Neutrophil oxidative burst is primed by supernatant from stored red cells : implications for Transfusion-Related Acute Lung Injury (TRALI)

Aim/Background: Transfusion-related acute lung injury (TRALI) is a potentially fatal adverse transfusion reaction. It is hypothesised to occur via a two-insult mechanism: the recipient’s underlying co-morbidity in addition to the transfusion of blood products activate neutrophils in the lung resulting in damaged endothelium and capillary leakage. Neutrophil activation may occur by antibody or non-antibody related mechanisms, with the length of storage of cellular blood products implicated in the latter. This study investigated non-antibody mediated priming and/or activation of neutrophil oxidative burst. Methods: A cytochrome C reduction assay was used to assess priming and activation of neutrophil oxidative burst by pooled supernatant (SN) from day 1 (D1; n=75) and day 42 (D42; n=113) packed red blood cells (PRBC). Pooled PRBC-SN were assessed in parallel with PAF (priming), fMLP (activating), PAF + fMLP (priming + activating) and buffer only (negative) controls. Cytochrome C reduction was measured over 30min at 37oC (inclusive of 10min priming). Neutrophil activation by PRBC-SN was assessed cf. buffer only and neutrophil priming by PRBC-SN was assessed by co-incubation with fMLP cf. fMLP alone. One-way ANOVA; Newman-Keuls post-test; p<0.05; n=10 independent assays. Results: Neither D1- nor D42- PRBC-SN alone activated neutrophil oxidative burst. In addition, D1-PRBC-SN did not prime fMLP-activated neutrophil oxidative burst. D42-PRBC-SN did, however, prime neutrophils for subsequent activation of oxidative burst by fMLP, the magnitude of response being similar to PAF (a known neutrophil priming agonist). Conclusion: These findings are consistent with the two-insult mechanism of TRALI. Factors released into the SN during PRBC storage contributed to neutrophil priming synergistically with other neutrophil stimulating agonists. This implicates PRBC storage duration as a key factor contributing to non-immune neutrophil activation in the development of TRALI in patients with pre-disposing inflammatory conditions.

Stored blood products augment inflammation in a two-event model of Transfusion Related Acute Lung Injury (TRALI)

Aim/Background TRALI is hypothesised to develop via a two-event mechanism involving both the patieint's underlying morbidity and blood product factors. The storage of cellular products has been implicated in cases of non-antibody mediated TRALI, however the pathophysiological mechanisms are undefined. We investigated blood product storage-related modulation of inflmmatory cells and medicators involved in TRALI. Methods In an in vitro mode, fresh human whole blood was mixed with culture media (control) or LPS as a 1st event and "transfused" with 10% (v/v) pooled supernatant (SN) from Day 1 (d1, n=75) or Day 42 (D42, n=113) packed red blood cells (PRBCs) as a 2nd event. Following 6hrs, culture SN was used to assess the overall inflammatory response (cytometric bead array) and a duplicate assay containing protein transport inhibitor was used to assess neutrophil- and monocyte-specific inflmamatory responses using multi-colour flow cytometry. Panels: IL-6, IL-8, IL-10, IL-12, IL-1, TNF, MCP-1, IP-10, MIP-1. One-way ANOVA 95% CI. Results In the absence of LPS, exposure to D1 or D42 PRBC-SN reduced monocyte expression of IL-6, IL-8 and Il-10. D42 PRBC-SN also reduced monocyte IP-10, and the overall IL-8 production was increased. In the presence of LPS, D1-PRBC SN only modified overall IP-10 levels which were reduced. However, cf LPS alone, the combination of LPS and D42 PRBC-SN resulted in increased neutrophil and monocyte productionof IL-1 and IL-8 as well as reduced monocyte TNF production. Additionally, LPS and D42 PRBC-SN resulted in overall inflmmatory changes: elevated IL-8,

Improving short utterance i-vector speaker verification using utterance variance modelling and compensation techniques

This paper proposes techniques to improve the performance of i-vector based speaker verification systems when only short utterances are available. Short-length utterance i-vectors vary with speaker, session variations, and the phonetic content of the utterance. Well established methods such as linear discriminant analysis (LDA), source-normalized LDA (SN-LDA) and within-class covariance normalisation (WCCN) exist for compensating the session variation but we have identified the variability introduced by phonetic content due to utterance variation as an additional source of degradation when short-duration utterances are used. To compensate for utterance variations in short i-vector speaker verification systems using cosine similarity scoring (CSS), we have introduced a short utterance variance normalization (SUVN) technique and a short utterance variance (SUV) modelling approach at the i-vector feature level. A combination of SUVN with LDA and SN-LDA is proposed to compensate the session and utterance variations and is shown to provide improvement in performance over the traditional approach of using LDA and/or SN-LDA followed by WCCN. An alternative approach is also introduced using probabilistic linear discriminant analysis (PLDA) approach to directly model the SUV. The combination of SUVN, LDA and SN-LDA followed by SUV PLDA modelling provides an improvement over the baseline PLDA approach. We also show that for this combination of techniques, the utterance variation information needs to be artificially added to full-length i-vectors for PLDA modelling.

Improving PLDA speaker verification with limited development data

This paper analyses the probabilistic linear discriminant analysis (PLDA) speaker verification approach with limited development data. This paper investigates the use of the median as the central tendency of a speaker’s i-vector representation, and the effectiveness of weighted discriminative techniques on the performance of state-of-the-art length-normalised Gaussian PLDA (GPLDA) speaker verification systems. The analysis within shows that the median (using a median fisher discriminator (MFD)) provides a better representation of a speaker when the number of representative i-vectors available during development is reduced, and that further, usage of the pair-wise weighting approach in weighted LDA and weighted MFD provides further improvement in limited development conditions. Best performance is obtained using a weighted MFD approach, which shows over 10% improvement in EER over the baseline GPLDA system on mismatched and interview-interview conditions.

Immunity against a Chlamydia infection and disease may be determined by a balance of IL-17 signaling

Most vaccines developed against Chlamydia using animal models provide partial protection against a genital tract infection. However, protection against the oviduct pathology associated with infertility is highly variable and often has no defining immunological correlate. When comparing two adjuvants (CTA1-DD and a combination of Cholera toxin plus CpG- oligodeoxynucleotide–CT/CpG) combined with the chlamydial major outer membrane protein (MOMP) antigen and delivered via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, we identified two vaccine groups with contrasting outcomes following infection. SL immunization with MOMP/CTA1-DD induced a 70% reduction in the incidence of oviduct pathology, without significantly altering the course of infection. Conversely, IN immunization with MOMP/CT/CpG prevented an ascending infection, but not the oviduct pathology. This anomaly presented a unique opportunity to study the mechanisms by which vaccines can prevent oviduct pathology, other than by controlling the infection. The IL-17 signaling in the oviducts was found to associate with both the enhancement of immunity to infection and the development of oviduct pathology. This conflicting role of IL-17 may provide some explanation for the discordance in protection between infection and disease and suggests that controlling immunopathology, as opposed to the rapid eradication of the infection, may be essential for an effective human chlamydial vaccine that prevents infertility.

The mouse model of Chlamydia genital tract infection: a review of infection, disease, immunity and vaccine development

Chlamydia trachomatis is the most common sexually transmitted bacterial infection worldwide. The impact of this pathogen on human reproduction has intensified research efforts to better understand chlamydial infection and pathogenesis. Whilst there are animal models available that mimic the many aspects of human chlamydial infection, the mouse is regarded as the most practical and widely used of the models. Studies in mice have greatly contributed to our understanding of the host-pathogen interaction and provided an excellent medium for evaluating vaccines. Here we explore the advantages and disadvantages of all animal models of chlamydial genital tract infection, with a focus on the murine model and what we have learnt from it so far.

Quantitative data collection and study validity

The quality of data collection methods selected and the integrity of the data collected are integral tot eh success of a study. This chapter focuses on data collection and study validity. After reading the chapter, readers should be able to define types of data collection methods in quantitative research; list advantages and disadvantages of each method; discuss factors related to internal and external validity; critically evaluate data collection methods and discuss the need to operationalise variables of interest for data collection.

Global story-telling in a socially-networked world

Journalists work in an intensively time-pressured environment, researching and writing to daily, often 24 hour, deadlines and always aware of the competition with other news outlets to be first with the news. This results, as Karen Sanders has observed, in journalists having very little time for reflection. “If they do reflect, it’s usually after a decision has been made” (Sanders 2003, 168). Yet time for reflection upon professional practice is important, especially in an era of extremely rapid and seismic technological change in the global media. This paper will reflect upon how freelance journalists can use advances in social media and web-based connectedness to tell global stories via mainstream media outlets. In exploring this question, I will examine the techniques and communications technologies used by three reporters working in the UK and Australia to find, investigate and break a series of articles, published simultaneously on the front pages of The Australian and The Times (London) newspapers, was a result of a six month investigation. The series exposed a 50-year cover-up of the serial abuse of children by one of the Church of England's most senior clergy, Robert Waddington, in Australia and the UK. It unearthed the existence of a culture of physical and sexual abuse at St Barnabas boarding school in Queensland, the sudden closure of the school and disappearance of student files - as well as Waddington's subsequent offences against children while Dean of Manchester Cathedral. We produced more than 20 articles. The coverage sparked church-ordered investigations in both countries, and also prompted the Archbishop of Canterbury to order a commission of inquiry – headed by a sitting UK judge - as well as a nationwide child safety audit of dioceses in Britain. In Australia, the church referred the case and handed its files to the Royal Commission into Child Sexual Abuse. The coverage marked the first publishing collaboration between The Australian and The Times to break an exclusive story in Australia and Britain simultaneously, on May 10, 2013.

Child sex scandal in two countries rocks Anglican church

A CHILD sex scandal involving victims in Australia and Britain has hit the top echelon of the Anglican Church, with allegations that some of its most senior clergymen failed to respond properly to complaints of horrific abuse. The former archbishop of York, now Lord (David) Hope of Thornes, yesterday expressed regret over failing to report to police allegations in 1999 and 2003 about a former Queensland Anglican school principal, who rose to become the head of education for the church in Britain. The late reverend Robert Waddington has been accused of beating and sexually abusing students during the 1960s at St Barnabas boarding school in Ravenshoe, north Queensland, and later, when he was in charge of the choir as dean of Manchester. A joint investigation by The Australian and The Times newspaper in London has revealed that church officials, including Lord Hope, failed to report the 1999 allegations of abuse made by a former Queensland student and similar claims made in 2003 by the family of a choirboy in Manchester. The alleged victims were never told of the existence of the other allegations.

Choirboy haunted by painful memories

IT was in the magnificent Manchester Cathedral that Eli Ward's pure soprano attracted the attention of the new dean, the Reverend Robert Waddington. When Waddington called for volunteers to help him polish the gold leaf on the altar railings, several choirboys came forward. Among them was Eli, a working-class 11-year-old from a council estate, who loved singing in the choir and was happy to help...

Former Archbishop of York ‘covered up’ sex abuse scandal

The former Archbishop of York stood accused last night of covering up allegations that a senior Church of England clergyman had abused choirboys and school pupils. Lord Hope of Thornes was made aware of the accusations against the Very Rev Robert Waddington, a former Dean of Manchester Cathedral and once the cleric in overall charge of Church schools, in 1999 and again in 2003. Waddington was stripped of his right to conduct church services but the archbishop did not report concerns about alleged past abuse or a potential continuing threat to children to police or child protection agencies. The extent of Waddington’s alleged history of abuse and the Church’s inaction has been revealed through a joint investigation by The Times and The Australian newspaper in Sydney.

Should I stay or should I go? The challenges and opportunities of moving between university systems

The scientific job market has evolved to a truly globalized market. This is epitomized not only by the English language being the de facto scientific language but also by the increasing share of native language journals that are being offered in multiple languages or have or will fully converted to English (such as, for example, the BISE journal in 2015). Similarly, a plethora of exchange programs exists that allow students and academic staff to visit other institutions and exchange knowledge, ideas, and learning opportunities. While student migration across scientific institutions is an established phenomenon (Gribble, 2008) with ample structures, policies, and schemes such as ERASMUS1 in place, academic staff migration between countries is still a challenge, even if exchange programs exist (Enders, 1998). One reason may be that different career paths, varying teaching loads and different evaluation schemes for what constitutes scientific excellence are notable. This also influences the decision of where to start and continue an academic career. While the university systems themselves have been examined previously (Galliers and Whitley, 2007; Lyytinen et al., 2007) and while there is knowledge about career requirements in different university systems (Dennis et al., 2006; Dean et al., 2011; Loos et al., 2013; Recker, 2013), we still do not know much about individual and contextual decisions of academics that either consider or execute a migration between university systems.

Accused headmaster turned me into pedophile, says convicted cleric Peter Gilbert

A CLERGYMAN who allegedly raped boys at a north Queensland boarding school in the 1960s has claimed he was ordered to take female hormones by his headmaster, who encouraged the "romantic love" of children among staff. Former Anglican brother Peter Gilbert - sentenced to seven years' jail in 2006 for the rape and indecent assault of children in the 1980s in South Australia - has blamed St Barnabas headmaster the late Robert Waddington for turning him into a pedophile. In a statement to one of his alleged victims, Gilbert said Waddington was molesting children himself and the Anglican priest would absolve the young teacher of his abuse of children in the confessional. The account has emerged as the top ranks of the Anglican church in Australia and Britain have been rocked by allegations of the covering-up of complaints made in 1999 and 2003 about Waddington's abuse while headmaster at the boarding school in Ravenshoe, north Queensland, and later, when he was dean of Manchester. A full investigation is being demanded into the handling of the complaints by the former Archbishop of York, now Lord (David) Hope of Thornes, and Australian church officials, including the former bishop of north Queensland, Clyde Wood.

UK church orders abuse inquiry

THE Church of England has ordered a formal independent investigation into the handling of child-sex allegations against a senior clergyman in Australia and Britain. Archbishop of York John Sentamu at the weekend commissioned the high-level inquiry into the alleged child sex abuse in the 1960s and 80s by the late Reverend Robert Waddington, and the church's response to complaints over the past 15 years. It comes as the head of Australia's Anglican Church, Archbishop Phillip Aspinall, flew to north Queensland to meet the region's bishop over the revelations, which centre on Waddington's stint as principal of St Barnabas boarding school at Ravenshoe, west of Cairns, and later as dean of Manchester.

St Barnabas abuse allegations build up

MORE victims have made child-sex allegations against senior Anglican clergymen at a shut-down north Queensland boarding school, as church officials confirmed they had sat on a 2004 report about complaints from Britain into one of the suspected serial abusers. Former students Mark McClintock and Greg Shaw have this week come forward with allegations against Robert Waddington, headmaster at St Barnabas boarding school, in Ravenshoe southwest of Cairns, in the 1960s. Waddington later returned to Britain and rose to become head of education for the Church of England and Dean of Manchester. Another former student at St Barnabas, who does not want to be named, also contacted The Weekend Australian with allegations of abuse in the 60s by former Anglican brother Peter Gilbert, who was hired by Waddington and jailed in 2006 for child-sex offences in South Australia.