Eigenvalues of higher order Sturm-Liouville boundary value problems with derivatives in nonlinear terms

We shall consider the Sturm-Liouville boundary value problem y(m)(t)+λF(t,y(t),y′(t),…,y(q)(t))=0, t∈(0,1), y(k)(0)=0, 0≤k≤m−3, ζy(m−2)(0)−θy(m−1)(0)=0, ρy(m−2)(1)+δy(m−1)(1)=0 where m≥3, 1≤q≤m−2, and λ>0. It is noted that the boundary value problem considered has a derivative-dependent nonlinear term, which makes the investigation much more challenging. In this paper we shall develop a new technique to characterize the eigenvalues λ so that the boundary value problem has a positive solution. Explicit eigenvalue intervals are also established. Some examples are included to dwell upon the usefulness of the results obtained.Published versio

Is It Time to Phase Out the Austin Moore Hemiarthroplasty? A Propensity Score Matched Case Control Comparison versus Cemented Hemiarthroplasty

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Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Identification of novel macrolides with antibacterial, anti-inflammatory and type I and III IFN-augmenting activity in airway epithelium

BACKGROUND: Exacerbations of asthma and COPD are triggered by rhinoviruses. Uncontrolled inflammatory pathways, pathogenic bacterial burden and impaired antiviral immunity are thought to be important factors in disease severity and duration. Macrolides including azithromycin are often used to treat the above diseases, but exhibit variable levels of efficacy. Inhaled corticosteroids are also readily used in treatment, but may lack specificity. Ideally, new treatment alternatives should suppress unwanted inflammation, but spare beneficial antiviral immunity. METHODS: In the present study, we screened 225 novel macrolides and tested them for enhanced antiviral activity against rhinovirus, as well as anti-inflammatory activity and activity against Gram-positive and Gram-negative bacteria. Primary bronchial epithelial cells were grown from 10 asthmatic individuals and the effects of macrolides on rhinovirus replication were also examined. Another 30 structurally similar macrolides were also examined. RESULTS: The oleandomycin derivative Mac5, compared with azithromycin, showed superior induction (up to 5-fold, EC50 = 5-11 μM) of rhinovirus-induced type I IFNβ, type III IFNλ1 and type III IFNλ2/3 mRNA and the IFN-stimulated genes viperin and MxA, yet had no effect on IL-6 and IL-8 mRNA. Mac5 also suppressed rhinovirus replication at 48 h, proving antiviral activity. Mac5 showed antibacterial activity against Gram-positive Streptococcus pneumoniae; however, it did not have any antibacterial properties compared with azithromycin when used against Gram-negative Escherichia coli (as a model organism) and also the respiratory pathogens Pseudomonas aeruginosa and non-typeable Haemophilus influenzae. Further non-toxic Mac5 derivatives were identified with various anti-inflammatory, antiviral and antibacterial activities. CONCLUSIONS: The data support the idea that macrolides have antiviral properties through a mechanism that is yet to be ascertained. We also provide evidence that macrolides can be developed with anti-inflammatory, antibacterial and antiviral activity and show surprising versatility depending on the clinical need

Reconstruction of epidemic curves for pandemic influenza A (H1N1) 2009 at city and sub-city levels

To better describe the epidemiology of influenza at local level, the time course of pandemic influenza A (H1N1) 2009 in the city of Hong Kong was reconstructed from notification data after decomposition procedure and time series analysis. GIS (geographic information system) methodology was incorporated for assessing spatial variation. Between May and September 2009, a total of 24415 cases were successfully geocoded, out of 25473 (95.8%) reports in the original dataset. The reconstructed epidemic curve was characterized by a small initial peak, a nadir followed by rapid rise to the ultimate plateau. The full course of the epidemic had lasted for about 6 months. Despite the small geographic area of only 1000 Km2, distinctive spatial variation was observed in the configuration of the curves across 6 geographic regions. With the relatively uniform physical and climatic environment within Hong Kong, the temporo-spatial variability of influenza spread could only be explained by the heterogeneous population structure and mobility patterns. Our study illustrated how an epidemic curve could be reconstructed using regularly collected surveillance data, which would be useful in informing intervention at local levels

Late diagnosed necrotizing fasciitis as a cause of multiorgan dysfunction syndrome: A case report

Necrotizing fasciitis is a rapidly progressive, life-threatening soft tissue bacterial infection. We present a serious case of a 43-year-old male who suffered from necrotizing fasciitis of the left leg in whom a delayed diagnosis caused multiorgan dysfunction

Fractal Analysis Reveals Reduced Complexity of Retinal Vessels in CADASIL

The Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) affects mainly small cerebral arteries and leads to disability and dementia. The relationship between clinical expression of the disease and progression of the microvessel pathology is, however, uncertain as we lack tools for imaging brain vessels in vivo. Ophthalmoscopy is regarded as a window into the cerebral microcirculation. In this study we carried out an ophthalmoscopic examination in subjects with CADASIL. Specifically, we performed fractal analysis of digital retinal photographs. Data are expressed as mean fractal dimension (mean-D), a parameter that reflects complexity of the retinal vessel branching. Ten subjects with genetically confirmed diagnosis of CADASIL and 10 sex and age-matched control subjects were enrolled. Fractal analysis of retinal digital images was performed by means of a computer-based program, and the data expressed as mean-D. Brain MRI lesion volume in FLAIR and T1-weighted images was assessed using MIPAV software. Paired t-test was used to disclose differences in mean-D between CADASIL and control groups. Spearman rank analysis was performed to evaluate potential associations between mean-D values and both disease duration and disease severity, the latter expressed as brain MRI lesion volumes, in the subjects with CADASIL. The results showed that mean-D value of patients (1.42±0.05; mean±SD) was lower than control (1.50±0.04; p = 0.002). Mean-D did not correlate with disease duration nor with MRI lesion volumes of the subjects with CADASIL. The findings suggest that fractal analysis is a sensitive tool to assess changes of retinal vessel branching, likely reflecting early brain microvessel alterations, in CADASIL patients