Identification of a novel neuregulin 1 at-risk haplotype in Han schizophrenia Chinese patients, but no association with the Icelandic/Scottish risk haplotype.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldTo determine if neuregulin 1 (NRG1) is associated with schizophrenia in Asian populations, we investigated a Han Chinese population using both a family trio design and a case-control design. A total of 25 microsatellite markers and single nucleotide polymorphisms (SNPs) were genotyped spanning the 1.1 Mb NRG1 gene including markers of a seven-marker haplotype at the 5' end of the gene found to be in excess in Icelandic and Scottish schizophrenia patients. The alleles of the individual markers forming the seven marker at-risk haplotype are not likely to be causative as they are not in excess in patients in the Chinese population studied here. However using unrelated patients, we find a novel haplotype (HAP(China 1)), immediately upstream of the Icelandic haplotype, in excess in patients (11.9% in patients vs 4.2% in controls; P=0.0000065, risk ratio (rr) 3.1), which was not significant when parental controls were used. Another haplotype (HAP(China 2)) overlapping the Icelandic risk haplotype was found in excess in the Chinese (8.5% of patients vs 4.0% of unrelated controls; P=0.003, rr 2.2) and was also significant using parental controls only (P=0.0047, rr 2.1). A four-marker haplotype at the 3' end of the NRG1 gene, HAP(China 3), was found at a frequency of 23.8% in patients and 13.7% in nontransmitted parental haplotypes (P=0.000042, rr=2.0) but was not significant in the case-control comparison. We conclude that different haplotypes within the boundaries of the NRG1 gene may be associated with schizophrenia in the Han Chinese

Association of neuregulin 1 with schizophrenia confirmed in a Scottish population

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldRecently, we identified neuregulin 1 (NRG1) as a susceptibility gene for schizophrenia in the Icelandic population, by a combined linkage and association approach. Here, we report the first study evaluating the relevance of NRG1 to schizophrenia in a population outside Iceland. Markers representing a core at-risk haplotype found in Icelanders at the 5' end of the NRG1 gene were genotyped in 609 unrelated Scottish patients and 618 unrelated Scottish control individuals. This haplotype consisted of five SNP markers and two microsatellites, which all appear to be in strong linkage disequilibrium. For the Scottish patients and control subjects, haplotype frequencies were estimated by maximum likelihood, using the expectation-maximization algorithm. The frequency of the seven-marker haplotype among the Scottish patients was significantly greater than that among the control subjects (10.2% vs. 5.9%, P=.00031). The estimated risk ratio was 1.8, which is in keeping with our report of unrelated Icelandic patients (2.1). Three of the seven markers in the haplotype gave single-point P values ranging from .000064 to .0021 for the allele contributing to the at-risk haplotype. This direct replication of haplotype association in a second population further implicates NRG1 as a factor that contributes to the etiology of schizophrenia

Overview of the spectrometer optical fiber feed for the Habitable-zone Planet Finder

The Habitable-zone Planet Finder (HPF) is a highly stabilized fiber fed precision radial velocity (RV) spectrograph working in the Near Infrared (NIR): 810 - 1280 nm . In this paper we present an overview of the preparation of the optical fibers for HPF. The entire fiber train from the telescope focus down to the cryostat is detailed. We also discuss the fiber polishing, splicing and its integration into the instrument using a fused silica puck. HPF was designed to be able to operate in two modes, High Resolution (HR- the only mode mode currently commissioned) and High Efficiency (HE). We discuss these fiber heads and the procedure we adopted to attach the slit on to the HR fibers.Comment: Presented at 2018 SPIE Astronomical Telescopes + Instrumentation, Austin, Texas, USA. 18 pages, 25 figures, and 2 table

Topical treatment of diabetic macular edema using dexamethasone ophthalmic suspension: A randomized, double-masked, vehicle-controlled study.

PURPOSE To evaluate topical dexamethasone ophthalmic suspension OCS-01 (Oculis SA, Lausanne, Switzerland) in diabetic macular edema (DME). METHODS This was a multicenter, double-masked, parallel-group, randomized, Phase 2 study. Patients aged 18-85 years with DME of 0. RESULTS Mean CMT showed a greater decrease from baseline with OCS-01 (N = 99) than vehicle (N = 45) at Week 12 (-53.6 vs -16.8 μm, p = 0.0115), with significant differences favouring OCS-01 from Weeks 2 to 12. OCS-01 was well-tolerated, and increased intraocular pressure was the most common adverse event. Mean change in ETDRS letter score from baseline to Week 12 met the p was +2.6 letters with topical OCS-01 and 1 letter with vehicle (p = 0.125). In a post-hoc analysis, there was a greater difference in patients with baseline BCVA ≤65 letters, the OCS-01 group improved 3.8 letters compared with 0.9 letters with vehicle. CONCLUSION Topical OCS-01 was significantly more effective than vehicle in improving central macular thickness in patients with DME. Visual improvement was better in eyes with lower baseline vision

Remote sensing of blood oxygenation using red-eye pupil reflection

To access publisher's full text version of this article click on the hyperlink belowObjective: To develop a technique for remote sensing of systemic blood oxygenation using red-eye pupil reflection. Approach: The ratio of the intensities of light from the bright pupil reflections at oxygen sensitive and isosbestic wavelengths is shown to be sensitive to the oxygenation of blood in the eye. A conventional retinal camera, fitted with an image-replicating imaging spectrometer, was used at standoff range to record snapshot spectral images of the face and eyes at eight different wavelengths. In our pilot study we measured optical-density ratios (ODRs) of pupil reflections at wavelengths of 780 nm and 800 nm, simultaneous with pulse oximetry, for ten healthy human subjects under conditions of normoxia and mild hypoxia (15% oxygen). The low absorption at these infrared wavelengths localises the sensing to the choroid. We propose that this can be used for as a proxy for systemic oximetry. Main results: A significant reduction (P < 0.001) in ODR of the pupil images was observed during hypoxia and returned to baseline on resumption of normoxia. We demonstrate that measurement of the choroidal ODR can be used to detect changes in blood oxygenation that correlate positively with pulse oximetry and with a noise-equivalent oximetry precision of 0.5%. Significance: We describe a new method to remotely and non-invasively sense the oxygen saturation of choroidal blood. The methodology provides a proxy for remote sensing of cerebral and systemic blood oxygenation. We demonstrate the technique at short range but it has potential for systemic oximetry at large standoff ranges

TOI-150: A transiting hot Jupiter in the TESS southern CVZ

We report the detection of a hot Jupiter ($M_{p}=1.75_{-0.17}^{+0.14}\ M_{J}$,$R_{p}=1.38\pm0.04\ R_{J}$) orbiting a middle-aged star ($\log g=4.152^{+0.030}_{-0.043}$) in the Transiting Exoplanet Survey Satellite (TESS) southern continuous viewing zone ($\beta=-79.59^{\circ}$). We confirm the planetary nature of the candidate TOI-150.01 using radial velocity observations from the APOGEE-2 South spectrograph and the Carnegie Planet Finder Spectrograph, ground-based photometric observations from the robotic Three-hundred MilliMeter Telescope at Las Campanas Observatory, and Gaia distance estimates. Large-scale spectroscopic surveys, such as APOGEE/APOGEE-2, now have sufficient radial velocity precision to directly confirm the signature of giant exoplanets, making such data sets valuable tools in the TESS era. Continual monitoring of TOI-150 by TESS can reveal additional planets and subsequent observations can provide insights into planetary system architectures involving a hot Jupiter around a star about halfway through its main-sequence life.Comment: 13 pages, 3 figures, 2 tables, accepted to ApJ

Localization of a gene for migraine without aura to chromosome 4q21.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldMigraine is a common form of headache and has a significant genetic component. Here, we report linkage results from a study in Iceland of migraine without aura (MO). The study group comprised patients with migraine recruited by neurologists and from the registry of the Icelandic Migraine Society, as well as through the use of a questionnaire sent to a random sample of 20,000 Icelanders. Migraine diagnoses were made and confirmed using diagnostic criteria established by the International Headache Society. A genome-wide scan with multipoint allele-sharing methods was performed on 289 patients suffering from MO. Linkage was observed to a locus on chromosome 4q21 (LOD=2.05; P=.001). The locus reported here overlaps a locus (MGR1) reported elsewhere for patients with migraine with aura (MA) in the Finnish population. This replication of the MGR1 locus in families with MO indicates that the gene we have mapped may contribute to both MA and MO. Further analysis indicates that the linkage evidence improves for affected females and, especially, with a slightly relaxed definition of MO (LOD=4.08; P=7.2 x 10(-6))

Crustal structure beneath western and eastern Iceland from surface waves and receiver functions

We determine the crustal structures beneath 14 broad-band seismic stations, deployed in western, eastern, central and southern Iceland, using surface wave dispersion curves and receiver functions. We implement a method to invert receiver functions using constraints obtained from genetic algorithm inversion of surface waves. Our final models satisfy both data sets. The thickness of the upper crust, as defined by the velocity horizon Vs= 3.7 km s−1, is fairly uniform at ∼6.5–9 km beneath the Tertiary intraplate areas of western and eastern Iceland, and unusually thick at 11 km beneath station HOT22 in the far south of Iceland. The depth to the base of the lower crust, as defined by the velocity horizon Vs= 4.1 km s−1 is ∼20–26 km in western Iceland and ∼27–33 km in eastern Iceland. These results agree with those of explosion profiles that detect a thinner crust beneath western Iceland than beneath eastern Iceland. An earlier report of a substantial low-velocity zone beneath the Middle Volcanic Zone in the lower crust is confirmed by a similar observation beneath an additional station there. As was found in previous receiver function studies, the most reliable feature of the results is the clear division into an upper sequence that is a few kilometres thick where velocity gradients are high, and a lower, thicker sequence where velocity gradients are low. The transition to typical mantle velocities is variable, and may range from being very gradational to being relatively sharp and clear. A clear Moho, by any definition, is rarely seen, and there is thus uncertainty in estimates of the thickness of the crust in many areas. Although a great deal of seismic data are now available constraining the structures of the crust and upper mantle beneath Iceland, their geological nature is not well understood

Mitosis in circulating tumor cells stratifies highly aggressive breast carcinomas.

BACKGROUND: Enumeration of circulating tumor cells (CTCs) isolated from the peripheral blood of breast cancer patients holds promise as a clinically relevant, minimally invasive diagnostic test. However, CTC utility has been limited as a prognostic indicator of survival by the inability to stratify patients beyond general enumeration. In comparison, histological biopsy examinations remain the standard method for confirming malignancy and grading malignant cells, allowing for cancer identification and then assessing patient cohorts for prognostic and predictive value. Typically, CTC identification relies on immunofluorescent staining assessed as absent/present, which is somewhat subjective and limited in its ability to characterize these cells. In contrast, the physical features used in histological cytology comprise the gold standard method used to identify and preliminarily characterize the cancer cells. Here, we superimpose the methods, cytologically subtyping CTCs labeled with immunohistochemical fluorescence stains to improve their prognostic value in relation to survival. METHODS: In this single-blind prospective pilot study, we tracked 36 patients with late-stage breast cancer over 24 months to compare overall survival between simple CTC enumeration and subtyping mitotic CTCs. A power analysis (1-β = 0. 9, α = 0.05) determined that a pilot size of 30 patients was sufficient to stratify this patient cohort; 36 in total were enrolled. RESULTS: Our results confirmed that CTC number is a prognostic indicator of patient survival, with a hazard ratio 5.2, p = 0.005 (95 % CI 1.6-16.5). However, by simply subtyping the same population based on CTCs in cytological mitosis, the hazard ratio increased dramatically to 11.1, p \u3c 0.001 (95 % CI 3.1-39.7). CONCLUSIONS: Our data suggest that (1) mitotic CTCs are relativity common in aggressive late-stage breast cancer, (2) mitotic CTCs may significantly correlate with shortened overall survival, and (3) larger and more defined patient cohort studies are clearly called for based on this initial pilot study