An update on emerging drugs for asthma

Peer reviewedPreprin

Allergic Rhinitis and its Associated Co-Morbidities at Bugando Medical Centre in Northwestern Tanzania; A Prospective Review of 190 Cases.

Allergic rhinitis is one of the commonest atopic diseases which contribute to significant morbidity world wide while its epidemiology in Tanzania remains sparse. There was paucity of information regarding allergic rhinitis in our setting; therefore it was important to conduct this study to describe our experience on allergic rhinitis, associated co-morbidities and treatment outcome in patients attending Bugando Medical Centre. This was descriptive cross-sectional study involving all patients with a clinical diagnosis of allergic rhinitis at Bugando Medical Centre over a three-month period between June 2011 and August 2011. Data was collected using a pre-tested coded questionnaire and analyzed using SPSS statistical computer software version 17.0. A total of 190 patients were studied giving the prevalence of allergic rhinitis 14.7%. The median age of the patients was 8.5 years. The male to female ratio was 1:1. Adenoid hypertrophy, tonsillitis, hypertrophy of inferior turbinate, nasal polyps, otitis media and sinusitis were the most common co-morbidities affecting 92.6% of cases and were the major reason for attending hospital services. Sleep disturbance was common in children with adenoids hypertrophy (χ2 = 28.691, P = 0.000). Allergic conjunctivitis was found in 51.9%. The most common identified triggers were dust, strong perfume odors and cold weather (P < 0.05). Strong perfume odors affect female than males (χ2 = 4.583, P = 0.032). In this study family history of allergic rhinitis was not a significant risk factor (P =0.423). The majority of patients (68.8%) were treated surgically for allergic rhinitis co morbidities. Post operative complication and mortality rates were 2.9% and 1.6% respectively. The overall median duration of hospital stay of in-patients was 3 days (2 - 28 days). Most patients (98.4%) had satisfactory results at discharge. The study shows that allergic rhinitis is common in our settings representing 14.7% of all otorhinolaryngology and commonly affecting children and adolescent. Sufferers seek medical services due to co-morbidities of which combination of surgical and medical treatment was needed. High index of suspicions in diagnosing allergic rhinitis and early treatment is recommended

Fredholmness of Toeplitz operators on the Fock space

The Fredholm property of Toeplitz operators on the $p$-Fock spaces $F_\alpha^p$ on $\mathbb{C}^n$ is studied. A general Fredholm criterion for arbitrary operators from the Toeplitz algebra $\mathcal{T}_{p,\alpha}$ on $F_\alpha^p$ in terms of the invertibility of limit operators is derived. This paper is based on previous work, which establishes corresponding results on the unit balls $\mathbb{B}^n$

Implementation of GIS-Based Applications in Water Governance

__Abstract__ Geographical Information Systems (GIS) are computer programs that are able to bring large amounts of data of both the physical and the social system together in one comprehensive overview shown digitally. GIS occurred very rapidly on the Dutch policy agenda. In this paper we analyze how the fast introduction process of GIS-based instruments in water management and more specifically in river flood management can be explained. By applying a range of classical models on agenda-setting, we show the important contribution of GIS to the water and flood issue in current spatial planning and policy development in the Netherland

Measuring productivity and efficiency: a Kalman filter approach

In the Kalman filter setting, one can model the inefficiency term of the standard stochastic frontier composed error as an unobserved state. In this study a panel data version of the local level model is used for estimating time-varying efficiencies of firms. We apply the Kalman filter to estimate average efficiencies of U.S. airlines and find that the technical efficiency of these carriers did not improve during the period 1999-2009. During this period the industry incurred substantial losses, and the efficiency gains from reorganized networks, code-sharing arrangements, and other best business practices apparently had already been realized

Diminution of Voltage Threshold Plays a Key Role in Determining Recruitment of Oculomotor Nucleus Motoneurons during Postnatal Development

The size principle dictates the orderly recruitment of motoneurons (Mns). This principle assumes that Mns of different sizes have a similar voltage threshold, cell size being the crucial property in determining neuronal recruitment. Thus, smaller neurons have higher membrane resistance and require a lower depolarizing current to reach spike threshold. However, the cell size contribution to recruitment in Mns during postnatal development remains unknown. To investigate this subject, rat oculomotor nucleus Mns were intracellularly labeled and their electrophysiological properties recorded in a brain slice preparation. Mns were divided into 2 age groups: neonatal (1–7 postnatal days, n = 14) and adult (20–30 postnatal days, n = 10). The increase in size of Mns led to a decrease in input resistance with a strong linear relationship in both age groups. A well-fitted inverse correlation was also found between input resistance and rheobase in both age groups. However, input resistance versus rheobase did not correlate when data from neonatal and adult Mns were combined in a single group. This lack of correlation is due to the fact that decrease in input resistance of developing Mns did not lead to an increase in rheobase. Indeed, a diminution in rheobase was found, and it was accompanied by an unexpected decrease in voltage threshold. Additionally, the decrease in rheobase co-varied with decrease in voltage threshold in developing Mns. These data support that the size principle governs the recruitment order in neonatal Mns and is maintained in adult Mns of the oculomotor nucleus; but during postnatal development the crucial property in determining recruitment order in these Mns was not the modifications of cell size-input resistance but of voltage threshold

Automated Detection of External Ventricular and Lumbar Drain-Related Meningitis Using Laboratory and Microbiology Results and Medication Data

OBJECTIVE: Monitoring of healthcare-associated infection rates is important for infection control and hospital benchmarking. However, manual surveillance is time-consuming and susceptible to error. The aim was, therefore, to develop a prediction model to retrospectively detect drain-related meningitis (DRM), a frequently occurring nosocomial infection, using routinely collected data from a clinical data warehouse. METHODS: As part of the hospital infection control program, all patients receiving an external ventricular (EVD) or lumbar drain (ELD) (2004 to 2009; n = 742) had been evaluated for the development of DRM through chart review and standardized diagnostic criteria by infection control staff; this was the reference standard. Children, patients dying <24 hours after drain insertion or with <1 day follow-up and patients with infection at the time of insertion or multiple simultaneous drains were excluded. Logistic regression was used to develop a model predicting the occurrence of DRM. Missing data were imputed using multiple imputation. Bootstrapping was applied to increase generalizability. RESULTS: 537 patients remained after application of exclusion criteria, of which 82 developed DRM (13.5/1000 days at risk). The automated model to detect DRM included the number of drains placed, drain type, blood leukocyte count, C-reactive protein, cerebrospinal fluid leukocyte count and culture result, number of antibiotics started during admission, and empiric antibiotic therapy. Discriminatory power of this model was excellent (area under the ROC curve 0.97). The model achieved 98.8% sensitivity (95% CI 88.0% to 99.9%) and specificity of 87.9% (84.6% to 90.8%). Positive and negative predictive values were 56.9% (50.8% to 67.9%) and 99.9% (98.6% to 99.9%), respectively. Predicted yearly infection rates concurred with observed infection rates. CONCLUSION: A prediction model based on multi-source data stored in a clinical data warehouse could accurately quantify rates of DRM. Automated detection using this statistical approach is feasible and could be applied to other nosocomial infections

Transient integral boundary layer method to calculate the translesional pressure drop and the fractional flow reserve in myocardial bridges

BACKGROUND: The pressure drop – flow relations in myocardial bridges and the assessment of vascular heart disease via fractional flow reserve (FFR) have motivated many researchers the last decades. The aim of this study is to simulate several clinical conditions present in myocardial bridges to determine the flow reserve and consequently the clinical relevance of the disease. From a fluid mechanical point of view the pathophysiological situation in myocardial bridges involves fluid flow in a time dependent flow geometry, caused by contracting cardiac muscles overlying an intramural segment of the coronary artery. These flows mostly involve flow separation and secondary motions, which are difficult to calculate and analyse. METHODS: Because a three dimensional simulation of the haemodynamic conditions in myocardial bridges in a network of coronary arteries is time-consuming, we present a boundary layer model for the calculation of the pressure drop and flow separation. The approach is based on the assumption that the flow can be sufficiently well described by the interaction of an inviscid core and a viscous boundary layer. Under the assumption that the idealised flow through a constriction is given by near-equilibrium velocity profiles of the Falkner-Skan-Cooke (FSC) family, the evolution of the boundary layer is obtained by the simultaneous solution of the Falkner-Skan equation and the transient von-Kármán integral momentum equation. RESULTS: The model was used to investigate the relative importance of several physical parameters present in myocardial bridges. Results have been obtained for steady and unsteady flow through vessels with 0 – 85% diameter stenosis. We compare two clinical relevant cases of a myocardial bridge in the middle segment of the left anterior descending coronary artery (LAD). The pressure derived FFR of fixed and dynamic lesions has shown that the flow is less affected in the dynamic case, because the distal pressure partially recovers during re-opening of the vessel in diastole. We have further calculated the wall shear stress (WSS) distributions in addition to the location and length of the flow reversal zones in dependence on the severity of the disease. CONCLUSION: The described boundary layer method can be used to simulate frictional forces and wall shear stresses in the entrance region of vessels. Earlier models are supplemented by the viscous effects in a quasi three-dimensional vessel geometry with a prescribed wall motion. The results indicate that the translesional pressure drop and the mean FFR compares favourably to clinical findings in the literature. We have further shown that the mean FFR under the assumption of Hagen-Poiseuille flow is overestimated in developing flow conditions

Interaction between Thymidylate Synthase and Its Cognate mRNA in Zebrafish Embryos

Thymidylate synthase (TS), which catalyzes the de novo synthesis of dUMP, is an important target for cancer therapy. In this report, the effects of 5-fluorouracil (5-FU) and ZD1694 on the regulation of TS gene expression were evaluated in zebrafish embryos. Our results revealed that the expression of TS was increased by about six-fold when embryos were treated with 1.0 µM 5-FU and there was a greater than 10-fold increase in the TS protein level after treatment with 0.4 µM ZD1694. Northern blot analysis confirmed that expression of TS mRNA was identical in treated or untreated embryos. Gel shift and immunoprecipitation assays revealed that zebrafish TS was specifically bound with its cognate mRNA in vitro and in vivo. We identified a 20 nt RNA sequence, TS:N20, localized to the 5′-UTR of TS mRNA, which corresponded to nt 13–32; TS:N20 bound to the TS protein with an affinity similar to that of the full-length TS mRNA. The MFold program predicted that TS:N20 formed a stable stem-loop structure similar to that of the cis-acting element found in human TS mRNA. Variant RNAs with either a deletion or mutation in the core motif of TS:N20 were unable to bind to the TS protein. In vitro translation experiments, using the rabbit lysate system, confirmed that zebrafish TS mRNA translation was significantly repressed when an excess amount of TS protein was included in the system. Additionally, a TS stability experiment confirmed that treatment of zebrafish embryos with 5-FU could increase the TS stability significantly, and the half life of TS protein was about 2.7 times longer than in untreated embryos. Our study revealed a structural requirement for the interaction of TS RNA with TS protein. These findings also demonstrated that the increase in TS protein induced by 5-FU occurs at the post-transcriptional level and that increased stability and translation efficiency both contributed to the increase in TS protein levels induced by TS inhibitors