Syndromic surveillance for influenza in two hospital emergency departments. Relationships between ICD-10 codes and notified cases, before and during a pandemic

<p>Abstract</p> <p>Background</p> <p>Interest in the use of emergency department (ED) data by syndromic surveillance systems to detect influenza outbreaks has been growing. Evaluations of these systems generally focus on events during influenza seasons. The aims of this study were to identify which emergency department disease codes best correlated with confirmed influenza cases and to determine if these same codes would be useful in the non-influenza season. The 2009 influenza pandemic in Victoria, Australia, provided further opportunity to examine the performance of the syndromic surveillance system during this event.</p> <p>Methods</p> <p>We undertook a retrospective analysis of data from the Victorian Department of Health's pilot syndromic surveillance programme, 'SynSurv'. SynSurv automatically captures patient information as it is entered by ED staff. This information includes patient demographics, their presenting symptoms and a preliminary diagnosis using ICD-10 coding. To determine which codes were best correlated with influenza notifications, weekly counts for each of the ICD-10 diagnosis codes ever used in the dataset were calculated and compared with the corresponding weekly count of confirmed influenza cases. Correlations between these codes and confirmed influenza cases in the non-influenza season were then undertaken. The data covered the period from July 2001 until August 2009 and included the 2009 influenza pandemic.</p> <p>Results</p> <p>There was a marked increase in weekly counts of both laboratory-confirmed influenza cases and relevant ICD-10 codes during the influenza pandemic period. The increase in laboratory confirmed cases was more than four times greater than the previous highest number reported, in 2007, even though the influenza-like-illness activity in the community was considered comparable to 2003 and 2007. We found five ICD-10 codes to be moderately and significantly correlated with influenza cases. None of these codes was correlated with laboratory confirmed influenza notifications outside the influenza season, at least in part because of the small number of influenza cases notified during that period.</p> <p>Conclusions</p> <p>This study suggests that the choice of codes made by ED staff to record a case of influenza-like illness is influenced by their perceptions of how much influenza is circulating at the time. The ability of syndromic surveillance to detect outbreaks early may be impeded because case diagnosis is influenced by what ED staff believes to be occurring in the community.</p

An analytic model of the Gruneisen parameter at all densities

We model the density dependence of the Gruneisen parameter as gamma(rho) = 1/2 + gamma_1/rho^{1/3} + gamma_2/rho^{q}, where gamma_1, gamma_2, and q>1 are constants. This form is based on the assumption that gamma is an analytic function of V^{1/3}, and was designed to accurately represent the experimentally determined low-pressure behavior of gamma. The numerical values of the constants are obtained for 20 elemental solids. Using the Lindemann criterion with our model for gamma, we calculate the melting curves for Al, Ar, Ni, Pd, and Pt and compare them to available experimental melt data. We also determine the Z (atomic number) dependence of gamma_1. The high-compression limit of the model is shown to follow from a generalization of the Slater, Dugdale-MacDonald, and Vashchenko-Zubarev forms for the dependence of the Gruneisen parameter.Comment: 14 Pages, LaTeX, 5 eps figues; changes in the tex

Overcoming the challenges and complexities of researching a vulnerable population within a palliative care context

While previous studies have investigated sleep issues in chronic illness and the effectiveness of Cognitive Behavioral Therapy for Insomnia (CBT-I), this has not been examined within palliative care. High rates of sleep difficulties have been found in patients receiving palliative care. We aimed to explore the practical feasibility of implementing CBT-I among palliative patients using techniques such as stimulus control therapy, progressive muscle relaxation and guided imagery/thought blocking. However, issues such as the intervention protocols being relatively labor intensive and time consuming for participants that were receiving palliative care, involving completion of daily diaries and quantitative outcome measures, led to high non-completion rates among participants. Consequently, a shift in methodology was required and a qualitative approach was adopted to explore participants’ experiences of sleep disturbance within palliative care. The aim was to gain an in-depth understanding of the specific issues and challenges within palliative care that impacted on sleep. Focus groups were conducted with patients, informal carers and hospice staff who all described how they experienced sleep difficulties. This provided a broader understanding of insomnia from multiple perspectives within palliative care. Furthermore, it helped inform how we will go about designing future studies in CBT-I in palliative care; having illuminated the appropriate adaptions required to current protocols. This case study will discuss the complexities and ethical issues we faced at each stage of the research process and how adopting both quantitative and qualitative approaches helped provide useful insights that will inform future research

Experimentally integrated dynamic modelling for intuitive optimisation of cell based processes and manufacture

Dynamic mechanistic modelling of cell culture is a key tool in bioprocess development to support optimisation and risk assessment. However, the approach is underutilised in the bioprocess industry due to challenges including lack of accessible tools to support a structured approach, the difficulty of realising computationally tractable (low parameter) yet realistic models, and the specialised skill sets required. We have proposed that these issues could be partly addressed by developing a parsimonious framework comprising a set of model building blocks, based on the ordinary differential equation modelling paradigm, representing common cell culture dynamics and modulation thereof. The framework is designed to avoid obvious pathological behaviours. Further, specific model instances within the framework can be simply visualised as a directed graph with vertices representing system species, dynamics and modulations, and arcs representing the interactions between them. The directed graph can be extended to describe the timing and nature of experimental interventions. A visual and intuitive route to describing models with an associated mathematical framework enables realisation in a software interface and integration with standard mathematical tools such as those for sensitivity analysis and parameter estimation. Such a framework is sufficient to represent some of the simple mechanisms underpinning bioprocesses that nonetheless lead to highly non-linear and counterintuitive outcomes. It also has a relatively low learning burden for users without formal mathematical training. The concept could be extended to include, for example, partial differential equation-based approaches to stochastic or spatially complex systems built up from a small number of parametrically parsimonious and well-behaved building blocks

Enabling human pluripotent stem cell derived megakaryocyte

Annually 4.5 million platelet units are transfused in Europe and the United States. These are obtained solely from allogeneic donations and have a shelf life of 5-7 days. To address the corresponding supply challenge, Moreau et al. have devised a novel process for producing megakaryocytes (MKs, the platelet precursor cell) in vitro. A transcription-factor driven, forward-programming approach converts human pluripotent stem cells into MKs. This strategy has the unique advantage of generating high yields of pure MKs in chemically defined medium through the establishment of 2-3 month long-term cultures. This could lead to the production of a consistent, reliable supply of platelets which overcomes the logistical, financial and biosafety challenges for health organisations worldwide. However to enable commercialisation of platelet manufacture, process optimisation and scale-up are essential. Medium can contribute a significant proportion of the cost of a cell based product. We have used tissue culture flasks to represent static culture and compared this to a scaled-down automated bioreactor system (ambr15, Sartorius) to evaluate feasibility and optimisation factors for the growth of forward programmed (FoP) MKs in scalable stirred-suspension culture. The medium supply and exchange strategy were analysed using high temporal resolution growth curves for three medium exchange regimes. We assessed the productivity of the medium, showing that approximately 1.3 million cells are produced per millilitre of medium. Common metabolites lactate and ammonium were unlikely to be limiting proliferation and only 20% of glucose was depleted. Using novel deterministic modelling software developed by our group, we have constructed a model of forward-programmed MKs growth. Based on inhibitor production, the model demonstrates the most efficient expansion strategy using the exchange strategies and observed growth characteristics of proliferating populations. Cell populations were identified using flow cytometry and phenotype analysis. This type of mechanistic modelling can be used to inform and optimise manufacturing strategy for scaled production of FoPMKs for platelet production and more generally for the manufacturing of cell based therapies

GREEN IGUANAS (\u3ci\u3eIGUANA IGUANA\u3c/i\u3e): THE UNINTENDED CONSEQUENCE OF SOUND WILDLIFE MANAGEMENT PRACTICES IN A SOUTH FLORIDA PARK

We examined the demographic response of the Green Iguana (Iguana iguana) to the removal of Raccoons in an urban maritime state park in southern Florida. The rapid growth of iguanas to sexual maturity in an underexploited, if not vacant, niche contributed to the rapid recruitment of a large and growing population during the four and one half years since removal of its limiting predator. We proffer here that at sites where Green Iguanas and high density Raccoons are syntopic, future Raccoon removal programs should be concurrent with an equally concerted effort to remove resident Green Iguanas. In this fashion, by replacing one limiting predator with another, a population explosion can be prevented and an advantage can be maintained in the local control of this exotic species

Application of quality by design tools to upstream processing of platelet precursor cells to enable in vitro manufacture of blood products

Annually 4.5 million platelet units are transfused in Europe and the United States. These are obtained solely from allogeneic donations and have a shelf life of 5-7 days. To address the corresponding supply challenge, Moreau et al.1 devised a novel process for producing megakaryocytes (MKs, the platelet precursor cell) in vitro. A transcription-factor driven, forward-programming (FOP) approach converts human pluripotent stem cells into MKs. This strategy has the unique advantage of generating high yields of pure MKs in chemically defined medium which could lead to the production of a consistent, reliable supply of platelets which overcomes the logistical, financial and biosafety challenges for health organisations worldwide. Here we follow a Quality by Design (QbD) approach to enable improvements to the upstream processing of FOPMKs. Firstly, we created a process flow diagram for production of in vitro platelets for transfusion, which segregated processes into individual unit operations for control and optimisation. Next, we developed a Quality Target Product Profile (QTPP) and identified Critical Quality Attributes (CQAs) for each stage. We conducted a range of experiments utilising Design of Experiments (DOE) and mechanistic modelling2 tools to link Critical Process Parameters (CPPs) to CQAs. For adherent culture, we identified a productivity limit related to surface area available for growth and a cell loss phase which was dependent on cell seeding density, RhoK inhibitor usage and seed density. Using suspension cultures of FOPMK. We noted that TPO and Doxycycline concentration were CPPs as these impacted cell net growth rate and phenotype trajectory. Furthermore, we noted that medium exhaustion led to a 30% loss of viable cells over 8 hours. Proof of concept studies also showed that FOPMKs can be cultured in scaled-down suspension systems (ambr-15 and spinner flask culture) whilst retaining CQAs. 1. Moreau, T. et al. Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming. Nat. Commun. 7, 1–15 (2016). 2. Stacey, A. J., Cheeseman, E. A., Glen, K. E., Moore, R. L. L. & Thomas, R. J. Experimentally integrated dynamic modelling for intuitive optimisation of cell-based processes and manufacture. Biochem. Eng. J. 132, 130–138 (2018)