Neutrophils in bacterial pneumonia: influx and clearance

Despite the advent of powerful modern antibiotics, pneumonia continues to be of great importance. Although most cases of community acquired pneumonia (CAP) will recover fully, some (including those previously fit and well) may die. Many hospital patients will suffer nosocomial pneumonia (NP), with a high mortality rate. This is particularly true on the intensive care unit.The neutrophil granulocyte is of particular importance in the defence of the lung. It contains many substances that are bactericidal. During pneumonia, it is recruited from the intravascular space into the lung interstitium and the air -spaces. There, its bactericidal products are capable not only of damaging and killing bacteria, but also of causing'bystander' damage to the host lung. During the course of pneumonia it is important that neutrophils are not only recruited rapidly to defend against bacteria, but that their recruitment should cease as soon as adequate numbers are attained or their function is no longer required. Not only that, but the neutrophils that have already been recruited must then be safely and speedily removed from the site of pneumonia.To investigate these dynamic processes, a rabbit model of pneumonia was used. Bacteria were instilled to a localised area via a fibre -optic bronchoscope. This allowed strict definition of the time of onset of pneumonia, and study of subsequent evolving processes. Two organisms were used; 1) Streptococcus pneumoniae, an organism characteristic of CAP and; 2) Escherichia coli, an organism characteristic of NP. It was hypothesised that in pneumonia due to the former (PneuS), the usual remarkably complete recovery witnessed clinically is due to the tissue load of neutrophils being carefully controlled. By contrast, pneumonia due to the latter (pneuE) is clinically much more severe and lung- damaging, due to a larger lung neutrophil burden. This could be because of earlier cessation of neutrophil influx and /or more rapid neutrophil clearance in pneuS than pneuE.Radiolabelled neutrophils from donor animals were injected at intervals after induction of pneumonia to assess the magnitude of ongoing neutrophil recruitment. In pneuS, neutrophil influx was significantly elevated above control levels at 6 hour but not 30 hour or subsequent time points. In pneuE, neutrophil influx was at least as high at 30 hours as at 6 hours. This confirms the hypothesis that neutrophil influx is more prolonged in pneuE than in pneuS.The requirement for the CDI8 adhesion molecule, (known to be important in recruitment of neutrophils) has been shown to change with time in the peritoneum. This could be an important facet of control of the development of inflammation. In pneuS, neutrophil recruitment is known to be CD18 independent. The previous finding of others that such antibodies inhibit neutrophil recruitment early (6 hours) in pneuE was confirmed. It was found there was no change in this CD18 dependency later on (at 30 hours). The chemokine IL -8 is thought to be particularly important in the recruitment of neutrophils. An anti -IL -8 blocking antibody was used to assess the importance of IL -8 in neutrophil recruitment at 6 and 30 hours. Although this inhibited IL -8 induced neutrophil shape change in vitro and intradermal IL -8 induced neutrophil influx in vivo, iand reversed the prolonged retention of tracer neutrophils in pneumonic lungs minutes after injection, the antibody failed to block neutrophil influx in either type of pneumonia at 6 or 30 hours. Indeed, there was a trend towards increased influx after treatment. High dose antibody produced the same effect. These surprising results are partly explained by higher bronchoalveolar lavage (BAL) and plasma levels of IL -8 after antibody treatment. This may be due to IL -8 /anti -IL -8 antibody complexes amplifying the inflammatory response, although no endothelially bound anti -IL -8 was detected. Alternatively, it may represent the release of negative feedback on IL -8 production.In both pneuS and pneuE, the early peak in BAL neutrophil numbers was followed by an increase in the number of apoptotic neutrophils. This in turn was followed by an 4 increased number of alveolar macrophages containing apoptotic bodies. Trypan blue positive, necrotic neutrophils were rare. This is consistent with neutrophil apoptosis and associated macrophage phagocytosis, (a process that limits the release of toxic neutrophil products), playing an important role in neutrophil clearance in pneumonia.BAL from animals with pneumonia promoted rabbit neutrophil apoptosis in vitro. In pneuS (but not pneuE) this correlated weakly though significantly with the amount of apoptotic neutrophils recovered from BAL and with BAL levels of IL -8, gro and MCP -1. It is suggested that a factor is elaborated within the lung during inflammation that promotes neutrophil apoptosis, thus giving negative feedback control on the lung neutrophil burden. The different relationships found between in vitro and in vivo in pneuS and pneuE may again contribute to the different clinical outcomes in the two diseases.In summary, an animal model demonstrated that neutrophil influx was more prolonged in pneuE than in pneuS. It is suggested this contributes to the more severe manifestations of the former clinically. CD18 was important to the influx of neutrophils in pneuE late as well as early in the disease. Anti -IL -8 antibody failed to inhibit neutrophil influx in either type of pneumonia, which may be due to immune -complex formation or release of negative feedback controls. Evidence that neutrophil apoptosis is involved in their clearance during pneumonia was obtained, together with evidence that a factor is released to promote neutrophil apoptosis and thus provide negative feedback control of inflammation during pneumonia. The control may differ in PneuS and PneuE, affecting outcome

Environmental impact assessment in the routing of high voltage overhead transmission lines : theory and practice in South Africa

Includes bibliographies.This study resulted from a perception held by the author that more attention is afforded to complying with the procedural elements of Environmental Impact Assessment (EIA) in South Africa, than to ensuring the validity of its technical content. The routing of high voltage overhead transmission lines provides a relevant field of study in which to address this perception. An initial literature review to contextualise the perceived problem showed that the questionable validity of the technical content of EIA was one of six shortcomings identified. To address the problem, an inductive approach was adopted to focus on the interpretation and prediction activities of EIA and two propositions, stated as research questions for discussion, were developed. These referred to the theoretical question of whether methods are specified for high voltage overhead transmission line EIAs, and to the practical question of whether the environmental impacts that are known to result from transmission line projects are effectively addressed in such EIAs in South Africa. Investigating these questions provides insights into whether the technical content of transmission line EIA is sufficiently rigorous in South Africa. The method of study takes the form of a sequentially more focused examination of the literature on EIA, from the strategic level, to the sectoral level and culminating at the project level. EIA methods specified for linear developments were identified at the sectoral level, while at the project level the known environmental impacts that result from high voltage overhead transmission lines were determined. A theoretical background was compiled in this way, which allowed for comparison with the practice as determined from benchmark and case study Environmental Impact Reports (EIRs)

Assessment in Scotland

Assessment practice will follow and reinforce the curriculum and promote high quality learning and teaching approaches. Assessment of children's and young people's progress and achievement during their broad general education to the end of S3 will be based on teachers' assessment of their knowledge and understanding, skills, attributes and capabilities, as described in the experiences and outcomes across the curriculum

Reflections on the value of autistic participation in a tri‐national teacher‐training project through discourses of acceptance, othering and power

The Transform Autism Education (TAE) project is a tri‐national teacher training scheme involving Greece, Italy and the UK, whose purpose is to set up training projects to facilitate the educational inclusion of autistic children. Running over three years from 2014 to 2017, the involvement of autistic participants has been the source of some discussion. Here, TAE team members Wood and Milton reflect on narratives of participation, acceptance and struggle which emerged during a workshop they ran in Greece. Derived from 11 non‐autistic and two autistic participants, and analysed via discourse analysis, these stories suggest a high value placed on autistic participation by non‐autistic TAE team members, but an unwitting tendency to ‘other’ autistic people and a lack of awareness of the power differential. Meanwhile, as the autistic team members describe how educational and social participation can be achieved, the implications for autism education researchers and practitioners are discussed

Identifying delirium in Parkinson's disease: a pilot study

This is the author accepted manuscript. The final version is avaialble from Wiley via the DOI in this recordData Availability Statement: Unidentifiable data may be shared on request.Introduction People with Parkinson's disease (PD) may be at increased risk of delirium and associated adverse outcomes. Delirium is an acute neuropsychiatric syndrome defined by confusion and inattention and is common in older adults. Previous studies may have underestimated the prevalence of delirium in PD due to overlapping symptoms, lack of awareness and poorly defined criteria. We aimed to identify the prevalence and incidence of delirium in inpatients with PD. Measurements Participants were inpatients with PD admitted over a four‐month period. Delirium prevalence was classified using a standardised assessment at a single visit based on the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM‐5) criteria. To capture remaining time in hospital, incident delirium was diagnosed using detailed clinical vignettes and a validated consensus method. Results Forty‐four PD patients consented to take part in the study, accounting for 53 admissions. Delirium prevalence was 34.0% (n=18); reviewing participants over the duration of their hospital stay identified 30 (56.6%) incident delirium cases. The admitting team screened 24.5% for delirium and delirium was documented in eight (14.8%) cases' medical notes. Cases with delirium were significantly older, had higher frailty scores and a longer hospital stay (p<0.05 for all). Conclusions Delirium is common in PD inpatients at admission and incidence increases during hospital stay, but delirium commonly missed. Our results highlight the importance of screening for delirium throughout patients' stay in hospital. Future studies should consider frequent evaluation over the duration of hospital stay to identify emergent delirium during the admission.Newcastle upon Tyne Hospitals NHS Foundation TrustParkinson’s UKNational Institute for Health Research (NIHR

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study

Background: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. // Methods: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)–Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II–Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status. During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. // Results: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (β = −2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). // Conclusions: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention

Elimination of Arctic Variant Rabies in Red Foxes, Metropolitan Toronto

To control the arctic variant of rabies virus in red foxes, 332,257 bait doses containing live, attenuated Evelyn-Rokitnicki-Abelseth rabies vaccine were distributed in greater metropolitan Toronto during 1989–1999. Human and pet contact with bait was minimal, and no adverse reactions to the vaccine were noted. Significantly fewer rabid foxes were found during the 17 years after fox baiting (5 cases during 1990–2006) than in the 17 years before (96 cases during 1973–1989). The last report of a rabid fox in metropolitan Toronto was in 1996 (reporting period through September 2006), which confirms that distributing oral rabies vaccine bait is a feasible tactic for the control of rabies in foxes in urban environments

Hospitalisation without delirium is not associated with cognitive decline in a population-based sample of older people-results from a nested, longitudinal cohort study

Background: Acute hospitalisation and delirium have individually been shown to adversely affect trajectories of cognitive decline but have not previously been considered together. This work aimed to explore the impact on cognition of hospital admission with and without delirium, compared to a control group with no hospital admissions. Methods: The Delirium and Cognitive Impact in Dementia (DECIDE) study was nested within the Cognitive Function and Ageing Study II (CFAS II)-Newcastle cohort. CFAS II participants completed two baseline interviews, including the Mini-Mental State Examination (MMSE). During 2016, surviving participants from CFAS II-Newcastle were recruited to DECIDE on admission to hospital. Participants were reviewed daily to determine delirium status. During 2017, all DECIDE participants and age, sex and years of education matched controls without hospital admissions during 2016 were invited to repeat the CFAS II interview. Delirium was excluded in the control group using the Informant Assessment of Geriatric Delirium Scale (i-AGeD). Linear mixed effects modelling determined predictors of cognitive decline. Results: During 2016, 82 of 205 (40%) DECIDE participants had at least one episode of delirium. At 1 year, 135 of 205 hospitalised participants completed an interview along with 100 controls. No controls experienced delirium (i-AGeD>4). Delirium was associated with a faster rate of cognitive decline compared to those without delirium (β =-2.2, P < 0.001), but number of hospital admissions was not (P = 0.447). Conclusions: These results suggest that delirium during hospitalisation rather than hospitalisation per se is a risk factor for future cognitive decline, emphasising the need for dementia prevention studies that focus on delirium intervention

Evaluation of Bedside Tests of Attention and Arousal Assessing Delirium in Parkinson's Disease, Dementia, and Older Adults

BACKGROUND: Delirium is a serious acute neuropsychiatric condition associated with altered attention and arousal. OBJECTIVE: To evaluate simple bedside tests for attention and arousal to detect delirium in those with and without Parkinson's disease (PD) and dementia. METHODS: Participants from two prospective delirium studies were pooled comprising 30 with PD without cognitive impairment, 24 with Lewy body cognitive impairment (PD dementia or dementia with Lewy bodies), 16 with another dementia and 179 PD and dementia-free older adults. Participants completed standardised delirium assessments including tests of attention: digit span, Memorial Delirium Assessment Scale (MDAS) attention and months of the year backwards; and arousal: Glasgow Coma Scale (GSC), Observational Scale of Level of Arousal (OSLA), Modified Richmond Agitation Scale and MDAS consciousness. Delirium was diagnosed using the DSM-5 criteria. RESULTS: On their first admission, 21.7%participants had prevalent delirium. Arousal measures accurately detected delirium in all participants (p <  0.01 for all), but only selected attention measures detected delirium in PD and dementia. In PD and dementia-free older adults, impaired digit span and OSLA were the optimal tests to detect delirium (area under the curve [AUC] = 0.838, p <  0.001) while in PD and dementia the optimal tests were MDAS attention and GCS LB. CONCLUSION: Simple bedside tests of attention and arousal at a single visit could accurately detect delirium in PD, dementia and PD and dementia-free older adults; however, the optimal tests differed between groups. Combined attention and arousal scores increased accuracy, which could have clinical utility to aid the identification of delirium neurodegenerative disorders