Contact tracing is conducted with the primary purpose of interrupting transmission from individuals who are likely to be infectious to others. Secondary analyses of data on the numbers of close ...contacts of confirmed cases could also: provide an early signal of increases in contact patterns that might precede larger than expected case numbers; evaluate the impact of government interventions on the number of contacts of confirmed cases; or provide data information on contact rates between age cohorts for the purpose of epidemiological modelling. We analysed data from 140,204 close contacts of 39,861 cases in Ireland from 1st May to 1st December 2020.
Negative binomial regression models highlighted greater numbers of contacts within specific population demographics, after correcting for temporal associations. Separate segmented regression models of the number of cases over time and the average number of contacts per case indicated that a breakpoint indicating a rapid decrease in the number of contacts per case in October 2020 preceded a breakpoint indicating a reduction in the number of cases by 11 days.
We found that the number of contacts per infected case was overdispersed, the mean varied considerable over time and was temporally associated with government interventions. Analysis of the reported number of contacts per individual in contact tracing data may be a useful early indicator of changes in behaviour in response to, or indeed despite, government restrictions. This study provides useful information for triangulating assumptions regarding the contact mixing rates between different age cohorts for epidemiological modelling.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The serial interval is the period of time between the onset of symptoms in an infector and an infectee and is an important parameter which can impact on the estimation of the reproduction number. ...Whilst several parameters influencing infection transmission are expected to be consistent across populations, the serial interval can vary across and within populations over time. Therefore, local estimates are preferable for use in epidemiological models developed at a regional level. We used data collected as part of the national contact tracing process in Ireland to estimate the serial interval of SARS-CoV-2 infection in the Irish population, and to estimate the proportion of transmission events that occurred prior to the onset of symptoms.
After data cleaning, the final dataset consisted of 471 infected close contacts from 471 primary cases. The median serial interval was 4 days, mean serial interval was 4.0 (95% confidence intervals 3.7, 4.3) days, whilst the 25th and 75th percentiles were 2 and 6 days respectively. We found that intervals were lower when the primary or secondary case were in the older age cohort (greater than 64 years). Simulating from an incubation period distribution from international literature, we estimated that 67% of transmission events had greater than 50% probability of occurring prior to the onset of symptoms in the infector.
Whilst our analysis was based on a large sample size, data were collected for the primary purpose of interrupting transmission chains. Similar to other studies estimating the serial interval, our analysis is restricted to transmission pairs where the infector is known with some degree of certainty. Such pairs may represent more intense contacts with infected individuals than might occur in the overall population. It is therefore possible that our analysis is biased towards shorter serial intervals than the overall population.
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We performed these experiments to determine if repeated exposure to episodic hypoxia induces long term facilitation (LTF)
in anaesthetized spontaneously breathing rats. A previous study in ...spontaneously breathing rats was unable to demonstrate
evidence of LTF with repeated hypoxia, but this may have been due to the low number of hypoxic episodes used. We hypothesized
that with sufficient exposure, episodic hypoxia LTF of genioglossus (GG), hyoglossus (HG) and diaphragm (Dia) activities would
be elicited. Experiments were performed in 24 anaesthetized spontaneously breathing rats with intact vagi. Peak and tonic
GG, HG and Dia EMG activities were recorded before, during and for 1 h following exposure to eight ( n = 8) or three ( n = 8) episodes of isocapnic hypoxia ( = 0.1) each of 3 min duration. A third time control series was also performed with exposure to normoxia alone ( = 0.28, n = 8). Short-term potentiation of GG and HG muscle activity developed during the early period after repeated exposure to eight
and three hypoxic episodes. LTF, however, occurred only after eight hypoxic episodes. This manifested as an increase in peak
GG and Dia inspiratory muscle activity and tonic HG activity. LTF of respiratory breathing frequency was also induced, reflected
by a reduction in inspiratory and expiratory time. These findings support our initial hypothesis that LTF in the anaesthetized,
spontaneously breathing rat is dependent on the number of exposures to hypoxia and show that the responses to repetitive hypoxia
are composed of both short and long-term facilitatory changes.
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Purpose
To evaluate the nature and extent of changes in the fundamental and harmonic components of the 31-Hz flicker electroretinogram (ERG) during light adaptation.
Methods
Full-field ERGs were ...recorded from five visually normal subjects (ages 21–60 years). Following 30 min of dark adaptation, the subjects were exposed to a uniform adapting field of 50 cd/m
2
. The field, which was presented for approximately 15 min, was intermittently modulated sinusoidally at 31.25 Hz. The ERG was recorded during the sinusoidal modulation, and Fourier analysis was used to obtain the amplitude and phase of the fundamental (F), second (2F), and third (3F) harmonic response components.
Results
F amplitude increased by almost a factor of two over approximately 6 min (time constant,
τ
, of 3.0 min). The 2F amplitude increased by a smaller amount, a factor of 1.4, and the time-course was approximately eight times faster than that of F (
τ
= 0.4 min). The 3F amplitude increased by a factor of 4.6, an increase that was larger than F or 2F, with a time-course that was between that of F and 2F (
τ
= 1.4 min). F phase was unaffected by light adaptation, whereas the 2F and 3F phases both increased by approximately 45° over similar time-courses (
τ
= 2.0 min).
Conclusions
Light adaptation had different effects on the fundamental, second, and third harmonic components of the 31-Hz flicker ERG, which resulted in a change in waveform shape during light adaptation. The previously reported flicker ERG amplitude growth is driven primarily, but not entirely, by changes in the fundamental.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
High pressure enriched oxygen is used in a wide number of areas, including aircraft, medical breathing apparatus, and a number of industrial processes including combustion. Unwanted ignition in such ...systems can cause significant damage to property and danger to life. It is important to gain as much information, and record relevant data for every oxygen incident, enabling both immediate analysis, and post-event evaluations (especially where circumstances are repeated). The lack of clear concise guidance can result in data loss. This work successfully develops investigation ‘road maps’ as guidance documents for investigators to use, even under difficult & time pressured conditions. The work demonstrates their usefulness and importance for information collection and the down-selection’ or elimination of possible ignition causes through their use with a ‘real world’ case study. The benefit of this work will be to enable faster and more effective investigation of oxygen incidents, ensuring key details are recorded (benefitting post-accident academic data & meta-study analysis). The roadmaps can also benefit designers of oxygen systems allowing them to test their designs and operating procedures against specific ignition scenarios.
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Obstruction of the upper airway (UA) is associated with episodes of hypoxia and upper airway negative pressure (UANP). In
the companion paper it is shown that episodic hypoxia elicits long-term ...facilitation (LTF) of tongue protrudor, retractor
and respiratory pump muscle activity. However, whether repeated exposure to UANP also induces LTF is unknown. We hypothesized
that repetitive exposure to UANP would induce LTF of UA and respiratory pump muscle activity and when coupled with hypoxia,
as occurs when the UA obstructs, would lead to an even greater facilitation of muscle activity and the response to UANP. Experiments
were performed in 24 anaesthetized, spontaneously breathing rats with intact vagi. To induce LTF, UANP stimuli (â10 cmH 2 O) of 5 s duration were delivered every 30 s for 3 min (± hypoxia). This was repeated eight times over 1 h, each 3 min episode
separated by 5 min of normoxia. Genioglossus (GG), hyoglossus (HG) and diaphragm (Dia) muscle activity was recorded before,
during and for 1 h following the last exposure to episodic UANP alone ( n = 8), UANP and hypoxia together ( n = 8) or normoxia alone ( n = 8). During the final hour, single pulses of UANP were applied at 1 min and every 10 min thereafter to determine whether
LTF of the response to UANP had been induced. Our results show that LTF of GG muscle activity and its response to UANP was
induced following exposure to episodic UANP stimuli alone and UANP applied during hypoxia. However, there was no significant
difference between these responses. Episodic UANP alone also induced LTF of HG muscle activity but this effect did not manifest
until 40 min following the last episode of repeated UANP stimulation. In the presence of hypoxia, no LTF of HG muscle response
to UANP was found. In conclusion, episodic UANP stimulation induces LTF of UA dilator and retractor tongue muscles, but no
further facilitation occurs when coupled with hypoxia. This response may serve as an important protective mechanism of respiratory
homeostasis during sleep, particularly in patients who suffer from obstructive sleep apnoea.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
(1) Background: Conduction disturbance requiring a new permanent pacemaker (PPM) after transcatheter aortic valve implantation (TAVI) has traditionally been a common complication. New implantation ...techniques with self-expanding platforms have reportedly reduced the incidence of PPM. We sought to investigate the predictors of PPM at 30 days after TAVI using Evolut R/PRO/PRO+; (2) Methods: Consecutive patients who underwent TAVI with the Evolut platform between October 2019 and August 2022 at University Hospital Galway, Ireland, were included. Patients who had a prior PPM (
= 10), valve-in-valve procedures (
= 8) or received >1 valve during the index procedure (
= 3) were excluded. Baseline clinical, electrocardiographic (ECG), echocardiographic and multislice computed tomography (MSCT) parameters were analyzed. Pre-TAVI MSCT analysis included membranous septum (MS) length, a semi-quantitative calcification analysis of the aortic valve leaflets, left ventricular outflow tract, and mitral annulus. Furthermore, the implantation depth (ID) was measured from the final aortography. Multivariate binary logistic analysis and receiver operating characteristic (ROC) curve analysis were used to identify independent predictors and the optimal MS and ID cutoff values to predict new PPM requirements, respectively; (3) Results: A total of 129 TAVI patients were included (age = 81.3 ± 5.3 years; 36% female; median EuroSCORE II 3.2 2.0, 5.4). Fifteen patients (11.6%) required PPM after 30 days. The patients requiring new PPM at 30 days were more likely to have a lower European System for Cardiac Operative Risk Evaluation II, increased prevalence of right bundle branch block (RBBB) at baseline ECG, have a higher mitral annular calcification severity and have a shorter MS on preprocedural MSCT analysis, and have a ID, as shown on the final aortogram. From the multivariate analysis, pre-TAVI RBBB, MS length, and ID were shown to be predictors of new PPM. An MS length of <2.85 mm (AUC = 0.85, 95%CI: (0.77, 0.93)) and ID of >3.99 mm (area under the curve (AUC) = 0.79, (95% confidence interval (CI): (0.68, 0.90)) were found to be the optimal cut-offs for predicting new PPM requirements; (4) Conclusions: Membranous septum length and implantation depth were found to be independent predictors of new PPM post-TAVI with the Evolut platform. Patient-specific implantation depth could be used to mitigate the requirement for new PPM.
► Use FLACS to model water fog mitigation of H2–air deflagrations in a silo ullage. ► Fog could significantly reduce the peak overpressure for mixtures up to 20% H2–air. ► Very high fog densities ...would be required to mitigate a 30% H2–air mixture. ► Ignition of corner H2 releases produces significantly higher overpressures.
During the decommissioning of certain legacy nuclear waste storage plants it is possible that significant releases of hydrogen gas could occur. Such an event could result in the formation of a flammable mixture within the silo ullage and, hence, the potential risk of ignition and deflagration occurring, threatening the structural integrity of the silo. Very fine water mist fogs have been suggested as a possible method of mitigating the overpressure rise, should a hydrogen–air deflagration occur. In the work presented here, the FLACS CFD code has been used to predict the potential explosion overpressure reduction that might be achieved using water fog mitigation for a range of scenarios where a hydrogen–air mixture, of a pre-specified concentration (containing 800L of hydrogen), uniformly fills a volume located in a model silo ullage space, and is ignited giving rise to a vented deflagration. The simulation results suggest that water fog could significantly reduce the peak explosion overpressure, in a silo ullage, for lower concentration hydrogen–air mixtures up to 20%, but would require very high fog densities to be achieved to mitigate 30% hydrogen–air mixtures.
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Serotonin (5-hydroxytryptamine, 5-HT) excites hypoglossal (XII) motoneurons in reduced preparations, and it has been suggested
that withdrawal of 5-HT may underlie reduced genioglossus (GG) muscle ...activity in sleep. However, systemic administration
of 5-HT agents in humans has limited effects on GG activity. Whether 5-HT applied directly to the XII motor nucleus increases
GG activity in an intact preparation either awake or asleep has not been tested.
The aim of this study was to develop a novel freely behaving animal model for in vivo microdialysis of the XII motor nucleus across sleep-wake states, and test the hypothesis that 5-HT application will increase
GG activity.
Eighteen rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and GG and
diaphragm electrodes for respiratory muscle recording. Microdialysis probes were implanted into the XII motor nucleus and
perfused with artificial cerebrospinal fluid (ACSF) or 10 m m 5-HT.
Normal decreases in GG activity occurred from wakefulness to non-rapid eye movement (non-REM) and REM sleep with ACSF ( P < 0.01). Compared to ACSF, 5-HT caused marked GG activation across all sleep-wake states (increases of 91-251 %, P < 0.015). Importantly, 5-HT increased sleeping GG activity to normal waking levels for as long as 5-HT was applied (3-5 h).
Despite tonic stimulation by 5-HT, periods of phasic GG suppression and excitation occurred in REM sleep compared with non-REM.
The results show that sleep-wake states differentially modulate GG responses to 5-HT at the XII motor nucleus. This animal
model using in vivo microdialysis of the caudal medulla will enable the determination of neural mechanisms underlying pharyngeal motor control
in natural sleep.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The hypoglossal motor nucleus innervates the genioglossus (GG) muscle of the tongue, a muscle that helps maintain an open
airway for effective breathing. Rapid-eye-movement (REM) sleep, however, ...recruits powerful neural mechanisms that can abolish
GG activity even during strong reflex stimulation such as by hypercapnia, effects that can predispose to sleep-related breathing
problems in humans. We have developed an animal model to chronically manipulate neurotransmission at the hypoglossal motor
nucleus using in vivo microdialysis in freely behaving rats. This study tests the hypothesis that glycine receptor antagonism at the hypoglossal
motor nucleus, either alone or in combination with GABA A receptor antagonism, will prevent suppression of GG activity in natural REM sleep during room air and CO 2 -stimulated breathing. Rats were implanted with electroencephalogram and neck muscle electrodes to record sleepâwake states,
and GG and diaphragm electrodes for respiratory muscle recording. Microdialysis probes were implanted into the hypoglossal
motor nucleus for perfusion of artificial cerebrospinal fluid (ACSF) and strychnine (glycine receptor antagonist, 0.1 m m ) either alone or combined with bicuculline (GABA A antagonist, 0.1 m m ) during room air and CO 2 -stimulated breathing. Compared to ACSF controls, glycine receptor antagonism at the hypoglossal motor nucleus increased respiratory-related
GG activity in room air ( P = 0.010) but not hypercapnia ( P = 0.221). This stimulating effect of strychnine in room air did not depend on the prevailing sleepâwake state ( P = 0.625) indicating removal of a non-specific background inhibitory glycinergic tone. Nevertheless, GG activity remained
minimal in those REM sleep periods without phasic twitches in GG muscle, with GG suppression from non-REM (NREM) sleep being
> 85% whether ACSF or strychnine was at the hypoglossal motor nucleus or the inspired gas was room air or 7% CO 2 . While GG activity was minimal in these REM sleep periods, there was a small but measurable increase in GG activity after
strychnine ( P < 0.05). GG activity was also minimal, and effectively abolished, in the REM sleep periods without GG twitches with combined
glycine and GABA A receptor antagonism at the hypoglossal motor nucleus. We conclude that these data in freely behaving rats confirm that inhibitory
glycine and GABA A receptor mechanisms are present at the hypoglossal motor nucleus and are tonically active, but that such inhibitory mechanisms
make only a small contribution to the marked suppression of GG activity and reflex responses observed in periods of natural
REM sleep.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK