Modelling Immunological Memory

Accurate immunological models offer the possibility of performing highthroughput experiments in silico that can predict, or at least suggest, in vivo phenomena. In this chapter, we compare various models of immunological memory. We first validate an experimental immunological simulator, developed by the authors, by simulating several theories of immunological memory with known results. We then use the same system to evaluate the predicted effects of a theory of immunological memory. The resulting model has not been explored before in artificial immune systems research, and we compare the simulated in silico output with in vivo measurements. Although the theory appears valid, we suggest that there are a common set of reasons why immunological memory models are a useful support tool; not conclusive in themselves

Modelling Immunological Memory

Accurate immunological models offer the possibility of performing highthroughput experiments in silico that can predict, or at least suggest, in vivo phenomena. In this chapter, we compare various models of immunological memory. We first validate an experimental immunological simulator, developed by the authors, by simulating several theories of immunological memory with known results. We then use the same system to evaluate the predicted effects of a theory of immunological memory. The resulting model has not been explored before in artificial immune systems research, and we compare the simulated in silico output with in vivo measurements. Although the theory appears valid, we suggest that there are a common set of reasons why immunological memory models are a useful support tool; not conclusive in themselves

Timing the evolution of antioxidant enzymes in cyanobacteria

How early photosynthesizers managed oxidative stress remains relatively unresolved. Analyses of enzymes dealing with reactive oxygen species traces the evolutionary history of superoxide dismutases and finds evidence of CuZnSOD in the ancestor of all cyanobacteria, dating back to the Archaean

Esophageal Clearance Patterns in Normal Older Adults as Documented with Videofluoroscopic Esophagram

Normal esophageal bolus transport in asymptomatic healthy older adults has not been well defined, potentially leading to ambiguity in differentiating esophageal swallowing patterns of dysphagic and healthy individuals. This pilot study of 24 young (45–64 years) and old (65+years) men and women was designed to assess radiographic esophageal bolus movement patterns in healthy adults using videofluoroscopic recording. Healthy, asymptomatic adults underwent videofluoroscopic esophagram to evaluate for the presence of ineffective esophageal clearance, namely, intraesophageal stasis and intraesophageal reflux. Intraesophageal stasis and intraesophageal reflux were visualized radiographically in these normal subjects. Intraesophageal stasis occurred significantly more frequently with semisolid (96%) compared with liquid (16%) barium, suggesting that a variety of barium consistencies, as opposed to only the traditional fluids, would better define the spectrum of esophageal transport. Intraesophageal reflux was observed more frequently in older males than in their younger counterparts. The rates of intraesophageal stasis and intraesophageal reflux were potentially high given that successive bolus presentations were spaced 10 seconds apart. These findings suggest a need for a more comprehensive definition regarding the range of normal esophageal bolus transport to (a) prevent misdiagnosis of dysphagia and (b) to enhance generalization to functional eating, which involves solid foods in addition to liquids

Gaining user insights into the research-to-operational elements of Impact-based Forecasting (IbF) from within the SHEAR programme : summary of findings

Impact based Forecasting (IbF) is an expanding and evolving area of research within National Meteorological and Hydrological Services (NMHSs) and the humanitarian sector, with a broad aim to enhance communication and timely action to reduce losses associated with natural hazards. Although the principles of IbF may seem new to some disciplines, they leverage knowledge built over several years within the risk and emergency management communities (Smith, 2013) and therefore although its application may be newer to some disciplines, many of the principles and practices are based on existing risk theory concepts. However, a key advance of IbF is the pull-through of these concepts into implementable prototypes, tools and services and in order to do this, a growth in interdisciplinary working. The World Meteorological Organisation (WMO), as well as global Non-Governmental Organisations (e.g. Red Cross Red Crescent) strongly advocate for a shift towards IbF and have developed supporting guidelines (WMO, 2015a; Red Cross Climate Centre, 2020; WMO, 2021) to enhance implementation of such techniques across the globe. In doing this the WMO have distinguished two main types of IbF, subjective and objective. A subjective IbF relies on expert interpretation to provide the impact-based elements to a forecast or warning, whilst an objective IbF utilises vulnerability and exposure datasets, together with hazard information to calculate the risk and/or impacts. It is noted however, that risk assessments almost always utilise a combination of both subjective and objective methods. There are a wide range of dependencies on how an IbF system might evolve, and it is these dependencies which have introduced variety into the approaches and methods used to generate impact-based forecasts and warnings. This variability is also driven by different interpretations of what IbF should provide. Some stakeholders desire to have information on the number of assets or people that might be affected; however, most IbF warnings systems currently provide categorical risk forecasts (i.e. very low, low, medium and high) with supporting generalised impact information. Although the difference between these styles of output may appear subtle it can have significant implications for the development of forecasting and warning applications and the upstream modelling requirements. IbF has rapidly become an umbrella term under which a plethora of methods are being tried and different disciplines engaged. This broad scope is beneficial for research as it enables blue-sky thinking, transdisciplinary research opportunities and ideally, sustained cooperation and collaboration between a wide range of groups (e.g. stakeholders, researchers, technologists, practitioners, decision-makers). However, these same benefits can pose challenges when moving towards operational implementation, particularly for NMHSs with reduced institutional capacities. It should also be noted that the term IbF is linked to a range of other activities and terminologies, including forecast-based action and forecast-based financing (FbF). The lens through which IbF is viewed therefore influences its role and the value it might provide in meeting the objective ‘to enhance usability by making forecasts and warnings more actionable’. Given the growing scope of IbF and the potential challenges this may have for implementation, this research aims to answer the following questions: (1) Is there a shared understanding of what IbF is across individuals involved in its development? (2) Is there a shared perception of the challenges, barriers and opportunities associated with implementing IbF operationally? To accomplish this aim, practitioners, forecasters and researchers, working within the NERC Science for Humanitarian Emergencies and Resilience (SHEAR) Programme, were invited to provide their perspectives on a range of IbF related topics through a set of semi-structured interviews. This report provides a synthesis of the interviewee transcripts from key informant interviews. In section 2 the methodology is described, while section 3 provides a review of the key findings from the complete set of interviews. The final section (section 4) provides recommendations and concluding remarks

Are Kenya Meteorological Department heavy rainfall advisories useful for forecast-based early action and early preparedness for flooding?

Preparedness saves lives. Forecasts can help improve preparedness by triggering early actions as part of pre-defined protocols under the Forecast-based Financing (FbF) approach; however it is essential to understand the skill of a forecast before using it as a trigger. In order to support the development of early-action protocols over Kenya, we evaluate the 33 heavy rainfall advisories (HRAs) issued by the Kenya Meteorological Department (KMD) during 2015–2019. The majority of HRAs warn counties which subsequently receive heavy rainfall within the forecast window. We also find a significant improvement in the advisory ability to anticipate flood events over time, with particularly high levels of skill in recent years. For instance actions with a 2-week lifetime based on advisories issued in 2015 and 2016 would have failed to anticipate nearly all recorded flood events in that period, whilst actions in 2019 would have anticipated over 70 % of the instances of flooding at the county level. When compared against the most significant flood events over the period which led to significant loss of life, all three such periods during 2018 and 2019 were preceded by HRAs, and in these cases the advisories accurately warned the specific counties for which significant impacts were recorded. By contrast none of the four significant flooding events in 2015–2017 were preceded by advisories. This step change in skill may be due to developing forecaster experience with synoptic patterns associated with extremes as well as access to new dynamical prediction tools that specifically address extreme event probability; for example, KMD access to the UK Met Office Global Hazard Map was introduced at the end of 2017. Overall we find that KMD HRAs effectively warn of heavy rainfall and flooding and can be a vital source of information for early preparedness. However a lack of spatial detail on flood impacts and broad probability ranges limit their utility for systematic FbF approaches. We conclude with suggestions for making the HRAs more useful for FbF and outline the developing approach to flood forecasting in Kenya

Getting the right balance: insole design alters the static balance of people with diabetes and neuropathy

BACKGROUND: Over 1 in 3 older people with diabetes sustain a fall each year. Postural instability has been identified as independent risk factor for falls within people with Diabetic Peripheral Neuropathy (DPN). People with DPN, at increased risk of falls, are routinely required to wear offloading insoles, yet the impact of these insoles on postural stability and postural control is unknown. The aim of this study was to evaluate the effect of a standard offloading insole and its constituent parts on the balance in people with DPN. METHODS: A random sample of 50 patients with DPN were observed standing for 3 × 30 s, and stepping in response to a light, under five conditions presented in a random order; as defined by a computer program; 1) no insole, 2) standard diabetic: a standard offloading insole made from EVA/poron®, and three other insoles with one design component systematically altered 3) flat: diabetic offloading insole with arch fill removed, 4) low resilient memory: diabetic offloading insole with the cover substituted with low resilience memory V9, 5) textured: diabetic offloading insole with a textured PVC surface added (Algeos Ltd). After each condition participants self-rated perceived steadiness. RESULTS: Insole design effected static balance and balance perception, but not stepping reaction time in people with DPN. The diabetic and memory shaped insoles (with arch fill) significantly increased centre of pressure velocity (14 %, P = 0.006), (13 %, P = 0.001), and path length (14 %, P = 0.006), (13 %, P = 001), when compared to the no insole condition. The textured shaped and flat soft insole had no effect on static balance when compared to the no insole condition (P > 0.05). CONCLUSION: Insoles have an effect on static balance but not stepping reaction time. This effect is independent of neuropathy severity. The addition of a textured cover seems to counter the negative effect of an arch fill, even in participants with severe sensation loss. Static balance is unaffected by material softness or resilience. Current best practice of providing offloading insoles, with arch fill, to increase contact area and reduce peak pressure could be making people more unstable. Whilst flat, soft insoles maybe the preferable design option for those with poor balance. There is a need to develop an offloading insole that can reduce diabetic foot ulcer risk, without compromising balance

Memories from VII World Congress of Music Therapy, Vitoria Gasteiz, 1993

Some of the participants share their memories and photos from the VII World Congress of Music Therapy, held in Vitoria-Gasteiz, Spain in 1993

NMR metabolomics of cerebrospinal fluid differentiates inflammatory diseases of the central nervous system

BACKGROUND: Myriad infectious and noninfectious causes of encephalomyelitis (EM) have similar clinical manifestations, presenting serious challenges to diagnosis and treatment. Metabolomics of cerebrospinal fluid (CSF) was explored as a method of differentiating among neurological diseases causing EM using a single CSF sample. METHODOLOGY/PRINCIPAL FINDINGS: 1H NMR metabolomics was applied to CSF samples from 27 patients with a laboratory-confirmed disease, including Lyme disease or West Nile Virus meningoencephalitis, multiple sclerosis, rabies, or Histoplasma meningitis, and 25 controls. Cluster analyses distinguished samples by infection status and moderately by pathogen, with shared and differentiating metabolite patterns observed among diseases. CART analysis predicted infection status with 100% sensitivity and 93% specificity. CONCLUSIONS/SIGNIFICANCE: These preliminary results suggest the potential utility of CSF metabolomics as a rapid screening test to enhance diagnostic accuracies and improve patient outcomes