Validation of a fornix depth measurer: a putative tool for the assessment of progressive cicatrising conjunctivitis

Background/aims Documentation of conjunctival forniceal foreshortening in cases of progressive cicatrising conjunctivitis (PCC) is important in ascertaining disease stage and progression. Lower fornix shortening is often documented subjectively or semi-objectively, whereas upper forniceal obliteration is seldom quantified. Although tools such as fornix depth measurers (FDMs) have been described, their designs limit upper fornix measurement. The purpose of this study was to custom-design a FDM to evaluate the upper fornix and to assess variability in gauging fornix depth. \ud \ud Methods A polymethylmethacrylate FDM was constructed using industry-standard jewellery computer software and machinery. Two observers undertook a prospective independent evaluation of central lower fornix depth in a heterogeneous cohort of patients with clinically normal and abnormal conjunctival fornices both subjectively and by using the FDM (in mm). Upper central fornix depth was also measured. Agreement was assessed using Bland–Altman plots. \ud \ud Results Fifty-one eyes were evaluated. There was 100% intraobserver agreement to within 1 mm for each observer for lower fornix measurement. The mean difference in fornix depth loss using the FDM between observer 1 and 2 was 1.19%, with 95% confidence of agreement (±2SD) of −15% to +20%. In total, 86% (44/51) of measurements taken by the two observers agreed to within 10% of total lower fornix depth (ie, ±1 mm) versus only 63% (32/51) of the subjective measurements. Mean upper fornix difference was 0.57 mm, with 95% confidence of agreement of between −2 and + 3 mm. \ud \ud Conclusions This custom-designed FDM is well tolerated by patients and shows low intraobserver and interobserver variability. This enables repeatable and reproducible measurement of upper and lower fornix depths, facilitating improved rates of detection and better monitoring of progression of conjunctival scarring

Dynamical Arrest in Attractive Colloids: The Effect of Long-Range Repulsion

We study gelation in suspensions of model colloidal particles with short-ranged attractive and long-ranged repulsive interactions by means of three-dimensional fluorescence confocal microscopy. At low packing fractions, particles form stable equilibrium clusters. Upon increasing the packing fraction the clusters grow in size and become increasingly anisotropic until finally associating into a fully connected network at gelation. We find a surprising order in the gel structure. Analysis of spatial and orientational correlations reveals that the gel is composed of dense chains of particles constructed from face-sharing tetrahedral clusters. Our findings imply that dynamical arrest occurs via cluster growth and association.Comment: Final version: Phys. Rev. Lett. 94, 208301 (2005

Understanding of prognosis in non-metastatic prostate cancer: a randomised comparative study of clinician estimates measured against the PREDICT prostate prognostic model

Abstract: PREDICT Prostate is an individualised prognostic model that provides long-term survival estimates for men diagnosed with non-metastatic prostate cancer (www.prostate.predict.nhs.uk). In this study clinician estimates of survival were compared against model predictions and its potential value as a clinical tool was assessed. Prostate cancer (PCa) specialists were invited to participate in the study. 190 clinicians (63% urologists, 17% oncologists, 20% other) were randomised into two groups and shown 12 clinical vignettes through an online portal. Each group viewed opposing vignettes with clinical information alone, or alongside PREDICT Prostate estimates. 15-year clinician survival estimates were compared against model predictions and reported treatment recommendations with and without seeing PREDICT estimates were compared. 155 respondents (81.6%) reported counselling new PCa patients at least weekly. Clinician estimates of PCa-specific mortality exceeded PREDICT estimates in 10/12 vignettes. Their estimates for treatment survival benefit at 15 years were over-optimistic in every vignette, with mean clinician estimates more than 5-fold higher than PREDICT Prostate estimates. Concomitantly seeing PREDICT Prostate estimates led to significantly lower reported likelihoods of recommending radical treatment in 7/12 (58%) vignettes, particularly in older patients. These data suggest clinicians overestimate cancer-related mortality and radical treatment benefit. Using an individualised prognostic tool may help reduce overtreatment

Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage.

Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1+SiglecF+ transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo. Human orthologs of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury

Cat and mouse search: the influence of scene and object analysis on eye movements when targets change locations during search

We explored the influence of early scene analysis and visible object characteristics on eye movements when searching for objects in photographs of scenes. On each trial, participants were shown sequentially either a scene preview or a uniform grey screen (250 ms), a visual mask, the name of the target and the scene, now including the target at a likely location. During the participant's first saccade during search, the target location was changed to: (i) a different likely location, (ii) an unlikely but possible location or (iii) a very implausible location. The results showed that the first saccade landed more often on the likely location in which the target re-appeared than on unlikely or implausible locations, and overall the first saccade landed nearer the first target location with a preview than without. Hence, rapid scene analysis influenced initial eye movement planning, but availability of the target rapidly modified that plan. After the target moved, it was found more quickly when it appeared in a likely location than when it appeared in an unlikely or implausible location. The findings show that both scene gist and object properties are extracted rapidly, and are used in conjunction to guide saccadic eye movements during visual search

Microbial and metabolic succession on common building materials under high humidity conditions.

Despite considerable efforts to characterize the microbial ecology of the built environment, the metabolic mechanisms underpinning microbial colonization and successional dynamics remain unclear, particularly at high moisture conditions. Here, we applied bacterial/viral particle counting, qPCR, amplicon sequencing of the genes encoding 16S and ITS rRNA, and metabolomics to longitudinally characterize the ecological dynamics of four common building materials maintained at high humidity. We varied the natural inoculum provided to each material and wet half of the samples to simulate a potable water leak. Wetted materials had higher growth rates and lower alpha diversity compared to non-wetted materials, and wetting described the majority of the variance in bacterial, fungal, and metabolite structure. Inoculation location was weakly associated with bacterial and fungal beta diversity. Material type influenced bacterial and viral particle abundance and bacterial and metabolic (but not fungal) diversity. Metabolites indicative of microbial activity were identified, and they too differed by material

New Perspectives on Ecological Mechanisms Affecting Coral Recruitment on Reefs

Coral mortality has increased in recent decades, making coral recruitment more important than ever in sustaining coral reef ecosystems and contributing to their resilience. This review summarizes existing information on ecological factors affecting scleractinian coral recruitment. Successful recruitment requires the survival of coral offspring through sequential life history stages. Larval availability, successful settlement, and post-settlement survival and growth are all necessary for the addition of new coral individuals to a reef and ultimately maintenance or recovery of coral reef ecosystems. As environmental conditions continue to become more hostile to corals on a global scale, further research on fertilization ecology, connectivity, larval condition, positive and negative cues influencing substrate selection, and post-settlement ecology will be critical to our ability to manage these diverse ecosystems for recovery. A better understanding of the ecological factors infl uencing coral recruitment is fundamental to coral reef ecology and management

Profiles of family-focused adverse experiences through childhood and early adolescence: the ROOTS project a community investigation of adolescent mental health.

BACKGROUND: Adverse family experiences in early life are associated with subsequent psychopathology. This study adds to the growing body of work exploring the nature and associations between adverse experiences over the childhood years. METHODS: Primary carers of 1143 randomly recruited 14-year olds in Cambridgeshire and Suffolk, UK were interviewed using the Cambridge Early Experiences Interview (CAMEEI) to assess family-focused adversities. Adversities were recorded retrospectively in three time periods (early and later childhood and early adolescence). Latent Class Analysis (LCA) grouped individuals into adversity classes for each time period and longitudinally. Adolescents were interviewed to generate lifetime DSM-IV diagnoses using the K-SADS-PL. The associations between adversity class and diagnoses were explored. RESULTS: LCA generated a 4-class model for each time period and longitudinally. In early childhood 69% were allocated to a low adversity class; a moderate adversity class (19%) showed elevated rates of family loss, mild or moderate family discord, financial difficulties, maternal psychiatric illness and higher risk for paternal atypical parenting; a severe class (6%) experienced higher rates on all indicators and almost exclusively accounted for incidents of child abuse; a fourth class, characterised by atypical parenting from both parents, accounted for the remaining 7%. Class membership was fairly stable (~ 55%) over time with escape from any adversity by 14 years being uncommon. Compared to those in the low class, the odds ratio for reported psychopathology in adolescents in the severe class ranged from 8 for disruptive behaviour disorders through to 4.8 for depressions and 2.0 for anxiety disorders. Only in the low adversity class did significantly more females than males report psychopathology. CONCLUSIONS: Family adversities in the early years occur as multiple rather than single experiences. Although some children escape adversity, for many this negative family environment persists over the first 15 years of life. Different profiles of family risk may be associated with specific mental disorders in young people. Sex differences in psychopathologies may be most pronounced in those exposed to low levels of family adversities.This is the published version of the article. It was published in BMC Psychiatry by BioMed Central. The online version can be found here: http://www.biomedcentral.com/1471-244X/11/109