OWNERSHIP STRUCTURES AND R&D INVESTMENTS OF U.S. AND JAPANESE FIRMS: AGENCY AND STEWARDSHIP PERSPECTIVES.

This study analyzes the impact of ownership structure on R&D investments in the United States and Japan. It begins with the premise that U.S. and Japanese firms have distinct patterns of ownership that may result in disparities in R&D investments. Agency theory and stewardship theory are used to hypothesize about the relationship between ownership and R&D investments. Empirical evidence shows that the level of ownership concentration, and its impact, differ across countries. We argue that these differences result from a mixture of motives and incentives

Inhibition of Toll-Like Receptor 2-Mediated Interleukin-8 Production in Cystic Fibrosis Airway Epithelial Cells via the α7-Nicotinic Acetylcholine Receptor

Cystic Fibrosis (CF) is an inherited disorder characterised by chronic inflammation of the airways. The lung manifestations of CF include colonization with Pseudomonas aeruginosa and Staphylococcus aureus leading to neutrophil-dominated airway inflammation and tissue damage. Inflammation in the CF lung is initiated by microbial components which activate the innate immune response via Toll-like receptors (TLRs), increasing airway epithelial cell production of proinflammatory mediators such as the neutrophil chemokine interleukin-8 (IL-8). Thus modulation of TLR function represents a therapeutic approach for CF. Nicotine is a naturally occurring plant alkaloid. Although it is negatively associated with cigarette smoking and cardiovascular damage, nicotine also has anti-inflammatory properties. Here we investigate the inhibitory capacity of nicotine against TLR2- and TLR4-induced IL-8 production by CFTE29o- airway epithelial cells, determine the role of α7-nAChR (nicotinic acetylcholine receptor) in these events, and provide data to support the potential use of safe nicotine analogues as anti-inflammatories for CF

Improved Performance of Near infrared Excitation Raman Spectroscopy Using Reflective Thin-film Gold on Glass Substrates for Cytology Samples

Confocal near-infrared Raman spectroscopy has been shown to have applications in the area of clinical biology. A source wavelength in the near infrared is preferred over visible wavelengths for inspecting biological samples due to superior wave number resolution and reduced photo damage. However, these excitation sources have a number of drawbacks when compared to lasers in the visible wavelength region, including the requirement to use expensive highly pure crystal substrates such as Raman grade calcium fluoride as well as long acquisition times due to the lower Raman scattering efficiency. This paper investigates the use of a reflective substrate comprising a low cost 100 nm thin-film gold on glass substrate, as an alternative. Similar to recent work that used stainless steel substrates, it is demonstrated that the thin-film gold coated substrates, which are relatively inexpensive, produce cell spectra with 1.65 times the signal to noise ratio when compared with spectra obtained from calcium fluoride under identical conditions, with no apparent background signal in the fingerprint region. Two prostate cell lines are examined having been deposited on glass, calcium fluoride, and thin-film gold on glass substrates using the Thin Prep standard. Background spectra from, and cell adhesion on, these three substrates are compared. A comparison of the intensities and signal to noise ratios of the resulting spectra, and their viability for classification using principle components analysis is performed, which further demonstrates the benefit of reflective substrates

A touchdown nucleic acid amplification protocol as an alternative to culture backup for immunofluorescence in the routine diagnosis of acute viral respiratory tract infections

BACKGROUND: Immunofluorescence and virus culture are the main methods used to diagnose acute respiratory virus infections. Diagnosing these infections using nucleic acid amplification presents technical challenges, one of which is facilitating the different optimal annealing temperatures needed for each virus. To overcome this problem we developed a diagnostic molecular strip which combined a generic nested touchdown protocol with in-house primer master-mixes that could recognise 12 common respiratory viruses. RESULTS: Over an 18 month period a total of 222 specimens were tested by both immunofluorescence and the molecular strip. The specimens came from 103 males (median age 3.5 y), 80 females (median age 9 y) and 5 quality assurance scheme specimens. Viruses were recovered from a number of specimen types including broncho-alveolar lavage, nasopharyngeal secretions, sputa, post-mortem lung tissue and combined throat and nasal swabs. Viral detection by IF was poor in sputa and respiratory swabs. A total of 99 viruses were detected in the study from 79 patients and 4 quality control specimens: 31 by immunofluorescence and 99 using the molecular strip. The strip consistently out-performed immunofluorescence with no loss of diagnostic specificity. CONCLUSIONS: The touchdown protocol with pre-dispensed primer master-mixes was suitable for replacing virus culture for the diagnosis of respiratory viruses which were negative by immunofluorescence. Results by immunofluorescence were available after an average of 4–12 hours while molecular strip results were available within 24 hours, considerably faster than viral culture. The combined strip and touchdown protocol proved to be a convenient and reliable method of testing for multiple viruses in a routine setting

Improved performance of near infrared excitation Raman spectroscopy using reflective thin-film gold on glass substrates for cytology samples

Confocal near-infrared Raman spectroscopy has been shown to have applications in the area of clinical biology. A source wavelength in the near infrared is preferred over visible wavelengths for inspecting biological samples due to superior wavenumber resolution and reduced photodamage. However, these excitation sources have a number of drawbacks when compared to lasers in the visible wavelength region, including the requirement to use expensive highly pure crystal substrates such as Raman grade calcium fluoride as well as long acquisition times due to the lower Raman scattering efficiency. This paper investigates the use of a reflective substrate comprising a low cost 100 nm thin-film gold on glass substrate, as an alternative. Similar to recent work that used stainless steel substrates, it is demonstrated that the thin-film gold coated substrates, which are relatively inexpensive, produce cell spectra with 1.65 times the signal to noise ratio when compared with spectra obtained from calcium fluoride under identical conditions, with no apparent background signal in the fingerprint region. Two prostate cell lines are examined having been deposited on glass, calcium fluoride, and thin-film gold on glass substrates using the ThinPrep standard. Background spectra from, and cell adhesion on, these three substrates are compared. A comparison of the intensities and signal to noise ratios of the resulting spectra, and their viability for classification using principle components analysis is performed, which further demonstrates the benefit of reflective substrates

Non-detection of Chlamydia species in carotid atheroma using generic primers by nested PCR in a population with a high prevalence of Chlamydia pneumoniae antibody

BACKGROUND: The association of Chlamydia pneumoniae with atherosclerosis is controversial. We investigated the presence of C. pneumoniae and other Chlamydia spp. in atheromatous carotid artery tissue. METHODS: Forty elective carotid endarterectomy patients were recruited (27 males, mean age 65 and 13 females mean age 68), 4 had bilateral carotid endarterectomies (n= 44 endarterectomy specimens). Control specimens were taken from macroscopically normal carotid artery adjacent to the atheromatous lesions (internal controls), except in 8 cases where normal carotid arteries from post mortem (external controls) were used. Three case-control pairs were excluded when the HLA DRB gene failed to amplify from the DNA. Genus specific primers to the major outer membrane protein (MOMP) gene were used in a nested polymerase chain reaction (nPCR) in 41 atheromatous carotid specimens and paired controls. PCR inhibition was monitored by spiking with target C. trachomatis. Atheroma severity was graded histologically. Plasma samples were tested by microimmunofluorescence (MIF) for antibodies to C. pneumoniae, C. trachomatis and C. psittaci and the corresponding white cells were tested for Chlamydia spp. by nPCR. RESULTS: C. pneumoniae was not detected in any carotid specimen. Twenty-five of 38 (66%) plasma specimens were positive for C. pneumoniae IgG, 2/38 (5%) for C. trachomatis IgG and 1/38 (3%) for C. psittaci IgG. CONCLUSIONS: We were unable to show an association between the presence of Chlamydia spp. and atheroma in carotid arteries in the presence of a high seroprevalence of C. pneumoniae antibodies in Northern Ireland

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials