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Background Computed tomography-derived fractional flow reserve (CT-FFR) has emerged as a promising non-invasive substitute for fractional flow reserve (FFR) measurement. Normally, CT-FFR providing functional significance of coronary artery disease (CAD) by using a simplified total coronary resistance index (TCRI) model. Yet the error or discrepancy caused by this simplified model remains unclear. Methods A total of 20 consecutive patients with suspected CAD who underwent CTA and invasive FFR measurement were retrospectively analyzed. CT-FFR and CT-(Pd/Pa)rest values derived from the coronary CTA images. The diagnostic performance of CT-FFR and CT-(Pd/Pa)rest were evaluated on a per-vessel level using C statistics with invasive FFR

To simulate the real distribution of pressure on the specimen in the Brazilian test, non-uniform distribution is assumed to be the form of pressure distribution on the disk. The analytic solutions of the stress field for an uncracked Brazilian disk under several typical non-uniformly distributed pressures are obtained by the power series expansion method and mathematical method. Then the analytic solutions of the mode I and mode II stress intensity factors for a centrally cracked Brazilian disk under the same pressures are obtained by the weight function method. The results show that the influence of distribution form on stress intensity factors cannot be ignored for the case of large relative crack length and load distribution angle. The applicable ranges of the formulae to calculate stress intensity factors under concentrated force, uniformly and non-uniformly distributed pressure are given according to the analysis results. In addition, the loading conditions for pure mode I and II fracture are discussed when a disk with a central crack is subjected to non-uniformly distributed pressure.

To explore the deterioration response of rock engineering structure under seasonal acid rain, a large number of mixed mode I-III fracture experiments were conducted on sandstone with the edge notched disc bending (ENDB) specimens. Before fracture tests, all the sandstone samples were respectively subjected to 0, 2, 4, 7 and 10 wetting–drying cycles with hydrochloric acid solution to simulate the periodic acid rain corrosion. In addition, the deterioration mechanism was revealed by chemical analysis and observing the variation in microstructure characteristics of the sandstone specimens with the scanning electron microscope (SEM). The results showed that the mixed mode I-III fracture toughness components (i.e. KIf, KIIIf) and effective fracture toughness (i.e. Keff) decreased gradually with increasing wetting–drying cycles. And the larger the loading angle or closer to the mode III, the greater deterioration degree of effective fracture toughness. Besides, the influence of periodic corrosion had an obvious time sensibility. All of these fracture parameters decreased greatly at the early stage of the cyclic procedure, and then, the rate gradually tended to be flat with the increase of the wetting–drying cycles. Moreover, the surface of the sandstone specimen became rougher, even multiple micro-cracks and holes were initiated after undergoing periodic acid corrosion. Macroscopically, it led to the decrease of its ability to resist fracture. The degradation effect could be attributed to the accumulation and coupling of multiple physical and chemical water–rock interactions.

A series of tests with centrally cracked Brazilian disc and un-cracked Brazilian disc specimens were conducted to investigate the relation between the mode II fracture toughness K IIC and tensile strength σ t of sandstone under different treatment conditions. The results indicated that there was a good linear relation between these two rock parameters. Further, this conclusion was also validated by theoretical analysis based on the generalized maximum tangential stress criterion. Moreover, an empirical formula K IIC = 0.2159 σ t was obtained using linear regression analysis, which can be confidently used to estimate the mode II fracture toughness with tensile strength of rocks.

The maximum tangential strain (MTSN) criterion has been modified to include the effects of T-stress and stress intensity factors in conditions of both plane stress and plane strain. Further, both the T-stress and Poisson's ratio affecting the crack propagation are also discussed according to the extended MTSN (EMTSN) criterion, which is a modified MTSN criterion. Finally, the generalized maximum tangential stress (GMTS) criterion and the EMTSN criterion are used to predict the test results obtained with central cracked Brazilian disc (CCBD) specimens. The results indicate that the T-stress and Poisson's ratio have a remarkable influence on the mixed mode fracture resistance based on the EMTSN criterion. Theoretical values of both the EMTSN and the GMTS criteria are in very good agreement with the test results. Moreover, the EMTSN criterion provides a better prediction for pure mode II.

BACKGROUND Although perianal complications of Crohn disease (CD) are commonly encountered in clinical practice, the epidemiology of perianal CD among populations of children is poorly understood. We sought to characterize the prevalence of perianal disease in a large and diverse population of pediatric patients with CD. METHODS We conducted retrospective analyses from a prospective observational cohort, the ImproveCareNow Network (May 2006-October 2014), a multicenter pediatric inflammatory bowel disease quality improvement collaborative. Clinicians prospectively documented physical examination and phenotype classification at outpatient visits. Perianal examination findings and concomitant phenotype change were used to corroborate time of new-onset perianal disease. Results were stratified by age, sex, and race and compared across groups with logistic regression. Cumulative incidence was estimated using Kaplan-Meier analyses and compared between groups with Cox proportional hazard regression models. RESULTS The registry included 7076 patients with CD (41% girls). Missing/conflicting entries resulted in 397 (6%) patient exclusions. Among the remaining 6679 cases, 1399 (21%) developed perianal disease. Perianal disease was more common among boys (22%) than girls (20%; P = 0.013) and developed sooner after diagnosis among those with later rather than early onset disease (P

Complex propagation patterns of hydraulic fractures often play important roles in naturally fractured formations due to complex mechanisms. Therefore, understanding propagation patterns and the geometry of fractures is essential for hydraulic fracturing design. In this work, a seepage&ndash, stress&ndash, damage coupled model based on the finite pore pressure cohesive zone (PPCZ) method was developed to investigate hydraulic fracture propagation behavior in a naturally fractured reservoir. Compared with the traditional finite element method, the coupled model with global insertion cohesive elements realizes arbitrary propagation of fluid-driven fractures. Numerical simulations of multiple-cluster hydraulic fracturing were carried out to investigate the sensitivities of a multitude of parameters. The results reveal that stress interference from multiple-clusters is responsible for serious suppression and diversion of the fracture network. A lower stress difference benefits the fracture network and helps open natural fractures. By comparing the mechanism of fluid injection, the maximal fracture network can be achieved with various injection rates and viscosities at different fracturing stages. Cluster parameters, including the number of clusters and their spacing, were optimal, satisfying the requirement of creating a large fracture network. These results offer new insights into the propagation pattern of fluid driven fractures and should act as a guide for multiple-cluster hydraulic fracturing, which can help increase the hydraulic fracture volume in naturally fractured reservoirs.

The effect of cyclic wetting and drying on the fracture toughness and crack propagation of rock has been studied using centrally cracked Brazilian disk specimens. The results show that the failure characteristics of sandstone change from brittle to ductile at higher wetting–drying cycles. With increase in the wetting–drying cycles both KIIC and KIC decrease, furthermore, the degradation degree of KIIC is always larger than that of KIC. The ratio of KIIC to KIC decreases with increase in the number of wetting–drying cycles. The experimental results and theoretical values of the fracture criterion agree very well with each other.

A new numerical method, verified by the analytical solution of the weight functions and experimental paths, is developed to evaluate the crack initiation and propagation generally in mixed mode (I-II). This numerical method combining the interaction integral method and the maximum tangential stress (MTS) criterion is based on the finite element method of secondary development. The influence of combined confining pressure and diametric forces on crack propagation trajectories for CCBD specimens are studied. It is indicated that the crack propagation direction independent of the confining pressure keeps the same with the line of original crack as the loading angle is equal to [Formula: see text]. But when the loading angle is greater than [Formula: see text], the curvature of the curve trajectory in the early stage of crack propagation increases with a larger confining pressure. Further, it is found that larger values of the loading angle and relative length will make the effect of confining pressure more significant at the early stage of crack growth.

Temporarily plugging staged fracturing (TPSF) can effectively increase the complexity of fracture network in naturally fractured reservoirs. In different geological and engineering conditions, how to evaluate the stress interference of multiple fractures and interaction of natural fractures should be investigated further. To realize the temporarily plugging, new perforation elements were developed, and modified pore pressure cohesive zone (PPCZ) model was combined to simulate the interaction between hydraulic fractures and natural fractures. All simulated results are validated by comparing with analytical model. Results show that lateral fractures can really break through the suppression from previous fractures and enhance the complexity of fracture network when using TPSF. Then, case studies are presented to investigate the influence of cluster spacing, horizontal stress difference and number of perforation clusters. The results reveal that, when increasing the cluster spacing, fractures propagate uniformly and influence less; when the spacing reaches at a certain degree (40 m), the complexity of fracture network will not change. Higher stress difference results in simpler fracture network, which owns a straighter propagation trajectory. Further, more perforation clusters lead to stronger interference among multiple fractures, and more divergence and coalescence will take place.

An analytical formula for calculating the T -stress in a centrally cracked Brazilian disk under both diametric forces and confining pressure, is presented by using the weight function method. It is very accurate for α ⩽ 0.95 with 100 terms, and can be expediently used for arbitrary crack lengths and loading angles. In addition, the effect of confining pressure on the T -stress is also investigated, and it is shown that the T -stress increases with increase of confining pressure. There is a significant effect of confining pressure on the T -stress for a centrally cracked Brazilian disk with a large crack length and loading angle.

An experimental study on the fracture toughness of rust stone under mixed mode loading conditions has been carried out with 18 central straight through Brazilian disc specimens. The test results and theoretical values based on the generalised maximum tangential stress criterion are also discussed in this paper. The results show that the pure mode I and pure mode II fracture toughness are 1·01 and 1·51 MPam0·5, respectively. The pure mode II fracture toughness is 1·49 times of the pure mode I fracture toughness, which is larger than the value of 0·87 obtained by the maximum tangential stress criterion. The T-stress and the size of fracture process zone (rc) have a great influence on the crack propagation path and mixed mode fracture toughness of rock materials. The generalised maximum tangential stress criterion, which takes into account the T-stress, can predict the experimental results very well.

•Wetting and drying cycles influencing rock fracture toughness and tensile strength is investigated.•It still presents a good linear relationship between KIC and σt of sandstone after cyclic wetting and drying.•The degradation degree of KIC is always larger than that of σt.•The crack propagation radius decreases with increasing number of wetting–drying cycles.

Background Although previous studies have found reminder/recall to be effective in increasing immunization rates, little guidance exists regarding the specific ages at which it is optimal to send reminder/recall notices. Purpose To assess the relative effectiveness of centralized reminder/recall strategies targeting age-specific vaccination milestones among children in urban areas during June 2008–June 2009. Methods Three reminder/recall strategies used capabilities of the Michigan Care Improvement Registry (MCIR), a statewide immunization information system: a 7-month recall strategy, a 12-month reminder strategy, and a 19-month recall strategy. Eligible children were randomized to notification (intervention) or no notification groups (control). Primary study outcomes included MCIR-recorded immunization activity (administration of ≥1 new dose, entry of ≥1 historic dose, entry of immunization waiver) within 60 days following each notification cycle. Results A total of 10,175 children were included: 2,072 for the 7-month recall, 3,502 for the 12-month reminder, and 4,601 for the 19-month recall. Immunization activity was similar between notification versus no notification groups at both 7 and 12 months. Significantly more 19-month-old children in the recall group (26%) had immunization activity compared to their counterparts who did not receive a recall notification (19%). Conclusions Although recall notifications can positively affect immunization activity, the effect may vary by targeted age group. Many 7- and 12-month-olds had immunization activity following reminder/recall; however, levels of activity were similar irrespective of notification, suggesting that these groups were likely to receive medical care or immunization services without prompting.

Objectives. We evaluated the use of a statewide immunization information system (IIS) to target influenza vaccine reminders to high-risk children during a pandemic. Methods. We used Michigan’s IIS to identify high-risk children (i.e., those with ≥ 1 chronic condition) aged 6 months to 18 years with no record of pH1N1 vaccination among children currently or previously enrolled in Medicaid (n = 202 133). Reminders were mailed on December 7, 2009. We retrospectively assessed children’s eligibility for evaluation and compared influenza vaccination rates across 3 groups on the basis of their high-risk and reminder status. Results. Of the children sent reminders, 53 516 were ineligible. Of the remaining 148 617 children, vaccination rates were higher among the 142 383 high-risk children receiving reminders than among the 6234 high-risk children with undeliverable reminders and the 142 383 control group children without chronic conditions who were not sent reminders. Conclusions. Midseason reminders to parents of unvaccinated high-risk children with current or past Medicaid enrollment were associated with increased pH1N1 and seasonal influenza vaccination rates. Future initiatives should consider strategies to expand targeting of high-risk groups and improve IIS reporting during pandemic events.

Objective. Immunization information systems (IISs) are valuable surveillance tools; however, population relocation may introduce bias when determining immunization coverage We explored alternative methods for estimating the vaccine-eligible population when calculating adolescent immunization levels using a statewide IIS. Methods. We performed a retrospective analysis of the Michigan State Care Improvement Registry (MCIR) for all adolescents aged 11–18 years registered in the MCIR as of October 2010. We explored four methods for determining denominators: (1) including all adolescents with MCIR records, (2) excluding adolescents with out-of-state residence, (3) further excluding those without MCIR activity ≥10 years prior to the evaluation date, and (4) using a denominator based on U.S. Census data. We estimated state- and county-specific coverage levels for four adolescent vaccines. Results. We found a 20% difference in estimated vaccination coverage between the most inclusive and restrictive denominator populations. Although there was some variability among the four methods in vaccination at the state level (2%–11%), greater variation occurred at the county level (up to 21%). This variation was substantial enough to potentially impact public health assessments of immunization programs. Generally, vaccines with higher coverage levels had greater absolute variation, as did counties with smaller populations. Conclusion. At the county level, using the four denominator calculation methods resulted in substantial differences in estimated adolescent immunization rates that were less apparent when aggregated at the state level. Further research is needed to ascertain the most appropriate method for estimating vaccine coverage levels using IIS data.

OBJECTIVE To assess the accuracy of using administrative data from state-managed programs to identify children with asthma in a statewide immunization information system. We wished to understand the degree to which alternative asthma case definitions applied to administrative data influence the accuracy of cases identified in an immunization information system. DESIGN & SETTING Children aged 2 to 18 years were sequentially classified into 3-case definition groups on the basis of Michigan Department of Community Health administrative data (2005-2006): (1) children with a Children's Special Health Care Services (CSHCS) Program qualifying diagnosis of asthma (CSHCS cases); (2) those having 1 or more asthma medication claims (Rx cases); or (3) those without asthma medications having 1 or more health services claim reporting an asthma diagnosis code (Dx cases). PARTICIPANTS Children were randomly selected from each asthma case definition group; parents were invited to participate in a telephone interview to document physician diagnosis of asthma, symptoms, activity limitations, medications, and asthma health services use. MAIN OUTCOME MEASURES The positive predictive value of parent report of a physician diagnosis of asthma; asthma severity, based on National Asthma Education and Prevention Program criteria. RESULTS : Of 440 completed interviews, 89% of parents confirmed the child's high-risk status, reporting physician diagnosis of asthma (83%), wheezy-cough (5%), or reactive airway disease (1%). The positive predictive value varied for CSHCS cases (100%), Rx cases (91%) and Dx cases (73%, P < .0001). Although reported asthma severity levels were similar among CSHCS and Rx cases (P = .9100), asthma severity was lower among Dx cases (P = .0218). CONCLUSIONS Medicaid administrative data can be used to accurately identify children with asthma and represents a feasible approach for Medicaid programs and health plans to identify priority groups for targeted influenza vaccination reminders.

Results: Among 3618 children with a high-risk condition, 2730 (75.5%) had not received a 2008 - 2009 influenza vaccination and were eligible at the time of notification. Among children assigned to the reminder group (n1374), 42.6% had an address determined to be either invalid, undeliverable, or both. Among those with valid addresses (n2001), a greater percentage of children with deliver- able reminders received at least one influenza vaccination (30.8%) during the outcome observation period than did children assigned to no reminder (24.3%, OR1.39, 95% CI1.13, 1.72); children with an undeliverable reminder had an influenza vaccination rate (22.8%) similar to children assigned to no reminder. Conclusions: Receipt of a reminder was positively associated with seasonal influenza vaccination. However, more than 40% of children assigned to receive a reminder were determined to have an invalid or undeliverable address, emphasizing the need for increased quality of IIS contact information.

Understanding of the tensile and flexural strengths of the glass–ceramic Macor bears important applications in materials science, aerospace, defense, and other engineering disciplines. In this article, we systematically investigate the rate dependence of the tensile strength and the flexural strength of Macor utilizing two methods: the Brazilian disk (BD) test and semi-circular bend (SCB) test. Both static tests and dynamic tests are conducted to explore the rate dependence of tensile and flexural strengths of Macor. The static measurement is conducted with a servo-controlled material testing machine, and the dynamic experiment is carried out with a 6.35-mm diameter split Hopkinson pressure bar (SHPB) system. The pulse-shaping technique is used to achieve dynamic force balance, and thus eliminates the loading inertial effect and enables quasi-static stress analysis. The experimental results show that both the tensile strength and the flexural strength of Macor are loading rate dependent. The flexural strength is observed to be consistently higher than the tensile strength.

Based on the closed-form expressions of the stress intensity factors for a central cracked circular disk, four error transfer functions of the stress intensity factors were introduced in order to analyze the effect of the relative crack length and the error of loading angle on the experimental results for Brazilian disk testing. The analyzed results show that the precision of K I and K II are relevant on the relative crack length and the error of loading angle. Further analysis show that the error of loading angle Δ θ has a significant effect on the errors of K I and K II under mixed-mode loading condition, but Δ θ has nearly no effect on the error of K I under pure mode I loading condition and smaller effect on that of K II under pure mode II loading condition. Finally, the recommended range of the relative crack length is between 0.4 and 0.6.

The series expressions of σθ, τrθ and σr in the uncracked circular disk under diametral-compression loading is given in the present paper. Also, the general expressions of the coefficients Aji corresponding to the stress components are derived. For central cracked circular disk subjected to diametrical forces or pressures, the explicit expressions of the stress intensity factors, KI and KII, are proposed by use of the fracture mechanics weight function. Under the pressure loading, the deviation of the stress intensity factors from those under force loading increases with increasing the load distribution angle. The advantage of the present formulae is that the stress intensity factors for any arbitrary relative crack length, loading angle and load distribution angle can be obtained explicitly and easily. The conditions for pure mode I loading do not vary depending upon the relative crack length and load distribution angle. However, the conditions for pure mode II loading are not only dependent on the relative crack length but also load distribution angle. Based on the present solution, the actual critical loading angle for pure mode II crack can be easily calculated according to the actual relative crack length and load distribution angle in the pure mode II fracture test.

Polycyclic aromatic hydrocarbons (PAHs) are a class of carcinogenic compounds that are both naturally and artificially produced. Many PAHs are pro-carcinogens that require metabolic activation. Recently, it has been shown that PAH can induce DNA single strand cleavage and formation of PAH-DNA covalent adduct upon irradiation with UVA light. The light-induced DNA cleavage parallels phototoxicity in one instance. The DNA photocleavage efficiency depends on the structure of the PAHs. This article reports the effect of both organic solvents and the presence of biologically relevant ions, Na+, Mg2+, Ca2+, K+, Fe3+, Cu2+, Zn+2, Mn2+, and I-, on the light-induced DNA cleavage by pyrene, 1-hydroxypyrene and 1-aminopyrene. Since both 1-hydroxypyrene (0.6 μM) and 1-aminopyrene (6 μM) dissolve well in the minimum organic solvents used (2% methanol, dimethylsulfoxide, and dimethylformamide), increasing the amount of the organic solvent resulted in the decrease of the amount of DNA single strand cleavage caused by the combination effect of 1-hydroxy or 1-aminopyrene and UVA light. The result with the less watersoluble pyrene shows that increase of the amount of the organic solvent can increase the amount of DNA single strand DNA photocleavage cause by the combination of pyrene and UVA light. Therefore, there are two effects by the organic solvents: (i) to dissolve PAH and (ii) to quench DNA photocleavage. The presence of Fe3+ and Zn2+ enhances, while the presence of Ca2+ and Mn2+ inhibits the DNA photocleavage caused by 1-aminopyrene and UVA light. Other metal ions have minimal effect. This means that the effect of ions on DNA photocleavage by PAHs is complex. The presence of KI enhances DNA photocleavage. This indicates that the triplet-excited state of 1-aminopyrene is involved in causing DNA cleavage

UVA light-induced DNA single strand cleavage by a set of 12 monomethyl substituted benz[a]anthracenes (MBAs) along with their parent compound, benz[a]anthracene (BA), and the potent carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA), was studied. On the basis of the relative DNA single strand photocleavage efficiency of the fourteen compounds, they are divided into three groups: (1) strong DNA cleavers, 4-MBA, 5-MBA, 6-MBA, 8-MBA, 9-MBA, 10-MBA, and BA; (2) medium DNA cleavers, 1-MBA, 2-MBA, 3-MBA, and 11-MBA; and (3) weak DNA cleavers, 7-MBA, 12-MBA, and DMBA. The relative DNA photocleavage efficiency parallels very well with the energy gap between the highest-occupied-molecular-orbital (HOMO) and the lowest-unoccupied-molecular-orbital (LUMO) of each MBA, indicating that the DNA cleavage is related to their excited-state properties. The 7 and 12 positions of BA are two unique sites. Methyl substitution at either 7 or 12 (or both) positions lowers the HOMO-LUMO gap and greatly diminishes the DNA photocleavage efficiency. UVA light-induced photodegradation of selected MBAs reveals that methyl substitution at either 7 or 12 (or both) positions greatly enhances the degradation rate. Photodegradation of 7-MBA, 12-MBA, and DMBA yields products that are much less effective in mediating DNA cleavage. Photodegradation of other MBAs, exemplified by 5-MBA, yields a photooxidation product 5-MBA-7,12-quinone which is relatively stable under light and is a stronger DNA photocleaver than 5-MBA itself. The higher efficiency of DNA photocleavage for MBAs with methyl substitution at positions other than 7 or 12 is due, at least in part, to the formation of 7,12-quinone. Light-induced DNA single strand cleavage efficiency for several MBAs parallels the light-induced toxicity observed by other research groups, suggesting that light-induced DNA cleavage of MBAs are the source for phototoxicity. Since some PAHs such as coal tar are used commercially as creams, therapeutic agents, or ointments, or those roofers and asphalt workers that are subject to contamination with PAHs, the combination of PAHs and light (in the skin) may present a greater health risk to humans.

The combination of UVA light and 1-aminopyrene, 1-hydroxypyrene, 1-hydroxybenzo[ a ]pyrene, 3-aminofluoranthene, 6-aminochrysene, or 5-, 6-, and 7-methylbenz[ a ]anthracenes causes DNA single-strand cleavage. 1-Hydroxypyrene, 1-hydroxybenzo[ a ]pyrene, and 5-methylbenz[ a ]anthracene have been shown to cause DNA cleavage, at least partially, by generating singlet oxygen. Therefore, the presence of histidine, a singlet oxygen quencher, should inhibit the DNA photocleavage. However, the presence of 50 mM histidine greatly enhances the DNA photocleavage caused by these compounds. This effect is due to the inhibition of the photodegradation of the PAH compounds. Therefore, care must be taken when interpreting the singlet oxygen quenching data by histidine. Histidine may coexist with PAHs that have entered the body. The presence of histidine can alter the photochemical reaction and, possibly, the phototoxicity mechanism of the PAHs.

Two sources of humic acid (HA) were added to a phosphate-buffered solution to determine the effect of HA on 1-aminopyrene (1-AP) photolysis rate under UV-A irradiation and natural solar irradiation. Microbial assemblages in a river water sample were used to determine the ecotoxicity of 1-AP and its photoproducts. The microbial bioassay includes spread plate counting and microbial mineralization of 14 C-D-glucose, succinate, and citrate. At 1-AP concentration of 8 w M, bacterial viability was not affected and heterotrophic activities were inhibited by 41% to 63% after exposure for 24 hr. Exposure to 1-AP photoproducts inhibited bacterial viability and heterotrophic activities by 58% and 77% to 84%, respectively. Therefore, photoinduced toxicity of 1-AP to microbial assemblages was observed in this study. With additions of HA at concentrations of 10-80 ppm, the photolysis rate constants of 1-AP (10 w M) in phosphate-buffered (pH 7.0; 1 mM) solutions were enhanced by up to fivefold. The magnitude of the enha...

UVA light-induced DNA single-strand cleavage by 1-hydroxy, 3-hydroxy, 7-hydroxy, and 9-hydroxybenzo[ a ]pyrenes (OH-B a Ps) and 6-acetoxybenzo[ a ]pyrene (6-OAc-B a P) was studied. Under experimental conditions, the concentrations of 1-OH, 3-OH, 7-OH, and 9-OH-B a Ps and 6-OAc-B a P needed to cause 25% of the supercoiled form I plasmid DNA to become relaxed form II DNA were found to be 0.6, 2.5, 1.0, 1.3, and 1.1 w M, respectively. These concentrations are all smaller than that of B a P, which was 6 w M. These results indicate that on photoirradiation, OH-B a Ps are more cytotoxic and/or genotoxic than their parent compound, B a P. Mechanistic studies reveal that singlet oxygen and superoxide free radicals are involved in causing DNA cleavage.

To demonstrate the feasibility and utility of using administrative claims data from commercial health plans to establish a high-risk indicator in a statewide immunization registry for enrollees with chronic conditions.Retrospective cohort analysis.Administrative data were used to identify children with 1 or more chronic conditions enrolled in 2 commercial health plans during the 2008-2009 and 2009-2010 influenza seasons and matched with a statewide immunization registry. The proportion of cases that successfully matched and historical health services utilization, including influenza vaccinations and missed opportunities, were assessed.A total of 93% of children with chronic conditions identified through administrative claims were successfully matched with the statewide registry. Less than one-third of children received the seasonal influenza vaccine in either the 2008-2009 (29%) or 2009-2010 (32%) seasons; 30% of children received the H1N1 vaccination in 2009-2010. Most children in the 2008-2009 (63%) and 2009-2010 (63%) seasons had at least 1 missed opportunity for seasonal influenza vaccination. Younger children had the highest percentage of missed opportunities while adolescents had the lowest rate of missed opportunities for vaccination. Conclusions It is feasible to identify children with chronic conditions using administrative data and to link them with a statewide immunization registry. Low influenza vaccination rates and high occurrences of missed opportunities among children with chronic conditions suggest the utility of integrating administrative claims data with statewide registries to support various outreach mechanisms, including physician-focused and parent-targeted reminder/recall, based on target age to improve vaccination rates.

Purpose Increases in adolescent vaccine coverage are needed. The aim of this study was to identify population-level clinical and demographic factors associated with adolescent vaccination. Methods A retrospective analysis of data from the Michigan Care Improvement Registry (MCIR), a statewide immunization registry, was performed for 2006–2010. The sample included 1,252,655 adolescents aged 11–18 years. Vaccine coverage levels were calculated for tetanus–diphtheria–acellular pertussis (Tdap), meningococcal conjugate (MCV4), flu (seasonal influenza), and human papillomavirus, females only (HPV) vaccines. For the subset of adolescents enrolled in Medicaid, claims data were used to obtain information about the type of visits in which vaccines were administered. Results As of 2010, statewide coverage levels for Tdap and MCV4 vaccines were 46.0% and 46.5%, respectively whereas only 15% of females had completed the HPV vaccine series. Only one in four female adolescents were up to date for all three of these vaccines. Statewide coverage among adolescents for flu vaccine during the 2009–2010 season was 8%. Age was the most significant predictor of HPV vaccination, whereas health care–associated factors (provider type and childhood immunization history) were the strongest predictors for the other three vaccines. Older adolescents were less likely to have received the flu vaccine but more likely to have receive HPV vaccine doses than younger adolescents. Among Medicaid-enrolled adolescents, most Tdap, MCV, and first-dose HPV vaccines, but only 29% of flu doses, were administered during preventive visits. Conclusions Noted variability in adolescent vaccine coverage by age, vaccine type, and health care–associated factors provides a framework for developing future outreach activities to increase adolescent vaccine use.

Nonlinear absorption at 532 nm in a series of metallo-porphyrin-like compounds using 8 ns and 23 ps laser pulses is reported. The experiments show that for picosecond pulses, reverse saturable absorption occurs only at low fluences, and saturable absorption occurs at high fluences, for nanosecond pulses, only reverse saturable absorption occurs. The density matrix equations of motion for a six-level model are deduced to explain these nonlinear absorption effects, and numerical results calculated by the model agree well with the experimental results.

Children with chronic conditions have an increased risk of complications from influenza and have low influenza vaccination rates.To assess the feasibility and effectiveness of using a statewide immunization information system (IIS) for seasonal influenza vaccine reminders from local health departments (LHDs) targeting children with high-risk conditions.A randomized community intervention.The study was conducted in a population of 3618 children aged 24-60 months with a high-risk condition residing in three Michigan counties. Children were identified using a statewide IIS in October 2008.Children were randomized to intervention (reminder) or control (no reminder) groups. Reminders for seasonal influenza vaccination were mailed by LHDs in November 2008.Feasibility of notification (address validity, address deliverability) was assessed (November 2008-February 2009), and frequencies of notification feasibility measures were determined (analyses conducted in 2010). Effectiveness of notification (seasonal influenza vaccine receipt) was assessed using bivariate logistic regression.Among 3618 children with a high-risk condition, 2730 (75.5%) had not received a 2008-2009 influenza vaccination and were eligible at the time of notification. Among children assigned to the reminder group (n=1374), 42.6% had an address determined to be either invalid, undeliverable, or both. Among those with valid addresses (n=2001), a greater percentage of children with deliverable reminders received at least one influenza vaccination (30.8%) during the outcome observation period than did children assigned to no reminder (24.3%, OR=1.39, 95% CI=1.13, 1.72); children with an undeliverable reminder had an influenza vaccination rate (22.8%) similar to children assigned to no reminder.Receipt of a reminder was positively associated with seasonal influenza vaccination. However, more than 40% of children assigned to receive a reminder were determined to have an invalid or undeliverable address, emphasizing the need for increased quality of IIS contact information.This study is registered at www.ClinicalTrials.gov NCT01431183.

Biological drugs represent an important and rapidly growing class of therapeutics useful in the treatment of a variety of disorders ranging from cancer to inflammation to infectious diseases. Unlike single chemical entities, the recombinant production of these drugs in living cells confers considerable structural and chemical heterogeneity to the biologically derived protein product that constitutes the active pharmaceutical ingredient (API). In mammalian based expression systems, much of this diversity is conferred through heterogeneous protein glycosylation. These post-translational modifications can have significant effects on the structure, biological function, and pharmacological properties of the API. In addition, the bulk proteins that comprise the API are further formulated through the use of multiple excipients designed to ensure product stability, solubility, and lot-to-lot consistency. Unfortunately, these matrices can interfere with commonly available analytical methods used in the thorough chemical characterization of the biological drug product. At the same time, a demonstration of the suitable extraction of the bulk drug substance in a manner and form that does not destabilize the active ingredient or introduce any structural bias with direct reference to the original drug product is both critical and necessary. Here, we use recombinant human follicle stimulating hormone (follitropin alpha for injection) from a pharmaceutical source as an example to illustrate a suitable purification strategy to effectively extract the bulk drug substance from the formulated drug product with high purity and yield. We assess the suitability of this extraction method in preserving the structural integrity and overall quality of the drug substance relative to the formulated drug product, placing a particular emphasis on glycosylation as a key product attribute. In so doing, we demonstrate that it is possible to effectively extract the active pharmaceutical ingredient from a formulated biological drug product in a manner that is consequently sufficient for its use in comparability studies.

An analytical model, verified by the finite element method, is developed to study the effect of confining pressure on stress intensity factors for the cracked Brazilian disk. The closed-form expressions for stress intensity factors under both confining pressure and diametric forces are obtained based on the weight function method. The results show that the confining pressure has no effect on the mode II stress intensity factor; however, the mode I stress intensity factor decreases with the increase of confining pressure and the change may be above 100% for a large confining pressure. In addition, the effect of confining pressure on the loading condition of pure mode II crack is also investigated. It is shown that the critical loading angle for pure mode II crack decreases as the confining pressure increases. Depending on the magnitude of confining pressure, the failure problem of a disk may be no longer a pure fracture problem. These results have established the theoretical foundation to measure the fracture toughness of materials under confining pressure.

immunized against varicella, and concerns exist regarding the safety and efficacy of this immunization in immunosuppressed patients. We aimed to evaluate the risk of varicellaand zoster-related hospitalization among children with IBD. Methods: A retrospective cohort study was performed utilizing data on varicellaand zoster-related hospitalizations from the 1997, 2000, 2003, 2006, 2009, and 2012 triennial Healthcare Cost and Utilization Project Kids' Inpatient Database (HCUP-KID). Hospitalizations with a primary diagnosis of varicella or herpes zoster were compared between children (ages 5 to 21) with and without IBD using logistic regression. Results: There were 12,219,138 admissions in the HCUP-KID database from 1997-2012, including 4,434 with varicella and 4,488 with zoster listed as the primary diagnosis. Children with IBD accounted for 57 (1.29%) and 74 (1.64%) of the varicellaand zoster-related hospitalizations, respectively. Primary admissions for varicella or zoster accounted for 0.4% of all hospitalizations of children carrying a diagnosis of IBD. Compared to children without IBD, those with IBD were at significantly higher risk for varicella-related hospitalization (OR 4.98, 95% CI 3.84-6.47) and zoster-related hospitalization (OR 6.35, 95% CI 5.04-7.99). This risk was higher among children with Crohn's disease (varicella OR 6.22, 95% CI 4.65-8.32, zoster OR 7.39, 95% CI 5.67-9.65) compared to children with ulcerative colitis (varicella OR 2.69, 95% CI 1.50-4.81, zoster OR 4.34, 95% CI 2.75-6.85). Conclusion: Children with IBD are at increased risk for varicellaand zosterrelated hospitalization. These results highlight the importance of efforts to immunize IBD patients without a history of varicella disease or varicella immunization, ideally before the initiation of immunosuppressive therapy. Furthermore, research is needed on the safety and efficacy of varicella vaccine in children with IBD on immunomodulators including antitumor necrosis factor-alpha agents.

Third‐order nonlinear optical response of a cadmium texaphyrin solution at 532 nm was measured using time‐resolved degenerate four‐wave mixing with picosecond pulses. The molecules of cadmium texaphyrin exhibit a large optical nonlinearity, which arises from the excited‐state population. The dynamics of the nonlinear optical response show an evident fluence dependence. The temporal response is characterized by three components, a slower, a faster, and a fastest, which are attributed to populations of the first triplet excited state, the first singlet excited state, and the higher singlet excited state, respectively.

Nonlinear absorption at 532 nm in a cadmium texaphyrin solution has been studied using 8 ns and 23 ps laser pulses. The experiments show that reverse saturable absorption occurs in the nanosecond case. For picosecond pulses, reverse saturable absorption occurs only at low fluences, and the transmission increases with increasing incident fluence at high fluences. A six‐level model is presented to explain these nonlinear absorption effects. Several photophysical parameters for cadmium texaphyrin, such as absorption cross sections at 532 nm and lifetimes, have been evaluated by theoretical simulations of the experimental results.

We measured third-order nonlinear optical susceptibility for solutions of asymmetric tripyrrane-containing 22 pi -electron aromatic macrocyclic cadmium (Cd2+) and gadolinium (Gd3+) complexes in methanol at 1064 nm using degenerate four-wave mixing and obtained the off-resonant third-order hyperpolarizabilities as 1.2*10-31 and 1.0*10-31 esu, respectively.

Recently, there is a rapidly growth of interest in 2D /spl Pi/-electron organic materials due to their large third-order nonlinear optical effects, thermal and physical stabilities and film forming property. In this paper, the nonlinearity of a new kind of macrocyclic metal-coordinated complex and their derivates was reported. >

The fluorescence spectroscopy of 7-azaindole (7aIn) incorporated in DNA oligonucleotides is investigated. Incorporation of 7aIn into DNA oligonucleotides is accomplished through standard solid-phase phosphoramidite chemistry. Fluorescence emission of the 7aIn chromophore shifts slightly to the red (from 386 nm to 388 nm) upon glycosylation at the N−1 position, but its relative fluorescence quantum yield increases 23 times, from 0.023 to 0.53. Upon incorporation into DNA, the fluorescence emission of 7aIn is greatly quenched with fluorescence quantum yields of 0.020 and 0.016 in single and double strand DNA, respectively. The fluorescence emission for 7aIn in DNA oligonucleotides shifts to the blue with an emission maximum at 379 nm. Both the strong fluorescence quenching and the blue shift of the emission spectrum signify that 7aIn is stacked with neighboring DNA bases in both single and double strand DNA. As the duplex DNA melts due to temperature increase, the fluorescence of the 7aIn chromophore increases, indicating the transition from the less fluorescent duplex DNA to the more fluorescent single strand DNA. Since this fluorescent 7aIn is a structural analog of purine, its fluorescence property may be utilized as a probe for studying nucleic acid structure and dynamics.

1-Hydroxypyrene (1-HP) is a carcinogenic and slightly water-soluble polycyclic aromatic hydrocarbon. Ecotoxicity and mutagenicity of 1-HP and its photoproducts, and the effect of Mn2+ and Cu2+ on their mutagenicity were measured with microbial assay in this study. The assay includes spread plate counting, direct counting, microbial mineralization of 14C-UL-D-glucose and Mutatox Test. At the concentration examined (0.8 microM), the photoproducts (after 1.5 h solar irradiation) of 1-HP inhibited microbial glucose mineralization activity (by 64%) after microbial assemblages of a local reservoir site were exposed for 1 day. However, heterotrophic bacteria were able to utilize 1-HP photoproducts as the growth substrates and increase viability counts by up to 4.75-folds. 1-HP exhibited positive response to Mutatox Test in both direct medium and S-9 medium, with the lowest observable effective concentration of 0.625 microM in the test with direct medium. After photolysis, 1-HP decreased its mutagenicity. Mn2+ (312.5 microM-5 mM) and Cu2+ (6.25-100 microM) themselves are not mutagenic. However, addition of the metal ions before or after photolysis modifies the light readings of 1-HP during the test. Therefore, presence of metal ions could affect the genotoxicity of 1-HP in aquatic environments, depending on timing of the addition.

1-Hydroxypyrene (HOP), a metabolite found in the urine of humans and laboratory animals exposed to polycyclic aromatic hydrocarbons (PAHs), is known to be both acutely toxic and genotoxic. It has been widely used as a biomarker for studying PAH exposure. In this research, we have found that, upon UVA irradiation, HOP causes DNA single-strand cleavages and forms HOP-DNA covalent adducts. The UVA-induced cleavage of supercoiled plasmid PhiX174 DNA is dependent upon both HOP concentration and UVA dosage. A longer irradiation time or higher HOP concentration induces more DNA cleavage. Results of the photocleavage experiments carried out in the presence of reactive oxygen species scavengers, histidine, sodium azide, mannitol, SOD, and desferal indicate that both the superoxide free radical and singlet oxygen are likely involved in causing DNA single-strand cleavage. The photocleavage is inhibited by the presence of an excited singlet-state quencher, KI, indicating that it is an excited-state reaction. Along with light-induced DNA cleavage, HOP also forms DNA covalent adducts while being degraded upon light irradiation. Light-induced degradation of 20 microM HOP follows first-order reaction kinetics in a 10% methanolic buffer (10 mM phosphate) solution in the absence or presence of 40 microM calf thymus DNA, with degradation half-lives of 20 or 15 min, respectively. The shorter degradation half-life in the presence of DNA is due to the formation of the HOP-DNA covalent adduct. The formation of the HOP-DNA covalent adduct is evidenced by comparing the UV-vis absorption and fluorescence emission spectra of the pure HOP with those of the HOP-DNA adduct. The covalent HOP-DNA adduct produced due to irradiation was purified by either extensive dialysis (3 x 500 mL buffer solutions), phenol and chloroform extraction followed by ethanol precipitation, or chloroform extraction alone. The isolated HOP-DNA adduct has an absorption peak at 353 nm, which is 8 nm red-shifted compared to that of free HOP. The fluorescence emission for HOP-DNA is at least 70 times weaker than that for free HOP in solution. In summary, the findings with HOP reveal that, in addition to metabolic activation that eventually leads to the formation of alkylated DNA adducts or other forms of DNA damage, HOP may be activated by light to produce DNA single-strand cleavage and covalent DNA adducts. These DNA lesions can be sources of toxicity.

The third-order nonlinear optical properties of a methyl substituted Texaphyrin, [(CH3-TXP)Cd]Cl, were studied by degenerate four wave mixing and Z-scan techniques using 40 ps laser pulses at 532 nm. The molecular second- order hyperpolarizability ((gamma) ), the excited-state absorption cross section ((sigma) ex), the nonlinear refractive cross section ((sigma) t), and the optical limiting performances at both nanosecond and picosecond time scales have been determined. We have also studied the third- order nonlinearity of SiNc, one of the most promising optical limiting materials in literature, for comparison. The (gamma) value for [(CH3-TXP)Cd]Cl is 6.9 X 10-31 esu, which is 4 times as larger as that of SiNc. The nonlinearity of [(CH3-TXP)Cd]Cl is predominantly electronic in origin with picosecond laser pulses. The excited-state absorption cross section ((sigma) ex) and the nonlinear refractive cross section ((sigma) t) obtained from the theoretical simulation and calculation of Z-scan results are 7.0 X 10-17 cm2 and 1.7 X 10-17 cm2, respectively. The complex shows strong optical limiting performance via reverse saturable absorption for 5 ns laser pulses. The nonlinear absorption of this molecule for 40 ps laser pulses exhibits a transition from reverse saturable absorption to saturable absorption when the fluence is higher than 0.3 J/cm2. These data suggest that this complex and related complexes are a promising class of nonlinear optical materials.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Nonlinear optical properties of asymmetric pentaazadentate expanded porphyrin metal complexes are investigated. The transmittance dependence of the target compounds on the incident laser intensity generates different nonlinear optical effects in the excited states. The reverse saturable absorption at 532 nm in the ns pulses and the saturable absorption for the pspulses at high fluences are observed in solutions. The nonlinear refractive indices n2 aremeasured by the Z-scan technique. The optical limiting based on the RSA and transverse refraction are demonstrated for ns and continuous laser. An optical limiter based on the RSA and self-refraction is performed, in which the limitating threshold and amplitude of output energy are reduced.

1-Aminopyrene (1-AP) is an environmental mutagen and a metabolite of 1-nitropyrene (1-NO2P). On light irradiation, 1-AP transforms into oxidation products with a half-life of 7.1 min in 10% methanolic buffer. The presence of DNA or free-radical/ singlet oxygen scavengers 1,4-dithiothreitol, histidine, or NaN3 slows down 1-AP photochemical reaction. The photoproducts identified include 1-hydroxyaminopyrene, 1-nitrosopyrene, 1-NO2P, 1-amino-x-hydroxypyrene, and three covalent dimers. Since it is known that 1-NO2P and 1-nitrosopyrene are genotoxic and 1-hydroxyaminopyrnene can react with DNA to form covalent adducts, we used the Mutatox test to assess the toxicity of 1-AP and its photoproducts. It was found that the lowest-observed-effect concentrations for 1-AP, 1-AP photoproducts, and 1-NO2P are 1.25 microM, 10 microM, and NA (no mutagenic response was seen at this concentration range) in direct medium (no S-9) and NA, 5 microM, and 0.625 microM in S-9 medium, respectively. Therefore, 1-AP photoproducts are more genotoxic than 1-AP itself in the S-9 medium and more mutagenic than 1-NO2P in the direct medium. Thus, 1-NO2P alone cannot account for all the mutagenicity of the photoproducts. Irradiation of 1-AP together with DNA leads to covalent DNA adduct formation possibly via the 1-hydroxyaminopyrene intermediate. In this study, ultraviolet-A (UVA) was used at approximately the same magnitude as the outdoor UVA irradiance. Considering the half-life of 1-AP in the test solutions in this study, the aquatic biota (including humans) near the surface layer of a static water body are most likely subjected to the photoinduced toxicity of the study compound. The biota at the lower depths will also be affected if turbulence becomes a significant factor in enhancing the exposure risk for aquatic organisms.