Similarities in consciousness occurring during sleep and sedation.

The subjective experiences of sedation or anaesthesia are underexplored. A recent study by Valli and colleagues (Br J Anaesth 2023; 131: 348-59) found similar frequency and content of recalled experiences after both non-rapid eye movement sleep and target-controlled infusions of propofol or dexmedetomidine titrated to verbal unresponsiveness. The authors find that the phenomenological similarities between consciousness during sleep and sedation mirror their physiological similarities. Intriguingly, in this small sample, conscious experience did not show a dose-dependent response suggesting other factors are important in determining the propensity for consciousness under sedation.

Conflicts of interest in the context of end of life care for potential organ donors in Australia.

End-of-life (EOL) care has become an integral part of intensive care medicine and includes the exploration of possibilities for deceased organ and tissue donation. Donation physicians are specialist doctors with expertise in EOL processes encompassing organ and tissue donation, who contribute significantly to improvements in organ and tissue donation services in many countries around the world. Donation physicians are usually also intensive care physicians, and thus they may be faced with the dual obligation of caring for dying patients and their families in the intensive care unit (ICU), whilst at the same time ensuring organ and tissue donation is considered according to best practice. This dual obligation poses specific ethical challenges that need to be carefully understood by clinicians, institutions and health care networks. These obligations are complementary and provide a unique skillset to care for dying patients and their families in the ICU. In this paper we review current controversies around EOL care in the ICU, including the use of palliative analgesia and sedation specifically with regards to withdrawal of cardiorespiratory support, the usefulness of the so-called doctrine of double effect to guide ethical decision-making, and the management of potential or perceived conflicts of interest in the context of dual professional roles.

Middle East respiratory syndrome coronavirus (MERS-CoV) - Surveillance and testing in North England from 2012 to 2019.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in Saudi Arabia in 2012 and caused an epidemic in the Middle East. Public Health England (PHE) Manchester is one of the two PHE centres in the UK that perform testing for MERS-CoV. The results of the PHE Manchester MERS surveillance from 2012 to 2019 are presented in this report. METHODS: Retrospective data were collected for returning travellers from the Middle East fitting the PHE MERS case definition. Respiratory samples were tested for respiratory viruses and MERS-CoV using an in-house RT-PCR assay. RESULTS: Four hundred and twenty-six (426) samples from 264 patients were tested for MERS Co-V and respiratory viruses. No MERS-CoV infections were identified by PCR. Fifty-six percent of samples were PCR positive for viral or bacterial pathogen with Influenza A as the predominant virus (44%). Sixty-two percent of all patients had a pathogen identified with the highest positivity from sputum samples. Patients with multiple samples demonstrated a 100% diagnostic yield. CONCLUSIONS: Although no cases of MERS were identified, the majority of patients had Influenza infection for which oseltamivir treatment was indicated and isolation warranted. Sputum samples were the most useful in diagnosing respiratory viruses with a 100% diagnostic yield from patients with multiple samples.

A New Evolutionary Algorithm-Based Home Monitoring Device for Parkinson's Dyskinesia.

Parkinson's disease (PD) is a neurodegenerative movement disorder. Although there is no cure, symptomatic treatments are available and can significantly improve quality of life. The motor, or movement, features of PD are caused by reduced production of the neurotransmitter dopamine. Dopamine deficiency is most often treated using dopamine replacement therapy. However, this therapy can itself lead to further motor abnormalities referred to as dyskinesia. Dyskinesia consists of involuntary jerking movements and muscle spasms, which can often be violent. To minimise dyskinesia, it is necessary to accurately titrate the amount of medication given and monitor a patient's movements. In this paper, we describe a new home monitoring device that allows dyskinesia to be measured as a patient goes about their daily activities, providing information that can assist clinicians when making changes to medication regimens. The device uses a predictive model of dyskinesia that was trained by an evolutionary algorithm, and achieves AUC>0.9 when discriminating clinically significant dyskinesia.

Grain-size dynamics beneath mid-ocean ridges: Implications for permeability and melt extraction.

Grain size is an important control on mantle viscosity and permeability, but is difficult or impossible to measure in situ. We construct a two-dimensional, single phase model for the steady state mean grain size beneath a mid-ocean ridge. The mantle rheology is modeled as a composite of diffusion creep, dislocation creep, dislocation accommodated grain boundary sliding, and a plastic stress limiter. The mean grain size is calculated by the paleowattmeter relationship of Austin and Evans (2007). We investigate the sensitivity of our model to global variations in grain growth exponent, potential temperature, spreading-rate, and mantle hydration. We interpret the mean grain-size field in terms of its permeability to melt transport. The permeability structure due to mean grain size may be approximated as a high permeability region beneath a low permeability region. The transition between high and low permeability regions occurs across a boundary that is steeply inclined toward the ridge axis. We hypothesize that such a permeability structure generated from the variability of the mean grain size may focus melt toward the ridge axis, analogous to Sparks and Parmentier (1991)-type focusing. This focusing may, in turn, constrain the region where significant melt fractions are observed by seismic or magnetotelluric surveys. This interpretation of melt focusing via the grain-size permeability structure is consistent with MT observation of the asthenosphere beneath the East Pacific Rise. KEY POINTS: The grain-size field beneath MORs can vary over orders of magnitude The grain-size field affects the rheology and permeability of the asthenosphere The grain-size field may focus melt toward the ridge axis.

Posterior compensatory network in cognitively intact elders with hippocampal atrophy.

Functional compensation in late life is poorly understood but may be vital to understanding long-term cognitive trajectories. To study this we first established an empirically derived threshold to distinguish hippocampal atrophy in those with Mild Cognitive Impairment (MCI n = 34) from those with proficient cognition (PRO n = 22), using data from a population-based cohort. Next, to identify compensatory networks we compared cortical activity patterns during a graded spatial working memory (SWM) task in only cognitively proficient individuals, either with (PROATR ) or without hippocampal atrophy (PRONIL ). Multivariate Partial Least Squares analyses revealed that these groups engaged spatially distinct SWM-related networks. In those with hippocampal atrophy and under conditions of basic-SWM demand, expression of a posterior compensatory network (PCN) comprised calcarine and posterior parietal cortex strongly correlated with superior SWM performance (r = -0.96). In these individuals, basic level SWM response times were faster and no less accurate than in those with no hippocampal atrophy. Cognitively proficient older individuals with hippocampal atrophy may, therefore, uniquely engage posterior brain areas when performing simple spatial working memory tasks.

Neonatal herpes simplex 2 infection presenting with supraglottitis.

Herpes simplex virus (HSV) is a double stranded DNA virus capable of causing primary and recurrent infection. We describe an unusual case of neonatal HSV-2 infection presenting with supraglottitis. Despite a 2 month course of intravenous aciclovir followed by 2 months of oral valaciclovir, the infant subsequently developed HSV-2 encephalitis which responded to further antiviral treatment. The subsequent diagnosis of encephalitis highlights the importance of testing CSF for HSV to establish the presence of CNS infection in neonates and thus the potential benefit of longer term suppressive antiviral therapy.

Improved outcome from invasive adenovirus infection in pediatric patients after hemopoietic stem cell transplantation using intensive clinical surveillance and early intervention.

Adenovirus is a common cause of morbidity and mortality after hemopoietic stem cell transplantation in children. Recently the incidence, risk factors, and outcome of such infections have been better defined using improved virologic detection methods, in particular polymerase chain reaction. We have introduced intensive virologic surveillance for adenovirus in our institution including at least weekly polymerase chain reaction testing of blood and stool samples. We report on 71 prospectively monitored transplants, including 40 from unrelated donors. In total, there were 8 cases of invasive adenovirus infection, 3 of whom died. Mortality was less than in previous studies as cases were managed with antiviral chemotherapy and reduction of immune suppression. In fatal cases, there was concurrent difficult graft versus host disease making withdrawal of immune suppression therapy impossible. We describe 2 cases of graft failure in association with adenovirus viremia and its treatment that were successfully managed with further donor cell infusion.

Recurrent hemiplegia associated with cerebral vasculopathy following third trimester maternal herpes zoster infection.

The chickenpox virus (varicella zoster virus; VZV) is known to cause large and small vessel central nervous system vasculopathies that may be associated with strokes in both adults and children. We present the case of a female aged 2 years 6 months who developed a chronic progressive small-vessel vasculopathy with radiological features of moyamoya disease as a manifestation of congenital varicella syndrome. Clinically, the condition was characterized by recurrent ischaemic strokes, which were brought under control using intravenous acyclovir. The case is unique in that it is the first report of congenital varicella syndrome to occur after a maternal herpes zoster infection. Furthermore, it is the first case of symptomatic VZV infection in a child to occur after a maternal infection occurring in the third trimester of pregnancy.

The impact of monitoring Epstein-Barr virus PCR in paediatric bone marrow transplant patients: can it successfully predict outcome and guide intervention?

BACKGROUND: Epstein-Barr virus (EBV) associated lymphoproliferative disease is a complication of haemopoietic stem cell transplantation (HSCT). In certain groups (unrelated and mismatched donor transplants, T-cell depleted) the risk may be as high as 25% with significant morbidity and mortality. Strategies to predict the impending development of this disorder and allow early intervention have therefore assumed importance. We routinely screen the peripheral blood of all recipients of allogeneic HSCT to detect EBV DNA by quantitative polymerase chain reaction (PCR) technology and report here how this correlates with clinical disease and management. PROCEDURE: Data on 28 successive patients who underwent HSCT at our institution were reviewed. The relationship between EBV reactivation demonstrated by quantitative PCR and development of post transplant lymphoproliferative disease (PTLD) was determined. RESULTS: EBV reactivation occurred in 68% of patients, however only 7% developed clinical PTLD. Patients with high level reactivation (n = 9) had more frequent episodes of reactivation and all patients who progressed to overt PTLD were found in this group. In contrast none of those patients with low level reactivation (n = 10) or persistently negative results (n = 9) showed any signs of clinical disease. Anti-CD20 monoclonal antibody (Rituximab) therapy was instigated in both cases of proven PTLD and three cases of high level reactivation with successful outcomes. Response to treatment was associated with a prompt decline in viral copy number. CONCLUSIONS: Our results indicate that EBV reactivation is a common occurrence in the paediatric allogeneic transplant setting and that only a proportion of patients will progress to PTLD. Frequent monitoring may help to predict those at highest risk and guide intervention.

Rapid detection and quantification of CMV DNA in urine using LightCycler-based real-time PCR.

A real-time quantitative PCR-hybridisation assay was developed for the detection of human cytomegalovirus DNA in clinical material. The assay is based on a LightCycler (LC) and provides both rapid results (<1 h) and quantification over a broad dynamic range (2 x 10(3)-5 x 10(8) CMV DNA copies/ml). Given that the assay showed a 3-fold increase in sensitivity compared to detection of early antigen fluorescent foci (DEAFF) testing of urine samples, we investigated the practicality of testing surveillance such specimens from immunocompromised patients at risk of CMV disease. Over a 12-month period, CMV DNA was detected in 81 (7%) of 1154 urine samples examined. A total of 28 patients tested positive; urine viral loads were higher in 13 infants being investigated for suspected congenital infection (median 1.6 x 10(5) copies/ml) compared with 15 transplant recipients (median 9 x 10(3) copies/ml). Urine samples could be tested directly without processing such that results were available in <1h. Real-time PCR provided information on the quantification of CMV DNA in urine and proved a reliable method for the surveillance of immunocompromised patients at risk of CMV disease. This approach should facilitate a better understanding of the epidemiology and natural history of CMV disease. Moreover, LC-based quantitative PCR is a potentially valuable tool for the management of CMV disease; assisting with the prompt initiation of treatment and assessing therapeutic response.