4,214 research outputs found
Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.
Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses
A circadian based inflammatory response – implications for respiratory disease and treatment
Circadian clocks regulate the daily timing of many of our physiological, metabolic and biochemical functions. The immune system also displays circadian oscillations in immune cell count, synthesis and cytokine release, clock gene expression in cells and organs of the immune system as well as clock-controlled genes that regulate immune function. Circadian disruption leads to dysregulation of immune responses and inflammation which can further disrupt circadian rhythms. The response of organisms to immune challenges, such as allergic reactions also vary depending on time of the day, which can lead to detrimental responses particularly during the rest and early active periods. This review evaluates what is currently known in terms of circadian biology of immune response and the cross-talk between circadian and immune system. We discuss the circadian pattern of three respiratory-related inflammatory diseases, chronic obstructive pulmonary disease, allergic rhinitis and asthma. Increasing our knowledge on circadian patterns of immune responses and developing chronotherapeutic studies in inflammatory diseases with strong circadian patterns will lead to preventive measures as well as improved therapies focussing on the circadian rhythms of symptoms and the daily variation of the patients’ responses to medication
A low energy core-collapse supernova without a hydrogen envelope
The final fate of massive stars depends on many factors, including mass,
rotation rate, magnetic fields and metallicity. Theory suggests that some
massive stars (initially greater than 25-30 solar masses) end up as Wolf-Rayet
stars which are deficient in hydrogen because of mass loss through strong
stellar winds. The most massive of these stars have cores which may form a
black hole and theory predicts that the resulting explosion produces ejecta of
low kinetic energy, a faint optical display and a small mass fraction of
radioactive nickel(1,2,3). An alternative origin for low energy supernovae is
the collapse of the oxygen-neon core of a relatively lowmass star (7-9 solar
masses) through electron capture(4,5). However no weak, hydrogen deficient,
core-collapse supernovae are known. Here we report that such faint, low energy
core-collapse supernovae do exist, and show that SN2008ha is the faintest
hydrogen poor supernova ever observed. We propose that other similar events
have been observed but they have been misclassified as peculiar thermonuclear
supernovae (sometimes labelled SN2002cx-like events(6)). This discovery could
link these faint supernovae to some long duration gamma-ray bursts. Extremely
faint, hydrogen-stripped core-collapse supernovae have been proposed to produce
those long gamma-ray bursts whose afterglows do not show evidence of
association with supernovae (7,8,9).Comment: Submitted 12 January 2009 - Accepted 24 March 200
Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study
BACKGROUND: Non-invasive diagnostic strategies aimed at identifying biomarkers of lung cancer are of great interest for early cancer detection. The aim of this study was to set up a new method for identifying and quantifying volatile organic compounds (VOCs) in exhaled air of patients with non-small cells lung cancer (NSCLC), by comparing the levels with those obtained from healthy smokers and non-smokers, and patients with chronic obstructive pulmonary disease. The VOC collection and analyses were repeated three weeks after the NSCLC patients underwent lung surgery. METHODS: The subjects' breath was collected in a Teflon(® )bulb that traps the last portion of single slow vital capacity. The 13 VOCs selected for this study were concentrated using a solid phase microextraction technique and subsequently analysed by means of gas cromatography/mass spectrometry. RESULTS: The levels of the selected VOCs ranged from 10(-12 )M for styrene to 10(-9 )M for isoprene. None of VOCs alone discriminated the study groups, and so it was not possible to identify one single chemical compound as a specific lung cancer biomarker. However, multinomial logistic regression analysis showed that VOC profile can correctly classify about 80 % of cases. Only isoprene and decane levels significantly decreased after surgery. CONCLUSION: As the combination of the 13 VOCs allowed the correct classification of the cases into groups, together with conventional diagnostic approaches, VOC analysis could be used as a complementary test for the early diagnosis of lung cancer. Its possible use in the follow-up of operated patients cannot be recommended on the basis of the results of our short-term nested study
The Neutral ISM in Nearby Luminous Compact Blue Galaxies
We observed 20 nearby Luminous Compact Blue Galaxies (LCBGs) in HI and
CO(J=2-1) with the GBT and JCMT. These ~L^star galaxies are blue, high surface
brightness, starbursting, high metallicity galaxies with an underlying older
stellar population. They are common at z~1, but rare in the local Universe. It
has been proposed that intermediate redshift LCBGs may be the progenitors of
local dwarf ellipticals or low luminosity spirals, or that they may be more
massive disks forming from the center outward to become L^star galaxies. To
discriminate among various possible evolutionary scenarios, we have measured
the dynamical masses and gas depletion time scales of this sample of nearby
LCBGs.
We find that local LCBGs span a wide range of dynamical masses, from 4 x 10^9
to 1 x 10^11 M_solar (measured within R_25). Molecular gas in local LCBGs is
depleted quite quickly, in 30 to 200 million years. The molecular plus atomic
gas is depleted in 30 million to 10 billion years; however, ~80% of the local
LCBGs deplete their gas in less than 5 billion years. As LCBGs are
heterogeneous in both dynamical mass and gas depletion time scales, they are
not likely to evolve into one homogeneous galaxy class.Comment: 4 pages, 2 figures, to be published in 4th
Cologne-Bonn-Zermatt-Symposium, Eds. S. Pfalzner, C. Kramer, C. Straubmeier,
and A. Heithause
Mycolactone Diffuses into the Peripheral Blood of Buruli Ulcer Patients - Implications for Diagnosis and Disease Monitoring.
BACKGROUND: Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), is unique among human pathogens in its capacity to produce a polyketide-derived macrolide called mycolactone, making this molecule an attractive candidate target for diagnosis and disease monitoring. Whether mycolactone diffuses from ulcerated lesions in clinically accessible samples and is modulated by antibiotic therapy remained to be established.
METHODOLOGY/PRINCIPAL FINDING: Peripheral blood and ulcer exudates were sampled from patients at various stages of antibiotic therapy in Ghana and Ivory Coast. Total lipids were extracted from serum, white cell pellets and ulcer exudates with organic solvents. The presence of mycolactone in these extracts was then analyzed by a recently published, field-friendly method using thin layer chromatography and fluorescence detection. This approach did not allow us to detect mycolactone accurately, because of a high background due to co-extracted human lipids. We thus used a previously established approach based on high performance liquid chromatography coupled to mass spectrometry. By this means, we could identify structurally intact mycolactone in ulcer exudates and serum of patients, and evaluate the impact of antibiotic treatment on the concentration of mycolactone.
CONCLUSIONS/SIGNIFICANCE: Our study provides the proof of concept that assays based on mycolactone detection in serum and ulcer exudates can form the basis of BU diagnostic tests. However, the identification of mycolactone required a technology that is not compatible with field conditions and point-of-care assays for mycolactone detection remain to be worked out. Notably, we found mycolactone in ulcer exudates harvested at the end of antibiotic therapy, suggesting that the toxin is eliminated by BU patients at a slow rate. Our results also indicated that mycolactone titres in the serum may reflect a positive response to antibiotics, a possibility that it will be interesting to examine further through longitudinal studies
Incoherent non-Fermi liquid scattering in a Kondo lattice
One of the most notorious non-Fermi liquid properties of both archetypal
heavy-fermion systems [1-4] and the high-Tc copper oxide superconductors [5] is
an electrical resistivity that evolves linearly with temperature, T. In the
heavy-fermion superconductor CeCoIn5 [5], this linear behaviour was one of the
first indications of the presence of a zero-temperature instability, or quantum
critical point. Here, we report the observation of a unique control parameter
of T-linear scattering in CeCoIn5, found through systematic chemical
substitutions of both magnetic and non-magnetic rare-earth, R, ions into the Ce
sub-lattice. We find that the evolution of inelastic scattering in Ce1-xRxCoIn5
is strongly dependent on the f-electron configuration of the R ion, whereas two
other key properties -- Cooper-pair breaking and Kondo-lattice coherence -- are
not. Thus, T-linear resistivity in CeCoIn5 is intimately related to the nature
of incoherent scattering centers in the Kondo lattice, which provides insight
into the anomalous scattering rate synonymous with quantum criticality [7].Comment: 4 pages, 3 figures (published version
Hydrogen-bond-mediated structural variation of metal guanidinium formate hybrid perovskites under pressure
The hybrid perovskites are coordination frameworks with the same topology as
the inorganic perovskites, but with properties driven by different chemistry,
including host-framework hydrogen bonding. Like the inorganic perovskites,
these materials exhibit many different phases, including structures with
potentially exploitable functionality. However, far less is known about their
behaviour under pressure. We have studied the structures of of manganese and
cobalt guanidinium formate under pressure using single-crystal X-ray and powder
neutron diffraction. Remarkably, when pressure reduces these materials' volume,
they transform to a phase isostructural to cadmium guanidinium formate, which
has an larger volume. Using DFT calculations, we show that this
counterintuitive behaviour depends on the hydrogen-bonded network of
guanidinium ions, which act as struts protecting the metal formate framework
against compression. Our results demonstrate more generally that engineering
desirable crystal structures in the hybrid perovskites will depend on achieving
suitable host-guest hydrogen-bonding geometries.Comment: 9 pages, 3 figure
Network analysis of human muscle adaptation to aging and contraction.
This is the final version. Available from Impact Journals via the DOI in this record. Resistance exercise (RE) remains a primary approach for minimising aging muscle decline. Understanding muscle adaptation to individual contractile components of RE (eccentric, concentric) might optimise RE-based intervention strategies. Herein, we employed a network-driven pipeline to identify putative molecular drivers of muscle aging and contraction mode responses. RNA-sequencing data was generated from young (21±1 y) and older (70±1 y) human skeletal muscle before and following acute unilateral concentric and contralateral eccentric contractions. Application of weighted gene co-expression network analysis identified 33 distinct gene clusters ('modules') with an expression profile regulated by aging, contraction and/or linked to muscle strength. These included two contraction 'responsive' modules (related to 'cell adhesion' and 'transcription factor' processes) that also correlated with the magnitude of post-exercise muscle strength decline. Module searches for 'hub' genes and enriched transcription factor binding sites established a refined set of candidate module-regulatory molecules (536 hub genes and 60 transcription factors) as possible contributors to muscle aging and/or contraction responses. Thus, network-driven analysis can identify new molecular candidates of functional relevance to muscle aging and contraction mode adaptations.Wellcome Trust Institutional Strategic Support AwardBiotechnology and Biological Sciences Research Counci
Superimposition of 3D cone-beam CT models of orthognathic surgery patients
To evaluate the registration of 3D models from cone-beam CT (CBCT) images taken before and after orthognathic surgery for the assessment of mandibular anatomy and position
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