Identifying subtypes of patients with neovascular age-related macular degeneration by genotypic and cardiovascular risk characteristics

<p>Abstract</p> <p>Background</p> <p>One of the challenges in the interpretation of studies showing associations between environmental and genotypic data with disease outcomes such as neovascular age-related macular degeneration (AMD) is understanding the phenotypic heterogeneity within a patient population with regard to any risk factor associated with the condition. This is critical when considering the potential therapeutic response of patients to any drug developed to treat the condition. In the present study, we identify patient subtypes or clusters which could represent several different targets for treatment development, based on genetic pathways in AMD and cardiovascular pathology.</p> <p>Methods</p> <p>We identified a sample of patients with neovascular AMD, that in previous studies had been shown to be at elevated risk for the disease through environmental factors such as cigarette smoking and genetic variants including the complement factor H gene (<it>CFH</it>) on chromosome 1q25 and variants in the <it>ARMS2</it>/HtrA serine peptidase 1 (<it>HTRA1</it>) gene(s) on chromosome 10q26. We conducted a multivariate segmentation analysis of 253 of these patients utilizing available epidemiologic and genetic data.</p> <p>Results</p> <p>In a multivariate model, cigarette smoking failed to differentiate subtypes of patients. However, four meaningfully distinct clusters of patients were identified that were most strongly differentiated by their cardiovascular health status (histories of hypercholesterolemia and hypertension), and the alleles of <it>ARMS2</it>/<it>HTRA1 </it>rs1049331.</p> <p>Conclusions</p> <p>These results have significant personalized medicine implications for drug developers attempting to determine the effective size of the treatable neovascular AMD population. Patient subtypes or clusters may represent different targets for therapeutic development based on genetic pathways in AMD and cardiovascular pathology, and treatments developed that may elevate CV risk, may be ill advised for certain of the clusters identified.</p

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Thermodynamic Properties and Anharmonic Effects in XAFS Based on Anharmonic Correlated Debye Model Debye–Waller Factors

Thermodynamic properties and anharmonic effects in X-ray absorption fine structure (XAFS) have been studied based on the anharmonic correlated Debye model Debye–Waller factors presented in terms of cumulant expansion. The derived analytical expressions of three first XAFS cumulants involve more information on phonon-phonon interactions taken from integration over the first Brillouin zone. Many-body effects are taken into account in the present one-dimensional model based on the first shell near neighbor contributions to the vibrations between absorber and backscatterer atoms. Morse potential is assumed to describe single-pair atomic interaction included in the derived anharmonic interatomic effective potential. The present theory can be applied to any crystal structure including complex systems. Numerical results for Cu and Ni are found to be in good agreement with experiment and with those of the other theories

Evaluation of soil water retention PTFs for tropical Mekong delta soils

The knowledge of soil water retention characteristic (SWRC) is crucial for solving many soil and water management problems related to agricultural, ecological, hydrological and environmental issues. However, the information on this soil property is usually missing in soil databases, since the methods for determination of SWRC are cumbersome and expensive. The dearth of this information in developing countries located in the tropics is even worse than elsewhere due to additional problems linked to personnel training and acquisition of needed equipment for these measurements. Pedotransfer functions (PTFs) which are used to estimate soil water retention characteristics (SWRC) from other available soil properties has been considered as an attractive alternative for direct SWRC measurement. Since developing new PTFs for particular regions is very arduous and mostly requires a large soil database of good quality, utilizing existing PTFs where possible is highly recommended. However, many PTFs have limited portability and predictive capacity, since they have been derived for specific soils within limited geomorphic and geographic domain. Predominant clayey soils being mainly exploited for intensive rice-based agriculture in the tropical Vietnamese Mekong Delta (VMD) have distinct characteristics, which implies that PTFs derived elsewhere could not be directly utilized without evaluating. Therefore, the objective of this study was to evaluate the applicability and reliability of published PTFs in predicting SWRC for tropical VMD soils. The predictive performance of a number of well-known regression based and pattern-recognition based PTFs developed from soils in both tropical and temperate regions were evaluated based on the dataset of 160 soil samples. The sampling locations were selected so that the dataset well represents the distribution of different soil types and textures in the delta. The ME, SDE and RMSE are validation indices used to assess PTFs’ performance. The results of this study show that most of the investigated PTFs which were derived from soils in both tropical and temperate climates have somewhat limited predictive potential for tropical Mekong Delta soils. The difference in soil texture (i.e. clay and sand content) as well as the mineralogy of the clay fractions in PTFs calibration datasets compared to evaluated dataset are mainly explain the inadequate performance of the investigated PTFs for tropical Mekong delta soils. In order to acquire accurate and reliable SWRC estimations for further uses in the Delta, it is necessary to develop new PTFs based on an extensive database of soils of tropical delta

Raphiocarpus Raphiocarpus taygiangensis (Gesneriaceae), a new species from Central Vietnam

Raphiocarpus taygiangensis, a new species of Gesneriaceae from Tay Giang District, Quang Nam Province, Central Vietnam, is here described and illustrated. The new species is diagnostic by the combination of its long stem, serrate leaf margin, purple spots, purple longitudinal lines, and glandular short hairs inside corolla. Morphological distinctiveness of the new species from the most similar species, Raphiocarpus axillaris, is discussed. The conservation status of this species is estimated as Vulnerable (VU D2) according to the IUCN Red List Criteria

Raphiocarpus taygiangensis (Gesneriaceae), a new species from central Vietnam

Raphiocarpus taygiangensis, a new species of Gesneriaceae family discovered in Tay Giang District, Quang Nam Province, Central Vietnam, is here described and illustrated. The new species is diagnosed by the combination of its stem up to 2 m long, sericeous hairs on young stem, leaf petiole and adaxial mid-vein, sparsely and minutely serrate leaf margin, axillary inflorescence spreading along stem, sparsely long gland-tipped hairs on peduncle, pedicel, calyx, outside corolla and pistil, calyx 5-disparted from base, purplish white flower with purple stripes inside corolla tube, and dish-shaped stigma formed by 2 semi-orbicular lobes horizontally expanding. Distinct features of the new species and its morphologically closest congener, Rhaphiocarpus axillaris, are compared and discussed. The conservation status of the described species is estimated as Vulnerable (VU D2) according to the IUCN Red List Criteria