Discrete Conditional Phase-type Model Utilising a Multiclass Support Vector Machine for the Prediction of Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a rare disease in which retinal blood vessels of premature infants fail to develop normally, and is one of the major causes of childhood blindness throughout the world. The Discrete Conditional Phase-type (DC-Ph) model consists of two components, the conditional component measuring the inter-relationships between covariates and the survival component which models the survival distribution using a Coxian phase-type distribution. This paper expands the DC-Ph models by introducing a support vector machine (SVM), in the role of the conditional component. The SVM is capable of classifying multiple outcomes and is used to identify the infant's risk of developing ROP. Class imbalance makes predicting rare events difficult. A new class decomposition technique, which deals with the problem of multiclass imbalance, is introduced. Based on the SVM classification, the length of stay in the neonatal ward is modelled using a 5, 8 or 9 phase Coxian distribution.

Treatment of retinopathy of prematurity in Northern Ireland, 2000-2011: a population-based study

Purpose To evaluate the incidence of treatment-requiring retinopathy of prematurity (ROP) over a 12-year-period in Northern Ireland. Methods The medical records of all infants treated for ROP from January 2000 to December 2011were retrospectively reviewed and cross-referenced with the Neonatal Intensive Care Outcomes Research and Evaluation (NICORE) database. Results The Northern Ireland population data showed an increase in the number of live births from 2000 to 2011. The proportion of babies born with a birth weight <1501 g and/or <32 weeks’ gestational age remained constant (χ2 trend = 3.220, P = 0.0727), although the proportion of these babies who died prior to 42 weeks’ gestation decreased from 2000 to 2011 (P = 0.0196 using χ2 for trend = 5.445; P = 0.0354 using χ2 = 20.809). The prevalence of treatment-requiring ROP in these infants increased from 1.05% in 2000 to 5.78% in 2011 (P < 0.001 using χ2 trend = 16.309; P < 0.001 using χ2 = 31.378). Conclusions The present population-based study highlights that the incidence of treatment- requiring ROP is increasing in Northern Ireland. The increasing number of infants requiring treatment will need to be taken into consideration in the commissioning process for ROP services in Northern Ireland.

Whole genome protein microarrays for serum profiling of immunodominant antigens of Bacillus anthracis

A commercial Bacillus anthracis (Anthrax) whole genome protein microarray has been used to identify immunogenic Anthrax proteins (IAP) using sera from groups of donors with (a) confirmed B. anthracis naturally acquired cutaneous infection, (b) confirmed B. anthracis intravenous drug use-acquired infection, (c) occupational exposure in a wool-sorters factory, (d) humans and rabbits vaccinated with the UK Anthrax protein vaccine and compared to naïve unexposed controls. Anti-IAP responses were observed for both IgG and IgA in the challenged groups; however the anti-IAP IgG response was more evident in the vaccinated group and the anti-IAP IgA response more evident in the B. anthracis-infected groups. Infected individuals appeared somewhat suppressed for their general IgG response, compared with other challenged groups. Immunogenic protein antigens were identified in all groups, some of which were shared between groups whilst others were specific for individual groups. The toxin proteins were immunodominant in all vaccinated, infected or other challenged groups. However, a number of other chromosomally-located and plasmid encoded open reading frame proteins were also recognized by infected or exposed groups in comparison to controls. Some of these antigens e.g., BA4182 are not recognized by vaccinated individuals, suggesting that there are proteins more specifically expressed by live Anthrax spores in vivo that are not currently found in the UK licensed Anthrax Vaccine (AVP). These may perhaps be preferentially expressed during infection and represent expression of alternative pathways in the B. anthracis "infectome." These may make highly attractive candidates for diagnostic and vaccine biomarker development as they may be more specifically associated with the infectious phase of the pathogen. A number of B. anthracis small hypothetical protein targets have been synthesized, tested in mouse immunogenicity studies and validated in parallel using human sera from the same study.

Reduction of Carbon Dioxide to Formate at Low Overpotential using a Superbase Ionic Liquid

A new low-energy pathway is reported for the electrochemical reduction of CO2 to formate and syngas at low overpotentials, utilizing a reactive ionic liquid as the solvent. The superbasic tetraalkyl phosphonium ionic liquid [P66614][124Triz] is able to chemisorb CO2 through equimolar binding of CO2 with the 1,2,4-triazole anion. This chemisorbed CO2 can be reduced at silver electrodes at overpotentials as low as 0.17 V, forming formate. In contrast, physically absorbed CO2 within the same ionic liquid or in ionic liquids where chemisorption is impossible (such as [P66614][NTf2]) undergoes reduction at significantly increased overpotentials, producing only CO as the product.

The addition of CO2 to four superbase ionic liquids: a DFT study

The addition of carbon dioxide to four superbase ionic liquids, [P3333][Benzim], [P3333][124Triz], [P3333][123Triz] and [P3333][Bentriz] was studied using a molecular DFT approach involving anions alone and individual ion pairs. Intermolecular bonding within the individual ion pairs is characterised by a number of weak hydrogen bonds, with the superbase anion geometrically arranged so as to maximize interactions between the heterocyclic N atoms and the cation. The pairing energies show no correlation to the observed CO2 adsorption capacity. Addition of CO2 to the anion alone clearly resulted in the formation of a covalently-bound carbamate function with the strength of binding correlated to experimental capacity. In the ion pair however the cation significantly alters the nature of the bonding such that the overall cohesive energy is reduced. Formation of a strong carbamate function occurs at the expense of weakening the interaction between anion and cation. In the more weakly absorbing ion pairs which contain [123Triz]- and [Bentriz]-, the carbamate-functionalised systems are very close in energy to adducts in which CO2 is more weakly bound, suggesting an equilibrium between the chemi- and physisorbed CO2.

Optimisation of singlet oxygen production from photosensitiser-incorporated, medically-relevant hydrogels

Photodynamic therapy and photodynamic antimicrobial chemotherapy are widely used, but despite this, the relationships between fluence, wavelength of irradiation and singlet oxygen (1O2) production are poorly understood. To establish the relationships between these factors in medically-relevant materials, the effect of fluence on 1O2 production from a tetrakis(4-N-methylpyridyl)porphyrin (TMPyP)-incorporated 2-hydroxyethyl methacrylate: methyl methacrylate: methacrylic acid (HEMA:MMA:MAA) copolymer, a total energy of 50.48 J/cm², was applied at varying illumination power, and times. 1O2 production was characterised using anthracene-9,10-dipropionic acid, disodium salt (ADPA) using a recently described method. Using two light sources, a white LED array and a white halogen source, the LED array was found to produce less 1O2 than the halogen source when the same power (over 500-600 nm) and time conditions were applied. Importantly, it showed that the longest wavelength Q band (590 nm) is primarily responsible for 1O2 generation, and that a linear relationship exists between increasing power and time and the production of singlet oxygen.

Innate Lymphoid Cells are the Predominant Source of Interleukin-17A During the Early Pathogenesis of Acute Respiratory Distress Syndrome

Rationale: IL-17A is purported to help drive early pathogenesis in acute respiratory distress syndrome (ARDS) by enhancing neutrophil recruitment. Whilst IL-17A is the archetypal cytokine of T helper (Th)17 cells, it is produced by a number of lymphocytes, the source during ARDS being unknown.

Objectives: To identify the cellular source and the role of IL17A in the early phase of lung injury

Methods: Lung injury was induced in WT (C57BL/6) and IL-17 KO mice with aerosolised LPS (100 µg) or Pseudomonas aeruginosa infection. Detailed phenotyping of the cells expressing RORγt, the transcriptional regulator of IL-17 production, in the mouse lung at 24 hours was carried out by flow cytometry.

Measurement and Main Results: A 100-fold reduction in neutrophil infiltration was observed in the lungs of the IL-17A KO compared to wild type (WT) mice. The majority of RORγt+ cells in the mouse lung were the recently identified type 3 innate lymphoid cells (ILC3). Detailed characterisation revealed these pulmonary ILC3s (pILC3s) to be discrete from those described in the gut. The critical role of these cells was verified by inducing injury in Rag2 KO mice which lack T cells but retain ILCs. No amelioration of pathology was observed in the Rag2 KO mice.

Conclusions: IL-17 is rapidly produced during lung injury and significantly contributes to early immunopathogenesis. This is orchestrated largely by a distinct population of pILC3 cells. Modulation of pILC3s’ activity may potentiate early control of the inflammatory dysregulation seen in ARDS, opening up new therapeutic targets.

Optimization of singlet oxygen production from photosensitizer-incorporated, medically relevant hydrogels

Photodynamic therapy and photodynamic antimicrobial chemotherapy are widely used, but despite this, the relationships between fluence, wavelength of irradiation and singlet oxygen ((1) O2 ) production are poorly understood. To establish the relationships between these factors in medically relevant materials, the effect of fluence on (1) O2 production from a tetrakis(4-N-methylpyridyl)porphyrin (TMPyP)-incorporated 2-hydroxyethyl methacrylate: methyl methacrylate: methacrylic acid (HEMA: MMA:MAA) copolymer, a total energy of 50.48 J/cm(2) , was applied at varying illumination power, and times. (1) O2 production was characterized using anthracene-9,10-dipropionic acid, disodium salt (ADPA) using a recently described method. Using two light sources, a white LED array and a white halogen source, the LED array was found to produce less (1) O2 than the halogen source when the same power (over 500 - 600 nm) and time conditions were applied. Importantly, it showed that the longest wavelength Q band (590 nm) is primarily responsible for (1) O2 generation, and that a linear relationship exists between increasing power and time and the production of singlet oxygen.