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Folate, including the folic acid form, is a key component of the one-carbon metabolic pathway used for DNA methylation. Changes in DNA methylation patterns during critical development periods are associated with disease outcomes and are associated with changes in nutritional status in pregnancy. The long-term impact of periconceptional folic acid supplementation on DNA methylation patterns is unknown.To determine the long-term impact of periconceptional folic acid supplementation on DNA methylation patterns, we examined the association of the recommended dosage (400 μg/d) and time period (periconceptional before pregnancy through first trimester) of folic acid supplementation with the DNA methylation patterns in the offspring at age 14-17 y compared with offspring with no supplementation.Two geographic sites in China from the 1993-1995 Community Intervention Program of folic acid supplementation were selected for the follow-up study. DNA methylation at 402,730 CpG sites was assessed using saliva samples from 89 mothers and 179 adolescents (89 male). The mean age at saliva collection was 40 y among mothers (range: 35-54 y) and 15 y among adolescents (range: 14-17 y). Epigenome-wide analyses were conducted to assess the interactions of periconceptional folic acid exposure, the 5,10-methylenetetrahydrofolate reductase (MTHFR)-C677T genotype, and epigenome-wide DNA methylation controlling for offspring sex, geographic region, and background cell composition in the saliva.In the primary outcome, no significant differences were observed in epigenome-wide methylation patterns between adolescents exposed and those non-exposed to maternal periconceptional folic acid supplementation after adjustment for potential confounders [false discovery rate (FDR) P values 0.05]. The MTHFR-C677T genotype did not modify this lack of association (FDR P values 0.05).Overall, there were no differences in DNA methylation between adolescents who were exposed during the critical developmental window and those not exposed to the recommended periconceptional/first-trimester dosage of folic acid.

Mathematics is considered to be an important discipline and every student globally is bound to learn mathematics in curriculum for better opportunities in future and leading a successful life. Basic math skills are important for success in school and everyday life. Yet many people experience uneasiness and fear when dealing with numerical data, often regarded as math anxiety but Math anxiety is not limited to a minority of individuals nor to one country. International comparisons of high school students show that some students in every country are anxious about math. A review of various research papers is presented in this article for exploring the factors of math anxiety among students and how math anxiety has affected the achievement among students in the subject of mathematics.

Purpose Information on incentives for COVID-19 testing is needed to understand effective practices that encourage testing uptake. We describe characteristics of those who received an incentive after performing a rapid antigen test. Design Cross-sectional descriptive analysis of survey data. Setting During April 29–May 9, 2021, COVID-19 rapid antigen testing was offered in 2 Maryland cities. Sample Convenience sample of 553 adults (≥18 years) who tested and received an incentive; 93% consented to survey. Measures Survey questions assessed reasons for testing, testing history, barriers, and demographics. Analysis Robust Poisson regressions were used to determine characteristic differences based on testing history and between participants who would re-test in the future without an incentive vs participants who would not. Results The most common reasons for testing were the desire to be tested (n = 280; 54%) and convenience of location (n = 146; 28%). Those motivated by an incentive to test (n = 110; 21%) were 5.83 times as likely to state they would not test again without an incentive, compared to those with other reasons for testing (95% CI: 2.67-12.72, P < .001). Critical Limitations No comparative study group. Conclusion Results indicate internal motivation and convenience were prominent factors supporting testing uptake. Incentives may increase community testing participation, particularly among people who have never tested. Keywords COVID-19, pandemic, incentives, health behavior, community testing.

Background Although most adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fully recover, a proportion have ongoing symptoms, or post-COVID conditions (PCC), after infection. The objective of this analysis was to estimate the number of United States (US) adults with activity-limiting PCC on 1 November 2021. Methods We modeled the prevalence of PCC using reported infections occurring from 1 February 2020 to 30 September 2021, and population-based, household survey data on new activity-limiting symptoms ≥1 month following SARS-CoV-2 infection. From these data sources, we estimated the number and proportion of US adults with activity-limiting PCC on 1 November 2021 as 95% uncertainty intervals, stratified by sex and age. Sensitivity analyses adjusted for underascertainment of infections and uncertainty about symptom duration. Results On 1 November 2021, at least 3.0–5.0 million US adults, or 1.2%–1.9% of the US adult population, were estimated to have activity-limiting PCC of ≥1 month’s duration. Population prevalence was higher in females (1.4%–2.2%) than males. The estimated prevalence after adjusting for underascertainment of infections was 1.7%–3.8%. Conclusions Millions of US adults were estimated to have activity-limiting PCC. These estimates can support future efforts to address the impact of PCC on the US population.

Supplementary Methods, Figure Legends 1-3 from Deoxycytidine Kinase Modulates the Impact of the ABC Transporter ABCG2 on Clofarabine Cytotoxicity

Supplementary Figure 2 from Deoxycytidine Kinase Modulates the Impact of the ABC Transporter ABCG2 on Clofarabine Cytotoxicity

Supplementary Figure 3 from Deoxycytidine Kinase Modulates the Impact of the ABC Transporter ABCG2 on Clofarabine Cytotoxicity

Supplementary Figure 1 from Deoxycytidine Kinase Modulates the Impact of the ABC Transporter ABCG2 on Clofarabine Cytotoxicity

An increase in adverse mental health symptoms occurred in the general population at the onset of the COVID-19 pandemic, which peaked in 2020 and subsequently decreased (1-3). The pandemic exacerbated existing stress and fatigue among public health workers responding to the public health crisis.* During March-April 2021, a survey of state, tribal, local, and territorial (STLT) public health workers found that 52.8% of respondents experienced symptoms of at least one of the following mental health conditions: depression, anxiety, or posttraumatic stress disorder (PTSD) (4); however, more recent estimates of mental health symptoms among this population are limited. To evaluate trends in these conditions from the previous year, the prevalence of symptoms of mental health conditions and suicidal ideation, a convenience sample of STLT public health workers was surveyed during March 14-25, 2022. In total, 26,069 STLT public health workers responded to the survey. Among respondents

Although most adults infected with SARS-CoV-2 fully recover, a proportion have ongoing symptoms, or post-COVID conditions (PCC), after infection. The objective of this analysis was to estimate the number of US adults with activity-limiting PCC on November 1, 2021.We modeled the prevalence of PCC using reported infections occurring from February 1, 2020 - September 30, 2021, and population-based, household survey data on new activity-limiting symptoms ≥1 month following SARS-CoV-2 infection. From these data sources, we estimated the number and proportion of US adults with activity-limiting PCC on November 1, 2021, as 95% uncertainty intervals, stratified by sex and age. Sensitivity analyses adjusted for under-ascertainment of infections and uncertainty about symptom duration.On November 1, 2021, at least 3.0-5.0 million US adults were estimated to have activity-limiting PCC of ≥1 month duration, or 1.2%-1.9% of US adults. Population prevalence was higher in females (1.4%-2.2%) than males. The estimated prevalence after adjusting for under-ascertainment of infections was 1.7%-3.8%.Millions of US adults were estimated to have activity-limiting PCC. These estimates can support future efforts to address the impact of PCC on the U.S. population.

Masks are effective at limiting transmission of SARS-CoV-2, the virus that causes COVID-19 (1), but the impact of policies requiring masks in school settings has not been widely evaluated (2-4). During fall 2021, some school districts in Arkansas implemented policies requiring masks for students in kindergarten through grade 12 (K-12). To identify any association between mask policies and COVID-19 incidence, weekly school-associated COVID-19 incidence in school districts with full or partial mask requirements was compared with incidence in districts without mask requirements during August 23-October 16, 2021. Three analyses were performed: 1) incidence rate ratios (IRRs) were calculated comparing districts with full mask requirements (universal mask requirement for all students and staff members) or partial mask requirements (e.g., masks required in certain settings, among certain populations, or if specific criteria could not be met) with school districts with no mask requirement; 2) ratios of observed-to-expected numbers of cases, by district were calculated; and 3) incidence in districts that switched from no mask requirement to any mask requirement were compared before and after implementation of the mask policy. Mean weekly district-level attack rates were 92-359 per 100,000 persons in the community* and 137-745 per 100,000 among students and staff members; mean student and staff member vaccination coverage ranged from 13.5% to 18.6%. Multivariable adjusted IRRs, which included adjustment for vaccination coverage, indicated that districts with full mask requirements had 23% lower COVID-19 incidence among students and staff members compared with school districts with no mask requirements. Observed-to-expected ratios for full and partial mask policies were lower than ratios for districts with no mask policy but were slightly higher for districts with partial policies than for those with full mask policies. Among districts that switched from no mask requirement to any mask requirement (full or partial), incidence among students and staff members decreased by 479.7 per 100,000 (p0.01) upon implementation of the mask policy. In areas with high COVID-19 community levels, masks are an important part of a multicomponent prevention strategy in K-12 settings (5).

The papers reproduced in this book are the proceedings of a conference commemorating the thought of Wilhelm Ropke, 50 years after his death in 1966, that took place at The Graduate Institute of Int...

An open-path cavity ring-down spectroscopy (CRDS) sensor has been developed for measurement of atmospheric ammonia (NH3) and represents the first use of open-path CRDS in the mid-infrared region. The sensor uses a continuous-wave distributed feedback quantum cascade laser at 10.33 μm to target strong absorption features. The optical cavity is constructed with two high-reflectivity mirrors (R = 0.9995). The open-path configuration removes inlet effects, which are very challenging for closed-path instruments, and can be enabling for compact, low-power designs. Sensor performance was validated in the laboratory by measuring known concentrations in a closed-path configuration. The open-path configuration was validated by comparison against a commercial closed-path CRDS instrument for outdoor measurements at a small feed lot. Ammonia concentrations from the two instruments showed good agreement with slope of 0.990 (R 2 = 0.92), for 5-min averages. The precision of the open-path instrument was found from Allan variance studies as 1.2 ppb (2-σ) for 3-s measurement durations.

Open-path cavity ring-down spectroscopy provides a potential means for sensitive detection of trace gas species in compact, lightweight packages. This contribution presents studies of attainable sensitivity along with details of methane and ammonia sensors.

Within a species, variation in the use of sexual signals is observed between different populations. For intersexual traits, differences in the environmental conditions experienced by populations can play an important role in driving variation in male ornaments and female preferences. However, little is known about the factors maintaining variation in intrasexual traits used in competition. In this study, we investigate the role of climatic conditions in maintaining variation in the expression of an intrasexual signal in the paper wasp Polistes dominulus. The results of an experiment in which pupae were housed under different temperature and humidity conditions revealed a strong effect of temperature during pupal development on the expression of the signal. Furthermore, a comparison of survival and body weight between wasps reared at different temperatures indicates that signal expression exhibits phenotypic plasticity in response to developmental temperature. The effect of temperature on signal expression is consistent with patterns of signal expression observed across populations in the wild and suggests that climatic conditions may act to constrain signal expression in some populations but not in others, driving variation in signal use within P. dominulus. Environmental conditions may therefore be important in defining the scope for intrasexual signalling in animal populations and, in doing so, may play a role in maintaining variation in intrasexual traits in the face of sexual selection.

Acute myeloid leukemia (AML) is a genetically heterogeneous cancer that frequently exhibits aberrant kinase signaling. We investigated a treatment strategy combining sorafenib, a multikinase inhibitor with limited single-agent activity in AML, and cytarabine, a key component of AML chemotherapy.Using 10 human AML cell lines, we determined the effects of sorafenib (10 μM) on antileukemic activity by measuring cell viability, proliferation, ERK1/2 signaling, and apoptosis. We also investigated the effects of sorafenib treatment on the accumulation of cytarabine and phosphorylated metabolites in vitro. A human equivalent dose of sorafenib in nontumor-bearing NOD-SCID-IL2Rγ(null) mice was determined by pharmacokinetic studies using high performance liquid chromatography with tandem mass spectrometric detection, and steady-state concentrations were estimated by the fit of a one-compartment pharmacokinetic model to concentration-time data. The antitumor activity of sorafenib alone (60 mg/kg) twice daily, cytarabine alone (6.25 mg/kg administered intraperitoneally), or sorafenib once or twice daily plus cytarabine was evaluated in NOD-SCID-IL2Rγ(null) mice bearing AML xenografts.Sorafenib at 10 μM inhibited cell viability, proliferation and ERK1/2 signaling, and induced apoptosis in all cell lines studied. Sorafenib also increased the cellular accumulation of cytarabine and metabolites resulting in additive to synergistic antileukemic activity. A dose of 60 mg/kg in mice produced a human equivalent sorafenib steady-state plasma exposure of 10 μM. The more dose-intensive twice-daily sorafenib plus cytarabine (n = 15) statistically significantly prolonged median survival in an AML xenograft model compared with sorafenib once daily plus cytarabine (n = 12), cytarabine alone (n = 26), or controls (n = 27) (sorafenib twice daily plus cytarabine, median survival = 46 days; sorafenib once daily plus cytarabine, median survival = 40 days; cytarabine alone, median survival = 36 days; control, median survival = 19 days; P.001 for combination twice daily vs all other treatments listed).Sorafenib in combination with cytarabine resulted in strong anti-AML activity in vitro and in vivo. These results warrant clinical evaluation of sorafenib with cytarabine-based regimens in molecularly heterogeneous AML.

Purine nucleoside antimetabolites, such as clofarabine, are effective antileukemic agents. However, their effectiveness depends on an initial activation step in which they are monophosphorylated by deoxycytidine kinase (dCK). Some purine nucleoside antimetabolites and their monophosphate derivatives are exported by the ABC transporter ABCG2. Because clofarabine is a dCK substrate, and we show substantial variation in dCK and ABCG2 in myeloid leukemia, we hypothesized that the activity of dCK may modulate ABCG2-mediated resistance to clofarabine by regulating the formation of clofarabine monophosphate. We show that ABCG2 influence on clofarabine cytotoxicity was markedly influenced by dCK activity. When dCK expression was reduced by siRNA, clofarabine cytotoxicity was strongly reduced by enhanced ABCG2-mediated efflux. Conversely, dCK overexpression blunted ABCG2-mediated efflux of clofarabine by increasing the formation of clofarabine nucleotides. The use of an ABCG2 inhibitor confirmed that ABCG2 export of clofarabine is maximal when dCK levels are minimal. Analysis of intracellular clofarabine metabolites suggested that ABCG2 exported clofarabine more readily than clofarabine monophosphate. That ABCG2 primarily effluxes clofarabine, but not chlorfarabine-monophosphate, was confirmed by HPLC analysis of drug exported from ABCG2-overexpressing cells. Because the level and function of dCK and ABCG2 vary substantially among other types of cancer, these findings have important implications not only for clofarabine therapy but for purine nucleoside therapy in general. Therefore, we propose that addition of ABCG2 inhibitors would effectively increase the antitumor efficacy of purine nucleosides by blocking drug efflux that may be a significant mode of resistance when dCK levels are low. Cancer Res; 71(5); 1781–91. ©2011 AACR.

The presence of live and dead emergent vegetation alters the microbial metabolism of communities within the water column of prairie pothole wetlands. To demonstrate the effects, dissolved CH4, dissolved O2, plant densities, and litter densities were measured in transects from emergent vegetation to open water zones. O2 concentrations were consistently lower and CH4 concentrations consistently higher in emergent zones. Plant surface cover most likely interferes with gas flux across the air-water interface in the emergent zone, impeding O2 transport into the water column and impeding CH4 transport out of the water column. Either directly or indirectly, the presence of emergent vegetation may alter aerobic and anaerobic metabolism; since wet and dry cycles can result in emergent plant cover from nearly absent to nearly 100%, understanding these dynamics over the long-term will require studies over a range of wetland stages.

In 1986 Catherine van Casselaer published a ground-breaking book, Lot’s Wife: lesbian Paris, 1890–1914, the first study of ‘Paris–Lesbos’. Strangely, both book and author appear to have vanished aw...

(1997). Electronic Monitoring of Offenders: A New Dimension in Community Sentencing or a Needless Diversion? International Review of Law, Computers & Technology: Vol. 11, No. 1, pp. 147-154.

The phosphorus (P) deficiency status of phytoplankton communities was measured using the physiological indicator, alkaline phosphatase activity (APA) and nutrient-addition growth bioassays in field sampled from four northeastern Minnesota lakes and the far western arm of Lake Superior. Phosphorus additions generally reduced APA, while other treatments increased activity. Samples receiving nitrogen (N) and P increased APA after a long lag period. P-addition bioassays of Lake Superior were consistent with phytoplankton P limitation and variations in APA indicated potential seasonal and spatial changes in P deficiency status. The results suggest that APA reliably reflected the phytoplankton P status, but may not provide sufficient information when N or NP limitation is present.

Background and aims – Plant species adapted to metalliferous soil are of high conservation value, and actions for preserving these species (some of them are endemics) are urgent given the threat of mining activities. In the framework of an integrated conservation programme of cuprophytes (plants that tolerate a soil with a high level of copper) in Katanga (D. R. Congo), this study aims at: (1) providing new data on species whose germination has never been studied so far; (2) gaining new insight into the storage behaviour of these species; (3) discussing implications for ex situ conservation of these highly threatened species. Methods – Germination tests were conducted on fresh seeds of nineteen species. These tests were repeated after 6, 12 and 24 months of storage in dry-cold conditions. Key results – Most species kept or increased their germination capacity after 2 years storage in dry-cold conditions. Nine species showed a slight decrease in their viability (from 100% to > 80%) after 2 years storage in dry-cold conditions. The present study gives evidence that at least six of the 19 studied species are desiccation-tolerant (orthodox). Among these, two are strict endemics, Haumaniastrum robertii and Faroa malaissei, and two are broad endemics, Diplolophium marthozianum and Gladiolus robiliartianus . This means that ex situ seed banking of these species could form a useful part of a more comprehensive conservation strategy. Only two species have been identified as desiccation-sensitive (recalcitrant), i.e.inappropriate for conservation in standard seed bank conditions. An orthodox behaviour has not been ruled out for the other species tested, but their response was less clear and needs further investigation.

Transect measurements, continuous monitoring, and synoptic surveys were used to examine patterns in light availability, temperature, and dissolved oxygen concentrations within and outside emergent vegetation zones in Goose Lake Marsh, a natural prairie pothole wetland in central Iowa. Water column light availability was less than 2% of ambient light in emergent vegetated areas due to canopy cover, small floating plants (lemnids), and plant litter. Water temperatures and dissolved oxygen concentrations were significantly lower and varied less diurnally in vegetated areas. Three habitat zones could be identified based on patterns in vegetation and dissolved oxygen: (1) a zone of dense emergent macrophytes providing significant submerged structure but with nearly or completely anoxic water, (2) a transition zone of sparse emergent macrophytes providing less structure but with more aerobic water, and (3) an open water zone with consistently acrobic water but with little submerged structure. Vegetation patterns are likely to control major aspects of wetland biogeochemistry and trophic dynamics, and wetlands should be viewed as complex mosaics of habitats with distinct structural and functional characteristics.

BACKGROUND: The holmium:YAG laser shrinks stromal collagen and changes corneal refractive power, reportedly without recurrent or persistent epithelial defects, stromal necrosis, or damage to the epithelium and endothelium observed with some other thermokeratoplasty techniques. METHODS: We studied the safety of the holmium:YAG laser using various patterns and energy densities after treating 12 poorly sighted eyes, two immediately prior to corneal transplantation and 10 followed for a mean period of 90 days (range, 60 to 180 days). Visual acuity, intraocular pressure and inflammation, central corneal endothelial cell density and thickness, and intraocular structures of the eye were indices evaluated regularly. Patients were also assessed for specific symptoms during the post-operative period. RESULTS: There were no problems with epithelial healing and no stromal necrosis or evidence of endothelial damage; no significant differences were noted in any of the endothelial cell indices examined. A mean change in corneal curvature of 1.10 diopter (D) was achieved, but varying amounts of regression of this effect was noted. CONCLUSIONS: Holmium:YAG laser thermal keratoplasty appears to be safe over a follow up of up to 180 days. Corneal refractive changes on the order of 1.05 D can be achieved using the parameters employed in this study. Whether or not larger, persistent corneal refractive change can be achieved with a holmium:YAG laser remains to be determined. [J Refract Surg. 1995,11:358-365.]

The Northern Lakes and Forests ecoregion of Minnesota contains thousands of lakes, characterized by their sensitivity to acid rain and typically low productivity. Four acid-sensitive lakes were studied from 1988 to 1991 to determine if phytoplankton were deficient in nitrogen, phosphorus, or both N and P and if the nutrient input via atmospheric deposition could increase primary production. The relative accuracy of predictions based on growth response bioassays, physiological assays, and nutrient deficiency indices was also evaluated. Our results show that (1) N enrichment generally caused a greater biomass response than P, although N + P almost always yielded the greatest effect and co-limitation was likely in two of the lakes, (2) predictions based on DIN:TP ratios generally agreed with the growth bioassays; TN:TP and DIN:SRP were not useful and could be misleading, and (3) atmospheric deposition could satisfy most of the daily algal N demand and increase the fertility of these lakes. These results suggest that although water quality protection based solely on P may not protect against this non-point source of nutrients, without these control strategies, P inputs would be expected to have a disproportionately greater stimulation of phytoplankton growth.

In this paper we explore the crucial role played by the use of large databases in the identification, development, and refinement of models that describe the toughness behavior of ferritic steels. Specifically, we seek to emphasize and illustrate the point that when physical models are calibrated using large databases this process can reveal trends not previously seen, or foreseen. In support of this idea two examples are cited. First, the evidence for a CVE master curve in fracture mode transition is reviewed, as a counterpoint to the commonly held belief that each Charpy tanh transition curve is unique, with little commonality even within specific alloys, let alone across all ferritic steels. Second, new evidence is presented that the degree of prior hardening experienced by a ferritic steel has a systematic effect on the scatter exhibited by KJc data. This evidence suggests that the KJc Master Curve model, in which the scatter of KJc follows a Weibull distribution having a Kmin = 20 MPa√m and a slope (scatter magnitude) of 4, requires refinement, especially for the higher To values characteristic of steels that have been hardened by, for example, neutron irradiation damage.Copyright © 2009 by ASME

In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA).To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule.Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002).Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals.Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs.At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P.001). Route of administration did not significantly influence the occurrence of systemic AEs.The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067.