Objective accommodative amplitude and dynamics with the 1CU accommodative intraocular lens

PURPOSE. To compare the objective accommodative amplitude and dynamics of eyes implanted with the one-compartment-unit (1CU; HumanOptics AG, Erlangen, Germany) accommodative intraocular lenses (IOLs) with that measured subjectively. METHODS. Twenty eyes with a 1CU accommodative IOL implanted were refracted and distance and near acuity measured with a logMAR (logarithm of the minimum angle of resolution) chart. The objective accommodative stimulus-response curve for static targets between 0.17 and 4.00 D accommodative demand was measured with the SRW-5000 (Shin-Nippon Commerce Inc., Tokyo, Japan) and PowerRefractor (PlusOptiX, Nürnberg, Germany) autorefractors. Continuous objective recording of dynamic accommodation was measured with the SRW-5000, with the subject viewing a target moving from 0 to 2.50 D at 0.3 Hz through a Badal lens system. Wavefront aberrometry measures (Zywave; Bausch & Lomb, Rochester, NY) were made through undilated pupils. Subjective amplitude of accommodation was measured with the RAF (Royal Air Force accommodation and vergence measurement) rule. RESULTS. Four months after implantation best-corrected acuity was -0.01 ± 0.16 logMAR at distance and 0.60 ± 0.09 logMAR at near. Objectively, the static amplitude of accommodation was 0.72 ± 0.38 D. The average dynamic amplitude of accommodation was 0.71 ± 0.47 D, with a lag behind the target of 0.50 ± 0.48 seconds. Aberrometry showed a decrease in power of the lens-eye combination from the center to the periphery in all subjects (on average, -0.38 ± 0.28 D/mm). Subjective amplitude of accommodation was 2.24 ± 0.42 D. Two years after 1CU implantation, refractive error and distance visual acuity remained relatively stable, but near visual acuity, and the subjective and objective amplitudes of accommodation decreased. CONCLUSIONS. The objective accommodating effects of the 1CU lens appear to be limited, although patients are able to track a moving target. Subjective and objective accommodation was reduced at the 2-year follow-up. The greater subjective amplitude of accommodation is likely to result from the eye's depth of focus of and the aspheric nature of the IOL. Copyright © Association for Research in Vision and Ophthalmology

miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS.

ObjectiveOnset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS. This study aimed to look for evidence of miRNA involvement in ped-MS pathogenesis.MethodsGWAS results from 486 ped-MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA-specific signals. First, enrichment of miRNA-target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR-SNPs) were tested for association with ped-MS, and pathway analysis was performed on associated target genes.ResultsMIGWAS analysis showed that miRNA-target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA-target gene pairs, including immune and neuronal signaling genes. The miR-SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling.InterpretationEvidence from GWAS suggests that miRNAs play a role in ped-MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA-target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility

The UV-Optical Color Dependence of Galaxy Clustering in the Local Universe

We measure the UV-optical color dependence of galaxy clustering in the local universe. Using the clean separation of the red and blue sequences made possible by the NUV - r color-magnitude diagram, we segregate the galaxies into red, blue and intermediate "green" classes. We explore the clustering as a function of this segregation by removing the dependence on luminosity and by excluding edge-on galaxies as a means of a non-model dependent veto of highly extincted galaxies. We find that \xi (r_p, \pi) for both red and green galaxies shows strong redshift space distortion on small scales -- the "finger-of-God" effect, with green galaxies having a lower amplitude than is seen for the red sequence, and the blue sequence showing almost no distortion. On large scales, \xi (r_p, \pi) for all three samples show the effect of large-scale streaming from coherent infall. On scales 1 Mpc/h < r_p < 10 Mpc/h, the projected auto-correlation function w_p(r_p) for red and green galaxies fits a power-law with slope \gamma ~ 1.93 and amplitude r_0 ~ 7.5 and 5.3, compared with \gamma ~ 1.75 and r_0 ~ 3.9 Mpc/h for blue sequence galaxies. Compared to the clustering of a fiducial L* galaxy, the red, green, and blue have a relative bias of 1.5, 1.1, and 0.9 respectively. The w_p(r_p) for blue galaxies display an increase in convexity at ~ 1 Mpc/h, with an excess of large scale clustering. Our results suggest that the majority of blue galaxies are likely central galaxies in less massive halos, while red and green galaxies have larger satellite fractions, and preferentially reside in virialized structures. If blue sequence galaxies migrate to the red sequence via processes like mergers or quenching that take them through the green valley, such a transformation may be accompanied by a change in environment in addition to any change in luminosity and color.Comment: accepted by MNRA

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

Host–guest selectivity in a series of isoreticular metal–organic frameworks: observation of acetylene-to-alkyne and carbon dioxide-to-amide interactions

In order to develop new porous materials for applications in gas separations such as natural gas upgrading, landfill gas processing and acetylene purification it is vital to gain understanding of host-substrate interactions at a molecular level. Herein we report a series of six isoreticular metal-organic frameworks (MOFs) for selective gas adsorption. These materials do not incorporate open metal sites and thus provide an excellent platform to investigate the effect of the incorporation of ligand functionality via amide and alkyne groups on substrate binding. By reducing the linker length of our previously reported MFM-136, we report much improved CO2/CH4 (50:50) and CO2/N2 (15:85) selectivity values of 20.2 and 65.4, respectively (1 bar and 273 K), in the new amide-decorated MOF, MFM-126. The CO2 separation performance of MFM-126 has been confirmed by dynamic breakthrough experiments. In situ inelastic neutron scattering and synchrotron FT-IR microspectroscopy were employed to elucidate dynamic interactions of adsorbed CO2 molecules within MFM-126. Upon changing the functionality to an alkyne group in MFM-127, the CO2 uptake decreases but the C2H2 uptake increases by 68%, leading to excellent C2H2/CO2 and C2H2/CH4 selectivities of 3.7 and 21.2, respectively. Neutron powder diffraction enabled the direct observation of the preferred binding domains in MFM-126 and MFM-127, and, to the best of our knowledge, we report the first example of acetylene binding to an alkyne moiety in a porous material, with over 50% of the acetylene observed within MFM-127 displaying interactions (less than 4 Å) with the alkyne functionality of the framework

Surface rupture of multiple crustal faults in the 2016 Mw 7.8 Kaikōura, New Zealand, earthquake

Multiple (>20 >20 ) crustal faults ruptured to the ground surface and seafloor in the 14 November 2016 M w Mw 7.8 Kaikōura earthquake, and many have been documented in detail, providing an opportunity to understand the factors controlling multifault ruptures, including the role of the subduction interface. We present a summary of the surface ruptures, as well as previous knowledge including paleoseismic data, and use these data and a 3D geological model to calculate cumulative geological moment magnitudes (M G w MwG ) and seismic moments for comparison with those from geophysical datasets. The earthquake ruptured faults with a wide range of orientations, sense of movement, slip rates, and recurrence intervals, and crossed a tectonic domain boundary, the Hope fault. The maximum net surface displacement was ∼12  m ∼12  m on the Kekerengu and the Papatea faults, and average displacements for the major faults were 0.7–1.5 m south of the Hope fault, and 5.5–6.4 m to the north. M G w MwG using two different methods are M G w MwG 7.7 +0.3 −0.2 7.7−0.2+0.3 and the seismic moment is 33%–67% of geophysical datasets. However, these are minimum values and a best estimate M G w MwG incorporating probable larger slip at depth, a 20 km seismogenic depth, and likely listric geometry is M G w MwG 7.8±0.2 7.8±0.2 , suggests ≤32% ≤32% of the moment may be attributed to slip on the subduction interface and/or a midcrustal detachment. Likely factors contributing to multifault rupture in the Kaikōura earthquake include (1) the presence of the subduction interface, (2) physical linkages between faults, (3) rupture of geologically immature faults in the south, and (4) inherited geological structure. The estimated recurrence interval for the Kaikōura earthquake is ≥5,000–10,000  yrs ≥5,000–10,000  yrs , and so it is a relatively rare event. Nevertheless, these findings support the need for continued advances in seismic hazard modeling to ensure that they incorporate multifault ruptures that cross tectonic domain boundaries

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes