12 months following LOT start. Progressed patients had higher 3-year mean cumulative healthcare costs than nonprogressed patients following LOT1 and LOT2 and this difference was greater for patients who progressed earlier. Conclusion: Disease progression was associated with significant increases in HCRU and costs. Delays in progression were associated with lower cumulative healthcare costs. Earlier use of more clinically effective treatments to delay progression may reduce the economic burden among these patients.

Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid function, and intelligence quotient at 7 years of age: Findings from the Sheyang Mini Birth Cohort Study

BackgroundPrenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive. ObjectivesThis study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function. MethodsThe study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function. ResultsThe molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (β = -6.21, 95 % confidence interval [CI]: −12.21, −0.21), with more pronounced associations observed among girls (β = -9.57, 95 % CI: −18.33, −0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ. ConclusionsIncreased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship.

Assessing the impacts of aquaculture on local fish communities using environmental DNA metabarcoding analysis

AbstractFish aquaculture potentially affects the local ecosystem through feed (leftovers) and feces. However, evaluation of its impacts on biodiversity, especially those of mobile organisms such as fish, is not straightforward. Here, we report a case study in which environmental DNA (eDNA) metabarcoding with MiFish universal primers for the 12S rRNA region of fish is used to detect and assess the impact of aquaculture on local fish communities. In Shizugawa Bay, Minamisanriku Town, Miyagi Prefecture, Japan, Oncorhynchus kisutch (coho salmon) is aquacultured in sea cages from November to July, but is absent from August to October. We conducted eDNA surveys in June, August, October, and December 2021 of water at depths of 5 m and 1 m above the bottom obtained from two sites, one approximately 100 m and the other approximately 2500 m from the nearest aquaculture site. The total number of operational taxonomic units (OTUs) detected was 122, with a maximum of 50 and a minimum of 10. With distance‐based redundancy analysis (dbRDA) and PERMANOVA applied to the eDNA‐based community compositional data, we detected a significant effect of the presence of O. kisutch aquaculture on fish biodiversity. The generalized linear model (GLM) applied to each detected OTUs indicated that the aquaculture was associated positively with Leucopsarion petersii (ice goby), and Oncorhynchus spp. and negatively with Chaenogobius annularis (forktongue goby). Environmental DNA metabarcoding surveys, combined with multivariate statics, are a promising tool to identify the dimension of biodiversity that human activity affects and would serve as a basic survey for sustainable use of the sea.

Right prefrontal activation associated with deviations from expected lipstick texture assessed with functional near-infrared spectroscopy.

There is a continuous consumer demand for ever superior cosmetic products. In marketing, various forms of sensory evaluation are used to measure the consumer experience and provide data with which to improve cosmetics. Nonetheless, potential downsides of existing approaches have led to the exploration of the use of neuroimaging methods, such as functional near-infrared spectroscopy (fNIRS), to provide addition information about consumers' experiences with cosmetics. The aim of the present study was to investigate the feasibility of a real-time brain-based product evaluation method which detects the incongruency between a product, in this case lipstick, and a consumer's expectations. Thirty healthy, female, habitual lipstick users were asked to apply six different lipsticks varying in softness and to rate the softness of and their willingness to pay (WTP) for each lipstick. Cerebral hemodynamic responses in frontal areas were measured with fNIRS during lipstick application and analyzed using the general linear model (GLM). Incongruency scores between softness and expectation were calculated in order to understand how far removed each lipstick was from a participant's optimal softness preference. The correlation between brain activation (beta scores) during the application of each lipstick and the respective incongruency scores from each participant were acquired using semi-partial correlation analysis, controlling for the effects of WTP. We revealed a significant intra-subject correlation between incongruency scores and activation in the right inferior frontal gyrus (IFG). This confirms that as the texture incongruency scores increased for the lipstick samples, activation in each individual's right IFG also increased. The correlation observed between incongruency perceived by participants and activation of the right IFG not only suggests that the right IFG may play an important role in detecting incongruity when there is a discrepancy between the perceived texture and the consumer's expectations but also that measuring activity in the IFG may provide a new objective measurement of the consumer experience, thus contributing to the development of superior cosmetics.

The influence of accelerated brain aging on coactivation pattern dynamics in Parkinson's disease.

Aging is widely acknowledged as the primary risk factor for brain degeneration, with Parkinson's disease (PD) tending to follow accelerated aging trajectories. We aim to investigate the impact of structural brain aging on the temporal dynamics of a large-scale functional network in PD. We enrolled 62 PD patients and 32 healthy controls (HCs). The level of brain aging was determined by calculating global and local brain age gap estimates (G-brainAGE and L-brainAGE) from structural images. The neural network activity of the whole brain was captured by identifying coactivation patterns (CAPs) from resting-state functional images. Intergroup differences were assessed using the general linear model. Subsequently, a spatial correlation analysis between the L-brainAGE difference map and CAPs was conducted to uncover the anatomical underpinnings of functional alterations. Compared to HCs (-3.73 years), G-brainAGE was significantly higher in PD patients (+1.93 years), who also exhibited widespread elevation in L-brainAGE. G-brainAGE was correlated with disease severity and duration. PD patients spent less time in CAPs involving activated default mode and the fronto-parietal network (DMN-FPN), as well as the sensorimotor and salience network (SMN-SN), and had a reduced transition frequency from other CAPs to the DMN-FPN and SMN-SN CAPs. Furthermore, the pattern of localized brain age acceleration showed spatial similarities with the SMN-SN CAP. Accelerated structural brain aging in PD adversely affects brain function, manifesting as dysregulated brain network dynamics. These findings provide insights into the neuropathological mechanisms underlying neurodegenerative diseases and imply the possibility of interventions for modifying PD progression by slowing the brain aging process.

Operative Time and Accrual of Postoperative Complications in Minimally Invasive Versus Open Myomectomy

Study ObjectiveTo compare the prevalence and accrual of 30-day postoperative complications by operative time for open myomectomy (OM) and minimally invasive myomectomy (MIM). DesignRetrospective cohort study SettingHospitals participating in the National Surgical Quality Improvement Program database from January 2015 to December 2021. PatientsFemale patients aged ≥18 years undergoing OM or MIM. InterventionsPatients were categorized into OM and MIM cohorts. Covariates associated with operative time and composite complications were identified using general linear model and chi-square or Fisher's exact test as appropriate. Adjusted spline regression was performed as a test of linearity between operative time and composite complications. Adjusted risk ratios of 30-day postoperative individual, minor, major, and composite complications by 60-minute operative time increments were estimated using Poisson regression with robust error variance. Measurements and Main ResultsOf 27 728 patients, 11 071 underwent MIM and 16 657 underwent OM. Mean operative times (SD) were 164.6 (82.0) for MIM and 129.2 (67.0) for OM. Raw composite complication rates were 5.5% for MIM and 15.8% for OM. Adjusted spline regression demonstrated linearity between operative time and relative risk of composite postoperative complications for both MIM and OM. MIM had higher adjusted relative risk (aRR, 95% CI) compared to OM of blood transfusion (1.55, 1.45–1.64 versus 1.29, 1.25–1.34), overall minor complications (1.13, 1.03–1.23 versus 1.01, 0.92–1.10), and overall major complications (1.43, 1.35–1.51 versus 1.27, 1.12–1.32). Operative time had greater impact on risk of composite complications for MIM than OM, reaching aRR 2.0 at 296 minutes versus 461 minutes for OM. ConclusionOM has a higher overall rate of composite, minor, and major complications compared to MIM. While operative time is independently and linearly associated with postoperative complications with myomectomy regardless of approach, optimizing surgical efficiency for MIM may be more critical than for OM.

Different heart rate variability profile during sleep in mid-later life adults with remitted early-onset versus late-onset depression

BackgroundIn mid-later life adults, early-onset and late-onset (i.e., onset ≥50 years) depression appear to be underpinned by different pathophysiology yet have not been examined in relation to autonomic function. Sleep provides an opportunity to examine the autonomic nervous system as the physiology changes across the night. Hence, we aimed to explore if autonomic profile is altered in mid-later life adults with remitted early-onset, late-onset and no history of lifetime depression. MethodsParticipants aged 50–90 years (n = 188) from a specialised clinic underwent a comprehensive clinical assessment and completed an overnight polysomnography study. General Linear Models were used to examine the heart rate variability differences among the three groups for four distinct sleep stages and the wake after sleep onset. All analyses controlled for potential confounders – age, sex, current depressive symptoms and antidepressant usage. ResultsFor the wake after sleep onset, mid-later life adults with remitted early-onset depression had reduced standard deviation of Normal to Normal intervals (SDNN; p = .014, d = −0.64) and Shannon Entropy (p = .004, d = −0.46,) than those with no history of lifetime depression. Further, the late-onset group showed a reduction in high-frequency heart rate variability (HFn.u.) during non-rapid eye movement sleep stage 2 (N2; p = .005, d = −0.53) and non-rapid eye movement sleep stage 3 (N3; p = .009, d = −0.55) when compared to those with no lifetime history. LimitationsCausality between heart rate variability and depression cannot be derived in this cross-sectional study. Longitudinal studies are needed to examine the effects remitted depressive episodes on autonomic function. ConclusionThe findings suggest differential autonomic profile for remitted early-onset and late-onset mid-later life adults during sleep stages and wake periods. The differences could potentially serve as peripheral biomarkers in conjunction with more disease-specific markers of depression to improve diagnosis and prognosis.

Collaborative model of care between orthopaedics and allied healthcare professionals (CONNACT) in knee osteoarthritis: Effectiveness-implementation hybrid randomized controlled trial of a community-based, multidisciplinary, stratified intervention

ObjectiveTo compare the clinical and cost effectiveness of the Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT), a community-based, stratified, multidisciplinary intervention consisting of exercise, education, psychological and nutrition delivered through a chronic care model to usual hospital care in adults with knee osteoarthritis (OA). MethodsPragmatic, parallel-arm, single-blinded superiority RCT trial. Community-dwelling, ambulant adults with knee OA (Kellgren-Lawrence grade > 1; Knee Injury and OA Outcome Score (KOOS4) ≤ 75) were enrolled. Primary outcome was KOOS4 at 12-months; secondary outcomes included: quality of life, physical performance measures, symptom satisfaction, psychological outcomes, dietary habits, and global perceived effect. Intention-to-treat analysis using generalized linear model (GLM) and regression modelling were conducted. Economic evaluation through a societal approach was embedded. Results110 participants (55 control, 55 intervention) were randomized. No between-group difference found for the primary outcome (MD [95%CI]: -1.86 [-9.11. 5.38]), although both groups demonstrated within-group improvement over 12-months. Among the secondary outcomes, the CONNACT group demonstrated superior dietary change (12 months) and physical performance measures (3 months), and global perceived effect (6 months). While there was no between-group difference in total cost, significant productivity gains (reduced indirect cost) were seen in the CONNACT group. ConclusionCONNACT was not superior to usual care at 1 year. Further efforts are needed to understand the underlying contextual and implementation factors in order to further improve and refine such community-based, stratified care models moving forward. Trial RegistrationClinicaltrials.gov Identifier: NCT03809975. Registered January 18 2019. https://clinicaltrials.gov/ct2/show/NCT03809975