Incidence and recurrence rate of sigmoid diverticulitis in patients requiring admission to hospital in Iceland from 1985 to 2014: nationwide population-based register study.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Diverticulitis is the most common complication of diverticular disease, affecting 10-25 per cent of patients with diverticula. A retrospective, nationwide, population-based cohort study was performed to analyse the incidence and recurrence rate of sigmoid diverticulitis requiring hospital admission. Methods: All patients discharged from hospital in Iceland during 1985-2014 who were diagnosed with diverticular disease were included. The χ2 test was used to analyse the trend of the incidence in the period 2002-2014. The Kaplan-Meier method and the Cox model were used to analyse recurrence. Results: Of 8660 admissions for diverticular disease, 4746 were due to diverticulitis, of which 2939 were for diverticulitis diagnosed for the first time. After the first attack, surgery was used to treat 661 patients. Of 2278 patients not treated by resection, 537 had a second attack (23·6 per cent). There was a significant decrease in the incidence of diverticulitis in patients aged 40-89 years during the period from 2002 to 2014 (P = 0·033). The risk of recurrence was associated with younger age at first attack and female sex (P < 0·001). Conclusion: There was a decline in the incidence of patients hospitalized with diverticulitis between 1995 and 2014, most prominent in older age groups. Different recurrence rates were reported in men and women, and in younger compared with older age groups

Individualised risk assessment for diabetic retinopathy and optimisation of screening intervals: a scientific approach to reducing healthcare costs.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.To validate a mathematical algorithm that calculates risk of diabetic retinopathy progression in a diabetic population with UK staging (R0-3; M1) of diabetic retinopathy. To establish the utility of the algorithm to reduce screening frequency in this cohort, while maintaining safety standards.The cohort of 9690 diabetic individuals in England, followed for 2 years. The algorithms calculated individual risk for development of preproliferative retinopathy (R2), active proliferative retinopathy (R3A) and diabetic maculopathy (M1) based on clinical data. Screening intervals were determined such that the increase in risk of developing certain stages of retinopathy between screenings was the same for all patients and identical to mean risk in fixed annual screening. Receiver operating characteristic curves were drawn and area under the curve calculated to estimate the prediction capability.The algorithm predicts the occurrence of the given diabetic retinopathy stages with area under the curve =80% for patients with type II diabetes (CI 0.78 to 0.81). Of the cohort 64% is at less than 5% risk of progression to R2, R3A or M1 within 2 years. By applying a 2 year ceiling to the screening interval, patients with type II diabetes are screened on average every 20 months, which is a 40% reduction in frequency compared with annual screening.The algorithm reliably identifies patients at high risk of developing advanced stages of diabetic retinopathy, including preproliferative R2, active proliferative R3A and maculopathy M1. Majority of patients have less than 5% risk of progression between stages within a year and a small high-risk group is identified. Screening visit frequency and presumably costs in a diabetic retinopathy screening system can be reduced by 40% by using a 2 year ceiling. Individualised risk assessment with 2 year ceiling on screening intervals may be a pragmatic next step in diabetic retinopathy screening in UK, in that safety is maximised and cost reduced by about 40%.Icelandic Research Counci

Individual risk assessment and information technology to optimise screening frequency for diabetic retinopathy.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.AIMS/HYPOTHESIS: The aim of this study was to reduce the frequency of diabetic eye-screening visits, while maintaining safety, by using information technology and individualised risk assessment to determine screening intervals. METHODS: A mathematical algorithm was created based on epidemiological data on risk factors for diabetic retinopathy. Through a website, www.risk.is , the algorithm receives clinical data, including type and duration of diabetes, HbA(1c) or mean blood glucose, blood pressure and the presence and grade of retinopathy. These data are used to calculate risk for sight-threatening retinopathy for each individual's worse eye over time. A risk margin is defined and the algorithm recommends the screening interval for each patient with standardised risk of developing sight-threatening retinopathy (STR) within the screening interval. We set the risk margin so that the same number of patients develop STR within the screening interval with either fixed annual screening or our individualised screening system. The database for diabetic retinopathy at the Department of Ophthalmology, Aarhus University Hospital, Denmark, was used to empirically test the efficacy of the algorithm. Clinical data exist for 5,199 patients for 20 years and this allows testing of the algorithm in a prospective manner. RESULTS: In the Danish diabetes database, the algorithm recommends screening intervals ranging from 6 to 60 months with a mean of 29 months. This is 59% fewer visits than with fixed annual screening. This amounts to 41 annual visits per 100 patients. CONCLUSION: Information technology based on epidemiological data may facilitate individualised determination of screening intervals for diabetic eye disease. Empirical testing suggests that this approach may be less expensive than conventional annual screening, while not compromising safety. The algorithm determines individual risk and the screening interval is individually determined based on each person's risk profile. The algorithm has potential to save on healthcare resources and patients' working hours by reducing the number of screening visits for an ever increasing number of diabetic patients in the world

Condensation in nongeneric trees

We study nongeneric planar trees and prove the existence of a Gibbs measure on infinite trees obtained as a weak limit of the finite volume measures. It is shown that in the infinite volume limit there arises exactly one vertex of infinite degree and the rest of the tree is distributed like a subcritical Galton-Watson tree with mean offspring probability $m<1$. We calculate the rate of divergence of the degree of the highest order vertex of finite trees in the thermodynamic limit and show it goes like $(1-m)N$ where $N$ is the size of the tree. These trees have infinite spectral dimension with probability one but the spectral dimension calculated from the ensemble average of the generating function for return probabilities is given by $2\beta -2$ if the weight $w_n$ of a vertex of degree $n$ is asymptotic to $n^{-\beta}$.Comment: 57 pages, 14 figures. Minor change

Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs posterior hyaloid removal. A prospective randomized trial

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Diabetes mellitus, as well as subsequent ocular complications such as cystoid macular edema (CME), are of fundametal socio-economic relevance. Therefore, we evaluated the influence of internal limiting membrane (ILM) removal on longterm morphological and functional outcome in patients with diabetes mellitus (DM) type 2 and chronic CME without evident vitreomacular traction. METHOD: Forty eyes with attached posterior hyaloid were included in this prospective trial and randomized intraoperatively. Prior focal (n = 31) or panretinal (n = 25) laser coagulation was permitted. Group I (n = 19 patients) underwent surgical induction of posterior vitreous detachment (PVD), group II (n = 20 patients) PVD and removal of the ILM. Eleven patients with detached posterior hyaloid (group III) were not randomized, and ILM removal was performed. One eye had to be excluded from further analysis. Examinations included ETDRS best-corrected visual acuity (BCVA), fluorescein angiography (FLA) and OCT at baseline, 3 and 6 months postoperatively. Main outcome measure was BCVA at 6 months, secondary was foveal thickness. RESULTS: Mean BCVA over 6 months remained unchanged in 85% of patients of group II, and decreased in 53% of patients of group I. Results were not statistically significant different [group I: mean decrease log MAR 95% CI (0.06; 0.32), group II: (-0.02; 0.11)]. OCT revealed a significantly greater reduction of foveal thickness following PVD with ILM removal [group I: mean change: 95% CI (-208.95 μm; -78.05 μm), group II: (-80.90 μm: +59.17 μm)]. CONCLUSION: Vitrectomy, PVD with or without ILM removal does not improve vision in patients with DM type 2 and cystoid diabetic macular edema without evident vitreoretinal traction. ILM delamination shows improved morphological results, and appears to be beneficial in eyes with preexisting PVD

Random tree growth by vertex splitting

We study a model of growing planar tree graphs where in each time step we separate the tree into two components by splitting a vertex and then connect the two pieces by inserting a new link between the daughter vertices. This model generalises the preferential attachment model and Ford's $\alpha$-model for phylogenetic trees. We develop a mean field theory for the vertex degree distribution, prove that the mean field theory is exact in some special cases and check that it agrees with numerical simulations in general. We calculate various correlation functions and show that the intrinsic Hausdorff dimension can vary from one to infinity, depending on the parameters of the model.Comment: 47 page

Laws of physics help explain capillary non-perfusion in diabetic retinopathy.

The purpose is to use laws of physics to elucidate the mechanisms behind capillary non-perfusion in diabetic retinopathy. In diabetic retinopathy, loss of pericytes weakens capillary walls and the vessel dilates. A dilated capillary has reduced resistance to flow, therefore increased flow in that vessel and decreased in adjoining capillaries. A preferential shunt vessel is thus formed from the dilated capillary and the adjacent capillaries become non-perfused. We apply the laws of Laplace and Hagen-Poiseuille to better understand the phenomena that lead to capillary non-perfusion. These laws of physics can give a foundation for physical or mathematical models to further elucidate this field of study. The law of Laplace predicts that a weaker vessel wall will dilate, assuming constant transmural pressure. The Hagen-Poiseuille equation for flow and the Ostwald-de Waele relationship for viscosity predict that a dilated vessel will receive a higher portion of the fluid flow than the adjoining capillaries. Viscosity will decrease in the dilated vessel, furthering the imbalance and resulting in a patch of non-perfused capillaries next to the dilated 'preferential' shunt vessel. Physical principles support or inspire novel hypotheses to explain poorly understood phenomena in ophthalmology. This thesis of pericyte death and capillary remodelling, which was first proposed by Cogan and Kuwabara, already agrees with histological and angiographical observations in diabetic retinopathy. We have shown that it is also supported by classical laws of physics

The Norwegian Mother, Father, and Child cohort study (MoBa) genotyping data resource: MoBaPsychGen pipeline v.1

BACKRGROUND: The Norwegian Mother, Father, and Child Cohort Study (MoBa) is a population-based pregnancy cohort, which includes approximately 114,500 children, 95,200 mothers, and 75,200 fathers. Genotyping of MoBa has been conducted through multiple research projects, spanning several years; using varying selection criteria, genotyping arrays, and genotyping centres. MoBa contains numerous interrelated families, which necessitated the implementation of a family-based quality control (QC) pipeline that verifies and accounts for diverse types of relatedness. METHODS: The MoBaPsychGen pipeline, comprising pre-imputation QC, phasing, imputation, and post-imputation QC, was developed based on current best-practice protocols and implemented to account for the complex structure of the MoBa genotype data. The pipeline includes QC on both single nucleotide polymorphism (SNP) and individual level. Phasing and imputation were performed using the publicly available Haplotype Reference Consortium release 1.1 panel as a reference. Information from the Medical Birth Registry of Norway and MoBa questionnaires were used to identify biological sex, year of birth, reported parent-offspring (PO) relationships, and multiple births (only available in the offspring generation). RESULTS: In total, 207,569 unique individuals (90% of the unique individuals included in the study) and 6,981,748 SNPs passed the MoBaPsychGen pipeline. The relatedness checks performed throughout the pipeline allowed identification of within-generation and across-generation first-degree, second-degree, and third-degree relatives. The individuals passing post-imputation QC comprised 64,471 families ranging in size from singletons to 84 unique individuals (singletons are included as families as other family members may not have been genotyped, imputed, or passed post-imputation QC). The relationships identified include 287 monozygotic twin pairs, 22,884 full siblings, 117,004 PO pairs, 23,299 second-degree relative pairs, and 10,828 third-degree relative pairs. DISCUSSION: MoBa contains a highly complex relatedness structure, with a variety of family structures including singletons, PO duos, full (mother, father, child) PO trios, nuclear families, blended families, and extended families. The availability of robustly quality-controlled genetic data for such a large cohort with a unique extended family structure will allow many novel research questions to be addressed. Furthermore, the MoBaPsychGen pipeline has potential utility in similar cohorts

A polygenic resilience score moderates the genetic risk for schizophrenia.

Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531–538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known “polygenic resilience score” that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder

Appearance of vertices of infinite order in a model of random trees

We study an equilibrium statistical mechanical model of tree graphs which are made up of a linear subgraph (the spine) to which leaves are attached. We prove that the model has two phases, a generic phase where the spine becomes infinitely long in the thermodynamic limit and all vertices have finite order and a condensed phase where the spine is finite with probability one and a single vertex of infinite order appears in the thermodynamic limit. We calculate the spectral dimension of the graphs in both phases and prove the existence of a Gibbs measure. We discuss generalizations of this model and the relationship with models of nongeneric random trees.Comment: 22 pages, 5 figure