Incidence and risk factors of open-angle glaucoma : the Rotterdam study

__Abstract__ Glaucoma is one of the poorest understood and defined eye diseases among those known since our era. Despite two millennia of writing about glaucoma, a straightforward and clear-cut definition is not available worldwide. In essence, glaucoma is an eye disease characterized by loss of retinal ganglion cells and their axons. Clinically, this loss becomes apparent by cupping, also called excavation, of the optic disc and concomitant visual field loss. There are many subgroups of glaucoma, separated by causes, genetics, or morphology, and within each group there may be tens of different glaucoma types. From the start, I would like to point out that this thesis focuses on primary open-angle glaucoma. This is glaucoma in which the persons have open angles in their anterior eye chamber, through which the intraocular fluid leaves the eye. Moreover, all causes of secondary glaucoma, such as inflammation, medication, and systemic disorders, should have been eliminated with a reasonable amount of certainty. Since open-angle glaucoma cases with pseudoexfoliation were not specifically excluded at baseline of the Rotterdam study, we prefer to refer to open-angle glaucoma instead of primary open-angle glaucoma although during follow-up, no pseudoexfoliation was observed

Atherosclerosis, C-reactive protein, and risk for open-angle glaucoma: The Rotterdam Study

PURPOSE. To test the hypotheses that atherosclerosis and elevated serum C-reactive protein (CRP) levels are risk factors for open-angle glaucoma (OAG). METHODS. In a prospective, population-based cohort study, all participants 55 years and older and at risk for incident OAG underwent, at baseline (1990-1993) and at follow-up (1997-1999), the same ophthalmic examination, including visual field testing and optic disc photography. Baseline atherosclerosis was assessed by means of echography of the carotid arteries, abdominal x-ray examination, and ankle-arm index; baseline serum CRP levels were used in the analyses. The diagnosis of OAG was based on an algorithm using optic disc measures and visual field loss. Odds ratios of OAG were computed with logistic regression analyses. Risk factors were categorized in tenues and according to standard deviation. RESULTS. After a mean follow-up of 6.5 years, incident OAG was diagnosed in 87 of 3842 (2.3%) participants at risk for OAG. Carotid artery plaques, carotid intima-media thickness, aortic calcifications, ankle-arm index, and CRP levels were not significant risk factors for OAG. The odds ratio, given for the highest and lowest tertiles, for carotid plaques was 1.43 (95% confidence interval [CI], 0.68-2.99), for carotid intima-media thickness 0.86 (95% CI, 0.47-1.57), for aortic calcifications 1.02 (95% CI, 0.60-1.75), for ankle-arm index 0.69 (95% CI, 0.38-1.25), and for CRP 1.19 (95% CI, 0.68-2.07). CONCLUSIONS. In this prospective, population-based study, neither atherosclerosis nor serum CRP level was an important risk factor for OAG.

A novel target‐enriched multilocus assay for sponges (Porifera): Red Sea Haplosclerida (Demospongiae) as a test case

With declining biodiversity worldwide, a better understanding of species diversity and their relationships is imperative for conservation and management efforts. Marine sponges are species-rich ecological key players on coral reefs, but their species diversity is still poorly understood. This is particularly true for the demosponge order Haplosclerida, whose systematic relationships are contentious due to the incongruencies between morphological and molecular phylogenetic hypotheses. The single gene markers applied in previous studies did not resolve these discrepancies. Hence, there is a high need for a genome-wide approach to derive a phylogenetically robust classification and understand this group's evolutionary relationships. To this end, we developed a target enrichment-based multilocus probe assay for the order Haplosclerida using transcriptomic data. This probe assay consists of 20,000 enrichment probes targeting 2956 ultraconserved elements in coding (i.e. exon) regions across the genome and was tested on 26 haplosclerid specimens from the Red Sea. Our target-enrichment approach correctly placed our samples in a well-supported phylogeny, in agreement with previous haplosclerid molecular phylogenies. Our results demonstrate the applicability of high-resolution genomic methods in a systematically complex marine invertebrate group and provide a promising approach for robust phylogenies of Haplosclerida. Subsequently, this will lead to biologically unambiguous taxonomic revisions, better interpretations of biological and ecological observations and new avenues for applied research, conservation and managing declining marine diversity

Atherosclerosis, C-reactive protein, and risk for open-angle glaucoma:The Rotterdam study

PURPOSE. To test the hypotheses that atherosclerosis and elevated serum C-reactive protein ( CRP) levels are risk factors for open-angle glaucoma ( OAG). METHODS. In a prospective, population-based cohort study, all participants 55 years and older and at risk for incident OAG underwent, at baseline ( 1990 - 1993) and at follow-up ( 1997 1999), the same ophthalmic examination, including visual field testing and optic disc photography. Baseline atherosclerosis was assessed by means of echography of the carotid arteries, abdominal x-ray examination, and ankle-arm index; baseline serum CRP levels were used in the analyses. The diagnosis of OAG was based on an algorithm using optic disc measures and visual field loss. Odds ratios of OAG were computed with logistic regression analyses. Risk factors were categorized in tertiles and according to standard deviation. RESULTS. After a mean follow-up of 6.5 years, incident OAG was diagnosed in 87 of 3842 ( 2.3%) participants at risk for OAG. Carotid artery plaques, carotid intima-media thickness, aortic calcifications, ankle-arm index, and CRP levels were not significant risk factors for OAG. The odds ratio, given for the highest and lowest tertiles, for carotid plaques was 1.43 ( 95% confidence interval [ CI], 0.68 - 2.99), for carotid intima-media thickness 0.86 ( 95% CI, 0.47 - 1.57), for aortic calcifications 1.02 ( 95% CI, 0.60 - 1.75), for ankle-arm index 0.69 ( 95% CI, 0.38 - 1.25), and for CRP 1.19 ( 95% CI, 0.68 - 2.07). CONCLUSIONS. In this prospective, population-based study, neither atherosclerosis nor serum CRP level was an important risk factor for OAG

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. Materials and methods: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged &lt;40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. Results: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs &lt;30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. Conclusions: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.</p

The Magnitude of Global Marine Species Diversity

Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are ∼226,000 eukaryotic marine species described. More species were described in the past decade (∼20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are ∼170,000 synonyms, that 58,000–72,000 species are collected but not yet described, and that 482,000–741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7–1.0 million marine species. Past rates of description of new species indicate there may be 0.5 ± 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century

Causes of incident visual field loss in a general elderly population - The Rotterdam study

To determine the incidence and causes of visual field loss (VFL) in a general elderly population. Central visual fields of both eyes were examined with suprathreshold perimetry in 3761 persons aged 55 years or older and free of VFL at baseline from the population-based Rotterdam Study. Goldmann perimetry was performed to confirm suprathreshold VFL. Causes of incident VFL (iVFL) were assessed based on all available ophthalmologic and neurological examination data and medical records. After a mean follow-up time of 6.3 years, 175 persons developed VFL. The overall incidence rate of iVFL was 7.4 per 1000 person-years, increasing to 21.1 per 1000 person-years in those aged 80 years and older. Glaucoma was the leading cause of iVFL in all age categories. The overall incidence of glaucomatous VFL was 2.0 per 1000 person-years. The incidence of all VFL increased 5-fold between 55 years and 80 years of age or older. After glaucoma, stroke was the second most common cause of iVFL in persons younger than 75 years, followed by age-related macular degeneration and retinal vascular occlusive diseas