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

Equilibrium spherically curved 2D Lennard-Jones systems

To learn about basic aspects of nano-scale spherical molecular shells during their formation, spherically curved two-dimensional N-particle Lennard-Jones systems are simulated, studying curvature evolution paths at zero-temperature. For many N-values (N<800) equilibrium configurations are traced as a function of the curvature radius R. Sharp jumps for tiny changes in R between trajectories with major differences in topological structure correspond to avalanche-like transitions. For a typical case, N=25, equilibrium configurations fall on smooth trajectories in state space which can be traced in the E-R plane. The trajectories show-up with local energy minima, from which growth in N at steady curvature can develop.Comment: 10 pages, 2 figures, to be published in Journal of Chemical Physic

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.

Management of trypanosomiasis and leishmaniasis

&lt;p&gt;Background: The current treatments for human African trypanosomiasis (HAT), Chagas disease and leishmaniasis (collectively referred to as the kinetoplastid diseases) are far from ideal but, for some, there has been significant recent progress. For HAT the only advances in treatment over the past two decades have been the introduction of an eflornithine/nifurtimox co-administration and a shorter regime of the old standard melarsoprol.&lt;/p&gt; &lt;p&gt;Sources of data: PubMed.&lt;/p&gt; &lt;p&gt;Areas of Agreement: There is a need for new safe, oral drugs for cost-effective treatment of patients and use in control programmes for all the trypanosomatid diseases.&lt;/p&gt; &lt;p&gt;Areas of controversy: Cutaneous leishmaniasis is not on the agenda and treatments are lagging behind.&lt;/p&gt; &lt;p&gt;Growing points: There are three compounds in development for the treatment of the CNS stage of HAT: fexinidazole, currently due to entry into phase II clinical studies, a benzoxaborole (SCYX-7158) in phase I trials and a diamidine derivative (CPD-0802), in advanced pre-clinical development. For Chagas disease, two anti-fungal triazoles are now in clinical trial. In addition, clinical studies with benznidazole, a drug previously recommended only for acute stage treatment, are close to completion to determine the effectiveness in the treatment of early chronic and indeterminate Chagas disease. For visceral leishmaniasis new formulations, therapeutic switching, in particular AmBisome, and the potential for combinations of established drugs have significantly improved the opportunities for the treatment in the Indian subcontinent, but not in East Africa.&lt;/p&gt; &lt;p&gt;Areas timely for developing research: Improved diagnostic tools are needed to support treatment, for test of cure in clinical trials and for monitoring/surveillance of populations in control programmes.&lt;/p&gt

Omitting re-excision for focally positive margins after breast-conserving surgery does not impair disease-free and overall survival

Purpose: In contrast to other countries, the Dutch breast cancer guideline does not recommend re-excision for focally positive margins after breast-conserving surgery (BCS) in invasive tumor and does recommend whole-breast irradiation including boost. We investigated whether omitting re-excision as compared to performing re-excision affects prognosis with a retrospective population-based cohort study. Methods: The total cohort included 32,119 women with primary BCS for T1–T3 breast cancer diagnosed between 2003 and 2008 from the nationwide Netherlands cancer registry. The subcohort included 10,433 patients in whom the resection margins were registered. Outcome measures were 5-year ipsilateral breast tumor recurrence (IBTR) rate, 5-year disease-free survival (DFS) rate, and 10-year overall survival (OS) rate. Results: In the total cohort, 25,878 (80.6%) did not have re-excision, 2368 (7.4%) had re-excision by BCS, and 3873 (12.1%) had re-excision by mastectomy. Five-year IBTR rates were 2.1, 2.8, and 2.9%, respectively (p = 0.001). In the subcohort, 7820 (75.0%) had negative margins without re-excision, 492 (4.7%) had focally positive margins without re-excision, 586 (5.6%) had focally positive margins and underwent re-excision, and 1535 (14.7%) had extensively positive margins and underwent re-excision. Five-year IBTR rate was 2.3, 2.9, 1.1, and 2.9%, respectively (p = 0.099). Compared to omitting re-excision, performing re-excision for focally positive margins was associated with lower risk of IBTR (adjusted HR 0.30, 95% CI 0.11–0.82), but not with DFS (adjusted HR 0.83 95% CI 0.59–1.17) nor with OS (adjusted HR 1.17 95% CI 0.87–1.59). Conclusion: Omitting re-excision in breast cancer patients for focally positive margins after BCS does not impair DFS and OS, provided that whole-breast irradiation including boost is given

Cerebellar Zones: A Personal History

Cerebellar zones were there, of course, before anyone noticed them. Their history is that of young people, unhindered by preconceived ideas, who followed up their observations with available or new techniques. In the 1960s of the last century, the circumstances were fortunate because three groups, in Leiden, Lund, and Bristol, using different approaches, stumbled on the same zonal pattern in the cerebellum of the cat. In Leiden, the Häggqvist myelin stain divulged the compartments in the cerebellar white matter that channel the afferent and efferent connections of the zones. In Lund, the spino-olivocerebellar pathways activated from individual spinal funiculi revealed the zonal pattern. In Bristol, charting the axon reflex of olivocerebellar climbing fibers on the surface of the cerebellum resulted in a very similar zonal map. The history of the zones is one of accidents and purposeful pursuit. The technicians, librarians, animal caretakers, students, secretaries, and medical illustrators who made it possible remain unnamed, but their contributions certainly should be acknowledged

Increased risks of third primary cancers of non-breast origin among women with bilateral breast cancer

Background: This study examined the risk of third cancer of non-breast origin (TNBC) among women with bilateral breast cancer (BBC; either synchronous or metachronous), focussing on the relation with breast cancer treatment.Methods:Risk was assessed, among 8752 Dutch women diagnosed with BBC between 1989 and 2008, using standardised incidence ratios (SIR) and Cox regression analyses to estimate the hazard ratio (HR) of TNBC for different treatment modalities.Results:Significant increased SIRs were observed for all TNBCs combined, haematological malignancies, stomach, colorectal, non-melanoma skin, lung, head and neck, endometrial, and ovarian cancer. A 10-fold increased risk was found for ovarian cancer among women younger than 50 years (SIR10.0, 95% confidence interval (CI)5.3-17.4). Radiotherapy was associated with increased risks of all TNBCs combined (HR1.3; 95%CI1.1-1.6, respectively). Endocrine therapy was associated with increased risks of all TNBCs combined (HR1.2; 95%CI1.0-1.5), haematological malignancies (HR2.0; 95%CI1.1-3.9), and head and neck cancer (HR3.3; 95%CI1.1-10.4). After chemotherapy decreased risks were found for all TNBCs combined (HR0.63; 95%CI0.5-0.87).Conclusion:Increased risk of TNBC could be influenced by genetic factors (ovarian cancer) or an effect of treatment (radiotherapy and endocrine therapy). More insight in the TNBC risk should further optimise and individualise treatment and surveillance protocols in (young) women with BBC

Targeting Conservation Investments in Heterogeneous Landscapes: A distance function approach and application to watershed management

To achieve a given level of an environmental amenity at least cost, decision-makers must integrate information about spatially variable biophysical and economic conditions. Although the biophysical attributes that contribute to supplying an environmental amenity are often known, the way in which these attributes interact to produce the amenity is often unknown. Given the difficulty in converting multiple attributes into a unidimensional physical measure of an environmental amenity (e.g., habitat quality), analyses in the academic literature tend to use a single biophysical attribute as a proxy for the environmental amenity (e.g., species richness). A narrow focus on a single attribute, however, fails to consider the full range of biophysical attributes that are critical to the supply of an environmental amenity. Drawing on the production efficiency literature, we introduce an alternative conservation targeting approach that relies on distance functions to cost-efficiently allocate conservation funds across a spatially heterogeneous landscape. An approach based on distance functions has the advantage of not requiring a parametric specification of the amenity function (or cost function), but rather only requiring that the decision-maker identify important biophysical and economic attributes. We apply the distance-function approach empirically to an increasingly common, but little studied, conservation initiative: conservation contracting for water quality objectives. The contract portfolios derived from the distance-function application have many desirable properties, including intuitive appeal, robust performance across plausible parametric amenity measures, and the generation of ranking measures that can be easily used by field practitioners in complex decision-making environments that cannot be completely modeled. Working Paper # 2002-01