Discrete Event Simulation for Decision Modeling in Health Care: Lessons from Abdominal Aortic Aneurysm Screening

Markov models are often used to evaluate the cost-effectiveness of new healthcare interventions but they are sometimes not flexible enough to allow accurate modeling or investigation of alternative scenarios and policies. A Markov model previously demonstrated that a one-off invitation to screening for abdominal aortic aneurysm (AAA) for men aged 65 y in the UK and subsequent follow-up of identified AAAs was likely to be highly cost-effective at thresholds commonly adopted in the UK (£20,000 to £30,000 per quality adjusted life-year). However, new evidence has emerged and the decision problem has evolved to include exploration of the circumstances under which AAA screening may be cost-effective, which the Markov model is not easily able to address. A new model to handle this more complex decision problem was needed, and the case of AAA screening thus provides an illustration of the relative merits of Markov models and discrete event simulation (DES) models. An individual-level DES model was built using the R programming language to reflect possible events and pathways of individuals invited to screening v. those not invited. The model was validated against key events and cost-effectiveness, as observed in a large, randomized trial. Different screening protocol scenarios were investigated to demonstrate the flexibility of the DES. The case of AAA screening highlights the benefits of DES, particularly in the context of screening studies

Autism with intellectual disability is associated with increased levels of maternal cytokines and chemokines during gestation.

Immune abnormalities have been described in some individuals with autism spectrum disorders (ASDs) as well as their family members. However, few studies have directly investigated the role of prenatal cytokine and chemokine profiles on neurodevelopmental outcomes in humans. In the current study, we characterized mid-gestational serum profiles of 22 cytokines and chemokines in mothers of children with ASD (N=415), developmental delay (DD) without ASD (N=188), and general population (GP) controls (N=428) using a bead-based multiplex technology. The ASD group was further divided into those with intellectual disabilities (developmental/cognitive and adaptive composite score<70) (ASD+ID, N=184) and those without (composite score⩾70) (ASD-noID, N=201). Levels of cytokines and chemokines were compared between groups using multivariate logistic regression analyses, adjusting for maternal age, ethnicity, birth country and weight, as well as infant gender, birth year and birth month. Mothers of children with ASD+ID had significantly elevated mid-gestational levels of numerous cytokines and chemokines, such as granulocyte macrophage colony-stimulating factor, interferon-γ, interleukin-1α (IL-1α) and IL-6, compared with mothers of children with either ASD-noID, those with DD, or GP controls. Conversely, mothers of children with either ASD-noID or with DD had significantly lower levels of the chemokines IL-8 and monocyte chemotactic protein-1 compared with mothers of GP controls. This observed immunologic distinction between mothers of children with ASD+ID from mothers of children with ASD-noID or DD suggests that the intellectual disability associated with ASD might be etiologically distinct from DD without ASD. These findings contribute to the ongoing efforts toward identification of early biological markers specific to subphenotypes of ASD

Ruptured gallbladder as the first presentation of breast cancer

<p>Abstract</p> <p>Background</p> <p>Perforation of the gall bladder as a first presentation of breast cancer has not been reported.</p> <p>Case presentation</p> <p>Here we present a case of an elderly lady with acute abdomen with evidence of possible perforation of gall bladder on CT scan. Histopathology of the cholecystectomy specimen revealed invasive lobular breast cancer.</p> <p>Her metastatic breast cancer with right sided primary discovered subsequent to her presentation with acute abdomen is managed successfully with Anastrozole.</p> <p>Conclusion</p> <p>We present a rare case of gall bladder perforation from metastatic breast cancer.</p

Magnetic-field-induced charge redistribution in disordered graphene double quantum dots

We have studied the transport properties of a large graphene double quantum dot under the influence of a background disorder potential and a magnetic field. At low temperatures, the evolution of the charge-stability diagram as a function of the B field is investigated up to 10 T. Our results indicate that the charging energy of the quantum dot is reduced, and hence the effective size of the dot increases at a high magnetic field. We provide an explanation of our results using a tight-binding model, which describes the charge redistribution in a disordered graphene quantum dot via the formation of Landau levels and edge states. Our model suggests that the tunnel barriers separating different electron/hole puddles in a dot become transparent at high B fields, resulting in the charge delocalization and reduced charging energy observed experimentally.This work was financially supported by the European GRAND project (ICT/FET, Contract No. 215752) and EPSRC

Do patients and family carers have different concerns about the use of medicines compared with healthcare professionals? A quantitative secondary analysis of healthcare concerns relating to adults with complex needs

OBJECTIVE: To identify concerns related to the use of medicines for adults with complex needs and explore whether these differed between healthcare professionals and patients/carers, in order to inform development of interventions to increase medication adherence. METHODS: A quantitative secondary analysis of a database of healthcare professionals' and patients'/carers' healthcare concerns, related to adults with complex needs. Categories of concerns related to medicines use were identified and concerns related to medication use coded against these. Data were analysed descriptively, and a Chi-square test conducted to test for differences in responses from healthcare professionals versus patients/carers. RESULTS: There was a significant difference in the types of medication concern raised by healthcare professionals versus those raised by patients/carers. Patients/carers expressed more concerns about side effects and interactions; healthcare professionals identified more concerns related to patient support and carers' knowledge/training. CONCLUSION: Healthcare professionals had significantly different concerns about medicines to patients; this may be a potential barrier to medication adherence. PRACTICE IMPLICATIONS: Healthcare professionals may need to adopt an approach to non-adherence that goes beyond education and counselling and adopts a wider patient perspective. Findings suggest that a greater focus on addressing side effects and interactions may be beneficial in increasing medication adherence

Responses of primate LGN cells to moving stimuli involve a constant background modulation by feedback from area MT

The feedback connections from the cortical motion area middle temporal (MT), to layer 6 of the primary visual cortex (V1), have the capacity to drive a cascaded feedback influence from the layer 6 cortico-geniculate cells back to the lateral geniculate nucleus (LGN) relay cells. This introduces the possibility of a re-entrant motion signal affecting the relay of the retinal input through the LGN to the visual cortex. The question is whether the response of LGN cells to moving stimuli involves a component derived from this feedback. By producing a reversible focal pharmacological block of the activity of an MT direction column we show the presence of such an influence from MT on the responses of magno, parvo and koniocellular cells in the macaque LGN. The pattern of effect in the LGN reflects the direction bias of the MT location inactivated. This suggests a moving stimulus is captured by iterative interactions in the circuit formed by visual cortical areas and visual thalamus

Acute Effects of Substitution, and Addition, of Carbohydrates and Fat to Protein on Gastric Emptying, Blood Glucose, Gut Hormones, Appetite, and Energy Intake

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A multi-technique experimental and modelling study of the porous structure of IG-110 and IG-430 nuclear graphite

In nuclear graphite, the wide range of void sizes precludes a full characterisation of pore volume by means of a single technique. A novel multi-technique approach, consisting of pycnometry, low pressure gas adsorption and mercury porosimetry is presented. The approach is validated for two nuclear-grade graphites designed for use in Generation IV nuclear reactors, namely IG-110 and IG-430. Damage and deformation caused to the structure of the graphite by mercury intrusion is estimated by consecutive intrusion experiments. The damage is assumed to be caused by the highest applied pressures of mercury. It is compensated by substituting that part of the percolation curve with one derived from adsorption measurements. The various measurements are inverse modelled in a way which intelligently bridges the size gap between the techniques. The resulting complete non-hierarchical pore structure covers sizes spanning 4 orders of magnitude. The new approach resolves the long standing issues associated with performing porosimetry on graphitic samples, and fills the gap in knowledge for the assessment of multilevel porosity within graphite. As an example of the possible applications of the resulting void network structure, we calculated the air network flow capacity, related to absolute permeability, for the two graphite samples

Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability

Prenatal exposure to the anti-seizure medication sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. First, we assessed the effect of gestational VPA on fetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses which are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied - inbred Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a model of genetic generalized epilepsy, and inbred Non-Epileptic Control rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Fetuses were extracted via C-section on gestational day 21 (one day prior to birth) and fetal brains were snap frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The functional consequences of VPA-induced gene expression were explored using pathway analysis and integration with genetic risk data for psychiatric disease and behavioural traits. The set of genes down-regulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function, and significantly enriched for heritability to human intelligence, schizophrenia and bipolar disorder. Our results provide a mechanistic link between chronic fetal VPA exposure and neurodevelopmental disability mediated by VPA-induced transcriptional dysregulation