The post-ICU presentation screen (PICUPS) and rehabilitation prescription (RP) for intensive care survivors part I: Development and preliminary clinimetric evaluation

BANCKGROUND: Patients who have had prolonged stays in intensive care have ongoing rehabilitation needs. This is especially true of COVID-19 ICU patients, who can suffer diverse long-term ill effects. Currently there is no systematic data collection to guide the needs for therapy input for either of these groups nor to inform planning and development of rehabilitation services. These issues could be resolved in part by the systematic use of a clinical tool to support decision-making as patients progress from the Intensive Care Unit (ICU), through acute hospital care and onwards into rehabilitation. We describe (i) the development of such a tool (the Post-ICU Presentation Screen (PICUPS)) and (ii) the subsequent preparation of a person-centred Rehabilitation Prescription (RP) to travel with the patient as they continue down the care pathway. METHODS: PICUPS development was led by a core group of experienced clinicians representing the various disciplines involved in post-ICU rehabilitation. Key constructs and item-level descriptors were identified by group consensus. Piloting was performed as part of wider clinical engagement in 26 acute hospitals across England. Development and validation of such a tool requires clinimetric analysis, and this was based on classical test theory. Teams also provided feedback about the feasibility and utility of the tool. RESULTS: Initial PICUPS design yielded a 24-item tool. In piloting, a total of 552 records were collated from 314 patients, of which 121 (38.5%) had COVID-19. No obvious floor or ceiling effects were apparent. Exploratory factor analysis provided evidence of uni-dimensionality with strong loading on the first principal component accounting for 51% of the variance and Cronbach’s alpha for the full-scale score 0.95 – although a 3-factor solution accounted for a further 21%. The PICUPS was responsive to change both at full scale- and item-level. In general, positive responses were seen regarding the tool’s ability to describe the patients during their clinical course, engage and flag the relevant professionals needed, and to inform what should be included in an RP. CONCLUSIONS: The PICUPS tool has robust scaling properties as a clinical measure and is potentially useful as a tool for identifying rehabilitation needs as patients step down from ICU and acute hospital care

Morphological characteristics of motor neurons do not determine their relative susceptibility to degeneration in a mouse model of severe spinal muscular atrophy

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice - including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA

Narrative explorations into the professional development of lecturers teaching higher education in English further education colleges

The diversification of settings in which higher education is delivered has resulted in a growing proportion of lecturers entering teaching from professional backgrounds. This is a challenging transition as lecturers are rarely given the space to consider the implications of this move on their identities and practice styles. Writing is recognised as a powerful methodology through which individuals can make sense of experiences and conceptualise them in light of historical, theoretical and social perspectives. In this paper we consider the experiences of 10 college lecturers who used writing to explore this transition as part of a professional development initiative to promote their writing skills. They were providing higher education in further education colleges across South West England. This project ran over two years, involving a year-long professional development intervention and a subsequent evaluation. Over this time the lecturers produced a number of written pieces. We present the different styles and forms of writing used, and how these engaged with their emergent voices and growing sense of legitimacy. We highlight how writing can provide a reflexive medium and assist in the identification of developmental goals, something particularly valuable during professional transitions

Economic evaluations of onchocerciasis interventions: a systematic review and research needs

Objective To provide a systematic review of economic evaluations that has been conducted for onchocerciasis interventions, to summarise current key knowledge and to identify research gaps. Method A systematic review of the literature was conducted on the 8th of August 2018 using the PubMed (MEDLINE) and ISI Web of Science electronic databases. No date or language stipulations were applied to the searches. Results We identified 14 primary studies reporting the results of economic evaluations of onchocerciasis interventions, seven of which were cost‐effectiveness analyses. The studies identified used a variety of different approaches to estimate the costs of the investigated interventions/programmes. Originally, the studies only quantified the benefits associated with preventing blindness. Gradually, methods improved and also captured onchocerciasis‐associated skin disease. Studies found that eliminating onchocerciasis would generate billions in economic benefits. The majority of the cost‐effectiveness analyses evaluated annual mass drug administration (MDA). The estimated cost per disability‐adjusted life year (DALY) averted of annual MDA varies between US$3 and US$30 (cost year variable). Conclusions The cost benefit and cost effectiveness of onchocerciasis interventions have consistently been found to be very favourable. This finding provides strong evidential support for the ongoing efforts to eliminate onchocerciasis from endemic areas. Although these results are very promising, there are several important research gaps that need to be addressed as we move towards the 2020 milestones and beyond

Perspective from a Younger Generation -- The Astro-Spectroscopy of Gisbert Winnewisser

Gisbert Winnewisser's astronomical career was practically coextensive with the whole development of molecular radio astronomy. Here I would like to pick out a few of his many contributions, which I, personally, find particularly interesting and put them in the context of newer results.Comment: 14 pages. (Co)authored by members of the MPIfR (Sub)millimeter Astronomy Group. To appear in the Proceedings of the 4th Cologne-Bonn-Zermatt-Symposium "The Dense Interstellar Medium in Galaxies" eds. S. Pfalzner, C. Kramer, C. Straubmeier, & A. Heithausen (Springer: Berlin

Randomised controlled trial of a supervised exercise rehabilitation program for colorectal cancer survivors immediately after chemotherapy: study protocol

Background Colorectal cancer (CRC) diagnosis and the ensuing treatments can have a substantial impact on the physical and psychological health of survivors. As the number of CRC survivors increases, so too does the need to develop viable rehabilitation programs to help these survivors return to good health as quickly as possible. Exercise has the potential to address many of the adverse effects of CRC treatment; however, to date, the role of exercise in the rehabilitation of cancer patients immediately after the completion of treatment has received limited research attention. This paper presents the design of a randomised controlled trial which will evaluate the feasibility and efficacy of a 12-week supervised aerobic exercise program (ImPACT Program) on the physiological and psychological markers of rehabilitation, in addition to biomarkers of standard haematological outcomes and the IGF axis. Methods/Design Forty CRC patients will be recruited through oncology clinics and randomised to an exercise group or a usual care control group. Baseline assessment will take place within 4 weeks of the patient completing adjuvant chemotherapy treatment. The exercise program for patients in the intervention group will commence a week after the baseline assessment. The program consists of three supervised moderate-intensity aerobic exercise sessions per week for 12 weeks. All participants will have assessments at baseline (0 wks), mid-intervention (6 wks), post-intervention (12 wks) and at a 6-week follow-up (18 wks). Outcome measures include cardio-respiratory fitness, biomarkers associated with health and survival, and indices of fatigue and quality of life. Process measures are participants' acceptability of, adherence to, and compliance with the exercise program, in addition to the safety of the program. Discussion The results of this study will provide valuable insight into the role of supervised exercise in improving life after CRC. Additionally, process analyses will inform the feasibility of implementing the program in a population of CRC patients immediately after completing chemotherapy

The politics of heroes through the prism of popular heroism

This is the author accepted manuscript. The final version is available from Palgrave Macmillan via the DOI in this record.In modern day Britain, the discourse of national heroification is routinely utilised by politicians, educationalists and cultural industry professionals, whilst also being a popular concept to describe deserving ‘do-gooders’ who contribute to British society in a myriad of ways. We argue that although this heroification discourse is enacted as a discursive device of encouraging politically and morally desirable behaviour, it is dissociated from the largely under-explored facets of contemporary popular heroism. To compensate for this gap, this paper explores public preferences for heroes using survey data representative of British adults. This analysis demonstrates a conceptual stretching in the understanding of heroism, and allows identifying age- and gender-linked dynamics which effect public choices of heroes. In particular, we demonstrate that age above all determines the preference for having a hero, but does not explain preferences for specific hero-types. The focus on gender illustrates that the landscape of popular heroism reproduces a male-dominated bias which exists in the wider political and cultural heroification discourse. Simultaneously, our study shows that if national heroification discourse in Britain remains male-centric, the landscape of popular heroism is characterised by a gendered trend towards privatisation of heroes being particularly prominent amongst women. In the conclusion, this paper argues for a conceptual revision and re-gendering of the national heroification discourse as a step towards both empirically grounded, and age- and gender-sensitive politics of heroes and heroines.AHR

Modulation of NKp30- and NKp46-Mediated Natural Killer Cell Responses by Poxviral Hemagglutinin

Natural killer (NK) cells are an important element in the immune defense against the orthopox family members vaccinia virus (VV) and ectromelia virus (ECTV). NK cells are regulated through inhibitory and activating signaling receptors, the latter involving NKG2D and the natural cytotoxicity receptors (NCR), NKp46, NKp44 and NKp30. Here we report that VV infection results in an upregulation of ligand structures for NKp30 and NKp46 on infected cells, whereas the binding of NKp44 and NKG2D was not significantly affected. Likewise, infection with ectromelia virus (ECTV), the mousepox agent, enhanced binding of NKp30 and, to a lesser extent, NKp46. The hemagglutinin (HA) molecules from VV and ECTV, which are known virulence factors, were identified as novel ligands for NKp30 and NKp46. Using NK cells with selectively silenced NCR expression and NCR-CD3ζ reporter cells, we observed that HA present on the surface of VV-infected cells, or in the form of recombinant soluble protein, was able to block NKp30-triggered activation, whereas it stimulated the activation through NKp46. The net effect of this complex influence on NK cell activity resulted in a decreased NK lysis susceptibility of infected cells at late time points of VV infection when HA was expression was pronounced. We conclude that poxviral HA represents a conserved ligand of NCR, exerting a novel immune escape mechanism through its blocking effect on NKp30-mediated activation at a late stage of infection