FEDERAL-STATE RESEARCH PROGRAMS IN RURAL ECONOMIC DEVELOPMENT - - NEEDS AND PROSPECTS

Community/Rural/Urban Development,

Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update

Purpose To examine the presence and functional significance of annular fundus autofluorescence abnormalities in patients with different retinal dystrophies. Methods Eighty one patients were ascertained who had a parafoveal ring of high density on fundus autofluorescence imaging. Sixty two had had a clinical diagnosis of retinitis pigmentosa (RP) or Usher syndrome with normal visual acuity. Others included a case of Leber congenital amaurosis and genetically confirmed cases of cone or cone-rod dystrophy (GUCA1A, RPGR, RIMS1), “cone dystrophy with supernormal rod ERG” (KCNV2) and X-linked retinoschisis (RS1). International-standard full-field and pattern electroretinography (ERG; PERG) were performed. Some patients with rod-cone or cone-rod dystrophy underwent multifocal ERG (mfERG) testing and photopic and scotopic fine matrix mapping (FMM). Results In patients with RP, the radius of the parafoveal ring of high density correlated with PERG P50 (R = 0.83, P < 0.0005, N = 62) and encircled areas of preserved photopic function. In the other patients, AF rings either resembled those seen in RP or encircled an area of central atrophy. Ring radius was inversely related to the PERG P50 component in 4 of 18 cases with a detectable response. FMM showed that arcs of high density were associated with a gradient of sensitivity change. Conclusions Parafoveal rings of high density autofluorescence are a non-specific manifestation of retinal dysfunction that can occur in different retinal dystrophies. Electrophysiology remains essential for accurate diagnosis. The high correlation of autofluorescence with PERG, mfERG and FMM demonstrates that AF abnormalities have functional significance and may help identify suitable patients and retinal areas amenable to future therapeutic intervention

Searching for the Kuhnian moment : the Black-Scholes-Merton formula and the evolution of modern finance theory

The Black-Scholes-Merton formula has been put to widespread use by options traders because it provides a means of calculating the theoretically 'correct' price of stock options. Traders can therefore see whether the market price of stock options undervalues or overvalues them compared with their hypothetical Black-Scholes-Merton price, before choosing to buy or sell options accordingly. As a consequence of this close relationship between options pricing theory and options pricing practice, a strong performativity loop was activated, whereby market prices quickly converged on the hypothetical Black-Scholes-Merton prices following the dissemination of the formula. The theory has therefore had significant real-world effects, but how should we characterize the initial instinct to derive the theory from a philosophy of science perspective? The two books under review suggest that a Kuhnian reading of the advancement of scientific knowledge might well be the most appropriate. But, on closer inspection, it becomes clear that the publication of the Black-Scholes-Merton formula should not be seen as a Kuhnian moment with paradigm-shaping attributes. It is shown that, at most, the formula acts as an important exemplar which, via its use in the training of options pricing theorists and options pricing practitioners, reinforces the entrenchment of finance theory within the orthodox economics worldview

Efficacy and safety of filgotinib in methotrexate-naive patients with rheumatoid arthritis with poor prognostic factors: post hoc analysis of FINCH 3

OBJECTIVE: This analysis evaluated efficacy and safety of filgotinib, a Janus-associated kinase 1-preferential inhibitor, in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) with multiple poor prognostic factors (PPFs). METHODS: This was a post hoc analysis of the phase III, randomised, double-blind, active-controlled, FINCH 3 study (clinicaltrials.gov NCT02886728). Patients received once-daily oral filgotinib 200 or 100 mg plus once-weekly oral MTX ≤20 mg (FIL200 + MTX and FIL100 + MTX), filgotinib 200 mg monotherapy (FIL200), or oral MTX monotherapy (MTX-mono) for up to 52 weeks. PPFs investigated were seropositivity for rheumatoid factor or anticyclic citrullinated peptide antibodies, high-sensitivity C reactive protein (CRP) ≥4 mg/L, Disease Activity Score in 28 joints with CRP (DAS28(CRP)) >5.1, and presence of erosions. Filgotinib efficacy and safety in patients with all four PPFs at baseline were explored versus MTX-mono within this subgroup and compared informally with the overall population. RESULTS: Of 1249 patients in FINCH 3, 510 (40.8%) had all PPFs. Efficacy of FIL200 + MTX among these patients was comparable to the overall population, with higher rates of 20%/50%/70% improvement from baseline by American College of Rheumatology criteria, DAS28(CRP) <2.6, and remission; greater improvement in physical function and pain; and better inhibition of structural damage relative to MTX-mono. FIL100 + MTX and FIL200 were not consistently more efficacious versus MTX-mono. Safety of filgotinib in patients with PPFs was comparable to the overall population; no new safety signals were observed. CONCLUSION: FIL200 + MTX efficacy and safety in patients with multiple PPFs were similar to the overall population

Origin and evolution of the octoploid strawberry genome.

Cultivated strawberry emerged from the hybridization of two wild octoploid species, both descendants from the merger of four diploid progenitor species into a single nucleus more than 1 million years ago. Here we report a near-complete chromosome-scale assembly for cultivated octoploid strawberry (Fragaria × ananassa) and uncovered the origin and evolutionary processes that shaped this complex allopolyploid. We identified the extant relatives of each diploid progenitor species and provide support for the North American origin of octoploid strawberry. We examined the dynamics among the four subgenomes in octoploid strawberry and uncovered the presence of a single dominant subgenome with significantly greater gene content, gene expression abundance, and biased exchanges between homoeologous chromosomes, as compared with the other subgenomes. Pathway analysis showed that certain metabolomic and disease-resistance traits are largely controlled by the dominant subgenome. These findings and the reference genome should serve as a powerful platform for future evolutionary studies and enable molecular breeding in strawberry

The USNO-B Catalog

USNO-B is an all-sky catalog that presents positions, proper motions, magnitudes in various optical passbands, and star/galaxy estimators for 1,042,618,261 objects derived from 3,643,201,733 separate observations. The data were obtained from scans of 7,435 Schmidt plates taken for the various sky surveys during the last 50 years. USNO-B1.0 is believed to provide all-sky coverage, completeness down to V = 21, 0.2 arcsecond astrometric accuracy at J2000, 0.3 magnitude photometric accuracy in up to five colors, and 85% accuracy for distinguishing stars from non-stellar objects. A brief discussion of various issues is given here, but the actual data are available from http://www.nofs.navy.mil and other sites.Comment: Accepted by Astronomical Journa

Alcohol management plans in Aboriginal and Torres Strait Islander (Indigenous) Australian communities in Queensland: community residents have experienced favourable impacts but also suffered unfavourable ones

Background: In Australia, 'Alcohol Management Plans' (AMPs) provide the policy infrastructure for State and Commonwealth Governments to address problematic alcohol use among Aboriginal and Torres Strait Islanders. We report community residents' experiences of AMPs in 10 of Queensland's 15 remote Indigenous communities.\ud \ud Methods: This cross-sectional study used a two-stage sampling strategy: N = 1211; 588 (48%) males, 623 (52%) females aged ≥18 years in 10 communities. Seven propositions about 'favourable' impacts and seven about 'unfavourable' impacts were developed from semi-structured interviews. For each proposition, one-sample tests of proportions examined participant agreement and multivariable binary logistic regressions assessed influences of gender, age (18–24, 25–44, 45–64, ≥65 years), residence (≥6 years), current drinking and Indigenous status. Confirmatory factor analyses estimated scale reliability (ρ), item loadings and covariances.\ud \ud Results: Slim majorities agreed that: AMPs reduced violence (53%, p = 0.024); community a better place to live (54%, 0.012); and children were safer (56%, p < 0.001). More agreed that: school attendance improved (66%, p < 0.001); and awareness of alcohol's harms increased (71%, p < 0.001). Participants were equivocal about improved personal safety (53%, p = 0.097) and reduced violence against women (49%, p = 0.362). The seven 'favourable' items reliably summarized participants' experiences of reduced violence and improved community amenity (ρ = 0.90).\ud \ud Stronger agreement was found for six 'unfavourable' items: alcohol availability not reduced (58%, p < 0.001); drinking not reduced (56%, p < 0.001)); cannabis use increased (69%, p < 0.001); more binge drinking (73%, p < 0.001); discrimination experienced (77%, p < 0.001); increased fines, convictions and criminal records for breaching restrictions (90%, p < 0.001). Participants were equivocal (51% agreed, p = 0.365) that police could enforce restrictions effectively. 'Unfavourable' items were not reliably reflected in one group (ρ = 0.48) but in: i) alcohol availability and consumption not reduced and ii) criminalization and discrimination.\ud \ud In logistic regressions, longer-term (≥ 6 years) residents more likely agreed that violence against women had reduced and that personal safety had improved but also that criminalization and binge drinking had increased. Younger people disagreed that their community was a better place to live and strongly agreed about discrimination. Current drinkers' views differed little from the sample overall.\ud \ud Conclusions: The present Government review provides an opportunity to reinforce 'favourable' outcomes while targeting: illicit alcohol, treatment and diversion services and reconciliation of criminalization and discrimination issues.\ud \u

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

Mental health policy process: a comparative study of Ghana, South Africa, Uganda and Zambia

<p>Abstract</p> <p>Background</p> <p>Mental illnesses are increasingly recognised as a leading cause of disability worldwide, yet many countries lack a mental health policy or have an outdated, inappropriate policy. This paper explores the development of appropriate mental health policies and their effective implementation. It reports comparative findings on the processes for developing and implementing mental health policies in Ghana, South Africa, Uganda and Zambia as part of the Mental Health and Poverty Project.</p> <p>Methods</p> <p>The study countries and respondents were purposively selected to represent different levels of mental health policy and system development to allow comparative analysis of the factors underlying the different forms of mental health policy development and implementation. Data were collected using semi-structured interviews and document analysis. Data analysis was guided by conceptual framework that was developed for this purpose. A framework approach to analysis was used, incorporating themes that emerged from the data and from the conceptual framework.</p> <p>Results</p> <p>Mental health policies in Ghana, South Africa, Uganda and Zambia are weak, in draft form or non-existent. Mental health remained low on the policy agenda due to stigma and a lack of information, as well as low prioritisation by donors, low political priority and grassroots demand. Progress with mental health policy development varied and respondents noted a lack of consultation and insufficient evidence to inform policy development. Furthermore, policies were poorly implemented, due to factors including insufficient dissemination and operationalisation of policies and a lack of resources.</p> <p>Conclusions</p> <p>Mental health policy processes in all four countries were inadequate, leading to either weak or non-existent policies, with an impact on mental health services. Recommendations are provided to strengthen mental health policy processes in these and other African countries.</p