The automatic recognition and counting of cough

BACKGROUND: Cough recordings have been undertaken for many years but the analysis of cough frequency and the temporal relation to trigger factors have proven problematic. Because cough is episodic, data collection over many hours is required, along with real-time aural analysis which is equally time-consuming. A method has been developed for the automatic recognition and counting of coughs in sound recordings. METHODS: The Hull Automatic Cough Counter (HACC) is a program developed for the analysis of digital audio recordings. HACC uses digital signal processing (DSP) to calculate characteristic spectral coefficients of sound events, which are then classified into cough and non-cough events by the use of a probabilistic neural network (PNN). Parameters such as the total number of coughs and cough frequency as a function of time can be calculated from the results of the audio processing. Thirty three smoking subjects, 20 male and 13 female aged between 20 and 54 with a chronic troublesome cough were studied in the hour after rising using audio recordings. RESULTS: Using the graphical user interface (GUI), counting the number of coughs identified by HACC in an hour long recording, took an average of 1 minute 35 seconds, a 97.5% reduction in counting time. HACC achieved a sensitivity of 80% and a specificity of 96%. Reproducibility of repeated HACC analysis is 100%. CONCLUSION: An automated system for the analysis of sound files containing coughs and other non-cough events has been developed, with a high robustness and good degree of accuracy towards the number of actual coughs in the audio recording

Dichlorido(4,7-diaza-1-azoniacyclo­nonane-κ2 N 4,N 7)palladium(II) p-toluene­sulfonate

The title compound, [PdCl2(C6H16N3)](C7H7SO3), consists of a PdII atom bonded to two N atoms of the 1,4,7-triaza­cyclo­nonane (TACN) ligand and two chloride ions, which define a distorted square-planar geometry. The third N atom of the TACN ligand is protonated and hydrogen bonds to the p-toluene­sulfonate anion. The Cl—Pd—Cl angle is larger than the N—Pd—N angle. The packing is dominated by layers, which are formed by the criss-crossing of two different hydrogen-bonded chains. One chain is composed of hydrogen-bonded Pd(TACNH)Cl2 + cations, while the second is formed through hydrogen bonding between the p-toluene­sulfonate anion and the Pd(TACNH)Cl2 + cation

Diagnosis and management of antiretroviral-therapy failure in resource-limited settings in sub-Saharan Africa: challenges and perspectives.

Despite the enormous progress made in scaling up antiretroviral therapy (ART) in sub-Saharan Africa, many challenges remain, not least of which are the identification and management of patients who have failed first-line therapy. Less than 3% of patients are receiving second-line treatment at present, whereas 15-25% of patients have detectable viral loads 12 months or more into treatment, of whom a substantial proportion might have virological failure. We discuss the reasons why virological ART failure is likely to be under-diagnosed in the routine health system, and address the current difficulties with standard recommended second-line ART regimens. The development of new diagnostic tools for ART failure, in particular a point-of-care HIV viral-load test, combined with simple and inexpensive second-line therapy, such as boosted protease-inhibitor monotherapy, could revolutionise the management of ART failure in resource-limited settings

Prion protein interacts with bace1 and differentially regulates its activity towards wild type and swedish mutant amyloid precursor protein

In Alzheimer disease amyloid-β (Aβ) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the β-secretase BACE1 is the rate-limiting step in the production of Aβ. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine Aβ were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, Aβ plaque deposition, or levels of soluble Aβ or Aβ oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect Aβ accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease

Hierarchical modelling and X-ray analysis of human dentine and enamel

Human teeth consist of enamel, dentine and cementum, hierarchical mineralised tissues with a two-level composite structure. The understanding of the mechanical behaviour of dentine and enamel in terms of their micro- and nano-scale structure has been somewhat limited. Here we present an overview of our recent work aimed at improving the understanding of the internal lattice strain response of the mineral crystallites of different orientations under external in situ loading. A range of experimental techniques was employed for the purpose of this analysis. Small- and Wide- Angle X-ray Scattering (SAXS/WAXS) were used to determine the internal lattice strain and orientational distribution of HAp crystals, while quantitative stress distribution evaluation in the birefringent mounting epoxy surrounding the sample was carried out in parallel using photoelasticity. Finite element analysis and advanced multi-scale Eshelby inclusion modelling were used to interpret the data. The satisfactory agreement achieved between the model and the experimental data, in terms of the values of multi-directional strain components under the action of differently orientated loads, demonstrates that our multi-scale approach captures successfully the structure-property relationships between the hierarchical architecture of human dental tissues and their response to the applied forces. Our systematic approach can be used to improve the insight into the mechanical properties of dentine and enamel, and of textured hierarchical biomaterials (such as bones) in general.</p

Training the next generation of clinical researchers: Evaluation of a graduate podiatrist research internship in rheumatology

Background: The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors. Methods: Nine new graduates completed the internship programme (July 2006-June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes. Results: Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent 'Jewel in the Crown' award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees. Seven important themes arose from the qualitative phases: perceptions of the internship pre-application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme. Conclusions: The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales

The Molecular Condensations Ahead of Herbig-Haro Objects. I. Multi-transition Observations of HH 2

We present a CSO and BIMA molecular line survey of the dense, quiescent molecular environment ahead of HH2. The molecular gas is cold, 13 K, and moderately dense, 3x10^5 cm^-3. A total of 14 species has been detected (including different isotopes and deuterated species). The relative abundances of the clump are compared with other dense molecular environments, including quiescent dark clouds, and active low and high mass star forming regions. This comparison confirms the peculiar chemical composition of the quiescent gas irradiated by the HH objects. Thus, from this comparison, we found that the HCO+, CH3OH and H2CO are strongly enhanced. SO and SO2 are weakly enhanced, whereas HCN and CS are underabundant. The CN abundance is within the range of value found in starless dark clouds, but it is low with respect to high mass star forming regions. Finally, the chemical composition of HH2 confirms the qualitative results of the Viti & Williams (1999) complex chemical model that follows the chemical behavior of a molecular clump irradiated by a HH object.Comment: 12 pages, 7 figures, to be published in Astronomy & Astrophysic

Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response

Poly(ADP-ribose) polymerase-1 (PARP-1) synthesizes and transfers ADP ribose polymers to target proteins, and regulates DNA repair and genomic integrity maintenance. PARP-1 also plays a crucial role in the progression of the inflammatory response, and its inhibition confers protection in several models of inflammatory disorders. Here, we investigate the impact of a selective PARP-1 inhibitor in experimental arthritis. PARP-1 inhibition with 5-aminoisoquinolinone (AIQ) significantly reduces incidence and severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of AIQ is associated with a striking reduction of the two deleterious components of the disease, i.e. the Th1-driven autoimmune and inflammatory responses. AIQ downregulates the production of various inflammatory cytokines and chemokines, decreases the antigen-specific Th1-cell expansion, and induces the production of the anti-inflammatory cytokine IL-10. Our results provide evidence of the contribution of PARP-1 to the progression of arthritis and identify this protein as a potential therapeutic target for the treatment of rheumatoid arthritis

Targeting Cx43 and N-Cadherin, Which Are Abnormally Upregulated in Venous Leg Ulcers, Influences Migration, Adhesion and Activation of Rho GTPases

Venous leg ulcers can be very hard to heal and represent a significant medical need with no effective therapeutic treatment currently available

Accommodating Dynamic Oceanographic Processes and Pelagic Biodiversity in Marine Conservation Planning

Pelagic ecosystems support a significant and vital component of the ocean's productivity and biodiversity. They are also heavily exploited and, as a result, are the focus of numerous spatial planning initiatives. Over the past decade, there has been increasing enthusiasm for protected areas as a tool for pelagic conservation, however, few have been implemented. Here we demonstrate an approach to plan protected areas that address the physical and biological dynamics typical of the pelagic realm. Specifically, we provide an example of an approach to planning protected areas that integrates pelagic and benthic conservation in the southern Benguela and Agulhas Bank ecosystems off South Africa. Our aim was to represent species of importance to fisheries and species of conservation concern within protected areas. In addition to representation, we ensured that protected areas were designed to consider pelagic dynamics, characterized from time-series data on key oceanographic processes, together with data on the abundance of small pelagic fishes. We found that, to have the highest likelihood of reaching conservation targets, protected area selection should be based on time-specific data rather than data averaged across time. More generally, we argue that innovative methods are needed to conserve ephemeral and dynamic pelagic biodiversity