Prevalence and Onset of Pediatric Sickle Cell Retinopathy.

PURPOSE: Children with sickle cell hemoglobinopathy (SCH) can demonstrate proliferative retinopathy with vision loss, but lack of consensus exists regarding screening regimens. We sought to determine the prevalence, age at onset, and risk factors associated with sickle cell retinopathy (SCR) to inform development of screening guidelines for asymptomatic children. DESIGN: Retrospective cohort study. PARTICIPANTS: Children with SCH over a 4-year period. METHODS: Prevalences of any retinopathy, nonproliferative retinopathy (NPR), and proliferative retinopathy (PR), determined as proportions of all children examined, were calculated. Subgroup analyses were completed by SCH genotype. Ages at first diagnosis were reported using standard descriptive statistics. The association of potential risk factors with retinopathy were assessed using univariate and multivariate linear and logistic regression. MAIN OUTCOME MEASURES: Outcomes were prevalence, age at onset, and type of SCR, based on examination by an ophthalmologist. Markers of SCH severity (number of emergency room or hospital admissions for crises, number of blood transfusions, hydroxyurea therapy, transcranial Doppler-confirmed cerebral vasculopathy), genotype, gender, and race were evaluated as SCR risk factors. RESULTS: Of 398 children (mean age, 9.6±4.6 years; range 0-18 years), 208 (52%) showed sickle cell homozygote (SS) genotype, 113 (28%) showed sickle cell hemoglobin C (SC) genotype, and 77 (19%) showed trait genotype. Forty-eight children (12.1%) demonstrated SCR, 44 of 398 children (11.1%; 95% confidence interval, 8.3%-14.5%) demonstrated NPR, and 9 of 398 children (2.3%; 95% confidence interval, 1.2%-4.2%) demonstrated PR. Prevalence was higher for SC than SS genotype for NPR (21% vs. 9%) and PR (5% vs. 1%); onset for SC genotype was earlier than that for SS genotype for NPR (youngest diagnosis 4.8 vs. 6.1 years) and PR (12.2 vs. 15.4 years). No other risk factors were associated significantly with SCR. CONCLUSIONS: Clinical markers of SCH severity assessed were not associated with SCR and are not necessary for screening guidelines. Based on our study and literature review, although screening could begin at age 5 years for NPR, screening of children without ophthalmologic symptoms to identify treatment-requiring PR could begin later, at 9 years of age for SC and 13 years of age for SS.

Effective Three-Body Interactions in Cs(6s)-Cs(nd) Rydberg Trimers.

Ultralong-range Rydberg trimer molecules are spectroscopically observed in an ultracold gas of Cs(nd_{3/2}) atoms. The anisotropy of the atomic Rydberg state allows for the formation of angular trimers, whose energies may not be obtained from integer multiples of dimer energies. These nonadditive trimers coexist with Rydberg dimers. The existence of such effective three-body interactions is confirmed with the observation of asymmetric line profiles and interpreted by a theoretical approach that includes relativistic spin interactions. Simulations of the observed spectra with and without angular trimer lines lend convincing support to the existence of effective three-body interactions.

Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease.

Inherited retinal degenerations cause progressive loss of photoreceptor neurons with eventual blindness. Corrective or neuroprotective gene therapies under development could be delivered at a predegeneration stage to prevent the onset of disease, as well as at intermediate-degeneration stages to slow the rate of progression. Most preclinical gene therapy successes to date have been as predegeneration interventions. In many animal models, as well as in human studies, to date, retinal gene therapy administered well after the onset of degeneration was not able to modify the rate of progression even when successfully reversing dysfunction. We evaluated consequences of gene therapy delivered at intermediate stages of disease in a canine model of X-linked retinitis pigmentosa (XLRP) caused by a mutation in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene. Spatiotemporal natural history of disease was defined and therapeutic dose selected based on predegeneration results. Then interventions were timed at earlier and later phases of intermediate-stage disease, and photoreceptor degeneration monitored with noninvasive imaging, electrophysiological function, and visual behavior for more than 2 y. All parameters showed substantial and significant arrest of the progressive time course of disease with treatment, which resulted in long-term improved retinal function and visual behavior compared with control eyes. Histology confirmed that the human RPGR transgene was stably expressed in photoreceptors and associated with improved structural preservation of rods, cones, and ON bipolar cells together with correction of opsin mislocalization. These findings in a clinically relevant large animal model demonstrate the long-term efficacy of RPGR gene augmentation and substantially broaden the therapeutic window for intervention in patients with RPGR-XLRP.

Rydberg-atom based radio-frequency electrometry using frequency modulation spectroscopy in room temperature vapor cells.

Rydberg atom-based electrometry enables traceable electric field measurements with high sensitivity over a large frequency range, from gigahertz to terahertz. Such measurements are particularly useful for the calibration of radio frequency and terahertz devices, as well as other applications like near field imaging of electric fields. We utilize frequency modulated spectroscopy with active control of residual amplitude modulation to improve the signal to noise ratio of the optical readout of Rydberg atom-based radio frequency electrometry. Matched filtering of the signal is also implemented. Although we have reached similarly, high sensitivity with other read-out methods, frequency modulated spectroscopy is advantageous because it is well-suited for building a compact, portable sensor. In the current experiment, ∼3 µV cm-1 Hz-1/2 sensitivity is achieved and is found to be photon shot noise limited.

SYSTEMIC BETA-BLOCKERS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate whether oral beta-blockers (BBs) are associated with a decreased number of intravitreal injections in patients with incident neovascular age-related macular degeneration. METHODS: A retrospective cohort study of subjects with a new diagnosis of neovascular age-related macular degeneration was conducted using a medical claims database from a large national US insurer. Two cohorts were created for comparison consisting of patients with regular use of BBs or calcium channel blockers. The main outcome measured was the difference in the mean number of intravitreal injections administered between the two cohorts. RESULTS: After inclusion and exclusion criteria, 239 BB and 155 calcium channel blocker subjects remained for analysis. Univariate analysis revealed that the mean number of injections in the BB cohort was 6.43 (95% confidence interval [CI] 5.90-6.95) versus 6.55 (95% CI 5.85-7.25) in the calcium channel blocker cohort (P = 0.78). After multivariate adjustment, the mean number of injections in the BB group was 6.32 (95% CI 5.77-6.87) versus 6.71 (95% CI 6.02-7.40) in the calcium channel blocker group. The overall difference between the 2 groups was -0.39 (95% CI difference -1.29 to 0.51; P = 0.40). CONCLUSION: The use of oral BBs is not associated with a decreased number of intravitreal injections in incident neovascular age-related macular degeneration patients.

Outcomes in Eyes with Retinal Angiomatous Proliferation in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).

PURPOSE: To compare baseline characteristics, visual acuity (VA), and morphologic outcomes between eyes with retinal angiomatous proliferation (RAP) and all other eyes among patients with neovascular age-related macular degeneration (NVAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs. DESIGN: Prospective cohort study within the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). PARTICIPANTS: Patients with NVAMD. METHODS: Reading center staff evaluated digital color fundus photographs, fluorescein angiography (FA) images, and optical coherence tomography (OCT) scans of eyes with NVAMD treated with either ranibizumab or bevacizumab over a 2-year period. Retinal angiomatous proliferation was identified by the intense intra-retinal leakage of fluorescein in combination with other associated features. MAIN OUTCOME MEASURES: Visual acuity; fluorescein leakage; scar; geographic atrophy (GA) on FA; retinal thickness, fluid, and subretinal hyperreflective material (SHRM) on OCT; and the number of intravitreal anti-VEGF injections at 1 and 2 years. RESULTS: Retinal angiomatous proliferation was present in 126 of 1183 (10.7%) study eyes at baseline. Mean VA improvement from baseline was greater (10.6 vs. 6.9 letters; P = 0.01) at 1 year, but similar at 2 years (7.8 vs. 6.2 letters; P = 0.34). At 1 year, eyes with RAP were more likely to have no fluid (46% vs. 26%; P < 0.001) on OCT, no leakage on FA (61% vs. 50%; P = 0.03), and greater reduction in foveal thickness (-240 µm vs. -161 µm; P < 0.001). They were more likely to demonstrate GA (24% vs. 15%; P = 0.01) and less likely to have scarring (17% vs. 36%; P < 0.001) or SHRM (36% vs. 48%; P = 0.01). These results were similar at 2 years. The mean change in lesion size at 1 year differed (-0.27 DA vs. 0.27 DA; P = 0.02), but was similar at 2 years (0.49 DA vs. 0.79 DA; P = 0.26). Among eyes treated PRN, eyes with RAP received a lower mean number of injections in year 1 (6.1 vs. 7.4; P = 0.003) and year 2 (5.4 vs. 6.6; P = 0.025). CONCLUSIONS: At both 1 and 2 years after initiation of anti-VEGF treatment in CATT, eyes with RAP were less likely to have fluid, FA leakage, scar, and SHRM and more likely to have GA than eyes without RAP. Mean improvement in VA was similar at 2 years.

Angiographic Cystoid Macular Edema and Outcomes in the Comparison of Age-Related Macular Degeneration Treatments Trials.

PURPOSE: To describe morphologic and visual outcomes in eyes with angiographic cystoid macular edema (CME) treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (nAMD). DESIGN: Prospective cohort study within a randomized clinical trial. PARTICIPANTS: A total of 1185 CATT study subjects. METHODS: Baseline fluorescein angiography (FA) images of all CATT study eyes were evaluated for CME. Grading of other characteristics on optical coherence tomography (OCT) and photographic images at baseline and during 2-year follow-up was completed by readers at the CATT Reading Centers. Three groups were created on the basis of baseline CME and intraretinal fluid (IRF) status: (1) CME, (2) IRF without CME, (3) neither CME nor IRF. MAIN OUTCOME MEASURES: Visual acuity (VA) and total central retinal thickness (CRT) on OCT at baseline, year 1, and year 2. RESULTS: Among 1131 participants with images of sufficient quality for determining CME and IRF at baseline, 92 (8.1%) had CME, 766 (67.7%) had IRF without CME, and 273 (24.1%) had neither. At baseline, eyes with CME had worse mean VA (letters) than eyes with IRF without CME and eyes with neither CME nor IRF (52 vs. 60 vs. 66 letters, P < 0.001); higher mean total CRT (µm) on OCT (514 vs. 472 vs. 404, P < 0.001); and greater hemorrhage, retinal angiomatous proliferation (RAP) lesions, and classic choroidal neovascularization (CNV). All groups showed improvement in VA at follow-up; however, the CME group started and ended with the worst VA among the 3 groups. Central retinal thickness, although higher at baseline for the CME group, was similar at 1 and 2 years follow-up for all groups. More eyes with CME (65.3%) developed scarring during 2 years of follow-up compared with eyes with IRF without CME (43.8%) and eyes with neither CME nor IRF (32.5%; P < 0.001). CONCLUSIONS: In CATT, eyes with CME had worse baseline and follow-up VA, although all groups showed similar rates of improvement in VA during 2 years of follow-up. Cystoid macular edema seems to be a marker for poorer visual outcomes in nAMD because of underlying baseline retinal dysfunction and subsequent scarring.

Strong Coupling of Rydberg Atoms and Surface Phonon Polaritons on Piezoelectric Superlattices.

We propose a hybrid quantum system where the strong coupling regime can be achieved between a Rydberg atomic ensemble and propagating surface phonon polaritons on a piezoelectric superlattice. By exploiting the large electric dipole moment and long lifetime of Rydberg atoms as well as tightly confined surface phonon polariton modes, it is possible to achieve a coupling constant far exceeding the relevant decay rates. The frequency of the surface mode can be selected so that it is resonant with a Rydberg transition by engineering the piezoelectric superlattice. We describe a way to observe the Rabi splitting associated with the strong coupling regime under realistic experimental conditions. The system can be viewed as a new type of optomechanical system.

Theory of Ultralong-Range Rydberg Molecule Formation Incorporating Spin-Dependent Relativistic Effects: Cs(6s)-Cs(np) as Case Study.

We calculate vibrational spectra of ultralong-range Cs(32p) Rydberg molecules that form in an ultracold gas of Cs atoms. We account for the partial-wave scattering of the Rydberg electrons from the Cs perturber atoms by including the full set of spin-resolved 1,3 SJ and 1,3 PJ scattering phase shifts, and allow for the mixing of singlet (S=0) and triplet (S=1) spin states through Rydberg electron spin-orbit and ground state electron hyperfine interactions. Excellent agreement with observed data in Saßmannshausen et al. [Phys. Rev. Lett. 2015, 113, 133201] in line positions and profiles is obtained. We also determine the spin-dependent permanent electric dipole moments for these molecules. This is the first such calculation of ultralong-range Rydberg molecules for which all of the relativistic contributions are accounted.

Projecting Critical Care Beyond the ICU: An Analysis of Tele-ICU Support for Rapid Response Teams.

BACKGROUND: The rapid response team (RRT) concept was developed to improve care for decompensating patients outside of the intensive care unit (ICU) setting. The tele-ICU service (eICU(®)) at Health First Hospitals (Brevard County, FL) has provided tele-critical care support for patients outside the ICU using a mobile platform (the eMobile platform) since 2012. In this study we sought to evaluate the ability of eMobile to support care administered by RRTs. MATERIALS AND METHODS: A retrospective review evaluating mobile cart activations for RRT calls was performed. Data on mobile cart deployments were recorded over a 33-month period from January 2012 through September 2014. RESULTS: Five hundred eighty mobile cart activations for critical care support were initiated by RRTs, and 577 were completed (>99%). For recorded gender, 223 patients (47%) were male, and 248 (53%) patients were female. Mean recorded age was 70 ± 16 years (median, 72 years). The most common patient conditions were respiratory distress (n = 190, 33%), altered mental status (n = 137, 24%) and hypotension (n = 59, 10%). The most common interventions were medication orders (n = 231, 40%) and laboratory studies (n = 92, 29%). For 566 eMobile calls with documented dispositions, 189 patients (33%) were managed without ICU upgrade. No adverse patient outcomes were recorded involving eMobile. Compared with the RRT program in 2009, the last year before testing of eMobile began (2010-2011), addition of tele-critical care support for calendar years 2012 and 2013 increased projected cost avoidance from unnecessary ICU transfers by a mean of 66% above the 2009 baseline. For Fiscal Year 2014, a projected cost avoidance analysis for unnecessary ICU transfers including costs of information technology (IT) support demonstrated a return on investment up to $1.66 for every $1 invested in IT support. CONCLUSIONS: Mobile critical care coupled with RRT is clinically effective and can generate meaningful cost avoidance.

Ocular Complications in Children with Diabetes Mellitus.

PURPOSE: The effectiveness of annual eye examinations in diabetic children is unclear. We sought to determine the prevalence and onset of ocular pathology in children with diabetes mellitus (DM), identify risk factors for ocular disease, and recommend a screening regimen for asymptomatic children. DESIGN: Retrospective, consecutive cohort study. PARTICIPANTS: Children aged less than 18 years with type 1 or 2 DM examined over a 4-year period. METHODS: All children underwent a complete eye examination, including dilated fundoscopy and cycloplegic refraction. A literature review was performed, identifying the youngest reported age and shortest reported duration of DM before the diagnosis of diabetic retinopathy (DR). MAIN OUTCOME MEASURES: Prevalence of DR, cataract, high refractive error, and strabismus. RESULTS: A total of 370 children (mean age, 11.2 years; range, 1-17.5 years) had 693 examinations, with a mean DM duration of 5.2 years (range, 0.1-16.2 years) and a mean hemoglobin A1c (HbA1c) of 8.6 (range, 5-≥14). No children had DR. A total of 12 children had cataract; 5 required extraction but were identified by decreased vision, not diabetic screening. A total of 19 children had strabismus; only 1 was microvascular paralytic strabismus. A total of 41 children had high refractive error. There were no associations between these conditions and duration or control of DM. In the literature, the youngest age at diagnosis of severe DR was 15 years, and the shortest duration of disease was 5 years. CONCLUSIONS: Diabetic retinopathy is rare in children regardless of duration and control of DM. On the basis of our study and literature review, screening examinations for type 1 diabetes could begin at age 15 years or at 5 years after the diagnosis of DM, whichever occurs later, unless the child is judged by the endocrinologist as being at unusually high risk. Other ocular complications are identifiable through existing amblyopia screening methods.

Observation of ultralong-range Rydberg molecules.

Rydberg atoms have an electron in a state with a very high principal quantum number, and as a result can exhibit unusually long-range interactions. One example is the bonding of two such atoms by multipole forces to form Rydberg-Rydberg molecules with very large internuclear distances. Notably, bonding interactions can also arise from the low-energy scattering of a Rydberg electron with negative scattering length from a ground-state atom. In this case, the scattering-induced attractive interaction binds the ground-state atom to the Rydberg atom at a well-localized position within the Rydberg electron wavefunction and thereby yields giant molecules that can have internuclear separations of several thousand Bohr radii. Here we report the spectroscopic characterization of such exotic molecular states formed by rubidium Rydberg atoms that are in the spherically symmetric s state and have principal quantum numbers, n, between 34 and 40. We find that the spectra of the vibrational ground state and of the first excited state of the Rydberg molecule, the rubidium dimer Rb(5s)-Rb(ns), agree well with simple model predictions. The data allow us to extract the s-wave scattering length for scattering between the Rydberg electron and the ground-state atom, Rb(5s), in the low-energy regime (kinetic energy, <100 meV), and to determine the lifetimes and the polarizabilities of the Rydberg molecules. Given our successful characterization of s-wave bound Rydberg states, we anticipate that p-wave bound states, trimer states and bound states involving a Rydberg electron with large angular momentum-so-called trilobite molecules-will also be realized and directly probed in the near future.

Postnatal Serum Insulin-Like Growth Factor I and Retinopathy of Prematurity in Latin American Infants.

PURPOSE: Identifying at-risk infants for retinopathy of prematurity (ROP) is complex in countries with emerging economies as infants that lack conventional risk factors, such as low birth weight (BW) and young gestational age (GA), still go on to develop severe ROP. Potential biomarkers, like serum insulin-like growth factor 1 (IGF-1) and slow postnatal weight gain, have been identified as good predictors for ROP in developed countries. We sought to determine the relationship between IGF-1 levels and ROP in two Latin American countries where the burden of disease is still significant. METHODS: Prospective cohort study of infants in Guadalajara, Mexico and La Plata, Argentina. Filter-paper bloodspot IGF-1 assays were performed weekly from birth until hospital discharge or 40 weeks' postmenstrual age (PMA). RESULTS: 112 infants were studied with a median BW of 1412 g (range 620 g-2390 g) and a median GA of 33 weeks (range 25-37). There was no significant difference in IGF-1 between infants who developed ROP and those who did not. CONCLUSION: Low IGF-1 was not associated with ROP in these infants. The lack of an association between ROP and IGF-1 in Latin America supports the observation that growth-based predictive models do not perform as well in this setting where more mature babies still develop severe ROP.

Refractive change in children with accommodative esotropia.

OBJECTIVE: To determine whether there is a measurable change in hyperopia in children with accommodative esotropia over time. METHODS AND ANALYSIS: A retrospective cohort of children with fully or partially accommodative esotropia diagnosed by age 7 years, followed to age 10 or older, and with at least two cycloplegic refractions, one before age 7 years and one after age 10 years. The annual change was calculated from linear mixed-effect models, overall and during two age periods with subgroup analysis by baseline refractive error (<4D, ≥4D) and type (partial, full) of accommodative esotropia. RESULTS: 405 subjects were studied. Mean age at first and last visit was 3.2 and 12.1 years, respectively, with mean 7.6 cycloplegic refractions. The annual change (95% CI) in refractive error was -0.071 (-0.087 to -0.055) D/yr. Between ages 3 and 7, hyperopia among children with baseline hyperopia <4D increased by 0.12 (0.08 to 0.16) D/yr, while hyperopia among those with baseline 4D or greater was stable (0.0D/yr, -0.03 to 0.04) (p<0.001). Hyperopia decreased from age 7 to 15 years in both subgroups: <4D subgroup -0.17 (-0.20 to -0.14) D/yr, ≥4D subgroup -0.18 (-0.21 to -0.15) D/yr (p=0.58). There was no significant difference in refractive change between fully (n=274) and partially (n=131) accommodative esotropia (p≥0.10). CONCLUSION: Hyperopia in children with accommodative esotropia is stable or increases up to age 7 years, depending on baseline hyperopia, but decreases gradually between ages 7 and 15 years regardless of baseline refractive error.

COMBINING INFORMATION FROM MULTIPLE DATA SOURCES TO ASSESS POPULATION HEALTH.

Information about an extensive set of health conditions on a well-defined sample of subjects is essential for assessing population health, gauging the impact of various policies, modeling costs, and studying health disparities. Unfortunately, there is no single data source that provides accurate information about health conditions. We combine information from several administrative and survey data sets to obtain model-based dummy variables for 107 health conditions (diseases, preventive measures, and screening for diseases) for elderly (age 65 and older) subjects in the Medicare Current Beneficiary Survey (MCBS) over the fourteen-year period, 1999-2012. The MCBS has prevalence of diseases assessed based on Medicare claims and provides detailed information on all health conditions but is prone to underestimation bias. The National Health and Nutrition Examination Survey (NHANES), on the other hand, collects self-reports and physical/laboratory measures only for a subset of the 107 health conditions. Neither source provides complete information, but we use them together to derive model-based corrected dummy variables in MCBS for the full range of existing health conditions using a missing data and measurement error model framework. We create multiply imputed dummy variables and use them to construct the prevalence rate and trend estimates. The broader goal, however, is to use these corrected or modeled dummy variables for a multitude of policy analysis, cost modeling, and analysis of other relationships either using them as predictors or as outcome variables.

Production of multicistronic HIV-1 based lentiviral vectors.

In the last decade lentiviral gene transfer vectors have gained significant place both in basic science and gene therapy applications. A number of gene transfer applications would benefit from vectors capable of expressing multiple genes. This chapter focuses on production of bicistronic and tricistronic lentiviral vectors based on the internal ribosomal entry site (IRES) sequence of encephalomyocarditis virus (EMCV) and/or foot-and-mouth disease virus (FMDV) cleavage factor 2A. Multigene vectors produced high titer viral particles and were able to simultaneously express two or three transgenes in transduced cells. The level of expression of individual transgenes varied depending on the transgene itself, its position within the construct, the total number of transgenes expressed, the strategy used for multigene expression, and the number of copies of proviral insertions.

Causes and Consequences of Phenotypic Plasticity in Complex Environments.

Phenotypic plasticity is a ubiquitous and necessary adaptation of organisms to variable environments, but most environments have multiple dimensions that vary. Many studies have documented plasticity of a trait with respect to variation in multiple environmental factors. Such multidimensional phenotypic plasticity (MDPP) exists at all levels of organismal organization, from the whole organism to within cells. This complexity in plasticity cannot be explained solely by scaling up ideas from models of unidimensional plasticity. MDPP generates new questions about the mechanism and function of plasticity and its role in speciation and population persistence. Here we review empirical and theoretical approaches to plasticity in response to multidimensional environments and we outline new opportunities along with some difficulties facing future research.

Dietary Zinc-Amino Acid Complex Does Not Affect Markers of Mammary Epithelial Integrity or Heat Stability of Milk in Mid-Lactating Cows.

Supplying dietary zinc in excess of traditional requirements has clear impacts on the gut epithelium, but little research has explored whether similar impacts on the mammary epithelium may occur. Our objective was to determine the effects of supplemental Zn sources, in excess of minimal requirements, on markers of mammary epithelial integrity in blood and in milk as well as the heat stability of milk in mid-lactation cows. Twelve multiparous Holstein cows (132 ± 21 days in milk and 51 ± 3 kg/day milk) were blocked according to milk yield and enrolled in a replicated 3 × 3 Latin square experiment. Experimental periods were 21 days, with 17 days allowed for diet adaptation and 4 days for sampling. Treatment sequences were randomly assigned to animals and treatments were as follows: (1) 0.97 g Zn/day provided as ZnSO4 (34.5 mg supplemental Zn/kg diet DM; 30-ZS), (2) 1.64 g Zn/day provided as ZnSO4 (56.5 mg supplemental Zn/kg diet DM; 60-ZS), and (3) 0.55 g Zn/day provided as ZnSO4 plus 1.13 g Zn/day provided as a zinc-methionine complex (58.2 mg supplemental Zn/kg diet DM; 60-ZM). Treatments were administered once daily as an oral bolus containing all supplemental trace minerals. Rumen-bypass methionine was also included in the 30-ZS and 60-ZS boluses to provide metabolizable methionine equivalent to that provided in 60-ZM rations. Milk samples were assessed for electrolytes, somatic cell transcript abundance of genes related to zinc metabolism, and heat coagulation time. Whole blood samples were analyzed for Na and K concentrations, and plasma samples were analyzed for lactose concentration. Cows fed 60-ZS or 60-ZM had greater zinc intake compared to 30-ZS. Dry matter intake and milk fat content tended to be greater in 60-ZS and 60-ZM cows compared to 30-ZS. Somatic cell linear score was similar among treatments. Treatments neither affected markers of mammary epithelial integrity in blood nor in milk of cows, including plasma concentration of lactose, milk concentrations of Na+ and K+, and SLC30A2 and CLU transcript abundance. Treatments had no effect on milk N fractions or heat coagulation time. This study provided no evidence that supplemental Zn above the established requirements can improve blood-milk epithelial barrier or heat stability of milk in healthy mid-lactation dairy cows.

Altered ocular parameters from circadian clock gene disruptions.

The pathophysiology of refractive errors is poorly understood. Myopia (nearsightedness) in particular both blurs vision and predisposes the eye to many blinding diseases during adulthood. Based on past findings of diurnal variations in the dimensions of the eyes of humans and other vertebrates, altered diurnal rhythms of these ocular dimensions with experimentally induced myopia, and evolving evidence that ambient light exposures influence refractive development, we assessed whether disturbances in circadian signals might alter the refractive development of the eye. In mice, retinal-specific knockout of the clock gene Bmal1 induces myopia and elongates the vitreous chamber, the optical compartment separating the lens and the retina. These alterations simulate common ocular findings in clinical myopia. In Drosophila melanogaster, knockouts of the clock genes cycle or period lengthen the pseudocone, the optical component of the ommatidium that separates the facet lens from the photoreceptors. Disrupting circadian signaling thus alters optical development of the eye in widely separated species. We propose that mechanisms of myopia include circadian dysregulation, a frequent occurrence in modern societies where myopia also is both highly prevalent and increasing at alarming rates. Addressing circadian dysregulation may improve understanding of the pathogenesis of refractive errors and introduce novel therapeutic approaches to ameliorate myopia development in children.

Ocular complications following treatment in the Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study.

PURPOSE: To determine the prevalence of treatment-related ocular complications and disease progression following treatment for retinopathy of prematurity (ROP). METHODS: This was a retrospective cohort study of eyes treated for ROP at 29 North American neonatal intensive care units in the Postnatal Growth and ROP (G-ROP) Study. Data from the time of treatment through 15 months were abstracted from medical records by certified data collectors. Treatment-related complication (cataract, hyphema, glaucoma, corneal abrasion/opacity), and disease-progression (retinal fold, dragging, or stage 4 or 5 detachment) were calculated by treatment modality. Vitreous hemorrhage was classified separately, because it can relate to treatment or disease progression. RESULTS: Of 7,483 infants included in the study, 1,004 eyes (512 infants) underwent ROP treatment: 970 eyes received laser as initial therapy; 34 eyes received intravitreal bevacizumab (IVB). Median follow-up after treatment was 18 weeks. Overall, one or more complications occurred in 2.6% (95% CI, 1.8%-3.8%) laser treated eyes and no (0%; 95% CI, 0.0%-10.1%) IVB eyes. Disease-progression occurred in 9.2% (95% CI, 7.6%-11.2%) laser treated eyes, no (0%; 95% CI, 0.0-12.9%) IVB-only eyes. Vitreous hemorrhage occurred in 5.4% (95% CI: 4.1% - 7.0%) laser treated eyes, no IVB-only eyes. CONCLUSIONS: Rates of complications are very low following ROP treatment with either laser or IVB. Of laser-treated eyes, 9% experienced disease progression despite treatment.