Turbulent Fluctuations in G-band and K-line Intensities Observed with the Rapid Oscillations in the Solar Atmosphere (ROSA) Instrument

Using the Rapid Oscillation in the Solar Atmosphere (ROSA) instrument at the Dunn Solar Telescope we have found that the spectra of fluctuations of the G-band (cadence 1.05 s) and Ca II K-line (cadence 4.2 s) intensities show correlated fluctuations above white noise out to frequencies beyond 300 mHz and up to 70 mHz, respectively. The noise-corrected G-band spectrum presents a scaling range (Ultra High Frequency “UHF”) for f = 25-100 mHz, with an exponent consistent with the presence of turbulent motions. The UHF power, is concentrated at the locations of magnetic bright points in the intergranular lanes, it is highly intermittent in time and characterized by a positive kurtosis κ. Combining values of G-band and K-line intensities, the UHF power, and κ, reveals two distinct “states” of the internetwork solar atmosphere. State 1, with κ ≍ 6, which includes almost all the data, is characterized by low intensities and low UHF power. State 2, with κ ≍ 3, including a very small fraction of the data, is characterized by high intensities and high UHF power. Superposed epoch analysis shows that for State 1, the K-line intensity presents 3.5 min chromospheric oscillations with maxima occurring 21 s after G-band intensity maxima implying a 150-210 km effective height difference. For State 2, the G-band and K-line intensity maxima are simultaneous, suggesting that in the highly magnetized environment sites of G-band and K-line emission may be spatially close together. Analysis of observations obtained with Hinode/SOT confirm a scaling range in the G-band spectrum up to 53 mHz also consistent with turbulent motions as well as the identification of two distinct states in terms of the H-line intensity and G-band power as functions of G-band intensity.

Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia

BACKGROUND: Exposure to environmental toxins during embryonic development may lead to epigenetic changes that influence disease risk in later life. Aflatoxin is a contaminant of staple foods in sub-Saharan Africa, is a known human liver carcinogen and has been associated with stunting in infants.

METHODS: We have measured aflatoxin exposure in 115 pregnant women in The Gambia and examined the DNA methylation status of white blood cells from their infants at 2-8 months old (mean 3.6 ± 0.9). Aflatoxin exposure in women was assessed using an ELISA method to measure aflatoxin albumin (AF-alb) adducts in plasma taken at 1-16 weeks of pregnancy. Genome-wide DNA methylation of infant white blood cells was measured using the Illumina Infinium HumanMethylation450beadchip.

RESULTS: AF-alb levels ranged from 3.9 to 458.4 pg/mg albumin. We found that aflatoxin exposure in the mothers was associated to DNA methylation in their infants for 71 CpG sites (false discovery rate < 0.05), with an average effect size of 1.7% change in methylation. Aflatoxin-associated differential methylation was observed in growth factor genes such as FGF12 and IGF1, and immune-related genes such as CCL28, TLR2 and TGFBI. Moreover, one aflatoxin-associated methylation region (corresponding to the miR-4520b locus) was identified.

CONCLUSIONS: This study shows that maternal exposure to aflatoxin during the early stages of pregnancy is associated with differential DNA methylation patterns of infants, including in genes related to growth and immune function. This reinforces the need for interventions to reduce aflatoxin exposure, especially during critical periods of fetal and infant development.

Development and evaluation of a novel integrated anti-icing/de-icing technology for carbon fibre composite aerostructures using an electro-conductive textile

The preliminary evaluation is described of a new electro-thermal anti-icing/de-icing device for carbon fibre composite aerostructures. The heating element is an electro-conductive carbon-based textile (ECT) by Gorix. Electrical shorting between the structural carbon fibres and the ECT was mitigated by incorporating an insulating layer formed of glass fibre plies or a polymer film. A laboratory-based anti-icing and de-icing test program demonstrated that the film-insulated devices yielded better performance than the glssass fibre insulated ones. The heating capability after impact damage was maintained as long as the ECT fabric was not breached to the extent of causing electrical shorting. A modified structural scarf repair was shown to restore the heating capacity of a damaged specimen.

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

Additionality of Incubator Support on Networks of University Spin-Out Firms

The formation rate of university spin-out firms has increased markedly over the past decade. While this is seen as an important channel for the commercialisation of academic research, concerns have centred around high failure rates and no-to-low growth among those which survive compared to other new technology based firms. Universities have responded to this by investing in incubators to assist spin-outs to overcome their liability of newness. Yet how effective are incubators in supporting these firms? Here we examine this in terms of the structural networks that spin-out firms form, the role of the incubator in this and the effect of this on the spin-out process.

Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection

Respiratory Syncytial Virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanised monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F-protein with subnanomolar affinity. ALX-0171 demonstrated superior in vitro neutralisation compared to palivizumab against prototypic RSV A and B strains. Moreover, ALX-0171 completely blocked replication below limit of detection in 87% of the viruses tested versus 18% for palivizumab at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease.

Corneal complications associated with topical ophthalmic use of nonsteroidal antiinflammatory drugs.

PURPOSE:

To explore the potential association between adverse corneal events and the use of topical nonsteroidal antiinflammatory drugs (NSAIDs).

SETTING:

Practice-based reports.

METHODS:

A detailed case-reporting form and request for medical records were sent to all practices reporting cases of corneal or conjunctival pathology in association with the use of topical NSAIDs to the American Society of Cataract and Refractive Surgery. Cases were classified as "mild," "moderate," or "severe" according to predetermined clinical criteria.

RESULTS:

Records of 140 eyes (129 patients) were reviewed; 51 cases (36.4%) were mild, 55 (39.3%) moderate, and 34 (24.3%) severe. An association with a specific topical NSAID was confirmed in 117 cases (81.8%). Most confirmed cases (53.8%) involved generic diclofenac (Falcon). Cases associated with brand diclofenac (Voltaren, CIBA Vision) and ketorolac (Acular, Allergan) were more likely to have ocular comorbidity and to have received significantly higher total doses of NSAIDs. Neither "off-label" use nor use of any specific agent was associated with severe compared to mild or moderate disease. However, patients with more severe adverse events were more likely to have a history of diabetes, previous surgery in the affected eye, and surgery other than cataract. Cases not occurring in the perioperative period had significantly worse outcomes, had significantly more ocular comorbidities, and received nearly 3 times the dose of NSAIDs.

CONCLUSIONS:

While topical NSAIDs as a class may be associated with severe adverse events, such events appeared to require potentiation in the form of high total doses, ocular comorbidities, or both with Acular and Voltaren. Severe adverse events might have been more likely to occur at lower doses and in routine postoperative settings with generic diclofenac.

Cortical, but not posterior subcapsular, cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.

PURPOSE:

To quantify the risk for age-related cortical cataract and posterior subcapsular cataract (PSC) associated with having an affected sibling after adjusting for known environmental and personal risk factors.

DESIGN:

Sibling cohort study.

PARTICIPANTS:

Participants in the ongoing Salisbury Eye Evaluation (SEE) study (n = 321; mean age, 78.1+/-4.2 years) and their locally resident siblings (n = 453; mean age, 72.6+/-7.4 years) were recruited at the time of Rounds 3 and 4 of the SEE study. INTERVENTION/TESTING METHODS: Retroillumination photographs of the lens were graded for the presence of cortical cataract and PSC with the Wilmer grading system. The residual correlation between siblings' cataract grades was estimated after adjustment for a number of factors (age; gender; race; lifetime exposure to ultraviolet-B light; cigarette, alcohol, estrogen, and steroid use; serum antioxidants; history of diabetes; blood pressure; and body mass index) suspected to be associated with the presence of cataract.

RESULTS:

The average sibship size was 2.7 per family. Multivariate analysis revealed the magnitude of heritability (h(2)) for cortical cataract to be 24% (95% CI, 6%-42%), whereas that for PSC was not statistically significant (h(2) 4%; 95% CI, 0%-11%) after adjustment for the covariates. The model revealed that increasing age, female gender, a history of diabetes, and black race increased the odds of cortical cataract, whereas higher levels of provitamin A were protective. A history of diabetes and steroid use increased the odds for PSC.

CONCLUSIONS:

This study is consistent with a significant genetic effect for age-related cortical cataract but not PSC.

Familial aggregation of hyperopia in an elderly population of siblings in Salisbury, Maryland.

PURPOSE: To determine whether hyperopia aggregates in families in an older mixed-race population. DESIGN: Cross-sectional familial aggregation study using sibships. METHODS: We recruited 759 subjects (mean age, 73.4 years) in 241 families through the population-based Salisbury Eye Evaluation study. Subjects underwent noncycloplegic refraction if best-corrected visual acuity (BCVA) was <or=20/40, had lensometry to measure their currently worn spectacles if BCVA was >20/40 with spectacles, or were considered to be plano (refraction of zero) if the BCVA was >20/40 without spectacles. Preoperative refraction from medical records was used for bilaterally pseudophakic subjects. RESULTS: Utilizing hyperopia cutoffs from 1.00 to 2.50 diopters, age-, race-, and gender-adjusted odds ratios for hyperopia with an affected sibling ranged from 2.72 (95% confidence interval [CI], 1.84-4.01) to 4.87 (95% CI, 2.54-9.30). The odds of hyperopia increased with age until 75 years, after which they remained relatively constant. Black men were significantly less likely to be hyperopic than white men, white women, or black women. CONCLUSIONS: Hyperopia appears to be under strong genetic control in this older population.

Heritability of refractive error and familial aggregation of myopia in an elderly American population.

PURPOSE: To determine the heritability of refractive error and the familial aggregation of myopia in an older population. METHODS: Seven hundred fifty-nine siblings (mean age, 73.4 years) in 241 families were recruited from the Salisbury Eye Evaluation (SEE) Study in eastern Maryland. Refractive error was determined by noncycloplegic subjective refraction (if presenting distance visual acuity was < or =20/40) or lensometry (if best corrected visual acuity was >20/40 with spectacles). Participants were considered plano (refractive error of zero) if uncorrected visual acuity was >20/40. Preoperative refraction from medical records was used for pseudophakic subjects. Heritability of refractive error was calculated with multivariate linear regression and was estimated as twice the residual between-sibling correlation after adjusting for age, gender, and race. Logistic regression models were used to estimate the odds ratio (OR) of myopia, given a myopic sibling relative to having a nonmyopic sibling. RESULTS: The estimated heritability of refractive error was 61% (95% confidence interval [CI]: 34%-88%) in this population. The age-, race-, and sex-adjusted ORs of myopia were 2.65 (95% CI: 1.67-4.19), 2.25 (95% CI: 1.31-3.87), 3.00 (95% CI: 1.56-5.79), and 2.98 (95% CI: 1.51-5.87) for myopia thresholds of -0.50, -1.00, -1.50, and -2.00 D, respectively. Neither race nor gender was significantly associated with an increased risk of myopia. CONCLUSIONS: Refractive error and myopia are highly heritable in this elderly population.

Determinants and heritability of intraocular pressure and cup-to-disc ratio in a defined older population.

PURPOSE:

To investigate the heritability of intraocular pressure (IOP) and cup-to-disc ratio (CDR) in an older well-defined population.

DESIGN:

Family-based cohort study.

PARTICIPANTS:

Through the population-based Salisbury Eye Evaluation study, we recruited 726 siblings (mean age, 74.7 years) in 284 sibships.

METHODS:

Intraocular pressure and CDR were measured bilaterally for all participants. The presence or absence of glaucoma was determined by a glaucoma specialist for all probands on the basis of visual field, optic nerve appearance, and history. The heritability of IOP was calculated as twice the residual between-sibling correlation of IOP using linear regression and generalized estimating equations after adjusting for age, gender, mean arterial pressure, race, self-reported diabetes status, and history of systemic steroid use. The heritability of CDR was calculated using the same model and adjustments as above, while also adjusting for IOP.

MAIN OUTCOME MEASURES:

Heritability and determinants of IOP and CDR, and impact of siblings' glaucoma status on IOP and CDR.

RESULTS:

We estimated the heritability to be 0.29 (95% confidence interval [CI], 0.12-0.46) for IOP and 0.56 (95% CI, 0.35-0.76) for CDR in this population. Mean IOP in siblings of glaucomatous probands was statistically significantly higher than in siblings of normal probands (mean difference, 1.02 mmHg; P = 0.017). The mean CDR in siblings of glaucomatous probands was 0.07 (or 19%) larger than in siblings of glaucoma suspect referrals (P = 0.045) and siblings of normal probands (P = 0.004).

CONCLUSIONS:

In this elderly population, we found CDR to be highly heritable and IOP to be moderately heritable. On average, siblings of glaucoma patients had higher IOPs and larger CDRs than siblings of nonglaucomatous probands.

Factors associated with spectacle-wear compliance in school-aged Mexican children.

PURPOSE: To study the prevalence and determinants of compliance with spectacle wear among school-age children in Oaxaca, Mexico, who were provided spectacles free of charge. METHODS: A cohort of 493 children aged 5 to 18 years chosen by random cluster sampling from primary and secondary schools in Oaxaca, Mexico, all of whom had received free spectacles through a local program, underwent unannounced, direct examination to determine compliance with spectacle wear within 18 months after initial provision of spectacles. Potential determinants of spectacle wear including age, gender, urban versus rural residence, presenting visual acuity, refractive error, and time since dispensing of the spectacles were examined in univariate and multivariate regression models. Children not currently wearing their spectacles were asked to select the reason from a list of possibilities, and reasons for noncompliance were analyzed within different demographic groups. RESULTS: Among this sample of children with a mean age of 10.4 +/- 2.6 years, the majority (74.5%) of whom were myopic (spherical equivalent [SE] < or = -0.50 D), 13.4% (66/493) were wearing their spectacles at the time of examination. An additional 34% (169/493) had the spectacles with them but were not wearing them. In regression models, the odds of spectacle wear were significantly higher among younger (OR = 1.19 per year of age; 95% CI, 1.05-1.33) rural (OR = 10.6; 95% CI, 5.3-21.0) children and those with myopia < or = -1.25 D (OR = 3.97; 95% CI, 1.98-7.94). The oldest children and children in urban-suburban areas were significantly more likely to list concerns about the appearance of the glasses or about being teased than were younger, rurally resident children. CONCLUSIONS: Compliance with spectacle wear may be very low, even when spectacles are provided free of charge, particularly among older, urban children, who have been shown in many populations to have the highest prevalence of myopia. As screening programs for refractive error become increasingly common throughout the world, new strategies are needed to improve compliance if program resources are to be maximized.

Willingness to pay for cataract surgery in rural Southern China.

PURPOSE: To study willingness to pay for cataract surgery, and its associations, in Southern China. DESIGN: Cross-sectional willingness-to-pay interview incorporating elements of the open-ended and bidding formats. PARTICIPANTS: Three-hundred thirty-nine persons presenting for cataract screening in Yangjiang, China, with presenting visual acuity (VA) < or = 6/60 in either eye due to cataract. METHODS: Subjects underwent measurement of their VA and a willingness-to-pay interview. Age, gender, literacy, education, and annual income also were recorded. MAIN OUTCOME MEASURES: Maximum amount that the subjects would be willing to pay for cataract surgery. RESULTS: Among 325 (95.9%) subjects completing the interview, 169 (52.0%) were 70 years or older, 213 (65.5%) were women, and 217 (66.8%) had an annual income of <5000 renminbi (5000 = US 625 dollars). Eighty percent (n = 257) of participants were willing to pay something for surgery (mean, 442+/-444 renminbi [US 55 dollars+/-55]). In regression models, older subjects were willing to pay less (8 renminbi [US 1 dollar] per year of age; P = 0.01). Blind subjects were significantly more likely (odds ratio, 5.7; 95% confidence interval, 1.7-19.3) to pay anything for surgery, but would pay on average 255 renminbi (US 32 dollars) less (P = 0.004). Persons at the highest annual income level (>10,000 renminbi [US 1250 dollars]) would pay 50 dollars more for surgery than those at the lowest level (<5000 renminbi) (P = 0.0003). The current cost of surgery in this program is 500 renminbi (US 63 dollars). CONCLUSIONS: Sustainable programs will need to attract younger, more well-to-do persons with better vision, while still providing access to the neediest patients.

The effects of sevoflurane and ketamine on intraocular pressure in children during examination under anesthesia

PURPOSE: We studied the effects on intraocular pressure (IOP) of anesthesia administered during examination under anesthesia (EUA) in children. DESIGN: Randomized clinical trial. METHODS: This randomized trial compared IOP after inhaled sevoflurane gas to that after intramuscular ketamine hydrochloride in children undergoing EUA. IOP was measured in 30 eyes with TonoPen XL (Mentor, Inc, Norwell, Massachusetts, USA) as soon as possible after anesthesia induction (T1) and two, four, six, and eight minutes thereafter. At the same times, we recorded systolic and diastolic blood pressure (SBP, DBP) and heart rate (HR). RESULTS: Compared with the mean IOP at T1, IOP in the sevoflurane group was significantly lower for all measurements from two to eight minutes thereafter (mean decrease in IOP: two minutes = 12%, four minutes = 19%; six minutes = 19%; eight minutes = 17%, all P < or = .01). In the ketamine group, mean IOP was not significantly changed from T1 through six minutes, whereas at eight minutes, it was 7% lower (P = .03). SBP and DBP were significantly lower for sevoflurane than for ketamine at all measurements from two minutes onward, and HR was lower for sevoflurane than for ketamine at two, four, and six minutes. CONCLUSIONS: IOP measured after ketamine sedation is more likely to represent the awake IOP than that after sevoflurane anesthesia. Changes in SBP, DBP, and HR caused by sevoflurane suggest that hemodynamic alterations may underlie its effects on IOP.

School-based approaches to the correction of refractive error in children.

The World Health Organization estimates that 13 million children aged 5-15 years worldwide are visually impaired from uncorrected refractive error. School vision screening programs can identify and treat or refer children with refractive error. We concentrate on the findings of various screening studies and attempt to identify key factors in the success and sustainability of such programs in the developing world. We reviewed original and review articles describing children's vision and refractive error screening programs published in English and listed in PubMed, Medline OVID, Google Scholar, and Oxford University Electronic Resources databases. Data were abstracted on study objective, design, setting, participants, and outcomes, including accuracy of screening, quality of refractive services, barriers to uptake, impact on quality of life, and cost-effectiveness of programs. Inadequately corrected refractive error is an important global cause of visual impairment in childhood. School-based vision screening carried out by teachers and other ancillary personnel may be an effective means of detecting affected children and improving their visual function with spectacles. The need for services and potential impact of school-based programs varies widely between areas, depending on prevalence of refractive error and competing conditions and rates of school attendance. Barriers to acceptance of services include the cost and quality of available refractive care and mistaken beliefs that glasses will harm children's eyes. Further research is needed in areas such as the cost-effectiveness of different screening approaches and impact of education to promote acceptance of spectacle-wear. School vision programs should be integrated into comprehensive efforts to promote healthy children and their families.