Physics of Solar Prominences: II - Magnetic Structure and Dynamics

Observations and models of solar prominences are reviewed. We focus on non-eruptive prominences, and describe recent progress in four areas of prominence research: (1) magnetic structure deduced from observations and models, (2) the dynamics of prominence plasmas (formation and flows), (3) Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and large-scale patterns of the filament channels in which prominences are located. Finally, several outstanding issues in prominence research are discussed, along with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape

Modelling the effects of bacterial cell state and spatial location on tuberculosis treatment: Insights from a hybrid multiscale cellular automaton model

This work was supported by the Medical Research Council [grant number MR/P014704/1] and the PreDiCT-TB consortium (IMI Joint undertaking grant agreement number 115337, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution.If improvements are to be made in tuberculosis (TB) treatment, an increased understanding of disease in the lung is needed. Studies have shown that bacteria in a less metabolically active state, associated with the presence of lipid bodies, are less susceptible to antibiotics, and recent results have highlighted the disparity in concentration of different compounds into lesions. Treatment success therefore depends critically on the responses of the individual bacteria that constitute the infection. We propose a hybrid, individual-based approach that analyses spatio-temporal dynamics at the cellular level, linking the behaviour of individual bacteria and host cells with the macroscopic behaviour of the microenvironment. The individual elements (bacteria, macrophages and T cells) are modelled using cellular automaton (CA) rules, and the evolution of oxygen, drugs and chemokine dynamics are incorporated in order to study the effects of the microenvironment in the pathological lesion. We allow bacteria to switch states depending on oxygen concentration, which affects how they respond to treatment. This is the first multiscale model of its type to consider both oxygen-driven phenotypic switching of the Mycobacterium tuberculosis and antibiotic treatment. Using this model, we investigate the role of bacterial cell state and of initial bacterial location on treatment outcome. We demonstrate that when bacteria are located further away from blood vessels, less favourable outcomes are more likely, i.e. longer time before infection is contained/cleared, treatment failure or later relapse. We also show that in cases where bacteria remain at the end of simulations, the organisms tend to be slower-growing and are often located within granulomas, surrounded by caseous material.Publisher PDFPeer reviewe

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Costs and Its Determinants in Pituitary Tumour Surgery

PurposeValue-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice we evaluated healthcare costs and cost drivers in perioperative care for pituitary tumour patients. MethodsWe retrospectively assessed financial and clinical data for surgical treatment up to the first year after surgery of pituitary tumour patients treated between 2015 and 2018 in a Dutch tertiary referral centre. Multivariable regression analyses were performed to identify determinants of higher costs. Results271 patients who underwent surgery were included. Mean total costs (SD) were euro16339 (13573) per patient, with the following cost determinants: surgery time (euro62 per minute; 95% CI: 50, 74), length of stay (euro1331 per day; 95% CI 1139, 1523), admission to higher care unit (euro12154 in total; 95% CI 6413, 17895), emergency surgery (euro10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (euro14232; 95% CI 9667, 18797). Intradural (euro7128; 95% CI 10421, 23836) and combined transsphenoidal/transcranial surgery (B: 38494; 95% CI 29191, 47797) were associated with higher costs than standard. Further, higher costs were found in these baseline conditions: Rathke's cleft cyst (euro9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (euro19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (euro14613; 95% CI 7613, 21613) and dependent functional status (euro12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were euro8879 (3210) and with complications euro17551 (14250). ConclusionsLength of hospital stay, and complications are the main drivers of costs in perioperative pituitary tumour healthcare as were some baseline features, e.g. larger tumors, cysts and dependent functional status. Costs analysis may correspond with healthcare resource utilization and guide further individualized care path development and capacity planning.Metabolic health: pathophysiological trajectories and therap

Costs and Its Determinants in Pituitary Tumour Surgery

PurposeValue-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice we evaluated healthcare costs and cost drivers in perioperative care for pituitary tumour patients. MethodsWe retrospectively assessed financial and clinical data for surgical treatment up to the first year after surgery of pituitary tumour patients treated between 2015 and 2018 in a Dutch tertiary referral centre. Multivariable regression analyses were performed to identify determinants of higher costs. Results271 patients who underwent surgery were included. Mean total costs (SD) were euro16339 (13573) per patient, with the following cost determinants: surgery time (euro62 per minute; 95% CI: 50, 74), length of stay (euro1331 per day; 95% CI 1139, 1523), admission to higher care unit (euro12154 in total; 95% CI 6413, 17895), emergency surgery (euro10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (euro14232; 95% CI 9667, 18797). Intradural (euro7128; 95% CI 10421, 23836) and combined transsphenoidal/transcranial surgery (B: 38494; 95% CI 29191, 47797) were associated with higher costs than standard. Further, higher costs were found in these baseline conditions: Rathke's cleft cyst (euro9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (euro19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (euro14613; 95% CI 7613, 21613) and dependent functional status (euro12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were euro8879 (3210) and with complications euro17551 (14250). ConclusionsLength of hospital stay, and complications are the main drivers of costs in perioperative pituitary tumour healthcare as were some baseline features, e.g. larger tumors, cysts and dependent functional status. Costs analysis may correspond with healthcare resource utilization and guide further individualized care path development and capacity planning