Burden of fungal disease in Ireland

Our objective was to estimate the burden of fungal disease on the island of Ireland, as part of a coordinated project estimating the global burden. Published epidemiology data describing fungal infection in Ireland were identified. Population and underlying disease data were collected for 2010 and a structured set of assumptions were applied to estimate burden of fungal disease based on immunosuppression, chronic disease, and other demographic information indicating predisposition to fungal infection. From Ireland’s population of 6.4 million, we estimate 117 000 patients develop significant fungal disease each year. By far the most common fungal disease is recurrent Candida vaginitis, with an estimated 95 000 episodes annually (3000 per 100 000 women). Other fungal diseases which may be less well recognized are severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis, with estimated episodes per year of 11 700 and 9000, respectively (182 and 140 per 100 000 population, respectively). The model also estimates 450 episodes of invasive aspergillosis, 200 of chronic pulmonary aspergillosis, 600 of oesophageal candidiasis and 450 of candidaemia per year (7, 3, 9 and 6 episodes per 100 000 population, respectively). This is, we believe, the first attempt to estimate the burden of fungal disease in our population and provides a basis for estimating its impact on human health and resource use.

A Temperature-Monitoring Vaginal Ring for Measuring Adherence

Background

Product adherence is a pivotal issue in the development of effective vaginal microbicides to reduce sexual transmission of HIV. To date, the six Phase III studies of vaginal gel products have relied primarily on self-reporting of adherence. Accurate and reliable methods for monitoring user adherence to microbicide-releasing vaginal rings have yet to be established.

Methods

A silicone elastomer vaginal ring prototype containing an embedded, miniature temperature logger has been developed and tested in vitro and in cynomolgus macaques for its potential to continuously monitor environmental temperature and accurately determine episodes of ring insertion and removal.

Results

In vitro studies demonstrated that DST nano-T temperature loggers encapsulated in medical grade silicone elastomer were able to accurately and continuously measure environmental temperature. The devices responded quickly to temperature changes despite being embedded in different thickness of silicone elastomer. Prototype vaginal rings measured higher temperatures compared with a subcutaneously implanted device, showed high sensitivity to diurnal fluctuations in vaginal temperature, and accurately detected periods of ring removal when tested in macaques.

Conclusions

Vaginal rings containing embedded temperature loggers may be useful in the assessment of product adherence in late-stage clinical trials.

Timing and climate forcing of volcanic eruptions for the past 2,500 years

Volcanic eruptions contribute to climate variability, but quantifying these contributions has been limited by inconsistencies in the timing of atmospheric volcanic aerosol loading determined from ice cores and subsequent cooling from climate proxies such as tree rings. Here we resolve these inconsistencies and show that large eruptions in the tropics and high latitudes were primary drivers of interannual-to-decadal temperature variability in the Northern Hemisphere during the past 2,500 years. Our results are based on new records of atmospheric aerosol loading developed from high-resolution, multi-parameter measurements from an array of Greenland and Antarctic ice cores as well as distinctive age markers to constrain chronologies. Overall, cooling was proportional to the magnitude of volcanic forcing and persisted for up to ten years after some of the largest eruptive episodes. Our revised timescale more firmly implicates volcanic eruptions as catalysts in the major sixth-century pandemics, famines, and socioeconomic disruptions in Eurasia and Mesoamerica while allowing multi-millennium quantification of climate response to volcanic forcing.

Deflagrations in hybrid CONe white dwarfs: a route to explain the faint Type Iax supernova 2008ha

Stellar evolution models predict the existence of hybrid white dwarfs (WDs) with a carbon-oxygen core surrounded by an oxygen-neon mantle. Being born with masses similar to 1.1 M-aS (TM), hybrid WDs in a binary system may easily approach the Chandrasekhar mass (M-Ch) by accretion and give rise to a thermonuclear explosion. Here, we investigate an off-centre deflagration in a near-M-Ch hybrid WD under the assumption that nuclear burning only occurs in carbon-rich material. Performing hydrodynamics simulations of the explosion and detailed nucleosynthesis post-processing calculations, we find that only 0.014 M-aS (TM) of material is ejected while the remainder of the mass stays bound. The ejecta consist predominantly of iron-group elements, O, C, Si and S. We also calculate synthetic observables for our model and find reasonable agreement with the faint Type Iax SN 2008ha. This shows for the first time that deflagrations in near-M-Ch WDs can in principle explain the observed diversity of Type Iax supernovae. Leaving behind a near-M-Ch bound remnant opens the possibility for recurrent explosions or a subsequent accretion-induced collapse in faint Type Iax SNe, if further accretion episodes occur. From binary population synthesis calculations, we find the rate of hybrid WDs approaching M-Ch to be of the order of 1 per cent of the Galactic SN Ia rate.

Interacting Supernovae and Supernova Impostors: SN 2009ip, is this the End?

We report the results of a three-year-long dedicated monitoring campaign of a restless luminous blue variable (LBV) in NGC 7259. The object, named SN 2009ip, was observed photometrically and spectroscopically in the optical and near-infrared domains. We monitored a number of erupting episodes in the past few years, and increased the density of our observations during eruptive episodes. In this paper, we present the full historical data set from 2009 to 2012 with multi-wavelength dense coverage of the two high-luminosity events between 2012 August and September. We construct bolometric light curves and measure the total luminosities of these eruptive or explosive events. We label them the 2012a event (lasting ~50 days) with a peak of 3 × 1041 erg s-1, and the 2012b event (14 day rise time, still ongoing) with a peak of 8 × 1042 erg s-1. The latter event reached an absolute R-band magnitude of about -18, comparable to that of a core-collapse supernova (SN). Our historical monitoring has detected high-velocity spectral features (~13,000 km s-1) in 2011 September, one year before the current SN-like event. This implies that the detection of such high-velocity outflows cannot, conclusively, point to a core-collapse SN origin. We suggest that the initial peak in the 2012a event was unlikely to be due to a faint core-collapse SN. We propose that the high intrinsic luminosity of the latest peak, the variability history of SN 2009ip, and the detection of broad spectral lines indicative of high-velocity ejecta are consistent with a pulsational pair-instability event, and that the star may have survived the last outburst. The question of the survival of the LBV progenitor star and its future fate remain open issues, only to be answered with future monitoring of this historically unique explosion.

Of no fixed form: The Irish Pavilion at Venice 2014 and beyond

This paper explores the theme of exhibiting architectural research through a particular example, the development of the Irish pavilion for the 14th architectural biennale, Venice 2014. Responding to Rem Koolhaas’s call to investigate the international absorption of modernity, the Irish pavilion became a research project that engaged with the development of the architectures of infrastructure in Ireland in the twentieth and twenty-first centuries. Central to this proposition was that infrastructure is simultaneously a technological and cultural construct, one that for Ireland occupied a critical position in the building of a new, independent post-colonial nation state, after 1921.

Presupposing infrastructure as consisting of both visible and invisible networks, the idea of a matrix become a central conceptual and visual tool in the curatorial and design process for the exhibition and pavilion. To begin with this was a two-dimensional grid used to identify and order what became described as a series of ten ‘infrastructural episodes’. These were determined chronologically across the decades between 1914 and 2014 and their spatial manifestations articulated in terms of scale: micro, meso and macro. At this point ten academics were approached as researchers. Their purpose was twofold, to establish the broader narratives around which the infrastructures developed and to scrutinise relevant archives for compelling visual material. Defining the meso scale as that of the building, the media unearthed was further filtered and edited according to a range of categories – filmic/image, territory, building detail, and model – which sought to communicate the relationship between the pieces of architecture and the larger systems to which they connect. New drawings realised by the design team further iterated these relationships, filling in gaps in the narrative by providing composite, strategic or detailed drawings.

Conceived as an open-ended and extendable matrix, the pavilion was influenced by a series of academic writings, curatorial practices, artworks and other installations including: Frederick Kiesler’s City of Space (1925), Eduardo Persico and Marcello Nizzoli’s Medaglio d’Oro room (1934), Sol Le Witt’s Incomplete Open Cubes (1974) and Rosalind Krauss’s seminal text ‘Grids’ (1979). A modular frame whose structural bays would each hold and present an ‘episode’, the pavilion became both a visual analogue of the unseen networks embodying infrastructural systems and a reflection on the predominance of framed structures within the buildings exhibited. Sharing the aspiration of adaptability of many of these schemes, its white-painted timber components are connected by easily-dismantled steel fixings. These and its modularity allow the structure to be both taken down and re-erected subsequently in different iterations. The pavilion itself is, therefore, imagined as essentially provisional and – as with infrastructure – as having no fixed form. Presenting archives and other material over time, the transparent nature of the space allowed these to overlap visually conveying the nested nature of infrastructural production. Pursuing a means to evoke the qualities of infrastructural space while conveying a historical narrative, the exhibition’s termination in the present is designed to provoke in the visitor, a perceptual extension of the matrix to engage with the future.

Scaling Up Market Anomalies

This paper implements momentum among a host of market anomalies. Our investment universe consists of the 15 top (long-leg) and 15 bottom (short-leg) anomaly portfolios. The proposed active strategy buys (sells short) a subset of the top (bottom) anomaly portfolios based on past one-month return. The evidence shows statistically strong and economically meaningful persistence in anomaly payoffs. Our strategy consistently outperforms a naive benchmark that equal weights anomalies and yields an abnormal monthly return ranging between 1.27% and 1.47%. The persistence is robust to the post-2000 period, and various other considerations, and is stronger following episodes of high investor sentiment.

Making Ireland Modern

Making Ireland Modern is a cross-disciplinary, inter-institutional, inter-media design and research project which emerged from an open competition (won by Boyd and McLaughlin) to commission/curate the Irish pavilion for the Venice biennale 2014. It explores the relationship between architecture, infrastructure and technology in the building of a new nation. Constructed as a demountable, open matrix of drawings, photographs, models and other artefacts, the exhibition (12 x 5 x 6 metres) presents ten infrastructural episodes – Negation, Electricity, Health, Transportation, Television, Aviation, Education, Telecommunications, Motorways, Data – spanning a period of one hundred years from 1916-2016. Exploring a range of scales from the detail design of objects to entire landscapes and other territories, Making Ireland Modern describes architecture’s role in transforming the physical and cultural identity of the new state through its intersession in the everyday lives of its population. In 2015, we were commissioned by the Arts Council of Ireland to expand and develop the pavilion for a three cities tour of Ireland as one of the five major strands of the Arts Council’s Art2016 programme of Irish State’s 1916-2016 centennial celebrations (2016).

Caseinolytic activity in gingival crevicular fluid from periodontitis patients

Introduction: Protease activity is essential for the progression of periodontal disease and several studies have shown that gingival crevicular fluid (GCF) proteases are associated with the attachment loss and bone destruction associated with periodontial disease. In addition to measuring protease levels using ELISA, it is also important to consider enzyme activity which can be measured using appropriate substrates. Aim: The aim of this work was to measure the proteolyitc activity in gingival crevicular fluid (GCF) from periodontitis patients using zymography and a fluorogenic protease substrate. Materials and Methods: Twenty four GCF samples were collected from patients with established periodontitis who had not received any periodontal treatment in the previous six months. A strip of perio-paper was inserted into the gingival crevice until light resistance was felt. After 30 seconds the perio-paper was removed and placed into 500 ul ice cold 0.01M sodium phosphate buffer, pH 7.2, containing 0.15M sodium chloride, vortex mixed for 30 seconds and stored at -80°C until required. GCF samples (10 ul) were electrophoresed on 4-16% Blue casein zymogram gels at 125V constant voltage for 90 min. Following electrophoresis the gel was washed in renaturation buffer for 30 min and then placed in developing buffer overnight. Areas of protease activity appeared as clear bands against a blue background. The total caseinolytic activity of each GCF sample was measured using a fluorescent assay with resorufin-labelled casein as the substrate. Results: The results showed that both casein zymography and fluorogenic assay methods were suitable for analysing caseinolytic activity in GCF samples from periodontitis patients. Caseinolytic activity was variable in the periodontitis samples studied and may reflect the episodic nature of the disease. Conclusion: Casein zymography and fluorogenic assay methods may be useful in future attempts to measure active episodes of periodontal disease.

ThermoSpots to detect hypothermia in children with severe acute malnutrition

INTRODUCTION: Hypothermia is a risk factor for increased mortality in children with severe acute malnutrition (SAM). Yet frequent temperature measurement remains unfeasible in under-resourced units in developing countries. ThermoSpot is a continuous temperature monitoring sticker designed originally for neonates. When applied to skin, its liquid crystals are designed to turn black with hypothermia and remain green with normothermia.

AIMS: To (i) estimate the diagnostic accuracy of ThermoSpots for detecting WHO-defined hypothermia (core temperature <35.5°C or peripheral temperature <35.0°C) in children with SAM and (ii) determine their acceptability amongst mothers.

METHODS: Children with SAM in a malnutrition unit in Malawi were enrolled during March-July 2010. The sensitivity and specificity of ThermoSpots were calculated by comparing the device colour against 'gold standard' rectal temperatures taken on admission and follow up peripheral temperatures taken until discharge. Guardians completed a questionnaire to assess acceptability.

RESULTS: Hypothermia was uncommon amongst the 162 children enrolled. ThermoSpot successfully detected the one rectal temperature and two peripheral temperatures recorded that met the WHO definition of hypothermia. Overall, 3/846 (0.35%) temperature measurements were in the WHO-defined hypothermia range. Interpreting the brown transition colour (between black and green) as hypothermia improved sensitivities. For milder hypothermia definitions, sensitivities declined (<35.4°C, 50.0%; <35.9°C, 39.2%). Specificity was consistently above 94%. From questionnaires, 40/43 (93%) mothers reported they were 90-100% happy with the device overall. Free-text answers revealed themes of "Skin Rashes", "User-satisfaction" and "Empowerment".

CONCLUSION: Although hypothermia was uncommon in this study, ThermoSpots successfully detected these episodes in malnourished children and were acceptable to mothers. Research in settings where hypothermia is common is needed to determine performance with certainty. Instructing users to act when the device's transition colour appears could improve accuracy. If reliable, ThermoSpots may offer simple, acceptable and continuous temperature measurement for high-burden areas and reduce the workload of over-stretched staff.