Correlations among metamorphopsia test scores, optical coherence tomography findings and multifocal electroretinogram responses in epiretinal membrane patients.

PURPOSE: To quantify metamorphopsia with a novel objective method in patients with epiretinal membrane (ERM) and to compare the relationships among metamorphopsia scores, spectral-domain optical coherence tomography (OCT) findings, and multifocal electroretinogram (mfERG) results. METHODS: This study included 52 eyes of 52 patients with idiopathic ERM who underwent comprehensive ophthalmologic examinations, including measurement of best-corrected visual acuity (BCVA), OCT, and mfERG. The degree of metamorphopsia was quantified using MonPack One® (Metrovision, Perenchies, France). On the topographic map of the early treatment diabetic retinopathy (ETDRS) grid, retinal thickness in the central, superior, inferior, nasal, and temporal subfields were measured, and metamorphopsia scores for each corresponding subfield were also obtained. The amplitudes and implicit times of mERG were elicited from each subfield. Then, the correlations among metamorphopsia scores, OCT findings, and mfERG responses were analyzed. RESULTS: The mean age of the patients was 65.3 ± 18.5 y, and the average metamorphopsia score of the individual subfields was 2.03 ± 1.18. Initial BCVA was 0.50 ± 0.12 logMAR, but there was no significant correlation between metamorphopsia scores and BCVA. The metamorphopsia scores from the central subfields showed significant correlations with central retinal thickness (CRT) (p = 0.001). The mean metamorphopsia scores in the central subfield showed a significant relationship with the mean N1 and P1 amplitudes (p = 0.001, p = 0.048, respectively), while no relationship was observed between metamorphopsia scores and mfERG amplitudes in other subfields. CONCLUSIONS: The degree of metamorphopsia in patients with ERM could be objectively quantified in each subfield using a novel metamorphopsia test. The metamorphopsia scores were significantly correlated with retinal thickness, especially at the central subfields, and the scores in the central subfields were significantly correlated with the N1 and P1 amplitudes of mfERG. Thus, the metamorphopsia test can be a useful method to evaluate metamorphopsia symptoms for patients with ERM.

Cost-effectiveness analysis of a physician deployment program to improve access to healthcare in rural and underserved areas in the Philippines.

OBJECTIVES: The objective of this study is to explore the cost-effectiveness of Doctor to the Barrios (DTTB), a physician deployment program in the Philippines. DESIGN: Cost-effectiveness analysis using decision tree models with a lifetime time horizon and probabilistic sensitivity analysis. SETTING: Societal and healthcare perspectives. POPULATION: Hypothetical cohort of children under 5 years in two provinces (Aklan and Nueva Ecija) and in a representative rural municipality. PARTICIPANTS: None. INTERVENTIONS: DTTB's impact on paediatric pneumonia and diarrhoea outcomes compared with a scenario without DTTB. MAIN OUTCOME MEASURES: Costs, effectiveness (in terms of lives saved and quality-adjusted life years (QALYs) gained) and incremental cost-effectiveness ratio (ICER). RESULTS: DTTB is cost-effective in the two provinces that were included in the study from societal and healthcare perspectives. Looking at a representative rural municipality, base case analysis and probabilistic sensitivity analyses suggest that DTTB has an ICER of 27 192 per QALY gained from a societal perspective. From a healthcare perspective, the base case ICER of DTTB is Philippine pesos (PHP) 71 839 per QALY gained and PHP 2 064 167 per life saved, and 10 000 Monte Carlo simulations produced similar average estimates. The cost per QALY of DTTB from a healthcare perspective is lower than the WHO recommended willingness-to-pay threshold of 100% of the country's per-capita gross domestic product. CONCLUSIONS: DTTB can be a cost-effective intervention, but its value varies by setting and the conditions of the municipality where it is implemented. By focusing on a narrow set of paediatric outcomes, this study has likely underestimated the health benefits of DTTB. Additional research is needed to understand the full extent of DTTB's impact on the health of communities in rural and remote areas. Future cost-effectiveness analysis should empirically estimate various parameters and include other health conditions in addition to pneumonia and diarrhoea in children.

Lkb1 regulates granule cell migration and cortical folding of the cerebellar cortex.

Cerebellar growth and foliation require the Hedgehog-driven proliferation of granule cell precursors (GCPs) in the external granule layer (EGL). However, that increased or extended GCP proliferation generally does not elicit ectopic folds suggests that additional determinants control cortical expansion and foliation during cerebellar development. Here, we find that genetic loss of the serine-threonine kinase Liver Kinase B1 (Lkb1) in GCPs increased cerebellar cortical size and foliation independent of changes in proliferation or Hedgehog signaling. This finding is unexpected given that Lkb1 has previously shown to be critical for Hedgehog pathway activation in cultured cells. Consistent with unchanged proliferation rate of GCPs, the cortical expansion of Lkb1 mutants is accompanied by thinning of the EGL. The plane of cell division, which has been implicated in diverse processes from epithelial surface expansions to gyrification of the human cortex, remains unchanged in the mutants when compared to wild-type controls. However, we find that Lkb1 mutants display delayed radial migration of post-mitotic GCPs that coincides with increased cortical size, suggesting that aberrant cell migration may contribute to the cortical expansion and increase foliation. Taken together, our results reveal an important role for Lkb1 in regulating cerebellar cortical size and foliation in a Hedgehog-independent manner.

Observing atmospheric formaldehyde (HCHO) from space: validation and intercomparison of six retrievals from four satellites (OMI, GOME2A, GOME2B, OMPS) with SEAC4RS aircraft observations over the Southeast US.

Formaldehyde (HCHO) column data from satellites are widely used as a proxy for emissions of volatile organic compounds (VOCs) but validation of the data has been extremely limited. Here we use highly accurate HCHO aircraft observations from the NASA SEAC4RS campaign over the Southeast US in August-September 2013 to validate and intercompare six retrievals of HCHO columns from four different satellite instruments (OMI, GOME2A, GOME2B and OMPS) and three different research groups. The GEOS-Chem chemical transport model is used as a common intercomparison platform. All retrievals feature a HCHO maximum over Arkansas and Louisiana, consistent with the aircraft observations and reflecting high emissions of biogenic isoprene. The retrievals are also interconsistent in their spatial variability over the Southeast US (r=0.4-0.8 on a 0.5°×0.5° grid) and in their day-to-day variability (r=0.5-0.8). However, all retrievals are biased low in the mean by 20-51%, which would lead to corresponding bias in estimates of isoprene emissions from the satellite data. The smallest bias is for OMI-BIRA, which has high corrected slant columns relative to the other retrievals and low scattering weights in its air mass factor (AMF) calculation. OMI-BIRA has systematic error in its assumed vertical HCHO shape profiles for the AMF calculation and correcting this would eliminate its bias relative to the SEAC4RS data. Our results support the use of satellite HCHO data as a quantitative proxy for isoprene emission after correction of the low mean bias. There is no evident pattern in the bias, suggesting that a uniform correction factor may be applied to the data until better understanding is achieved.

Why do Models Overestimate Surface Ozone in the Southeastern United States?

Ozone pollution in the Southeast US involves complex chemistry driven by emissions of anthropogenic nitrogen oxide radicals (NOx ≡ NO + NO2) and biogenic isoprene. Model estimates of surface ozone concentrations tend to be biased high in the region and this is of concern for designing effective emission control strategies to meet air quality standards. We use detailed chemical observations from the SEAC4RS aircraft campaign in August and September 2013, interpreted with the GEOS-Chem chemical transport model at 0.25°×0.3125° horizontal resolution, to better understand the factors controlling surface ozone in the Southeast US. We find that the National Emission Inventory (NEI) for NOx from the US Environmental Protection Agency (EPA) is too high. This finding is based on SEAC4RS observations of NOx and its oxidation products, surface network observations of nitrate wet deposition fluxes, and OMI satellite observations of tropospheric NO2 columns. Our results indicate that NEI NOx emissions from mobile and industrial sources must be reduced by 30-60%, dependent on the assumption of the contribution by soil NOx emissions. Upper tropospheric NO2 from lightning makes a large contribution to satellite observations of tropospheric NO2 that must be accounted for when using these data to estimate surface NOx emissions. We find that only half of isoprene oxidation proceeds by the high-NOx pathway to produce ozone; this fraction is only moderately sensitive to changes in NOx emissions because isoprene and NOx emissions are spatially segregated. GEOS-Chem with reduced NOx emissions provides an unbiased simulation of ozone observations from the aircraft, and reproduces the observed ozone production efficiency in the boundary layer as derived from a regression of ozone and NOx oxidation products. However, the model is still biased high by 8±13 ppb relative to observed surface ozone in the Southeast US. Ozonesondes launched during midday hours show a 7 ppb ozone decrease from 1.5 km to the surface that GEOS-Chem does not capture. This bias may reflect a combination of excessive vertical mixing and net ozone production in the model boundary layer.