We have developed GAMMI, an approach to the inference of cis-regulatory modules that employs an evolutionary search to identify modules conserved across a set of DNA sequences from different species. ...This paper describes the motivation and system design for GAMMI, and presents the results of initial tests of the system using artificial sequences with implanted artificial modules. Based on these preliminary tests, GAMMI appears to be a promising approach to the module inference problem.
A straightforward method for the preparation of alkali-metal phthaloylphosphide (isophosphindoline-1,3-dione(1−) ion) salts from phosphine, diethyl phthalate or its ring-substituted analogues, and an ...alkali-metal tert-alkoxide is described. Spectroscopic and physical characterizations are provided for three representative examples.
To report the protocol of a trial designed to evaluate the efficacy, safety and mechanism of action of low-dose atropine (0.01%) eye-drops for reducing progression of myopia in UK children.
...Multicentre, double-masked, superiority, placebo-controlled, randomised trial. We will enrol children aged 6-12 years with myopia of -0.50 dioptres or worse in both eyes.We will recruit 289 participants with an allocation ratio of 2:1 (193 atropine; 96 placebo) from five centres. Participants will instil one drop in each eye every day for 2 years and attend a research centre every 6 months. The vehicle and preservative will be the same in both study arms.The primary outcome is SER of both eyes measured by autorefractor under cycloplegia at 2 years (adjusted for baseline). Secondary outcomes include axial length, best corrected distance visual acuity, near visual acuity, reading speed, pupil diameter, accommodation, adverse event rates and allergic reactions, quality of life (EQ-5D-Y) and tolerability at 2 years. Mechanistic evaluations will include: peripheral axial length, peripheral retinal defocus, anterior chamber depth, iris colour, height and weight, activities questionnaire, ciliary body biometry and chorioretinal thickness. Endpoints from both eyes will be pooled in combined analysis using generalised estimating equations to allow for the correlation between eyes within participant. Three years after cessation of treatment, we will also evaluate refractive error and adverse events.
The Childhood Atropine for Myopia Progression in the UK study will be the first randomised trial reporting outcomes of low-dose atropine eye-drops for children with myopia in a UK population.
ISRCTN99883695, NCT03690089.
Chronic rhinosinusitis (CRS) is one of the most common long-term illnesses in the United States. The etiology of CRS is unknown, and no effective treatment has been established.
We investigated the ...hypothesis that abnormal immunologic responses to ubiquitous airborne fungi contribute to the pathogenesis of this disease.
The proliferative and cytokine responses of PBMCs to extracts from 4 common airborne fungi—including Alternaria, Aspergillus, Cladosporium, and Penicillium—were examined by in vitro culture. Serum specimens were tested for specific IgE and IgG to these fungi.
PBMCs from approximately 90% of the patients with CRS, but not those from normal individuals, produced both IL-5 and IL-13 when exposed to Alternaria. Furthermore, PBMCs from patients with CRS produced significantly more IFN-γ than PBMCs from normal individuals in response to Alternaria (median, 553 pg/mL vs 98 pg/mL; P < .01). Levels of serum IgG antibodies to Alternaria and Cladosporium were clearly increased in patients with CRS compared with normal individuals (P < .01). Less than 30% of the patients with CRS had specific IgE antibodies to Alternaria or Cladosporium. The increased humoral (serum IgG) response strongly correlated with the increased cellular (IL-5 production) response to Alternaria (r=0.619; P < .01).
Patients with CRS show exaggerated humoral and cellular responses, both Th1 and Th2 types, to common airborne fungi, particularly Alternaria. The anomalous immune and inflammatory responses to ubiquitous fungi may explain the chronicity of airway inflammation in CRS.
One traditional model of research on mixed-reality systems, is the laboratory-based experiment where a number of small variants of a user experience are presented to participants under the guidance ...of an experimenter. This type of experiment can give reliable and generalisable results, but there are arguments for running experiments that are distributed and remote from the laboratory. These include, expanding the participant pool, reaching specific classes of user, access to a variety of equipment, and simply because laboratories might be inaccessible. However, running experiments out of the laboratory brings a different set of issues into consideration. Here, we present some lessons learnt in running eleven distributed and remote mixed-reality experiments. We describe opportunities and challenges of this type of experiment as well as some technical lessons learnt.
Tropical cyclones play an increasingly important role in shaping ecosystems. Understanding and generalizing their responses is challenging because of meteorological variability among storms and its ...interaction with ecosystems. We present a research framework designed to compare tropical cyclone effects within and across ecosystems that: a) uses a disaggregating approach that measures the responses of individual ecosystem components, b) links the response of ecosystem components at fine temporal scales to meteorology and antecedent conditions, and c) examines responses of ecosystem using a resistance–resilience perspective by quantifying the magnitude of change and recovery time. We demonstrate the utility of the framework using three examples of ecosystem response: gross primary productivity, stream biogeochemical export, and organismal abundances. Finally, we present the case for a network of sentinel sites with consistent monitoring to measure and compare ecosystem responses to cyclones across the United States, which could help improve coastal ecosystem resilience.
IntroductionDue to growth and ageing of the world’s population, the number of individuals worldwide with vision impairment (VI) and blindness is projected to increase rapidly over the coming decades. ...VI and blindness are an important cause of years lived with disability. However, the association of VI and blindness with mortality, including the risk of bias in published studies and certainty of the evidence, has not been adequately studied in an up-to-date systematic review and meta-analysis.Methods and analysisThe planned systematic review and meta-analysis will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Databases, including MEDLINE Ovid, Embase Ovid and Global Health, will be searched for relevant studies. Two reviewers will then screen studies and review full texts to identify studies for inclusion. Data extraction will be performed, and for included studies, the risk of bias and certainty of the evidence will be assessed using the Grades of Recommendation, Assessment, Development and Evaluation approach. The prognostic factor in this study is visual function, which must have been measured using a standard objective ophthalmic clinical or research instrument. We will use standard criteria from WHO to categorise VI and blindness. All-cause mortality may be assessed by any method one or more years after baseline assessment of vision. Results from included studies will be meta-analysed according to relevant sections of the Meta-analysis Of Observational Studies in Epidemiology checklist.Ethics and disseminationThis review will only include published data; therefore, ethics approval will not be sought. The findings of this review and meta-analysis will be published in an open-access, peer-reviewed journal and will be included in the ongoing Lancet Global Health Commission on Global Eye Health.
Immunologic effects of perioperative transfusion and postoperative infection have been purported to influence cancer recurrence rates.
Records of all head and neck cancer patients having surgical ...extirpation of the primary tumor and/or regional nodes at our institution over a 5-year period were reviewed. Time to recurrence was the outcome measure. All variables were evaluated via univariate analysis using log rank tests, with Cox proportional hazards used for multivariate analyses.
Univariate analysis identified the following as potential prognostic factors associated with recurrence: nodal stage, total lymphocyte count, overall stage, amount transfused, occurrence of a transfusion, and the American Society of Anesthesiologists status. Various backward stepwise multivariate regression models showed that neither transfusion nor postoperative infection independently influenced recurrence. However, transfusion of 3 or more units did surface as an independent contributor to recurrence, and in certain subgroups there was a trend toward improved survival for those who had a postoperative infection.
In this series, neither perioperative transfusion nor postoperative infection independently influenced recurrence.
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