Linear Mixed-effects Multiple Regression Research Articles

A randomized trial to assess the acceleration of viral clearance by the combination Favipiravir/Ivermectin/Niclosamide in mild-to-moderate COVID-19 adult patients (FINCOV)

BackgroundThe efficacy of the viral clearance and clinical outcomes of favipiravir (FPV) in outpatients being treated for coronavirus disease 2019 (COVID-19) is unclear. Ivermectin (IVM), niclosamide (NCL), and FPV demonstrated synergistic effects in vitro for exceed 78% inhibiting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) replication. MethodsA phase 2, open-label, 1:1, randomized, controlled trial was conducted on Thai patients with mild-to-moderate COVID-19 who received either combination FPV/IVM/NCL therapy or FPV alone to assess the rate of viral clearance among individuals with mild-to-moderate COVID-19. ResultsSixty non-high-risk comorbid patients with mild-to-moderate COVID-19 were randomized; 30 received FPV/IVM/NCL, and 30 received FPV alone. Mixed-effects multiple linear regression analysis of the cycle threshold value from SARS-CoV-2 PCR demonstrated no statistically significant differences in viral clearance rates between the combined FPV/IVM/NCL therapy group and the FPV-alone group. World Health Organization Clinical Progression scores and symptomatic improvement did not differ between arms on days 3, 6, and 10, and no adverse events were reported. No patients required hospitalization, intensive care unit admission, or supplemental oxygen or died within 28 days. C-reactive protein on day 3 was lower in the FPV/IVM/NCL group. ConclusionViral clearance rates did not differ significantly between the FPV/IVM/NCL combination therapy and FPV-alone groups of individuals with mild-to-moderate COVID-19, although the combined regimen demonstrated a synergistic effect in vitro. No discernible clinical benefit was observed. Further research is required to explore the potential benefits of FVP beyond its antiviral effects.Trial registration: TCTR20230403007, Registered 3 April 2023 - Retrospectively registered,https://trialsearch.who.int/Trial2.aspx?TrialID=TCTR20230403007

Influence of Environmental Factors and Genome Diversity on Cumulative COVID-19 Cases in the Highland Region of China: Comparative Correlational Study.

The novel coronavirus SARS-CoV-2 caused the global COVID-19 pandemic. Emerging reports support lower mortality and reduced case numbers in highland areas; however, comparative studies on the cumulative impact of environmental factors and viral genetic diversity on COVID-19 infection rates have not been performed to date. The aims of this study were to determine the difference in COVID-19 infection rates between high and low altitudes, and to explore whether the difference in the pandemic trend in the high-altitude region of China compared to that of the lowlands is influenced by environmental factors, population density, and biological mechanisms. We examined the correlation between population density and COVID-19 cases through linear regression. A zero-shot model was applied to identify possible factors correlated to COVID-19 infection. We further analyzed the correlation of meteorological and air quality factors with infection cases using the Spearman correlation coefficient. Mixed-effects multiple linear regression was applied to evaluate the associations between selected factors and COVID-19 cases adjusting for covariates. Lastly, the relationship between environmental factors and mutation frequency was evaluated using the same correlation techniques mentioned above. Among the 24,826 confirmed COVID-19 cases reported from 40 cities in China from January 23, 2020, to July 7, 2022, 98.4% (n=24,430) were found in the lowlands. Population density was positively correlated with COVID-19 cases in all regions (ρ=0.641, P=.003). In high-altitude areas, the number of COVID-19 cases was negatively associated with temperature, sunlight hours, and UV index (P=.003, P=.001, and P=.009, respectively) and was positively associated with wind speed (ρ=0.388, P<.001), whereas no correlation was found between meteorological factors and COVID-19 cases in the lowlands. After controlling for covariates, the mixed-effects model also showed positive associations of fine particulate matter (PM2.5) and carbon monoxide (CO) with COVID-19 cases (P=.002 and P<.001, respectively). Sequence variant analysis showed lower genetic diversity among nucleotides for each SARS-CoV-2 genome (P<.001) and three open reading frames (P<.001) in high altitudes compared to 300 sequences analyzed from low altitudes. Moreover, the frequencies of 44 nonsynonymous mutations and 32 synonymous mutations were significantly different between the high- and low-altitude groups (P<.001, mutation frequency>0.1). Key nonsynonymous mutations showed positive correlations with altitude, wind speed, and air pressure and showed negative correlations with temperature, UV index, and sunlight hours. By comparison with the lowlands, the number of confirmed COVID-19 cases was substantially lower in high-altitude regions of China, and the population density, temperature, sunlight hours, UV index, wind speed, PM2.5, and CO influenced the cumulative pandemic trend in the highlands. The identified influence of environmental factors on SARS-CoV-2 sequence variants adds knowledge of the impact of altitude on COVID-19 infection, offering novel suggestions for preventive intervention.

Psychosis in Alzheimer’s disease is associated with specific changes in brain MRI volume, cognition and neuropathology

Psychosis in Alzheimer’s Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with AD neuropathological change (ADNC) and ante-mortem volumetric brain magnetic resonance imaging (MRI). Presence of psychosis was determined using the Neuropsychiatric Inventory Questionnaire. Clinical Dementia Rating Sum-of-boxes (CDR-SB) was longitudinally compared between groups with a follow-up of 3000 days using mixed-effects multiple linear regression. Neuropsychological tests closest to the time of MRI and brain regional volumes were cross-sectionally compared. Psychosis was associated with lower age of death, higher longitudinal CDR-SB scores, multi-domain cognitive deficits, higher neuritic plaque severity, Braak stage, Lewy Body pathology (LB) and right temporal lobe regional atrophy. Division according to the presence of LB showed differential patterns of AD-typical pathology, cognitive deficits and regional atrophy. In conclusion, psychosis in ADNC with and without LB has clinical value and associates with subgroup patterns of neuropathology, cognition and regional atrophy.

Assessment of Microvascular Changes After Rhegmatogenous Retinal Detachment Repair Using Wide-Field Swept-Source Optical Coherence Tomography Angiography.

Our objective was to evaluate retinal microvascular changes and visual outcomes following rhegmatogenous retinal detachment (RRD) repair using wide-field swept-source optical coherence tomography angiography (WF SS-OCTA). The study included 116 eyes of 111 patients with macula-off (n = 68) or macula-on (n = 48) RRD treated with a single successful procedure, 79 fellow eyes, and 183 eyes of control patients imaged with WF SS-OCTA (3 ×3, 6 ×6, and 12 ×12 mm images). Mixed-effects multiple linear regression models were used for statistical analysis. Vessel density (VD) and vessel skeletonized density (VSD) of the superficial capillary plexus (3 ×3 mm scans) and full-thickness retina (12 ×12 mm) were significantly reduced in RRD eyes compared to fellow and control eyes. Decreased VSD and VD in all layers (3 ×3 mm and 6 ×6 mm) were significantly associated with greater preoperative extent of retinal detachment (P < 0.05) and poorer postoperative best-corrected visual acuity (BCVA) in RRD eyes (P < 0.05). Macula-off status was associated with increased foveal avascular zone irregularity (12 ×12 mm, P = 0.02). Decreased VD on WF SS-OCTA is associated with poorer postoperative BCVA following RRD repair. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Towards the validation of quantitative contrast sensitivity as a clinical endpoint: correlations with vision-related quality of life in bilateral AMD

AimTo investigate if active learning of contrast sensitivity (CS) in bilateral age-related macular degeneration (AMD) correlates better than visual acuity (VA) with vision-related quality of life (VRQoL) using factor analysis-calibrated...

Achieving good health with a low environmental footprint – A comparison of national indicators

Background Integrated metrics that account for resource use and human health are essential to help identify and support human development pathways that safeguard planetary health. We identify countries that achieved the highest levels of health and development at the lowest cost to Earth’s natural capital and report ecological within-country analyses of associations between indicators of environmental sustainability, human health, and development. Methods We used mixed-effects multiple linear regression models of Healthy Life Expectancy (HALE) and Human Capital (HC) related to Ecological Footprint (EF) and CO2 production emissions, controlling for Gini coefficient and population density applied to data of 216 countries from 1991-2016. We performed stratified analyses by country income level and used likelihood-ratio tests to test for interaction. Results Only Jamaica (1991) and Sri Lanka (2016) achieved high HALE at sustainable EF levels. Each 10% increase in EF was associated with 0·20 (95%CI 0·16,0·24) and 0·21 (95%CI 0·19,0·23) increases in HALE and HC respectively; increases in CO2 production emissions were also associated with increased HALE and HC. There was strong evidence for interaction by income level for each model (p&lt;0·016). Stratified analyses showed that in high income nations HALE and HC decreased with increased levels of EF and CO2. Conclusions Countries with high health metrics at sustainable EF levels may offer valuable lessons for sustainable national development policies. Increased environmental footprint and CO2 emissions appear associated with higher levels of human health and development only up to a certain level of income.

Modeling driver’s braking and steering behavior along horizontal curves of two-lane rural highways for ADAS applications

Objective Drivers continuously manipulate the vehicle’s steering and pedals (throttle, brake) while driving. Inadequate or excessive manipulation leads to crashes, possibly leading to injuries. An Advanced Driving Assistance System (ADAS) can warn drivers of inadequate or excessive manipulation to avert risky situations. Such systems evolve continuously and need more road infrastructure inputs for better driving assistance. Rural highways showcased more fatalities than urban counterparts, with more road departure crashes along horizontal curves than straight sections. Hence, the present study explores drivers’ braking and steering behavior along the horizontal curves of two-lane rural highways and proposes a suitable runoff risk model. Methods Sixty-eight drivers participated in a driving simulator study, where they drove along fifty-two horizontal curves in free-flow conditions. Typical five brake and three steering measures found in past studies were evaluated. Based on data distribution of brake and steering measures, Tobit and mixed-effects multiple linear regression models were developed to understand the association of these measures with the approach speed and geometric parameters of horizontal curves. Further, a generalized linear mixed runoff (road departure) risk model with a logit link function was developed to identify the effective measures among all brake and steering variables. Results The brake and steering measures were significantly associated with the approach speed and the geometric parameters such as curve radius, gradient, and turn type (left or right). Further, the runoff risk analysis revealed a significant effect of braking distance (BD) and standard deviation of steering wheel position (SDSWP). The interaction between BD and SDSWP was significant, suggesting that the runoff risk increased with SDSWP; however, it decreased with BD. Conclusions The runoff risk intensified with higher steering instability along horizontal curves, while it can be reduced with effective brake pedal usage. The study suggests better usage of brakes than steering before entering the curve. It potentially reduces the vehicle speed, thus ensuring more time to perceive the curve and help reduce the driver’s steering instability. The models developed in this study can be used in the ADAS systems upon validation with the field observations.

A multi-center, pragmatic, effectiveness-implementation (hybrid I) cluster randomized controlled trial to evaluate a child-oriented goal-setting approach in paediatric rehabilitation (the ENGAGE approach): a study protocol

BackgroundChild-oriented goal-setting in pediatric rehabilitation may improve child motivation, engagement in therapy, child outcomes related to therapy, and service delivery efficiency. The primary objective of this trial is to determine the effectiveness of a principles-driven, child-focused approach to goal-setting, Enhancing Child Engagement in Goal-Setting (ENGAGE), on pediatric rehabilitation outcomes compared to usual practice. The three secondary objectives are to 1) compare costs and secondary outcomes of the ENGAGE approach to usual practice, 2) determine the influence of child, parent and therapist characteristics on child engagement in therapy and rehabilitation outcomes, and 3) identify barriers and facilitators to the implementation of ENGAGE.MethodsThis research protocol describes a pragmatic, multi-site, cluster, effectiveness-implementation (hybrid type 1 design) randomized controlled trial. Therapists (n = 12 clusters of two therapists) at participating sites (n = 6) will be randomized to 1) the ENGAGE intervention group, or 2) usual care (control) using a computer-generated, permuted-block randomization sequence with site as a stratification variable designed by a statistician (RR). Each therapist will recruit four children 5–12 years old with neurodevelopmental conditions (n = 96), who will receive ENGAGE or usual care, according to therapist group allocation. ENGAGE therapists will be trained to use a 'toolbox' of evidence-driven, theory-informed principles to optimize child and parent motivation, engagement in the goal-setting process, and performance feedback strategies. Outcomes include goal performance (primary outcome), engagement in therapy, functional abilities, participation, and parent and child quality of life. Qualitative interviews with children, parents, ENGAGE therapists, and managers will explore challenges to implementation and potential mitigation strategies. Mixed effects multiple linear regression models will be developed for each outcome to assess group differences adjusted for clustering. A cost-effectiveness analysis will combine cost and a measure of effectiveness into an incremental cost-effectiveness ratio. Qualitative data on implementation will be analyzed inductively (thematic analysis) and deductively using established implementation science frameworks.DiscussionThis study will evaluate the effects of collaborative goal-setting in pediatric rehabilitation and inform effective implementation of child-focused goal-setting practices.Trial RegistrationNCT05017363 (registered August 23, 2021 on ClinicalTrials.gov).

Pain and Barriers to Accessing Health Services Among People Who Use Drugs

BackgroundThe opioid overdose crisis underscores the need for health services among people who use drugs (PWUD) with concurrent pain. AimsInvestigating the effect of pain on barriers to accessing health services among PWUD. DesignProspective cohort study. SettingsA setting of universal access to no-cost medical care in Vancouver, Canada from June 2014 to May 2016. Participants/SubjectsPWUD who completed at least one study interview. MethodsData derived from interviewer-administered questionnaires were used for multivariable generalized linear mixed-effects multiple regression (GLMM) analyses. ResultsAmong 1,348 PWUD, 469 (34.8%) reported barriers to accessing health services at least once during the study period. The median average pain severity was 3 (IQR: 0-6) out of 10. A dose-response relationship was observed between greater pain and increased odds of reporting barriers to accessing health services (adjusted odds ratio [AOR]: 1.59, 95% confidence interval [CI]: 1.15-2.21, p = .005 for mild versus no pain; AOR: 1.76, 95% CI: 1.30-2.37, p < .001 for moderate versus no pain; AOR: 2.55, 95% CI: 1.92-3.37, p < .001 for severe versus no pain). Common barriers included poor treatment by health professionals, socio-structural barriers such as transportation or mobility, and long wait lists or wait times. ConclusionsPain may be a significant risk factor associated with increased barriers to accessing health services among PWUD. Attention to pain management may improve access to health services, and reducing barriers to health services may conversely improve pain management and its related risks and harms.

Retinal Imaging Findings in Carriers With PSEN1-Associated Early-Onset Familial Alzheimer Disease Before Onset of Cognitive Symptoms

Individuals with autosomal dominant mutations for Alzheimer disease are valuable in determining biomarkers present prior to the onset of cognitive decline, improving the ability to diagnose Alzheimer disease as early as possible. Optical coherence tomography (OCT) has surfaced as a potential noninvasive technique capable of analyzing central nervous system tissues for biomarkers of Alzheimer disease. To evaluate whether OCT can detect early retinal alterations in carriers of the presenilin 1 (PSEN1 [OMIM 104311]) E280A mutation who are cognitively unimpaired. A cross-sectional imaging study conducted from July 13, 2015, to September 16, 2020, included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired and 10 healthy noncarrier family members, all leveraged from a homogenous Colombian kindred. Statistical analysis was conducted from September 9, 2017, to September 16, 2020. Mixed-effects multiple linear regression was performed to compare the thickness values of the whole retina and individual retinal layers on OCT scans between mutation carriers and noncarriers. Simple linear-effects and mixed-effects multiple linear regression models were used to assess whether age was an effect modifier for PSEN1 mutation of amyloid β levels and retinal thickness, respectively. Fundus photographs were used to compare the number of arterial and venous branch points, arterial and venous tortuosity, and fractal dimension. This study included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired (7 women [70%]; mean [SD] age, 36.3 [8.1] years) and 10 healthy noncarrier family members (7 women [70%]; mean [SD] age, 36.4 [8.2] years). Compared with noncarrier controls, PSEN1 mutation carriers who were cognitively unimpaired had a generalized decrease in thickness of the whole retina as well as individual layers detected on OCT scans, with the inner nuclear layer (outer superior quadrant, β = -3.06; P = .007; outer inferior quadrant, β = -2.60; P = .02), outer plexiform layer (outer superior quadrant, β = -3.44; P = .03), and outer nuclear layer (central quadrant, β = -8.61; P = .03; inner nasal quadrant, β = -8.39; P = .04; inner temporal quadrant, β = -9.39; P = .02) showing the greatest amount of statistically significant thinning. Age was a significant effect modifier for the association between PSEN1 mutation and amyloid β levels in cortical regions (β = 0.03; P = .001) but not for the association between PSEN1 mutation and retinal thickness. No statistical difference was detected in any of the vascular parameters studied. These findings suggest that OCT can detect functional and morphologic changes in the retina of carriers of familial Alzheimer disease who are cognitively unimpaired several years before clinical onset, suggesting that OCT findings and retinal vascular parameters may be biomarkers prior to the onset of cognitive decline.

Greater Pain Severity is Associated with Inability to Access Addiction Treatment Among a Cohort of People Who Use Drugs.

AimGiven that co-occurring pain is prevalent among people who use drugs (PWUD), we sought to explore the effect of pain severity on accessing addiction treatment.MethodsData were derived from two prospective cohort studies of PWUD in Vancouver, Canada from June 2014 to May 2016. Multivariable generalized linear mixed-effects multiple regression (GLMM) analyses were used to investigate the association between average pain severity and self-reported inability to access addiction treatment.ResultsAmong 1348 PWUD, 136 (10.1%) reported being unable to access addiction treatment at least once over the study period. Individuals who reported being unable to access addiction treatment had a significantly higher median average pain severity score (median=5, IQR=0–7) compared to individuals reporting no inability to access addiction treatment (median=3, IQR=0–6, p=0.038). Greater pain severity was independently associated with higher odds of reporting inability to access addiction treatment (AOR: 1.75, 95%CI: 1.08–2.82 for mild-moderate vs no pain; AOR: 1.98, 95%CI: 1.27–3.09 for moderate-severe vs no pain).ConclusionPWUD with greater pain severity may be at higher risk of being unable to access addiction treatment, or vice versa. While further research is needed to confirm causal associations, these data suggest that there may be underlying pathways or mechanisms through which pain may be associated with access to addiction treatment for PWUD.

Growth Through 24 Months of Age in Infants Receiving Formulas with or Without Added Bovine Milk Fat Globule Membrane (MFGM) or Human Milk Through the First Year of Life: An RCT

Abstract Objectives To evaluate growth through 24 months of age in infants receiving added bovine milk fat globule membrane (MFGM) in infant formula through 12 months of age. Concentration of MFGM from bovine milk fractions and incorporation in infant formula may better approximate the composition of complex milk lipids in human milk. Methods In the double-blind, randomized, controlled Chilean Infant Nutrition Trial (ChiNuT; NCT0262613), term infants whose mothers chose to initiate exclusive infant formula feeding before 4 months of age were randomized to receive: a standard cow's milk-based infant formula (SF, n = 174) or a similar formula with added whey protein-lipid concentrate (5 g/L; source of bovine MFGM) (bMFGM, n = 176). A reference group of infants exclusively receiving human milk (HM, n = 236) was also recruited. Growth through 24 months of age was the primary outcome. Length-for-age (LAZ), weight-for-age (WAZ) and body mass index (BMI)-for-age (BAZ) growth z-scores were analyzed by mixed-effects multiple linear regression models adjusted by sex, age (days), and maternal pregestational BMI (kg/m2). Results No significant group differences in sex, gestational age at birth, birthweight, maternal age and maternal education were detected, with the exception of maternal pregestational BMI (mean(SD)) (HM: 27.0(5.2) lower vs SF: 28.6(6.2) or bMFGM: 28.9(6.1); P = 0.002). Groups were similar at baseline (weight, length, WAZ, BAZ) with the exception of LAZ (lower in the bMFGM compared to HM group; P &amp;lt; 0.05). No significant differences in growth z-scores (absolute at 6, 9, 12, and 24 months of age or change between baseline and each study time point) were detected between SF and MFGM groups. Both randomized study formula groups were associated with higher growth z-score increases from baseline compared to the HM reference group between 6 and 24 months (P less than 0.05). Mean growth z-scores fell within the range of −1 to 1 (16th to 84th percentile) for SF, bMFGM, and HM groups at all study time points. Conclusions Added bovine MFGM in a routine cow's milk-based infant formula through 12 months of age supported normal growth through 24 months of age. Funding Sources The study was funded by Mead Johnson Nutrition (MJN). Teresa Murguia-Peniche, Steven Wu, and Jennifer Wampler are currently employed by MJN. Carol Lynn Berseth was previously employed by MJN.

Impact of family structure and socio-demographic characteristics on child health and wellbeing in same-sex parent families: A cross-sectional survey.

Children with same-sex attracted parents develop well in terms of their health and wellbeing. There are many recognised factors that have an impact on child health, in general, including individual, family and wider social mediators. The aim of this study is to determine the impact of family structure and socio-demographic characteristics on child health and wellbeing in Australian same-sex parent families. A cross-sectional survey of self-identified same-sex attracted parents from across Australia was used to collect information on child health and wellbeing between May and December 2012. Mixed-effects multiple linear regression models were used to identify associations between family structure/socio-demographic characteristics and child wellbeing. Child health outcomes were measured using the Child Health Questionnaire and the Strengths and Difficulties Questionnaire. In same-sex parent families, biological relationships, parental gender and parental education were not significantly associated with health and wellbeing. Parental income, rurality and stable parental relationships were associated with health and wellbeing, and living in a single-parent household was associated with poorer wellbeing. Stable dual parent families offer good outcomes for children with same-sex attracted parents. Family processes are most important. This study does not support the assertion that children require both male and female parents, nor that biological relationships are essential to health and wellbeing. This study provides scientific data from a cross-sectional Australian-based study to describe and understand health determinants for children in family contexts that comprise same-sex parent and all family contexts. It recommends equitable, stigma-free family support.

Impact of Maryland’s 2011 alcohol sales tax increase on alcoholic beverage sales

ABSTRACTBackground: Increasing alcohol taxes has proven effective in reducing alcohol consumption, but the effects of alcohol sales taxes on sales of specific alcoholic beverages have received little research attention. Data on sales are generally less subject to reporting biases than self-reported patterns of alcohol consumption. Objectives: We aimed to assess the effects of Maryland’s July 1, 2011 three percentage point increase in the alcohol sales tax (6–9%) on beverage-specific and total alcohol sales. Methods: Using county-level data on Maryland’s monthly alcohol sales in gallons for 2010–2012, by beverage type, multilevel mixed effects multiple linear regression models estimated the effects of the tax increase on alcohol sales. We controlled for seasonality, county characteristics, and national unemployment rates in the main analyses. Results: In the 18 months after the tax increase, average per capita sales of spirits were 5.1% lower (p < 0.001), beer sales were 3.2% lower (p < 0.001), and wine sales were 2.5% lower (p < 0.01) relative to what would have been expected from sales trends in the 18 months prior to the tax increase. Overall, the alcohol sales tax increase was associated with a 3.8% decline in total alcohol sold relative to what would have been expected based on sales in the prior 18 months (p < 0.001). Conclusion: The findings suggest that increased alcohol sales taxes may be as effective as excise taxes in reducing alcohol consumption and related problems. Sales taxes also have the added advantages of rising with inflation and taxing the highest priced beverages most heavily.

When experience meets language statistics: Individual variability in processing English compound words.

Statistical patterns of language use demonstrably affect language comprehension and language production. This study set out to determine whether the variable amount of exposure to such patterns leads to individual differences in reading behavior as measured via eye-movements. Previous studies have demonstrated that more proficient readers are less influenced by distributional biases in language (e.g., frequency, predictability, transitional probability) than poor readers. We hypothesized that a probabilistic bias that is characteristic of written but not spoken language would preferentially affect readers with greater exposure to printed materials in general and to the specific pattern engendering the bias. Readers of varying reading experience were presented with sentences including English compound words that can occur in 2 spelling formats with differing probabilities: concatenated (windowsill, used 40% of the time) or spaced (window sill, 60%). Linear mixed effects multiple regression models fitted to the eye-movement measures showed that the probabilistic bias toward the presented spelling had a stronger facilitatory effect on compounds that occurred more frequently (in any spelling) or belonged to larger morphological families, and on readers with higher scores on a test of exposure-to-print. Thus, the amount of support toward the compound's spelling is effectively exploited when reading, but only when the spelling patterns are entrenched in an individual's mental lexicon via overall exposure to print and to compounds with alternating spelling. We argue that research on the interplay of language use and structure is incomplete without proper characterization of how particular individuals, with varying levels of experience and skill, learn these language structures.

Serum pregnancy-associated plasma protein-A in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

To define the contribution of maternal variables which influence the measured level of maternal serum pregnancy-associated plasma protein-A (PAPP-A) in screening for pregnancy complications. Maternal characteristics and medical history were recorded and serum PAPP-A was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of PAPP-A were determined from a linear mixed-effects multiple regression. Serum PAPP-A was measured in 94,966 cases in the first trimester, 7785 in the second trimester and 8286 in the third trimester. Significant independent contributions to serum PAPP-A were provided by gestational age, maternal weight, height, racial origin, cigarette smoking, diabetes mellitus, method of conception, previous pregnancy with or without pre-eclampsia (PE) and birth-weight Z-score of the neonate in the previous pregnancy. The effects of some variables were similar and those for others differed in the three different trimesters. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum PAPP-A and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed PE and in those without this pregnancy complication. A model was fitted to express the measured serum PAPP-A across the three trimesters of pregnancy as MoMs, after adjusting for variables from maternal characteristics and medical history that affect this measurement.

Serum free β-human chorionic gonadotropin in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

To define the contribution of maternal variables which influence the measured level of maternal serum free β-human chorionic gonadotropin (β-hCG) in screening for pregnancy complications. Maternal characteristics and medical history were recorded and serum free β-hCG was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of free β-hCG were determined from a linear mixed-effects multiple regression. Serum free β-hCG was measured in 94 985 cases in the first trimester, 7879 in the second trimester and 8424 in the third trimester. Significant independent contributions to serum free β-hCG were provided by gestational age, maternal weight, age and racial origin, cigarette smoking, method of conception, diabetes mellitus and family history of pre-eclampsia (PE) in the mother of the patient. The effects of some variables were similar and those for others differed in each trimester. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum free β-hCG and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates both in pregnancies that developed PE and in those without this pregnancy complication. A model was fitted to express measured serum free β-hCG across the three trimesters of pregnancy as MoMs after adjusting for variables from maternal characteristics and medical history that affect this measurement.

Serum alpha-fetoprotein in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

To define the contribution of maternal variables which influence the measured level of maternal serum alpha-fetoprotein (AFP) in screening for pregnancy complications. Maternal characteristics and medical history were recorded and serum AFP was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of AFP were determined from a linear mixed-effects multiple regression. Serum AFP was measured in 17 071 cases in the first trimester, 8583 in the second trimester and 8607 in the third trimester. Significant independent contributions to serum AFP were provided by gestational age, maternal weight, racial origin, gestational age at delivery and birth-weight Z-score of the neonate of the previous pregnancy and interpregnancy interval. Cigarette smoking was found to significantly affect serum AFP in the first trimester only. The machine used to measure serum AFP was also found to have a significant effect. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum AFP and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed pre-eclampsia and in those without this pregnancy complication. A model was fitted to express measured serum AFP across the three trimesters of pregnancy as MoMs, after adjusting for variables from maternal characteristics and medical history that affect this measurement.

Mean arterial pressure in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

To define the contribution of maternal variables that influence the measured mean arterial pressure (MAP) in screening for pregnancy complications. Maternal characteristics and medical history were recorded, and MAP was measured, in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6 weeks, 19 + 0 to 24 + 6 weeks and 30 + 0 to 34 + 6 weeks or 35 + 0 to 37 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths at ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of MAP were determined from linear mixed-effects multiple regression analysis. MAP was measured in 75 841 cases in the first trimester, 30 447 in the second trimester and 31 673 in the third trimester. Significant independent contributions to MAP were provided by gestational age, maternal age, weight, height, Afro-Caribbean racial origin, cigarette smoking, family history of pre-eclampsia (PE), history of PE in the previous pregnancy, interpregnancy interval, chronic hypertension and diabetes mellitus. The effects of some variables were similar, and for others differed, in the three different trimesters. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured MAP and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed PE and in those without this complication. A model was fitted to express the measured MAP as MoMs after adjustment for variables from maternal characteristics and medical history that affect this measurement.

Serum soluble fms-like tyrosine kinase-1 in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

To define the contribution of maternal variables which influence the measured level of maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1) in screening for pregnancy complications. Maternal characteristics and medical history were recorded and serum sFlt-1 was measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6, 19 + 0 to 24 + 6 and 30 + 0 to 34 + 6 or 35 + 0 to 37 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of sFlt-1 were determined from a linear mixed-effects multiple regression. Serum sFlt-1 was measured in 7066 cases in the first trimester, 8078 in the second trimester and 10,464 in the third trimester. Significant independent contributions to serum sFlt-1 were provided by gestational age, maternal weight, racial origin, cigarette smoking, birth-weight Z-score of the neonate in the previous pregnancy and interpregnancy interval. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured level of serum sFlt-1 and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed pre-eclampsia and in those without this pregnancy complication. A model was fitted to express measured serum sFlt-1 across the three trimesters of pregnancy as MoMs, after adjusting for variables from maternal characteristics and medical history that affect this measurement.