The Darlington and Northallerton Long Term Asthma Study: pulmonary function

BACKGROUND: The Darlington and Northallerton Asthma Study is an observational cohort study started in 1983. At that time little was published about long term outcome in asthma and the contribution of change in reversible disease or airway remodelling to any excess deterioration in function. The study design included regular review of overall and fixed function lung. We report the trends over fifteen years. METHODS: All asthmatics attending secondary care in 1983, 1988 and 1993 were recruited. Pulmonary function was recorded at attendance and potential best function estimated according to protocol. Rate of decline was calculated over each 5-year period and by linear regression analysis in those seen every time. The influence of potential explanatory variables on this decline was explored. RESULTS: 1724 satisfactory 5-year measurements were obtained in 912 subjects and in 200 subjects on all occasions. Overall rate of decline (ml/year (95%CI)) calculated from 5-year periods was FEV1 ♂41.0 (34.7–47.3), ♀28.9 (23.2–34.6) and best FVC ♂63.1 (55.1–71.2)ml/year, ♀45.8 (40.0–51.6).The principal association was with age. A dominant cubic factor suggested fluctuations in the rate of change in middle life with less rapid decline in youth and more rapid decline in the elderly. Rapid decline was possibly associated with short duration. Treatment step did not predict rate of deterioration. CONCLUSIONS: Function declined non-linearly and more rapidly than predicted from normal subjects. It reports for the first time a cubic relationship between age and pulmonary function. This should be taken into account when interpreting other articles reporting change in function over time

Comparison of the peripheral blood eosinophil count using near-patient testing and standard automated laboratory measurement in healthy, asthmatic and COPD subjects

Near-patient testing (NPT) allows clinical decisions to be made in a rapid and convenient manner and is often cost effective. In COPD the peripheral blood eosinophil count has been demonstrated to have utility in providing prognostic information and predicting response to treatment during an acute exacerbation. For this potential to be achieved having a reliable NPT of blood eosinophil count would be extremely useful. Therefore, we investigated the use of the HemoCue® WBC Diff System and evaluated its sensitivity and specificity in healthy, asthmatic and COPD subjects. This method requires a simple skin prick of blood and was compared to standard venepuncture laboratory analysis. The HemoCue® WBC Diff System measured the peripheral blood eosinophil count in healthy, asthma and COPD subjects with very close correlation to the eosinophil count as measured by standard venepuncture. The correlations were unaffected by disease status. This method for the measurement of the peripheral blood eosinophil count has the potential to provide rapid near-patient results and thus influence the speed of management decisions in the treatment of airway diseases

Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

Upper- and mid-mantle interaction between the Samoan plume and the Tonga-Kermadec slabs

Mantle plumes are thought to play a key role in transferring heat from the core\u2013mantle boundary to the lithosphere, where it can significantly influence plate tectonics. On impinging on the lithosphere at spreading ridges or in intra-plate settings, mantle plumes may generate hotspots, large igneous provinces and hence considerable dynamic topography. However, the active role of mantle plumes on subducting slabs remains poorly understood. Here we show that the stagnation at 660 km and fastest trench retreat of the Tonga slab in Southwestern Pacific are consistent with an interaction with the Samoan plume and the Hikurangi plateau. Our findings are based on comparisons between 3D anisotropic tomography images and 3D petrological-thermo-mechanical models, which self-consistently explain several unique features of the Fiji\u2013Tonga region. We identify four possible slip systems of bridgmanite in the lower mantle that reconcile the observed seismic anisotropy beneath the Tonga slab (VSH4VSV) with thermo-mechanical calculations

Appetite suppressants and valvular heart disease - a systematic review

Background Although appetite suppressants have been implicated in the development of valvular heart disease, the exact level of risk is still uncertain. Initial studies suggested that as many as 1 in 3 exposed patients were affected, but subsequent research has yielded substantially different figures. Our objective was to systematically assess the risk of valvular heart disease with appetite suppressants. Methods We accepted studies involving obese patients treated with any of the following appetite suppressants: fenfluramine, dexfenfluramine, and phentermine. Three types of studies were reviewed: controlled and uncontrolled observational studies, and randomized controlled trials. Outcomes of interest were echocardiographically detectable aortic regurgitation of mild or greater severity, or mitral regurgitation of moderate or greater severity. Results Of the 1279 patients evaluated in seven uncontrolled cohort studies, 236 (18%) and 60 (5%) were found to have aortic and mitral regurgitation, respectively. Pooled data from six controlled cohort studies yielded, for aortic regurgitation, a relative risk ratio of 2.32 (95% confidence intervals 1.79 to 3.01, p < 0.00001) and an attributable rate of 4.9%, and for mitral regurgitation, a relative risk ratio of 1.55 (95% confidence intervals 1.06 to 2.25, p = 0.02) with an attributable rate of 1.0%. Only one case of valvular heart disease was detected in 57 randomized controlled trials, but this was judged unrelated to drug therapy. Conclusions The risk of valvular heart disease is significantly increased by the appetite suppressants reviewed here. Nevertheless, when considering all the evidence, valvulopathy is much less common than suggested by the initial, less methodologically rigorous studies

Edoxaban: an update on the new oral direct factor Xa inhibitor.

Edoxaban is a once-daily oral anticoagulant that rapidly and selectively inhibits factor Xa in a concentration-dependent manner. This review describes the extensive clinical development program of edoxaban, including phase III studies in patients with non-valvular atrial fibrillation (NVAF) and symptomatic venous thromboembolism (VTE). The ENGAGE AF-TIMI 48 study (N = 21,105; mean CHADS2 score 2.8) compared edoxaban 60 mg once daily (high-dose regimen) and edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin [international normalized ratio (INR) 2.0-3.0] and found that both regimens were non-inferior to warfarin in the prevention of stroke and systemic embolism in patients with NVAF. Both edoxaban regimens also provided significant reductions in the risk of hemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. The Hokusai-VTE study (N = 8,292) in patients with symptomatic VTE had a flexible treatment duration of 3-12 months and found that following initial heparin, edoxaban 60 mg once daily was non-inferior to dose-adjusted warfarin (INR 2.0-3.0) for the prevention of recurrent VTE, and also had a significantly lower risk of bleeding events. Both studies randomized patients at moderate-to-high risk of thromboembolic events and were further designed to simulate routine clinical practice as much as possible, with edoxaban dose reduction (halving dose) at randomisation or during the study if required, a frequently monitored and well-controlled warfarin group, a well-monitored transition period at study end and a flexible treatment duration in Hokusai-VTE. Given the phase III results obtained, once-daily edoxaban may soon be a key addition to the range of antithrombotic treatment options

Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

"© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

Resection of the liver for colorectal carcinoma metastases - A multi-institutional study of long-term survivors

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primarycarcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized. © 1988 American Society of Colon and Rectal Surgeons

Modification of the nanostructure of lignocellulose cell walls via a non-enzymatic lignocellulose deconstruction system in brown rot wood-decay fungi

Abstract Wood decayed by brown rot fungi and wood treated with the chelator-mediated Fenton (CMF) reaction, either alone or together with a cellulose enzyme cocktail, was analyzed by small angle neutron scattering (SANS), sum frequency generation (SFG) spectroscopy, Fourier transform infrared (FTIR) analysis, X-ray diffraction (XRD), atomic force microscopy (AFM), and transmission electron microscopy (TEM). Results showed that the CMF mechanism mimicked brown rot fungal attack for both holocellulose and lignin components of the wood. Crystalline cellulose and lignin were both depolymerized by the CMF reaction. Porosity of the softwood cell wall did not increase during CMF treatment, enzymes secreted by the fungi did not penetrate the decayed wood. The enzymes in the cellulose cocktail also did not appear to alter the effects of the CMF-treated wood relative to enhancing cell wall deconstruction. This suggests a rethinking of current brown rot decay models and supports a model where monomeric sugars and oligosaccharides diffuse from the softwood cell walls during non-enzymatic action. In this regard, the CMF mechanism should not be thought of as a “pretreatment” used to permit enzymatic penetration into softwood cell walls, but instead it enhances polysaccharide components diffusing to fungal enzymes located in wood cell lumen environments during decay. SANS and other data are consistent with a model for repolymerization and aggregation of at least some portion of the lignin within the cell wall, and this is supported by AFM and TEM data. The data suggest that new approaches for conversion of wood substrates to platform chemicals in biorefineries could be achieved using the CMF mechanism with >75% solubilization of lignocellulose, but that a more selective suite of enzymes and other downstream treatments may be required to work when using CMF deconstruction technology. Strategies to enhance polysaccharide release from lignocellulose substrates for enhanced enzymatic action and fermentation of the released fraction would also aid in the efficient recovery of the more uniform modified lignin fraction that the CMF reaction generates to enhance biorefinery profitability

Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments