Biotinidase activity is affected by both seasonal temperature and filter collection cards.

This study set out to examine pre-analytical factors affecting the frequency of positive results in newborn screening for biotinidase deficiency. This investigation was prompted by an increase in the annual screen positive rate for biotinidase deficiency in Ontario from 2.65x10-4 in 2016 to 6.57x10-4 in 2017. Season and trend decomposition was used to separate seasonality from an underlying trend in the time series of biotindase activity measurements for the period 2014-01-12 to 2019-07-27 (n = 798,770). This analysis revealed a marked seasonal effect (winter = median + ⩽ 17 MRU, summer = mean - ⩽20 MRU) and a non-linear negative trend. Seasonal temperature was correlated with biotinidase results (Pearson's r = 0.79) but not with the observed negative trend (Pearson's r = 0.0025). Time series analysis of biotinidase results grouped by print lot of filter paper revealed that recently printed filter paper cards inhibit biotinidase and that this inhibition resolved over time. This study demonstrates that biotindase activity is inhibited by both increased seasonal temperature and collection on newly printed filter cards.

'Somewhere between science and superstition': Religious outrage, horrific science, and The Exorcist (1973).

Science and religion pervade the 1973 horror The Exorcist (1973), and the film exists, as the movie's tagline suggests, 'somewhere between science and superstition'. Archival materials show the depth of research conducted by writer/director William Friedkin in his commitment to presenting and exploring emerging scientific procedures and accurate Catholic ritual. Where clinical and barbaric science fails, faith and ritual save the possessed child Reagan MacNeil (Linda Blair) from her demons. The Exorcist created media frenzy in 1973, with increased reports in the popular press of demon possessions, audience members convulsing and vomiting at screenings, and apparent religious and specifically Catholic moral outrage. However, the official Catholic response to The Exorcist was not as reactionary as the press claimed. The United States Conference of Catholic Bishops' Office of Film and Broadcasting (USCCB-OFB) officially and publicly condemned the film as being unsuitable for a wide audience, but reviews produced for the office by priests and lay Catholics and correspondence between the Vatican and the USCCB-OFB show that the church at least notionally interpreted it as a positive response to the power of faith. Warner Bros. Studios, however, were keen to promote stories of religious outrage to boost sales and news coverage - a marketing strategy that actively contradicted Friedkin's respectful and collaborative approach to working with both religious communities and medical professionals. Reports of Catholic outrage were a means of promoting The Exorcist rather than an accurate reflection of the Catholic Church's nuanced response to the film and its scientific and religious content.

Innovation in a crisis: rethinking conferences and scholarship in a pandemic and climate emergency.

It is a cliché of self-help advice that there are no problems, only opportunities. The rationale and actions of the BSHS in creating its Global Digital History of Science Festival may be a rare genuine confirmation of this mantra. The global COVID-19 pandemic of 2020 meant that the society's usual annual conference - like everyone else's - had to be cancelled. Once the society decided to go digital, we had a hundred days to organize and deliver our first online festival. In the hope that this will help, inspire and warn colleagues around the world who are also trying to move online, we here detail the considerations, conversations and thinking behind the organizing team's decisions.

Non-invasive cardiac output monitoring during catheter interventions in patients with cavopulmonary circulations.

INTRODUCTION: Functionally univentricular hearts palliated with superior or total cavopulmonary connection result in circulations in series. The absence of a pre-pulmonary pump means that cardiac output is more difficult to adjust and control. Continuous monitoring of cardiac output is crucial during cardiac catheter interventions and can provide new insights into the complex physiology of these lesions. MATERIALS AND METHODS: The Icon cardiac output monitor was used to study the changes in cardiac output during catheter interventions in 15 patients (median age: 6.1 years, range: 4.8-15.3 years; median weight: 18.5 kg, range: 15-63 kg) with cavopulmonary circulations. A total of 19 interventions were undertaken in these patients and the observed changes in cardiac output were recorded and analysed. RESULTS: Cardiac output was increased with creation of stent fenestrations after total cavopulmonary connection (median increase of 22.2, range: 6.7%-28.6%) and also with drainage of significant pleural effusions (16.7% increase). Cardiac output was decreased with complete or partial occlusion of fenestrations (median decrease of 10.6, range: 7.1%-13.4%). There was a consistent increase in cardiac output with stenting of obstructive left pulmonary artery lesions (median increase of 7.7, range: 5%-14.3%, p = 0.007). CONCLUSIONS: Icon provides a novel technique for the continuous, non-invasive monitoring of cardiac output. It provides a further adjunct for monitoring of physiologically complex patients during catheter interventions. These results are consistent with previously reported series involving manipulation of fenestrations. This is the first report identifying an increase in cardiac output with stenting of obstructive pulmonary arterial lesions.

Single-centre use of implantable loop recorders in patients with congenital heart disease.

AIMS: To determine the efficacy of the implantable loop recorder (ILR) in patients with congenital heart disease. METHODS AND RESULTS: Retrospective data analyses of all patients with congenital heart disease undergoing ILR implantation in a congenital cardiac centre. Of 78 ILRs implanted between July 2000 and October 2007, 22 (15 male) patients had congenital heart disease. The median age at implantation was 15.5 years (7.0-46.5). Six patients had neurodevelopmental delay. Indications for implantation were syncope (n = 15), palpitations (n = 4), and pre-syncope (n = 3). Median implantation time was 19 months (1-30). Explantation data were available in 16 patients (73%). Implantable loop recorders were explanted following establishment of positive diagnosis (n = 3), negative diagnosis (n = 7), and at the end of battery life (n = 4). One patient died with the ILR in situ. One device eroded after 2 months without further complication. Following ILR interrogation, diagnosed arrhythmias included ventricular tachycardia (n = 2) and sinus node dysfunction (n = 1). On the basis of these findings, two patients had intracardiac defibrillators and one patient had a dual-chamber pacemaker implanted. CONCLUSION: Implantable loop recorders lead to a positive or negative arrhythmic diagnosis following explantation in 71% of patients with congenital heart disease. This is particularly beneficial in patients with neurodevelopmental delay where accurate history is often limited.

Immune responses elicited by bacterial minicells capable of simultaneous DNA and protein antigen delivery.

Recent events surrounding emerging infectious diseases, bioterrorism and increasing multidrug antibiotic resistance in bacteria have drastically increased current needs for effective vaccines. Many years of study have shown that live, attenuated pathogens are often more effective at delivering heterologous protein or DNA to induce protective immune responses. However, these vaccine carriers have inherent safety concerns that have limited their development and their use in many patient populations. Studies using nonliving delivery mechanisms have shown that providing both protein antigen and DNA encoding the antigen to an individual induces an improved, more protective immune response but rarely, if ever, are both delivered simultaneously. Here, non-replicating bacterial minicells derived from a commensal E. coli strain are shown to effectively induce antigen-specific immune responses after simultaneous protein and DNA delivery. These data demonstrate the potential use of achromosomal bacterial minicells as a vaccine carrier.