PCR for the detection of pathogens in neonatal early onset sepsis.

BACKGROUND: A large proportion of neonates are treated for presumed bacterial sepsis with broad spectrum antibiotics even though their blood cultures subsequently show no growth. This study aimed to investigate PCR-based methods to identify pathogens not detected by conventional culture. METHODS: Whole blood samples of 208 neonates with suspected early onset sepsis were tested using a panel of multiplexed bacterial PCRs targeting Streptococcus pneumoniae, Streptococcus agalactiae (GBS), Staphylococcus aureus, Streptococcus pyogenes (GAS), Enterobacteriaceae, Enterococcus faecalis, Enterococcus faecium, Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium, a 16S rRNA gene broad-range PCR and a multiplexed PCR for Candida spp. RESULTS: Two-hundred and eight samples were processed. In five of those samples, organisms were detected by conventional culture; all of those were also identified by PCR. PCR detected bacteria in 91 (45%) of the 203 samples that did not show bacterial growth in culture. S. aureus, Enterobacteriaceae and S. pneumoniae were the most frequently detected pathogens. A higher bacterial load detected by PCR was correlated positively with the number of clinical signs at presentation. CONCLUSION: Real-time PCR has the potential to be a valuable additional tool for the diagnosis of neonatal sepsis

Cold-spray of aluminium with and without ceramic combined with plasma electrolytic oxidation

Cold spraying is developing rapidly and has a wide spectrum of applications: protection against corrosion, preparation of high conductivity coatings, repair of damaged metal components, metal additive manufacturing, thermal management. Plasma electrolytic oxidation (PEO) is widely used to improve the corrosion and wear resistance of lightweight metals such as aluminum alloys by the formation of a ceramic oxide layer. When applied on aluminium alloys, the PEO oxide layer is mainly composed with γ-Al2O3 (in major proportion) and corundum, α-Al2O3. Increasing the proportion of corundum is an objective in order to improve the corrosion and wear resistance properties. For this purpose, a duplex treatment combining cold spray and PEO is investigate [1]. Particularly it consists in firstly cold spraying an aluminium coating containing a certain amount of α-Al2O3 which is then PEO processed. Our results show that, while the projected alpha alumina particles are observable on cross sections of untreated samples and for short PEO treatment times (lower than 20 min), this is no longer the case for long PEO treatment times (over than 35 min) (see the figure). In fact, under these conditions, it is no longer possible to observe the alpha alumina particles in the PEO layer. More interesting still, the proportion of alpha alumina in the layers resulting from a duplex treatment is greater than that obtained in the layer resulting from a cold spray treatment by scanning electron microscope

Implementation of influenza point-of-care-testing and patient-cohorting during a high-incidence season: a retrospective analysis of impact on infection prevention and control and clinical outcomes.

BACKGROUND: During high-incidence influenza seasons, a robust infection prevention and control policy is imperative to reduce nosocomial transmission of influenza. AIM: To assess the impact of Emergency Department (ED) influenza point-of-care-testing (POCT) and influenza-ward patient-cohorting on infection prevention and control and clinical outcomes. METHODS: Influenza POCT was operational in our adult ED from 21st January 2018 and an influenza-ward from 25th January 2018. A retrospective 'before-after' analysis was performed with pre-intervention defined as 1st November 2017-20th January 2018 and post-intervention 21st January-30th April 2018. Primary outcome was rate of hospital-acquired influenza (HAI). Secondary outcomes included antiviral prescription and length of stay. The length of time inpatients remain influenza RNA detected by polymerase chain reaction (PCR) was also analysed

Developing a serocorrelate of protection against invasive group B streptococcus disease in pregnant women: a feasibility study.

BACKGROUND: Group B streptococcus is the leading cause of infection in infants. Currently, intrapartum antibiotic prophylaxis is the major strategy to prevent invasive group B streptococcus disease. However, intrapartum antibiotic prophylaxis does not prevent maternal sepsis, premature births, stillbirths or late-onset disease. Maternal vaccination may offer an alternative strategy. Multivalent polysaccharide protein conjugate vaccine development is under way and a serocorrelate of protection is needed to expedite vaccine licensure. OBJECTIVES: The ultimate aim of this work is to determine the correlate of protection against the major group B streptococcus disease-causing serotypes in infants in the UK. The aim of this feasibility study is to test key operational aspects of the study design. DESIGN: Prospective cohort study of pregnant women and their infants in a 6-month period (1 July to 31 December 2018). SETTING: Five secondary and tertiary hospitals from London and South England. National iGBS disease surveillance was conducted in all trusts in England and Wales. PARTICIPANTS: Pregnant women aged ≥ 18 years who were delivering at one of the selected hospitals and who provided consent during the study period. There were no exclusion criteria. INTERVENTIONS: No interventions were performed. MAIN OUTCOME MEASURES: (1) To test the feasibility of collecting serum at delivery from a large cohort of pregnant women. (2) To test the key operational aspects for a proposed large serocorrelates study. (3) To test the feasibility of collecting samples from those with invasive group B streptococcus. RESULTS: A total of 1823 women were recruited during the study period. Overall, 85% of serum samples were collected at three sites collecting only cord blood. At the two sites collecting maternal, cord and infant blood samples, the collection rate was 60%. A total of 614 women were screened for group B streptococcus with a colonisation rate of 22% (serotype distribution: 30% III, 25% Ia, 16% II, 14% Ib, 14% V and 1% IV). A blood sample was collected from 34 infants who were born to colonised women. Maternal and infant blood and the bacterial isolates for 15 newborns who developed invasive group B streptococcal disease during the study period were collected (serotype distribution: 29% III, 29% II, 21% Ia, 7% Ib, 7% IV and 7% V). LIMITATIONS: Recruitment and sample collection were dependent on the presence of research midwives rather than the whole clinical team. In addition, individualised consent limited the number of women who could be approached each day, and site set-up for the national surveillance study and the limited time period of this feasibility study limited recruitment of all eligible participants. CONCLUSIONS: We have verified the feasibility of collecting and processing rectovaginal swabs and blood samples in pregnant women, as well as samples from those with invasive group B streptococcal disease. We have made recommendations for the recruitment of cases within the proposed GBS3 study and for controls both within GBS3 and as an extension of this feasibility study. FUTURE WORK: A large case-control study comparing specific immunoglobulin G levels in mothers whose infants develop invasive group B streptococcal disease with those in colonised mothers whose infants do not develop invasive group B streptococcal disease is recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN49326091; IRAS project identification number 246149/REC reference number 18/WM/0147. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 67. See the NIHR Journals Library website for further project information

Gain-of-Function Mutation in Filamin A Potentiates Platelet Integrin αβ Activation

OBJECTIVE: Dominant mutations of the X-linked filamin A () gene are responsible for filaminopathies A, which are rare disorders including brain periventricular nodular heterotopia, congenital intestinal pseudo-obstruction, cardiac valves or skeleton malformations, and often macrothrombocytopenia. APPROACH AND RESULTS: We studied a male patient with periventricular nodular heterotopia and congenital intestinal pseudo-obstruction, his unique X-linked allele carrying a stop codon mutation resulting in a 100-amino acid-long FLNa C-terminal extension (NP_001447.2: ). Platelet counts were normal, with few enlarged platelets. FLNa was detectable in all platelets but at 30% of control levels. Surprisingly, all platelet functions were significantly upregulated, including platelet aggregation and secretion, as induced by ADP, collagen, or von Willebrand factor in the presence of ristocetin, as well as thrombus formation in blood flow on a collagen or on a von Willebrand factor matrix. Most importantly, patient platelets stimulated with ADP exhibited a marked increase in αβ integrin activation and a parallel increase in talin recruitment to β, contrasting with normal Rap1 activation. These results are consistent with the mutant FLNa affecting the last step of αβ activation. Overexpression of mutant FLNa in the HEL megakaryocytic cell line correlated with an increase (compared with wild-type FLNa) in PMA-induced fibrinogen binding to and in talin and kindlin-3 recruitment by αβ. CONCLUSIONS: Altogether, our results are consistent with a less binding of mutant FLNa to β and the facilitated recruitment of talin by β on platelet stimulation, explaining the increased αβ activation and the ensuing gain-of-platelet functions

Do adults with high functioning autism or Asperger Syndrome differ in empathy and emotion recognition?

The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (i) their self-reported ability to empathise with others and/or (ii) their ability to read mental states in others’ eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and ‘Reading the Mind in the Eyes’ Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions

Interim Design Report

The International Design Study for the Neutrino Factory (the IDS-NF) was established by the community at the ninth "International Workshop on Neutrino Factories, super-beams, and beta- beams" which was held in Okayama in August 2007. The IDS-NF mandate is to deliver the Reference Design Report (RDR) for the facility on the timescale of 2012/13. In addition, the mandate for the study [3] requires an Interim Design Report to be delivered midway through the project as a step on the way to the RDR. This document, the IDR, has two functions: it marks the point in the IDS-NF at which the emphasis turns to the engineering studies required to deliver the RDR and it documents baseline concepts for the accelerator complex, the neutrino detectors, and the instrumentation systems. The IDS-NF is, in essence, a site-independent study. Example sites, CERN, FNAL, and RAL, have been identified to allow site-specific issues to be addressed in the cost analysis that will be presented in the RDR. The choice of example sites should not be interpreted as implying a preferred choice of site for the facility

The impact of immunosuppressive therapy on secondary infections and antimicrobial use in COVID-19 inpatients: a retrospective cohort study.

BACKGROUND: Immunosuppressive therapies have become a cornerstone of the management of severe COVID-19. The impact of these therapies on secondary infections and antimicrobial prescribing remains unclear. We sought to assess antimicrobial use and the incidence of bacterial and fungal infections in patients with severe COVID-19, and to explore their associations with receipt of immunosuppressive therapies. METHODS: Our retrospective cohort study included 715 hospitalised, adult patients with severe COVID-19 admitted to St George's Hospital, London, UK, during the first UK pandemic wave (1st March-10th June 2020). Co-infections (occurring within 48 h of admission) and secondary infections (≥ 48 h) were defined as a positive microbiological culture with supporting clinical, radiological or laboratory data to suggest true infection. Cox regression models with time-dependent covariates were used to explore the association between immunosuppressant use and secondary infection. RESULTS: Microbiologically confirmed co-infection occurred in 4.2% (n = 30) and secondary infection in 9.3% (n = 66) of the cohort (n = 715) and were associated with in-hospital mortality (48% vs 35%, OR 1.8, 95%CI 1.1-2.7, p = 0.01). Respiratory (n = 41, 39%) and bloodstream infections (n = 38, 36%) predominated, with primarily Gram-negative pathogens. 606 (84.7%) patients received an antimicrobial, amounting to 742 days of therapy per 1000 patient-days (DOTs). In multivariable models, receipt of high-dose steroids (≥ 30 mg prednisolone or equivalent) or tocilizumab was significantly associated with increased antimicrobial consumption (+ 5.5 DOTs, 95%CI 3.4-7.7 days) but not secondary infection (HR 0.56, 95%CI 0.26-1.18). CONCLUSIONS: Bacterial and fungal infections in severe COVID-19 were uncommon. Receipt of steroids or tocilizumab was independently associated with antimicrobial consumption despite its lack of association with secondary infection. These findings should galvanise efforts to promote antimicrobial stewardship in patients with COVID-19

Experimental and numerical investigation of cavitation-induced erosion in thermal sprayed single splats

Hydraulic components are coated by thermal spraying to protect them against cavitation erosion. These coatings are built up by successive deposition of single splats. The behavior of a single splat under mechanical loading is still very vaguely understood. Yttria-stabilized zirconia (YSZ) and stainless-steel splats were obtained by plasma spraying onto stainless steel substrates. The velocity and temperature of particles upon impact were measured and the samples were subsequently exposed to cavitation erosion tests. An acoustic cavitation simulation estimated the water jet velocity and hammer stresses exerted by bubble collapse on the surface of the specimen. Although the results suggested that high stress levels resulted from cavitation loading, it was clear that weak adhesion interfaces played a crucial role in the accelerated cavitation-induced degradation.EPSRC (UK

Extraction and sensitive detection of toxins A and B from the human pathogen Clostridium difficile in 40 seconds using microwave-accelerated metal-enhanced fluorescence.

Clostridium difficile is the primary cause of antibiotic associated diarrhea in humans and is a significant cause of morbidity and mortality. Thus the rapid and accurate identification of this pathogen in clinical samples, such as feces, is a key step in reducing the devastating impact of this disease. The bacterium produces two toxins, A and B, which are thought to be responsible for the majority of the pathology associated with the disease, although the relative contribution of each is currently a subject of debate. For this reason we have developed a rapid detection assay based on microwave-accelerated metal-enhanced fluorescence which is capable of detecting the presence of 10 bacteria in unprocessed human feces within 40 seconds. These promising results suggest that this prototype biosensor has the potential to be developed into a rapid, point of care, real time diagnostic assay for C. difficile