Toward nanometer-scale optical photolithography: utilizing the near-field of bowtie optical nanoantennas

Optically resonant metallic bowtie nanoantennas are utilized as fabrication tools for the first time, resulting in the production of polymer resist nanostructures <30 nm in diameter at record low incident multiphoton energy densities. The nanofabrication is accomplished via nonlinear photopolymerization, which is initiated by the enhanced, confined optical fields surrounding the nanoantenna. The position, size, and shape of the resist nanostructures directly correlate with rigorous finite-difference time-domain computations of the field distribution, providing a nanometer-scale measurement of the actual field confinement offered by single optical nanoantennas. In addition, the size of the photoresist regions yields strong upper bounds on photoacid diffusion and resist resolution in SU-8, demonstrating a technique that can be generalized to the study of many current and yet-to-be-developed photoresist systems.     

Superior outcomes in pediatric renal transplantation

BACKGROUND: Nationally, results of renal transplantation in children, particularly in small children, are inferior to those obtained in adults. OBJECTIVE: To determine factors important for success in renal transplantation in children. DESIGN: Results of 108 consecutive renal transplantations performed in patients aged 7 months to 18 years were reviewed and compared with those reported by the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), the national registry. RESULTS: One-, 2-, and 3-year graft survival rates (+/-SE) were 99% +/- 1%, 95% +/- 3%, and 93% +/- 4%, respectively, for living donor grafts and 97% +/- 3%, 92% +/- 6%, and 92% +/- 6%, respectively, for cadaver grafts. Incidence of acute rejection was half that reported by NAPRTCS. There were no graft losses for technical reasons (19% in NAPRTCS). Twelve percent of patients were younger than 2 years (6% in NAPRTCS); 17% were 2 to 5 years old (16% in NAPRTCS). Most small children received an adult-sized kidney. Ninety-three percent of recipients weighing 15 kg or less received postoperative mechanical ventilation assistance to optimize fluid resuscitation and perfusion of adult-sized kidneys. Structural abnormalities of the urinary tract were present in 53.7% of the patients (48.5% in NAPRTCS; adults, 5.3%). Nephroureterectomy was required in 38 children; in 27 (71%) of them, it was performed at the time of transplant surgery. CONCLUSIONS: Excellent results can be obtained in pediatric renal transplantation by strict adherence to surgical detail, tight immunosuppressive management, aggressive fluid management in the small child, and careful integration of urologic and transplant surgery.     

Effect of local youth-access regulations on progression to established smoking among youths in Massachusetts

Objective

To test whether community‐level restrictions on youth access to tobacco (including both ordinances and enforcement) are associated with less smoking initiation or less progression to established smoking among adolescents.

Design

Prospective cohort study of a random sample of adolescents in Massachusetts whose smoking status was assessed by telephone interviews at baseline and 2‐year follow‐up, and linked to a state‐wide database of town‐level youth‐access ordinances and enforcement practices.

Participants

A random sample of 2623 adolescents aged 12–17 years who lived in 295 towns in Massachusetts in 2001–2 and were followed in 2003–4.

Main outcome measures

The relationship between the strength of local youth access restrictions (including both ordinances and level of enforcement) and (1) never‐smokers'' smoking initiation rates and (2) experimenters'' rate of progression to established smoking was tested in a multilevel analysis that accounted for town‐level clustering and adjusted for potential individual, household and town‐level confounders.

Results

Over 2 years, 21% of 1986 never‐smokers initiated smoking and 25% of 518 experimenters became established smokers. The adjusted odds ratio (OR) for smoking initiation was 0.89 (95% CI 0.61 to 1.31) for strong versus weak youth‐access policies and 0.93 (95% CI 0.67 to 1.29) for medium versus weak policies. The adjusted OR for progression to established smoking among adolescents who had experimented with smoking was 0.79 (95% CI 0.45 to 1.39) for strong versus weak local smoking restrictions and 0.85 (95% CI 0.50 to 1.45) for medium versus weak restrictions.

Conclusions

This prospective cohort study found no association between community‐level youth‐access restrictions and adolescents'' rate of smoking initiation or progression to established smoking over 2 years.Nearly 90% of smokers start smoking during adolescence.¹ Consequently, preventing teenagers from starting to smoke is a public health priority.^2,3 To start smoking, adolescents need access to tobacco products. A teenager''s first few cigarettes usually come from friends or family members, but, once smoking becomes more established, youths turn to commercial sources of cigarettes (eg, stores and vending machines) to ensure a reliable supply.^3,4,5,6 They are able to do so despite laws in all US states that ban the sale of tobacco to minors, because compliance with these laws is limited.^3,7,8If youths could be prevented from easily obtaining cigarettes from commercial sources, it is hypothesised that fewer youths would become smokers.^3,8 Efforts to reduce youth access to tobacco have focused on enforcing bans on tobacco sales to minors in retail stores—the source of most tobacco bought by youths. A complementary strategy bans self‐service displays of tobacco products in retail stores. These displays facilitate youth access to tobacco by encouraging shoplifting and by minimising a young person''s contact with a salesperson, thereby making it more likely that a sale will occur.^3,8,9,10 Cigarette sales in vending machines have also been targeted because vending machines are more important tobacco sources for younger teens who have more difficulty in buying tobacco in stores.^3,8 Effective strategies include banning vending machine sales of cigarettes or limiting vending machines to adults‐only locations. Equipping vending machines with locking devices that must be deactivated by a clerk who presumably verifies the purchaser''s age has little evidence of efficacy.³Measures to restrict youths'' access to tobacco products have been widely advocated since the early 1990s and are now incorporated into global tobacco control efforts.¹¹ The World Health Organization''s Framework Convention on Tobacco Control includes a provision requiring ratifying nations to adopt and implement laws that prohibit the sale of tobacco to minors.¹² In the US, the federal Synar amendment has, since 1996, required all states to have and enforce youth‐access laws and document a specific level of compliance or risk loss of federal block grant funds.¹³ Many US communities have gone beyond state laws and adopted local ordinances with stronger youth‐access provisions.^3,7,14 In Massachusetts, for example, the number of towns with some form of youth‐access regulation increased from 35 (10%) in 1994 to 244 (70%) in 2000.³Despite the widespread adoption of youth‐access restrictions, this approach remains controversial because evidence to support its efficacy in reducing adolescent smoking is limited.^{3,8,11,15,16,17} In 2004, a systematic review of interventions to reduce minors'' access to commercial sources of tobacco products was conducted by the Cochrane Tobacco Addiction Group. It concluded that active enforcement of youth‐access laws could reduce illegal sales to minors, but found little evidence that these interventions reduced the prevalence of adolescent smoking or perceived ease of access to tobacco products.^18,19 An earlier meta‐analysis also found no evidence that increases in merchant compliance with youth‐access laws were associated with the prevalence of youth smoking,²⁰ although that review''s methods were challenged.¹⁷Another source of evidence comes from observational studies. These do not test specific interventions but examine the association between adolescent''s exposure to youth‐access laws or perceived ease of access to tobacco products and their prevalence of smoking. These studies have conflicting results. A cross‐sectional study of adolescents in 314 towns in Massachusetts found no consistent association between living in a town with a youth‐access ordinance and prevalence of adolescent smoking or perceived ease of access to tobacco products, but the study had no data on the extent to which merchants actually complied with the laws.²¹ By contrast, a cross‐sectional study of 75 communities in Oregon found a small positive linear relationship between a town''s measured rate of illegal sales to minors and the prevalence of smoking of 11th graders, but not of 8th graders.²² A cross‐sectional analysis of 11 towns in Illinois found that teenagers in towns with higher rates of illegal tobacco sales to minors were more likely to initiate but not to continue to smoke,²³ However, the cross‐sectional design of these studies limits their ability to support causal inferences. Among 12 communities in New York, those reaching a high (>80%) rate of retailer compliance with youth‐access laws had a smaller increase in adolescents'' rate of frequent smoking over 4 years, as measured by two cross‐sectional school surveys.²⁴Few observational studies have used the stronger prospective cohort design. A cohort study of 592 adolescent non‐smokers in Massachusetts found that those living in towns with a local tobacco sales ordinance at baseline were less likely to progress to established smoking over 4 years than youths in towns without these ordinances. However, the finding lost statistical significance after adjustment for potential confounders and there was no information on actual compliance with the laws.²⁵ Gilpin et al²⁶ followed two cohorts of adolescent non‐smokers in California over 3 years. In the first cohort, followed when merchant compliance with youth access laws was low, smoking initiation rates did not differ between youths who initially perceived that cigarettes were difficult or easy to obtain. In the second cohort, conducted after overall merchant compliance state‐wide had improved, youths who perceived that cigarettes were hard to obtain were less likely to initiate smoking.The current study adds to the existing literature on the effect of youth access restriction in several ways.¹ It includes data from a representative cohort of adolescents living in a large number of communities that range in size and demographic characteristics.² A town‐level clustered multilevel analysis allows us to control for a large variety of individual, environmental and town‐level characteristics, including the community''s baseline anti‐smoking sentiment.³ A longitudinal design provides stronger evidence for causal inferences.⁴ The extent to which youth‐access laws are actually enforced is measured.⁵ The study deconstructs smoking uptake into two components: youths'' experimentation with tobacco products and their progression to established tobacco use. Restrictions on youth‐access laws are hypothesised to affect the latter more than the former.^3,8     

Expression of steroidogenic enzymes during equine testicular development

In the mammalian testis, Leydig cells are primarily responsible for steroidogenesis. In adult stallions, the major endocrine products of Leydig cells include testosterone and estrogens. 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4)-isomerase (3βHSD) and 17α-hydroxylase/17,20-lyase (P450c17) are two key steroidogenic enzymes that regulate testosterone synthesis. Androgens produced by P450c17 serve as substrate for estrogen synthesis. The aim of this study was to investigate localization of the steroidogenic enzymes P450c17, 3βHSD, and P450arom and to determine changes in expression during development in the prepubertal, postpubertal, and adult equine testis based upon immunohistochemistry (IHC) and real-time quantitative PCR. Based on IHC, 3βHSD immunolabeling was observed within seminiferous tubules of prepubertal testes and decreased after puberty. On the other hand, immunolabeling of 3βHSD was very weak or absent in immature Leydig cells of prepubertal testes and increased after puberty. HSD3B1 (3βHSD gene) mRNA expression was higher in adult testes compared with prepubertal (P=0.0001) and postpubertal testes (P=0.0041). P450c17 immunolabeling was observed in small clusters of immature Leydig cells in prepubertal testes and increased after puberty. CYP17 (P450c17 gene) mRNA expression was higher in adult testes compared with prepubertal (P=0.030) and postpubertal testes (P=0.0318). A weak P450arom immunolabel was observed in immature Leydig cells of prepubertal testes and increased after puberty. Similarly, CYP19 (P450arom gene) mRNA expression was higher in adult testes compared with prepubertal (P=0.0001) and postpubertal (P=0.0001) testes. In conclusion, Leydig cells are the primary cell type responsible for androgen and estrogen production in the equine testis.     

Successful transplantation of adult-sized kidneys into infants requires maintenance of high aortic blood flow

Geographical Information Systems-computerised systems for the capture, storage, retrieval, analysis and display of spatial data-have recently been promoted as important tools for the study of public health. Attention must also be given to the issues involved in this relatively new application, especially in Australian conditions. These include the coarse spatial resolution of most health and social data, the propagation of error through the need to use estimates and concordance tables to handle data in mismatched official spatial boundaries, the inflexible analytical capacity of most GIS for the needs of epidemiology, and difficulties in access to data, which are compounded by the absence of a good metadata register. The conflict between the need for spatial precision in GIS and preserving the confidentiality of health data is a salient issue. Medical geographers and public health researchers using GIS must recognise these issues in order to work together and toward extending the use of GIS technology beyond broad ecological and accessibility studies.     

Minimum effective dose of folic acid for food fortification to prevent neural-tube defects

BACKGROUND: Although a daily supplement of 400 micrograms folic acid has been shown to prevent neural-tube defects (NTD), most women do not take the recommended supplement. Thus, food fortification is to be introduced in the USA and is being considered in the UK. Because of safety concerns, the USA has chosen a level of fortification that will increase the average woman's intake by only 100 micrograms. Such an increase, although safe, may be ineffective; but a trial to assess its efficacy would be unethical. Because women with red-cell folate concentrations above 400 micrograms/L have a very low risk of NTD, we undertook a randomised trial of several folic acid doses to find out how much is needed to reach this protective concentration. METHODS: We screened 323 women. 172 with red-cell folate between 150 micrograms/L and 400 micrograms/L were invited to take part in the trial. 121 women were randomly assigned placebo or 100 micrograms, 200 micrograms, or 400 micrograms daily of additional folic acid. Compliance was monitored by having the women sign a dated sheet when taking the tablet. 95 women completed the 6-month study. FINDINGS: There were significant increases in red-cell folate in all folic acid groups. The placebo group showed no significant change. The median incremental changes and median post-treatment concentrations were 67 micrograms/L (95% CI 43-120) and 375 micrograms/L (354-444) in the 100 micrograms/day group, 130 micrograms/L (108-184) and 475 micrograms/L (432-503) in the 200 micrograms/day group, and 200 micrograms/L (125-312) and 571 micrograms/L (481-654) in the 400 micrograms/day group. INTERPRETATION: A fortification programme that delivered 400 micrograms folic acid daily to women would protect against NTD, but at the expense of unnecessarily high exposure for many people. Delivery of 200 micrograms daily is also effective against NTD and safer for the general population. Based on projections from the positive folate balance in the group that received 100 micrograms daily, this dose taken continually, as it will be in fortified food, will also produce an important decrease in NTD.