Community Teens' COVID-19 Experience: Implications for Engagement Moving Forward.

Data collected from pediatric primary care settings during the pandemic suggest an increase in internalizing symptoms and disparities in care based upon minoritized identity status(es). To inform care moving forward, the current study characterized the pandemic and related technology usage experiences of teenaged pediatric patients from communities with high hardship indexes. As part of a larger mixed-methods study, 17 teens (Mean age = 15.99 ± .99) and 10 caregivers independently voiced experiences related to the pandemic during remote focus group and interview sessions. Thematic analyses were used to assess qualitative data; descriptive analyses were used to characterize qualitative data. Despite no direct queries about the pandemic, 41% of teens and 40% of caregivers described their lived experiences during the pandemic. Two subthemes emerged within the primary theme of COVID-19: (1) Wellness/Mental Health and (2) Smartphone Use and Utility. Although distress and negative effects were voiced, questionnaire data indicated normative psychosocial functioning for both teen self-report and caregiver proxy report. Informed by the voiced experiences of teens and their caregivers from communities with high hardship indexes, methods for better assessing and managing internalizing symptoms in teen patients are presented. A multi-modal and multi-informant approach that leverages technology to garner information about teens' experiences and deliver care may help improve the well-being of teens in communities systemically burdened with disparities.

An Iterative Method of Modeling Pump-Treat-Inject System with "Partial Treatment".

Pump-and-treat technologies are widely used in groundwater remediation and site cleanup. Such technologies involve pumping contaminated groundwater to the surface for treatment. Following treatment, the water is often reinjected back into the aquifer (referred to as pump-treat-inject or PTI) for potential reuse. The treatment system is often designed to remove dissolved-phase contaminants in groundwater such that water meets applicable cleanup standards (herein referred to as "full treatment"). However, in some cases, the treatment system may not effectively reduce the dissolved-phase concentrations (herein referred to as "partial treatment") for some of the contaminants present in groundwater. Modeling PTI under partial treatment conditions is challenging because contaminant concentrations in injected water depend on the pumped water concentrations and the system treatment efficiency. Essentially, the injected water concentration (a transport model input) is unknown prior to transport simulation. This study presents a novel iterative approach to modeling PTI under partial treatment scenarios, where the injected water concentration is linked to the modeled pumped water concentration. The method was developed for a complicated three-dimensional (3D) flow and transport modeling study conducted for a confidential remediation site where PTI with partial treatment was applied. However, due to the complexity of the 3D model and the confidential information of the site, a simple two-dimensional (2D) numerical model is presented to demonstrate the iterative method. The 2D model test runs and the 3D model application in a remediation site showed that the iterative simulation results quickly converged to a viable final solution.

A Scoping Review of Associations Between Cannabis Use and Anxiety in Adolescents and Young Adults.

Cannabis and anxiety are both rising issues that impact young people. This review seeks to explore the association between anxiety and cannabis in adolescents and young adults (AYA). A database search was run retrospectively from July 2020 through calendar year 2013. Articles had to present outcomes examining cannabis use and symptoms of anxiety, be written in English, contain samples with ≥ 50% who are age 25 or younger, and be published in a peer-reviewed journal. Forty-seven studies were identified that examined the relationship between anxiety and cannabis use. Twenty-three studies found a positive association that greater anxiety among AYA was associated with greater cannabis use. In contrast, seven studies found a negative association that greater anxiety was related to less cannabis use. And finally, 17 studies found no clear association between anxiety and cannabis use. Further research is needed to better understand the relationship between anxiety and cannabis use.

mHealth Uses and Opportunities for Teens from Communities with High Health Disparities: A Mixed-Methods Study.

Despite widespread access to smartphones, teens from communities facing significant behavioral health disparities typically have low mobile health (mHealth) engagement. The purpose of this study was to characterize teen and caregiver perspectives about smartphone use and access, mHealth, and how mHealth could address teens' behavioral health needs during the pandemic and beyond. Remote recruitment and methodologies were used to engage 17 teens (M age = 15.9 ± 0.9) and 10 caregivers living in urban communities with significant socioeconomic and health disparities. Participants completed a focus group or interview session (based on preference) and self-report questionnaires (e.g., behavioral health history, pandemic impacts, technology use). Qualitative and quantitative data were analyzed using thematic and descriptive analyses, respectively. Both quantitative and qualitative data indicated relevant behavioral health concerns for teens and their families, impacts from the pandemic, and frequent smartphone use. Primary teen and caregiver themes included (1) health and wellness concerns, (2) barriers, (3) use of smartphones, (4) impacts of smartphones, and (5) opinions/suggestions for mHealth. This multi-method and multi-informant study highlighted the lived experiences of teens from marginalized communities and offered key insights to increase the acceptability and real-world engagement of mHealth tools. To address barriers to care for this population beyond the pandemic, clear messaging must be used for mHealth tools (e.g., data privacy, expectations of use). These findings testify to the importance of collaboration with teens and caregivers from communities facing large health disparities in future mHealth design, development, and deployment.

Neighborhood Deprivation is Associated with Increased Risk of Prenatal Smoke Exposure.

Despite years of advisories against the behavior, smoking among pregnant women remains a persistent public health issue in the USA. Recent estimates suggest that 9.4% of women smoke before pregnancy and 7.1% during pregnancy in the USA. Epidemiological research has attempted to pinpoint individual-level and neighborhood-level factors for smoking during pregnancy, including educational attainment, employment status, housing conditions, poverty, and racial demographics. However, most of these studies have relied upon self-reported measures of smoking, which are subject to reporting bias. To more accurately and objectively assess smoke exposure in mothers during pregnancy, we used Bayesian index models to estimate a neighborhood deprivation index (NDI) for block groups in Durham County, North Carolina, and its association with cotinine, a marker of smoke exposure, in pregnant mothers (n = 887 enrolled 2005-2011). Results showed a significant positive association between NDI and log cotinine (beta = 0.20, 95% credible interval = [0.11, 0.29]) after adjusting for individual covariates (e.g., race/ethnicity and education). The two most important variables in the NDI according to the estimated index weights were percent females without a high school degree and percent Black population. At the individual level, Hispanic and other race/ethnicity were associated with lowered cotinine compared with non-Hispanic Whites. Higher education levels were also associated with lowered cotinine. In summary, our findings provide stronger evidence that the socio-geographic variables of educational attainment and neighborhood racial composition are important factors for smoking and secondhand smoke exposure during pregnancy and can be used to target intervention efforts.

Residential Proximity to Major Roadways and Prevalent Hypertension Among Older Women and Men: Results From the Chinese Longitudinal Healthy Longevity Survey.

Background and Objectives: Prior studies suggested that residential proximity to major roadways was associated with increased risks of cardiovascular diseases in developed countries, for which one explanation is that road proximity could heighten the risks of hypertension. However, the association of residential distance to major roadways with hypertension is still unclear in low- and middle-income countries (LMICs) with levels of air pollution and socioeconomic development distinctively different from developed countries. Methods: We derived data from the eighth wave of the Chinese Longitudinal Healthy Longevity Survey, a nationwide prospective cohort. The present study included 12,881 individuals older than 65 years (mean age, 85.2 ± 11.7 years) with 55.8% of them being female. We ascertained the residential proximity to major roadways based on self-reports and hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. We then used logistic regression to examine the association between residential distance to major roadways and hypertension. Results: The odds ratios (ORs) of hypertension for participants living 50 to 100, 101 to 200, and ≥200 meters from major roads were 1.17 [95% confidence interval (95% CI) = 1.02-1.33], 1.21 (95% CI = 1.05-1.41), and 1.22 (95% CI = 1.10-1.34), respectively, compared to those living within 50 m (P for trend < 0.001). Significant effects of modifications from socioeconomic status and accessibility to health care resources were observed (Ps for interaction < 0.05). Compared to living within 50 m from a major roadway, the ORs of hypertension for living ≥50 m were higher in manual/agricultural workers, low-education groups, participants without household ventilation, and participants lacking in health education and health care resources. We observed considerable variations across geographic regions with the association in question attenuating in Eastern China but remaining significant in other regions. Conclusion: Residential proximity to major roadways was associated with lower odds of hypertension among older adults in China. The utility of residential proximity to major roadways as a marker of increased risks of hypertension and cardiovascular diseases may need to be revisited in LMICs.

Orsay Virus CP-δ Adopts a Novel ß-Bracelet Structural Fold and Incorporates into Virions as a Head Fiber.

Fiber proteins are commonly found in eukaryotic and prokaryotic viruses, where they play important roles in mediating viral attachment and host cell entry. They typically form trimeric structures and are incorporated into virions via noncovalent interactions. Orsay virus, a small RNA virus which specifically infects the laboratory model nematode Caenorhabditis elegans, encodes a fibrous protein δ that can be expressed as a free protein and as a capsid protein-δ (CP-δ) fusion protein. Free δ has previously been demonstrated to facilitate viral exit following intracellular expression; however, the biological significance and prevalence of CP-δ remained relatively unknown. Here, we demonstrate that Orsay CP-δ is covalently incorporated into infectious particles, the first example of any attached viral fibers known to date. The crystal structure of δ(1-101) (a deletion mutant containing the first 101 amino acid [aa] residues of δ) reveals a pentameric, 145-Å long fiber with an N-terminal coiled coil followed by multiple ß-bracelet repeats. Electron micrographs of infectious virions depict particle-associated CP-δ fibers with dimensions similar to free δ. The δ proteins from two other nematode viruses, Le Blanc and Santeuil, which both specifically infect Caenorhabditis briggsae, were also found to form fibrous molecules. Recombinant Le Blanc δ was able to block Orsay virus infection in worm culture and vice versa, suggesting these two viruses likely compete for the same cell receptor(s). Thus, we propose that while CP-δ likely mediates host cell attachment for all three nematode viruses, additional downstream factor(s) ultimately determine the host specificity and range of each virus.IMPORTANCE Viruses often have extended fibers to mediate host cell recognition and entry, serving as promising targets for antiviral drug development. Unlike other known viral fibers, the δ proteins from the three recently discovered nematode viruses are incorporated into infectious particles as protruding fibers covalently linked to the capsid. Crystal structures of δ revealed novel pentameric folding repeats, which we term ß-bracelets, in the intermediate shaft region. Based on sequence analysis, the ß-bracelet motif of δ is conserved in all three nematode viruses and could account for ∼60% of the total length of the fiber. Our study indicated that δ plays important roles in cell attachment for this group of nematode viruses. In addition, the tightly knitted ß-bracelet fold, which presumably allows δ to survive harsh environments in the worm gut, could be applicable to bioengineering applications given its potentially high stability.

Effect of silver nanospheres and nanowires on human airway smooth muscle cells: role of sulfidation.

Background: The toxicity of inhaled silver nanoparticles on contractile and pro-inflammatory airway smooth muscle cells (ASMCs) that control airway calibre is unknown. We explored the oxidative activities and sulfidation processes of the toxic-inflammatory response. Method: Silver nanospheres (AgNSs) of 20 nm and 50 nm diameter and silver nanowires (AgNWs), short S-AgNWs, 1.5 µm and long L-AgNWs, 10 µm, both 72 nm in diameter were manufactured. We measured their effects on cell proliferation, mitochondrial reactive oxygen species (ROS) release and membrane potential, and also performed electron microscopic studies. Main results and findings: The greatest effects were observed for the smallest particles with the highest specific surface area and greatest solubility that were avidly internalised. ASMCs exposed to 20 nm AgNSs (25 µg mL-1) for 72 hours exhibited a significant decrease in DNA incorporation (-72.4%; p < 0.05), whereas neither the 50 nm AgNSs nor the s-AgNWs altered DNA synthesis or viability. There was a small reduction in ASMC proliferation for the smaller AgNS, although Ag+ at 25 µL mL-1 reduced DNA synthesis by 93.3% (p < 0.001). Mitochondrial potential was reduced by both Ag+ (25 µg mL-1) by 47.1% and 20 nm Ag NSs (25 µg mL-1) by 40.1% (*both at p < 0.05), but was not affected by 50 nm AgNSs and the AgNWs. None of the samples showed a change in ROS toxicity. However, malondialdehyde release, associated with greater total ROS, was observed for all AgNPs, to an extent following the geometric size (20 nm AgNS: 213%, p < 0.01; 50 nm AgNS: 179.5%, p < 0.01 and L-AgNWs by 156.2%, p < 0.05). The antioxidant, N-acetylcysteine, prevented the reduction in mitochondrial potential caused by 20 nm AgNSs. The smaller nanostructures were internalised and dissolved within the ASMCs with the formation of non-reactive silver sulphide (Ag2S) on their surface, but with very little uptake of L-AgNWs. When ASMCs were incubated with H2S-producing enzyme inhibitors, the spatial extent of Ag2S formation was much greater. Conclusion: The intracellular toxicity of AgNPs in ASMCs is determined by the solubility of Ag+ released and the sulfidation process, effects related to particle size and geometry. Passivation through sulfidation driven by biogenic H2S can outcompete dissolution, thus reducing the toxicity of the smaller intracellular Ag nanostructures.

A Meta-Analysis of Clinical Outcomes After Radiofrequency Ablation and Microwave Ablation for Lung Cancer and Pulmonary Metastases.

PURPOSE: We conducted a meta-analysis assessing clinical outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) for treating lung cancer. METHODS: Databases were searched up to 2017 to identify high-quality studies. The results were presented as pooled estimates with 95% confidence intervals (CIs). RESULTS: Fifty-three studies were included, and up to 3,432 patients were pooled. The estimated 1-, 2-, 3-, 4-, and 5-year overall survival (OS) rates were higher for RFA-treated patients compared with those treated by MWA. The median OS, median progression-free survival (PFS), median local tumor PFS, complete ablation rate, and adverse events did not differ significantly. Subgroup analyses by tumor type showed that the median OS for RFA-treated patients with pulmonary metastases was higher than that of the MWA-treated patients. CONCLUSION: Thermal ablation, both RFA and MWA, is an effective approach for treating lung cancer with low risk of adverse events. RFA is associated with longer survival than MWA, and patients with pulmonary metastases showed better survival after RFA compared with MWA-treated patients.

The development of a Simplified, Effective, Labour Monitoring-to-Action (SELMA) tool for Better Outcomes in Labour Difficulty (BOLD): study protocol.

BACKGROUND: The partograph is currently the main tool available to support decision-making of health professionals during labour. However, the rate of appropriate use of the partograph is disappointingly low. Apart from limitations that are associated with partograph use, evidence of positive impact on labour-related health outcomes is lacking. The main goal of this study is to develop a Simplified, Effective, Labour Monitoring-to-Action (SELMA) tool. The primary objectives are: to identify the essential elements of intrapartum monitoring that trigger the decision to use interventions aimed at preventing poor labour outcomes; to develop a simplified, monitoring-to-action algorithm for labour management; and to compare the diagnostic performance of SELMA and partograph algorithms as tools to identify women who are likely to develop poor labour-related outcomes. METHODS/DESIGN: A prospective cohort study will be conducted in eight health facilities in Nigeria and Uganda (four facilities from each country). All women admitted for vaginal birth will comprise the study population (estimated sample size: 7,812 women). Data will be collected on maternal characteristics on admission, labour events and pregnancy outcomes by trained research assistants at the participating health facilities. Prediction models will be developed to identify women at risk of intrapartum-related perinatal death or morbidity (primary outcomes) throughout the course of labour. These predictions models will be used to assemble a decision-support tool that will be able to suggest the best course of action to avert adverse outcomes during the course of labour. To develop this set of prediction models, we will use up-to-date techniques of prognostic research, including identification of important predictors, assigning of relative weights to each predictor, estimation of the predictive performance of the model through calibration and discrimination, and determination of its potential for application using internal validation techniques. DISCUSSION: This research offers an opportunity to revisit the theoretical basis of the partograph. It is envisioned that the final product would help providers overcome the challenging tasks of promptly interpreting complex labour information and deriving appropriate clinical actions, and thus increase efficiency of the care process, enhance providers' competence and ultimately improve labour outcomes. Please see related articles ' http://dx.doi.org/10.1186/s12978-015-0027-6 ' and ' http://dx.doi.org/10.1186/s12978-015-0028-5 '.

Necroptosis takes place in human immunodeficiency virus type-1 (HIV-1)-infected CD4+ T lymphocytes.

Human immunodeficiency virus type 1 (HIV-1) infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD), indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1), a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α) plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis.

DDX5 facilitates HIV-1 replication as a cellular co-factor of Rev.

HIV-1 Rev plays an important role in the late phase of HIV-1 replication, which facilitates export of unspliced viral mRNAs from the nucleus to cytoplasm in infected cells. Recent studies have shown that DDX1 and DDX3 are co-factors of Rev for the export of HIV-1 transcripts. In this report, we have demonstrated that DDX5 (p68), which is a multifunctional DEAD-box RNA helicase, functions as a new cellular co-factor of HIV-1 Rev. We found that DDX5 affects Rev function through the Rev-RRE axis and subsequently enhances HIV-1 replication. Confocal microscopy and co-immunoprecipitation analysis indicated that DDX5 binds to Rev and this interaction is largely dependent on RNA. If the DEAD-box motif of DDX5 is mutated, DDX5 loses almost all of its ability to bind to Rev, indicating that the DEAD-box motif of DDX5 is required for the interaction between DDX5 and Rev. Our data indicate that interference of DDX5-Rev interaction could reduce HIV-1 replication and potentially provide a new molecular target for anti-HIV-1 therapeutics.

Occupational exposure to woodsmoke and oxidative stress in wildland firefighters.

Experimental studies indicate that exposure to woodsmoke could induce oxidative stress. However studies have not been conducted among the general population and specialized occupational groups despite the existence of elevated woodsmoke exposure situations. Therefore, we investigated whether there were across workshift changes in oxidative stress biomarkers among wildland firefighters who are occupationally exposed to elevated levels of woodsmoke. We collected pre- and post-workshift urine samples from 19 wildland firefighters before and after prescribed burns. We measured malondialdehyde (MDA) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in the samples, and analyzed whether there were cross-shift changes in their levels, and the relationships between the changes and the length of firefighting career, age of firefighter, and quantified workshift exposure to particulate matter. Overall no significant cross-shift change was observed for 8-oxodG or MDA in the urine samples of the firefighters. Changes in both biomarkers were also not associated with PM2.5, which was used as a marker of exposure. However, overall unadjusted geometric mean 8-oxo-dG levels in the samples (31 µg/g creatinine) was relatively higher compared to those measured in healthy individuals in many occupational or general population studies. Additionally, cross-shift changes in 8-oxo-dG excretion were dependent on the length of firefighting career (p=0.01) or age of the subject (p=0.01). Significant increases in 8-oxo-dG level from pre-shift to post-shift were observed for those who had been firefighters for 2 years or less. The results indicate that oxidative stress response measured as cross-shift changes in 8-oxo-dG may depend on age or the length of a firefighter's career. These results suggest the need to investigate the longer term health effects of cumulative exposure of woodsmoke exposure among wildland firefighters, because increased body burden of oxidative stress is a risk factor for many diseases and is theorized to be involved in aging.

Changes of plasma vWF level in response to the improvement of air quality: an observation of 114 healthy young adults.

Plasma von Willebrand factor (vWF) is an important factor involving in hemostasis and various cardiovascular diseases. Air pollution is related to many respiratory and cardiovascular diseases. During the Olympic Games Beijing 2008 period (August 8 to September 17, 2008) when air quality in Beijing improved greatly, we studied the relationship between plasma vWF level and the factors of air pollution index (API), ABO blood group, and polymorphisms in vWF gene in healthy young adults. We recruited 114 healthy medical students. In a period of more than 4 months around the period of Olympic Games Beijing 2008, six blood samples at stages 1 and 2 (before Olympic Games), stages 3 and 4 (during Olympic Games), and stages 5 and 6 (after Olympic Games) were taken from every participant for the measurement of plasma vWF level and genotyping of three SNPs (rs7954855, rs7965413, and rs216311) in vWF gene. Daily air pollution index near their living places was obtained from the officially published data. The average API began to decrease from stage 2, reached to nadir in stages 3 and 4, and increased but was still lower in stages 5 and 6. Plasma vWF decreased during the experimental period in all participants. The average plasma vWF decreased from stage 2 and remained lower in stages 3-6. vWF level varied greatly among the participants (from 30 to 170 %) but decreased proportionately when we analyzed their levels individually. Participants with O blood type had lower plasma vWF level than those with A, B, and AB blood types. Those with the SNP in vWF gene causing homozygous threonine at codon 1381 had lower plasma vWF level than those with homozygous alanine or heterozygous alanine/threonine. In the 114 normal individuals, the average plasma vWF level decreased during the period of Olympic Games Beijing 2008 when air quality improved greatly. This suggests that control of air pollution may be useful to prevent some diseases such as cardiovascular diseases.

Genetic and epigenetic mechanisms collaborate to control SERPINA3 expression and its association with placental diseases.

SERPINA3 (Serpin peptidase inhibitor clade A member 3), also known as a1-antichymotrypsin, is a serine protease inhibitor involved in a wide range of biological processes. Recently, it has been shown to be up-regulated in human placental diseases in association with a hypomethylation of the 5' region of the gene. In the present study, we show that the promoter of SERPINA3 is transcriptionally activated by three transcription factors (TFs) (SP1, MZF1 and ZBTB7B), the level of induction being dependent on the rs1884082 single nucleotide polymorphism (SNP) located inside the promoter, the T allele being consistently induced to a higher level than the G, with or without added TFs. When the promoter was methylated, the response to ZBTB7B was allele specific (the G allele was strongly induced, while the T allele was strongly down-regulated). We propose an adaptive model to explain the interest of such a regulation for placental function and homeostasis. Overexpression of SERPINA3 in JEG-3 cells, a trophoblast cell model, decreased cell adhesion to the extracellular matrix and to neighboring cells, but protects them from apoptosis, suggesting a way by which this factor could be deleterious at high doses. In addition, we show in different human populations that the T allele appears to predispose to Intra Uterine Growth Restriction (IUGR), while a G allele at a second SNP located in the second exon (rs4634) increases the risk of preeclampsia. Our results provide mechanistic views inside the involvement of SERPINA3 in placental diseases, through its regulation by a combination of epigenetic, genetic and TF-mediated regulations.

A semi-analytical solution based on a numerical solution of the solute transport of a conservative and nonreactive tracer.

In the evaluation of potential risk from ingestion of groundwater near an impacted site, numerical simulation of fate and transport processes of chemicals of concern is often required. If there is potential concern about multiple chemicals, numerical simulation of each chemical separately is often needed. In this paper, a semi-analytical solution is presented based on a numerical solution of the transport of a conservative and nonreactive tracer. When multiple chemicals undergoing sorption and first-order degradation need to be modeled, we can avoid performing individual numerical simulations for each chemical by applying the semi-analytical solution. Numerical test runs were conducted to verify the semi-analytical solution; simulation results reveal that the concentrations derived from the semi-analytical solution are identical to those derived from the individual numerical fate and transport model simulations. The semi-analytical solution requires steady-state flow conditions, no continuing contaminant source, and similar initial source concentration distributions.

A method of accelerating transport simulation when groundwater pumping is simulated.

In solving groundwater transport problems with numerical models, the computation time (CPU processing time) of transport simulation is approximately inversely proportional to the transport time-step size. Therefore, large time-step sizes are favorable for achieving short computation time. However, transport time-step size must be sufficiently small to avoid numerical instability if an explicit scheme is used (and to guarantee enough model accuracy if an implicit scheme is used). For a transport model involving groundwater pumping, a small transport time-step size is often required due to the high groundwater velocities near the pumping well. Small grid spacing often specified near the pumping well also limits the time-step size. This paper presents a method to increase transport time-step size in a transport model when groundwater pumping is simulated. The key to this approach is to numerically decrease the groundwater seepage velocities in grid cells near the pumping well by increasing the effective porosity so that the transport time-step size can be increased without violating stability constraints. Numerical tests reveal that by using the proposed method, the computation time of transport simulation can be reduced significantly, while the transport simulation results change very little.

Picosecond pulses from a cryogenically cooled, composite amplifier using Yb:YAG and Yb:GSAG.

A cryogenic Yb amplifier using two laser materials, Gd3Sc2Al3O12 and Y3Al5O12 (YAG), has been used to obtain 70 W average power at 5 kHz pulse repetition frequency; the output was compressed to 1.6 ps, compared with an input compressible to 1.4 ps. The gain broadening obtained by combining two media enables shorter pulses than using Yb:YAG alone but retains the power-scaling advantages of cryogenic Yb:YAG.

Measurement of inflammation and oxidative stress following drastic changes in air pollution during the Beijing Olympics: a panel study approach.

Ambient air pollution has been linked to cardiovascular and respiratory morbidity and mortality in epidemiology studies. Frequently, oxidative and nitrosative stress are hypothesized to mediate these pollution effects, however precise mechanisms remain unclear. This paper describes the methodology for a major panel study to examine air pollution effects on these and other mechanistic pathways. The study took place during the drastic air pollution changes accompanying the 2008 Olympics in Beijing, China. After a general description of air pollution health effects, we provide a discussion of panel studies and describe the unique features of this study that make it likely to provide compelling results. This study should lead to a clearer and more precise definition of the role of oxidative and nitrosative stress, as well as other mechanisms, in determining acute morbidity and mortality from air pollution exposure.

Pharmacological properties of N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate (552-02), a novel epithelial sodium channel blocker with potential clinical efficacy for cystic fibrosis lung disease.

Amiloride improves mucociliary clearance (MC) by blocking airway epithelial sodium channels (ENaC) and expanding airway surface liquid (ASL). However, the low potency and rapid absorption of amiloride by airway epithelia translated into a short duration of efficacy as an aerosolized therapy for cystic fibrosis (CF) patients. To improve ENaC blocker CF pharmacotherapy, a more potent and durable ENaC blocker tailored for aerosol delivery was synthesized. Parion compound N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate (552-02) was tested for potency and reversibility of ENaC block, epithelial absorption and biotransformation, selectivity, durability of ASL expansion under isotonic and hypertonic conditions in canine and human CF bronchial epithelial cells, and drug dissociation on ENaC in Xenopus oocytes. Short-circuit current assessed compound potency and reversibility, patch-clamp recordings of ENaC current assessed drug off-rate (k(off)), a gravimetric method and confocal microscopy measured mucosal water retention and ASL height, and drug absorption and biotransformation were assessed using liquid chromatography-mass spectrometry. Amiloride and 552-02 were tested in vivo for MC activity in sheep immediately and 4 to 6 h after aerosol dosing. Compared with amiloride, compound 552-02 was 60 to 100-fold more potent, it was 2 to 5-fold less reversible, it was slower at crossing the epithelium, and it exhibited a 170-fold slower k(off) value. 552-02 exhibited greater ASL expansion over 8 h in vitro, and it was more effective than amiloride at increasing MC immediately and 4 to 6 h after dosing. When combining hypertonic saline and 552-02, a synergistic effect on ASL expansion was measured in canine or CF bronchial epithelia. In summary, the preclinical data support the clinical use of 552-02 +/- hypertonic saline for CF lung disease.