New Frontiers-class Uranus Orbiter: Exploring the feasibility of achieving multidisciplinary science with a mid-scale mission

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The case for a New Frontiers-class Uranus Orbiter:System science at an underexplored and unique world with a mid-scale mission

Current knowledge of the Uranian system is limited to observations from the flyby of Voyager 2 and limited remote observations. However, Uranus remains a highly compelling scientific target due to the unique properties of many aspects of the planet itself and its system. Future exploration of Uranus must focus on cross-disciplinary science that spans the range of research areas from the planet's interior, atmosphere, and magnetosphere to the its rings and satellites, as well as the interactions between them. Detailed study of Uranus by an orbiter is crucial not only for valuable insights into the formation and evolution of our solar system but also for providing ground truths for the understanding of exoplanets. As such, exploration of Uranus will not only enhance our understanding of the ice giant planets themselves but also extend to planetary dynamics throughout our solar system and beyond. The timeliness of exploring Uranus is great, as the community hopes to return in time to image unseen portions of the satellites and magnetospheric configurations. This urgency motivates evaluation of what science can be achieved with a lower-cost, potentially faster-turnaround mission, such as a New Frontiers–class orbiter mission. This paper outlines the scientific case for and the technological and design considerations that must be addressed by future studies to enable a New Frontiers–class Uranus orbiter with balanced cross-disciplinary science objectives. In particular, studies that trade scientific scope and instrumentation and operational capabilities against simpler and cheaper options must be fundamental to the mission formulation

Efficacy and safety of bimatoprost in glaucoma and ocular hypertension in non-responder patients

AIM: To establish the efficacy and safety of bimatoprost 0.03% monotherapy in glaucoma and ocular hypertension (OHT) patients with inadequate intraocular pressure (IOP)on current therapy. METHODS: Pre- and post-switch IOPs were analyzed for 59 consecutive patients who were switched from current therapy to bimatoprost monotherapy between 2011-2015. Demographic information, diagnosis, and any adverse events were recorded. Change in IOP post-pre switch was analyzed using a 2-sided Student's paired t-test at the 5% significance level. RESULTS: There was a statistically significant mean reduction in IOP at the first follow up visit, which was maintained at subsequent follow up visits for patients regardless of diagnosis, or pre-switch treatment (P<0.001). Subgroup analysis also demonstrated a statistically significant mean reduction in IOP when looking at OHT patients only, as well as patients with any diagnosis switched from latanoprost monotherapy to bimatoprost monotherapy (P<0.001). CONCLUSION: This is the largest independent data set which supports switching glaucoma patients with poor response to current treatment onto bimatoprost monotherapy before considering other adjuvant medical or more invasive therapy

Low frequency of HLA DRB1*03 - DQB1*02 and DQB1*0302 haplotypes in Romania is consistent with the country's low incidence of Type I diabetes

Aims/hypothesis. Our study aimed to determine the association of HLA class II HLA-DQB1 alleles with Type I (insulin-dependent) diabetes mellitus and the frequencies of these alleles in the Romanian population, which has one of the lowest incidences of Type I diabetes in children aged 0-14 years in Europe at 3-4 cases per 100 000 person-years. Methods. We used the sequence specific primer-polymerase chain reaction (PCR-SSP) technique to type HLA-DQB1 alleles, the HLA-DRB1 alleles DRB1*03 and one single nucleotide polymorphism (SNP) in the insulin gene (INS). We studied 204 Type I diabetic Romanian families, 196 of which were simplex with 70.3 % of subjects diagnosed under 14 years of age. Data was analysed using a modified version of the Transmission Disequilibrium Test, the Transmission Disequilibrium Test itself, and the affected family-based control method. Results. We found, as expected, the strong positive DQB1*02-DRB1*03 and DQB1*0302, and negative DQB1*0602, HLA class II allele associations with Type I diabetes in these Romanian families. However, using the affected family-based control method, we found relatively low population frequencies of DQB1*02-DRB1*03 and DQB1*0302 alleles in Romania (15.8%) compared with Sardinia (31.3%), a high incidence European region (35 cases per 100 000 person-years in children aged 0-14 years). The INS locus had a strong effect in this data set with 80.5 % transmission of the susceptible INS allele from parents to affected siblings (relative risk = 4.1). Conclusion/interpretation. Part of the explanation for the low incidence of Type I diabetes in Romania could be the lower frequency of the DRB1*03 - DQB1*02 and DQB1*0302 susceptibility haplotypes in this country

A New Technique for the Quantification of Peripheral Edema with Application in both Unilateral and Bilateral Cases

Current noninvasive techniques for the routine and frequent quantification of peripheral lymphedema in patients are total limb volume measurement (by water immersion or by circumferential measurements) and bioelectrical impedance analysis (BIA). However both of these techniques require standardizing the measurement using a contralateral measurement from the unaffected limb. Hence these techniques are essentially restricted to unilateral lymphedema. This paper describes the results from a preliminary study to investigate an alternative approach to the analysis of the data from multiple frequency BIA to produce an index of lymphedema without the need for normalization to another body segment. Twenty patients receiving surgical treatment for breast cancer were monitored prior to surgery and again after diagnosis with unilateral lymphedema. The data recorded were total limb volume, by circumferential measurements; and BIA measurements of both limbs. From these measurements total limb volumes and extracellular fluid volumes were calculated and expressed as ratios of the affected limb to that of the unaffected limb. An index of the ratio of the extracellular fluid volume to the intracellular fluid volume was determined. This ECW/ICW index was calculated for both the affected and unaffected limbs at both measurement times. Results confirmed that the established techniques of total limb volume and extracellular fluid volume normalized to the unaffected contralateral limb were accurate in the detection of lymphedema (p < 10(-6)). Comparison of the ECW/ICW index from the affected limb after diagnosis with that from the pre-surgery measurement revealed a significant (p < 10(-6)) and considerable (75%) increase. The results of this pilot study suggest that by using multiple frequency bioelectrical impedance analysis, an index of the ECW/ICW ratio can be obtained and this index appears to have an equal, or better, sensitivity than the other techniques in detecting lymphedema. More importantly, this index does not require normalization to another body segment and can be used to detect all types of peripheral edema including both unilateral and bilateral lymphedema

The BepiColombo Mercury Imaging X-Ray Spectrometer: Science Goals, Instrument Performance and Operations

The Mercury Imaging X-ray Spectrometer is a highly novel instrument that is designed to map Mercury's elemental composition from orbit at two angular resolutions. By observing the fluorescence X-rays generated when solar-coronal X-rays and charged particles interact with the surface regolith, MIXS will be able to measure the atomic composition of the upper similar to 10-20 mu m of Mercury's surface on the day-side. Through precipitating particles on the night-side, MIXS will also determine the dynamic interaction of the planet's surface with the surrounding space environment. MIXS is composed of two complementary elements: MIXS-C is a collimated instrument which will achieve global coverage at a similar spatial resolution to that achieved (in the northern hemisphere only - i.e. similar to 50 - 100 km) by MESSENGER; MIXS-T is the first ever X-ray telescope to be sent to another planet and will, during periods of high solar activity (or intense precipitation of charged particles), reveal the X-ray flux from Mercury at better than 10 km resolution. The design, performance, scientific goals and operations plans of the instrument are discussed, including the initial results from commissioning in space.Peer reviewe

Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB–FKBPL–NOTCH4 region of chromosome 6p21.3

Age-related macular degeneration (AMD) is a leading cause of visual loss in Western populations. Susceptibility is influenced by age, environmental and genetic factors. Known genetic risk loci do not account for all the heritability. We therefore carried out a genome-wide association study of AMD in the UK population with 893 cases of advanced AMD and 2199 controls. This showed an association with the well-established AMD risk loci ARMS2 (age-related maculopathy susceptibility 2)-HTRA1 (HtrA serine peptidase 1) (P =2.7 × 10(-72)), CFH (complement factor H) (P =2.3 × 10(-47)), C2 (complement component 2)-CFB (complement factor B) (P =5.2 × 10(-9)), C3 (complement component 3) (P =2.2 × 10(-3)) and CFI (P =3.6 × 10(-3)) and with more recently reported risk loci at VEGFA (P =1.2 × 10(-3)) and LIPC (hepatic lipase) (P =0.04). Using a replication sample of 1411 advanced AMD cases and 1431 examined controls, we confirmed a novel association between AMD and single-nucleotide polymorphisms on chromosome 6p21.3 at TNXB (tenascin XB)-FKBPL (FK506 binding protein like) [rs12153855/rs9391734; discovery P =4.3 × 10(-7), replication P =3.0 × 10(-4), combined P =1.3 × 10(-9), odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.3-1.6] and the neighbouring gene NOTCH4 (Notch 4) (rs2071277; discovery P =3.2 × 10(-8), replication P =3.8 × 10(-5), combined P =2.0 × 10(-11), OR = 1.3, 95% CI = 1.2-1.4). These associations remained significant in conditional analyses which included the adjacent C2-CFB locus. TNXB, FKBPL and NOTCH4 are all plausible AMD susceptibility genes, but further research will be needed to identify the causal variants and determine whether any of these genes are involved in the pathogenesis of AMD