With the onset of prevention trials for individuals at high risk for Alzheimer disease, there is increasing need for accurate risk prediction to inform study design and enrollment, but available risk ...estimates are limited. We developed risk estimates for the incidence of mild cognitive impairment (MCI) or dementia among cognitively unimpaired individuals by APOE-e4 dose for the genetic disclosure process of the Alzheimer's Prevention Initiative Generation Study, a prevention trial in cognitively unimpaired APOE-e4/e4 homozygote individuals.
We included cognitively unimpaired individuals aged 60-75 y, consistent with Generation Study eligibility criteria, from the National Alzheimer's Coordinating Center (NACC) (n = 5,073, 158 APOE-e4/e4), the Rotterdam Study (n = 6,399, 156 APOE-e4/e4), the Framingham Heart Study (n = 4,078, 67 APOE-e4/e4), and the Sacramento Area Latino Study on Aging (SALSA) (n = 1,294, 11 APOE-e4/e4). We computed stratified cumulative incidence curves by age (60-64, 65-69, 70-75 y) and APOE-e4 dose, adjusting for the competing risk of mortality, and determined risk of MCI and/or dementia by genotype and baseline age. We also used subdistribution hazard regression to model relative hazard based on age, APOE genotype, sex, education, family history of dementia, vascular risk, subjective memory concerns, and baseline cognitive performance. The four cohorts varied considerably in age, education, ethnicity/race, and APOE-e4 allele frequency. Overall, cumulative incidence was uniformly higher in NACC than in the population-based cohorts. Among APOE-e4/e4 individuals, 5-y cumulative incidence was as follows: in the 60-64-y age stratum, it ranged from 0% to 5.88% in the three population-based cohorts versus 23.06% in NACC; in the 65-69-y age stratum, from 9.42% to 10.39% versus 34.62%; and in the 70-75-y age stratum, from 18.64% to 33.33% versus 38.34%. Five-year incidence of dementia was negligible except for APOE-e4/e4 individuals and those over 70 y. Lifetime incidence (to age 80-85 y) of MCI or dementia for the APOE-e4/e4 individuals in the long-term Framingham and Rotterdam cohorts was 34.69%-38.45% at age 60-64 y, 30.76%-40.26% at 65-69 y, and 33.3%-35.17% at 70-75 y. Confidence limits for these estimates are often wide, particularly for APOE-e4/e4 individuals and for the dementia outcome at 5 y. In regression models, APOE-e4 dose and age both consistently increased risk, as did lower education, subjective memory concerns, poorer baseline cognitive performance, and family history of dementia. We discuss several limitations of the study, including the small numbers of APOE-e4/e4 individuals, missing data and differential dropout, limited ethnic and racial diversity, and differences in definitions of exposure and outcome variables.
Estimates of the absolute risk of MCI or dementia, particularly over short time intervals, are sensitive to sampling and a variety of methodological factors. Nonetheless, such estimates were fairly consistent across the population-based cohorts, and lower than those from a convenience cohort and those estimated in prior studies-with implications for informed consent and design for clinical trials targeting high-risk individuals.
The late pre-Hispanic period in the US Southwest (A.D. 1200–1450) was characterized by large-scale demographic changes, including long-distance migration and population aggregation. To reconstruct ...how these processes reshaped social networks, we compiled a comprehensive artifact database from major sites dating to this interval in the western Southwest. We combine social network analysis with geographic information systems approaches to reconstruct network dynamics over 250 y. We show how social networks were transformed across the region at previously undocumented spatial, temporal, and social scales. Using well-dated decorated ceramics, we track changes in network topology at 50-y intervals to show a dramatic shift in network density and settlement centrality from the northern to the southern Southwest after A.D. 1300. Both obsidian sourcing and ceramic data demonstrate that long-distance network relationships also shifted from north to south after migration. Surprisingly, social distance does not always correlate with spatial distance because of the presence of network relationships spanning long geographic distances. Our research shows how a large network in the southern Southwest grew and then collapsed, whereas networks became more fragmented in the northern Southwest but persisted. The study also illustrates how formal social network analysis may be applied to large-scale databases of material culture to illustrate multigenerational changes in network structure.
It has been hypothesized that oxidative stress may underlie the development of preeclampsia. In this large, multicenter, randomized, double-blind trial involving low-risk, nulliparous women, ...supplementation with 1000 mg of vitamin C and 400 IU of vitamin E, beginning in the 9th to 16th week of pregnancy, did not reduce the rates of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension.
Supplementation with 1000 mg of vitamin C and 400 IU of vitamin E, beginning in the 9th to 16th week of pregnancy, did not reduce the rates of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension.
Preeclampsia has been considered to be a two-stage disorder. Abnormal placentation or perfusion results in an increased inflammatory response and endothelial dysfunction, which in turn lead to the characteristic maternal syndrome.
1
Oxidative stress is one of several mechanisms that have been proposed to cause manifestations of the disease; it has been suggested that the generation of free radicals in response to reduced placental perfusion may lead to clinical manifestations.
2
Support for this concept is provided by data showing that there are oxidative modifications of proteins,
3
,
4
lipids,
2
,
5
,
6
and DNA
7
in the blood and tissue of women with preeclampsia . . .
Multiple regression Roberts, Aki; Roberts, John M., Jr
2021., 2020-12-30
eBook
Multiple Regression: A Practical Introduction is a text for an advanced undergraduate or beginning graduate course in statistics for social science and related fields. Also, students preparing for ...more advanced courses can self-study the text to refresh and solidify their statistical background. Drawing on decades of teaching this material, the authors present the ideas in an approachable and nontechnical manner, with no expectation that readers have more than a standard introductory statistics course as background. Multiple regression asks how a dependent variable is related to, or predicted by, a set of independent variables. The book includes many interesting example analyses and interpretations, along with exercises. Each dataset used for the examples and exercises is small enough for readers to easily grasp the entire dataset and its analysis with respect to the specific statistical techniques covered. A website for the book at https://edge.sagepub.com/roberts1e includes SPSS, Stata, SAS, and R code and commands for each type of analysis or recoding of variables in the book. Solutions to two of the end-of-chapter exercise types are also available for students to practice. The instructor side of the site contains editable PowerPoint slides, other solutions, and a test bank.
Nominal interest rates may remain substantially below the averages of the last half century, because central banks’ inflation objectives lie below the average level of inflation, and estimates of the ...real interest rate that are likely to prevail over the long run fall notably short of the average real interest rate experienced during this period. Persistently low nominal interest rates may lead to more frequent and costly episodes at the effective lower bound (ELB) on nominal interest rates. We revisit the frequency and potential costs of such episodes in a world of low interest rates, using both a dynamic stochastic general equilibrium (DSGE) model and the Federal Reserve’s largescale econometric model, the FRB/US model. Four main conclusions emerge. First, monetary policy strategies based on traditional, simple policy rules lead to poor economic performance when the equilibrium interest rate is low, with economic activity and inflation more volatile and systematically falling short of desirable levels. Moreover, the frequency and length of ELB episodes under such policy approaches are estimated to be significantly higher than in previous studies. Second, a risk adjustment to a simple rule—whereby monetary policymakers are more accommodative, on average, than prescribed by the rule—ensures that inflation averages its 2 percent objective, and requires that policymakers systematically seek inflation near 3 percent when the ELB is not binding. Third, commitment strategies, whereby monetary accommodation is not removed until either inflation or economic activity overshoots its longrun objective, are very effective in both the DSGE and FRB/US models. And fourth, our simulation results suggest that the adverse effects on economic and price stability associated with the ELB may be substantial at inflation targets near 2 percent if the equilibrium real interest rate is low and monetary policy follows a traditional approach. Whether such adverse effects could justify a higher inflation target depends upon the degree to which monetary policy strategies that differ substantially from such traditional approaches are feasible, and an assessment of a broader array of the inflation target’s effects on economic welfare.
In this multicenter, placebo-controlled, randomized trial of intravenous magnesium sulfate in women at imminent risk for delivery between 24 and 31 weeks of gestation, magnesium sulfate did not ...significantly reduce the primary composite outcome of moderate or severe cerebral palsy or death. However, it did result in a reduced rate of cerebral palsy among survivors (a prespecified secondary outcome), which may suggest the possibility of benefit.
In women at imminent risk for delivery between 24 and 31 weeks of gestation, magnesium sulfate did not significantly reduce the primary composite outcome of moderate or severe cerebral palsy or death. However, it did result in a reduced rate of cerebral palsy among survivors.
Cerebral palsy is characterized by abnormal control of movement and posture that results in limitation of activity. It is caused by nonprogressive damage or dysfunction of the developing fetal or infant brain
1
and is a leading cause of chronic childhood disability, with profound medical, emotional, and economic consequences.
2
Preterm birth is a risk factor for cerebral palsy, and the magnitude of the risk is inversely correlated with gestational age at birth.
3
During the past 20 to 30 years, the survival of infants born markedly preterm has improved dramatically, and whereas some data suggest that the rate of cerebral palsy among . . .
Honeybee (Apis mellifera) health is threatened globally by the complex interaction of multiple stressors, including the parasitic mite Varroa destructor and a number of pathogenic viruses. Australia ...provides a unique opportunity to study this pathogenic viral landscape in the absence of V. destructor. We analysed 1,240A. mellifera colonies across Australia by reverse transcription-polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS). Five viruses were prevalent: black queen cell virus (BQCV), sacbrood virus (SBV), Israeli acute paralysis virus (IAPV) and the Lake Sinai viruses (LSV1 and LSV2), of which the latter three were detected for the first time in Australia. We also showed several viruses were absent in our sampling, including deformed wing virus (DWV) and slow bee paralysis virus (SBPV). Our findings highlight that viruses can be highly prevalent in A. mellifera populations independently of V. destructor. Placing these results in an international context, our results support the hypothesis that the co-pathogenic interaction of V. destructor and DWV is a key driver of increased colony losses, but additional stressors such as pesticides, poor nutrition, etc. may enable more severe and frequent colony losses to occur.
Calcite veins are a common product of hydrothermal fluid circulation. Clumped-isotope palaeothermometry is a promising technique for fingerprinting the temperature of hydrothermal fluids, but ...clumped-isotope systematics can be reset at temperatures of > ca. 100 °C. To model whether the reconstructed temperatures represent calcite precipitation or closed-system resetting, the precipitation age must be known. LA-ICP-MS U–Pb dating of calcite is a recently developed approach to direct dating of calcite and can provide precipitation ages for modelling clumped-isotope systematics in calcite veins. In this study, clumped-isotope and LA-ICP-MS U–Pb calcite analyses were combined in basalt-hosted calcite veins from three settings in Scotland. Samples from all three localities yielded precipitation temperatures of ca. 75–115 °C from clumped-isotope analysis, but veins from only two of the sites were dateable, yielding precipitation ages of 224 ± 8 Ma and 291 ± 33 Ma (2
σ
). Modelling from the dated samples enabled confident interpretation that no closed-system resetting had occurred in these samples. However, the lack of a precipitation age from the third location meant that a range of possible thermal histories had to be modelled meaning that confidence that resetting had not occurred was lower. This highlights the importance of coupling clumped-isotope thermometry and LA-ICP-MS U–Pb calcite dating in determining the temperature of hydrothermal fluids recorded in calcite veins. This paired approach is shown to be robust in constraining the timing and precipitation temperature of calcite formation, and thus for tracking hydrothermal processes.
A new urea-containing metal–organic framework (MOF) was synthesized to act as a heterogeneous catalyst. Ureas are well-known for self-recognition and aggregation behavior, resulting in loss of ...catalytic competency. The catalyst spatial isolation achievable in a porous MOF environment suggests a potentially general solution. The combination of a symmetrical urea tetracarboxylate strut, 4,4′-bipyridine, and Zn(NO3)2·6H2O under solvothermal conditions afforded a new microporous MOF (NU-601). This material is indeed an effective hydrogen-bond-donor catalyst for Friedel–Crafts reactions between pyrroles and nitroalkenes, whereas a homogeneous urea is much less competent. The higher rates of reaction of small substrates relative to larger ones with NU-601 strongly suggest that catalysis primarily occurs within the pores of this new material rather than on its exterior. To the best of our knowledge, this approach is the first example of specific engineering of successful hydrogen-bonding catalysis into a MOF material.
Maternal insulin resistance and preeclampsia Hauth, John C., MD; Clifton, Rebecca G., PhD; Roberts, James M., MD ...
American journal of obstetrics and gynecology,
04/2011, Volume:
204, Issue:
4
Journal Article
Peer reviewed
Open access
Objective The purpose of this study was to determine whether mid-trimester insulin resistance is associated with subsequent preeclampsia. Study Design This was a secondary analysis of 10,154 ...nulliparous women who received vitamin C and E or placebo daily from 9-16 weeks gestation until delivery. Of these, 1187 women had fasting plasma glucose and insulin tested between 22 and 26 weeks gestation. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index. Results Obese women were twice as likely to have a HOMA-IR result of ≥75th percentile. Hispanic and African American women had a higher percentage at ≥75th percentile for HOMA-IR than white women (42.2%, 27.2%, and 16.9%, respectively; P < .001). A HOMA-IR result of ≥75th percentile was higher among the 85 nulliparous women who subsequently had preeclampsia, compared with women who remained normotensive (40.5% vs 24.8%; adjusted odds ratio, 1.9; 95% confidence interval, 1.1–3.2). Quantitative insulin sensitivity check index results were similar to the HOMA-IR results. Conclusion Midtrimester maternal insulin resistance is associated with subsequent preeclampsia.
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