Not all intravenous immunoglobulin preparations are equally well tolerated

Intravenous immunoglobulin (IVIG) is used for many indications beyond the original substitution in primary antibody deficiency. Whereas many reports mention adverse reactions, no comparative data exist concerning the incidence of side-effects among the different brands of IVIG. We describe here our experience with the use of different IVIG formulations and their tolerability in a select cohort of 40 patients. The IVIG dose ranged from 0.4 to 3 g/kg/day and was given for 1–2742 days. Fourteen patients (35%) experienced mild to severe adverse reactions during or within 48 h of administration of standard IVIG preparation, which did not recur after switching to an alternative preparation. Adverse reactions included headache, fever, chills, nausea, emesis, hypotension and muscle cramps. One patient experienced a severe adverse reaction; he had a 3-day headache following IVIG infusion. Among the 16 patients who received alternative preparation initially, none experienced adverse reactions. In conclusion, this study shows that IVIG preparations are not all equally well tolerated in patients. The data suggest that, perhaps to a comparable extent to the preparation itself, the infusion rate has a major effect. If a reduction in the infusion rate does not minimize side-effects, one should consider switching the IVIG formulation

Bosentan therapy for chronic thromboembolic pulmonary hypertension. A national open label study assessing the effect of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (BOCTEPH-Study).

we performed an open-label national study to evaluate the effects of Bosentan on haemodynamics, exercise capacity, quality of life, safety and tolerability in patients with chronic thromboembolic pulmonary hypertension (CTEPH). fifteen patients with CTEPH not eligible or waiting for surgery were enrolled. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included quality of life (measured by the Minnesota living with heart failure questionnaire, MLHF), 6 minute walk distance (6MWD), World Health Organization (WHO) functional class, Borg dyspnoea scale, plasma endothelin, serum values of disease severity such as uric acid, N-terminal-pro brain natriuretic peptide (NTproBNP), C-reactive protein measured by a highly sensitive method (CRPs) and other serum and haemodynamic parameters. after six months of treatment with bosentan, the PVR decreased from 852 (319) to 657(249) dyn*s*m-5 (p = 0.02). Quality of life considerably improved from a mean total score of 48(14) to 35(17) (p = 0.003) with improvements in the physical (from 25(5) to 17(7)) and emotional (from 11(6) to 6(5)) subscores (p = 0.005 and 0.011), respectively. The 6MWD improved from 389(78) to 443(79) meters (p = 0.005). 4 patients (27%) improved and 11 patients (73%) maintained their WHO class with no deterioration during the six months of bosentan treatment (p = 0.02). Uric acid serum levels declined from 525(145) to 453(151) micromol/l (p = 0.006), NTproBNP and CRPs declined insignificantly. Endothelin serum levels increased from 4.3(1.5) to 5.9(2.2) pg/ml (p = 0.025). Patients tolerated the treatment well, and there were no severe adverse events or deaths. this open-label study suggests a beneficial effect of bosentan therapy not only on pulmonary haemodynamics, but also on quality of life and exercise capacity for patients with severe CTEPH

How robust are future projections of forest landscape dynamics? Insights from a systematic comparison of four forest landscape models

Projections of landscape dynamics are uncertain, partly due to uncertainties in model formulations. However, quantitative comparative analyses of forest landscape models are lacking. We conducted a systematic comparison of all forest landscape models currently applied in temperate European forests (LandClim, TreeMig, LANDIS-II, iLand). We examined the uncertainty of model projections under several future climate, disturbance, and dispersal scenarios, and quantified uncertainties by variance partitioning. While projections under past climate conditions were in good agreement with observations, uncertainty under future climate conditions was high, with between-model biomass differences of up to 200 t ha−1. Disturbances strongly influenced landscape dynamics and contributed substantially to uncertainty in model projections (~25–40% of observed variance). Overall, model differences were the main source of uncertainty, explaining at least 50% of observed variance. We advocate a more rigorous and systematic model evaluation and calibration, and a broader use of ensemble projections to quantify uncertainties in future landscape dynamics

Monitoring the oceanic flow between Africa and Antarctica: Report of the first GoodHope cruise

The southern ocean plays a major role in the global oceanic circulation role in the global oceanic circulation, as a component of the Meridional Overturning Circulation, and it is postulated that it has a great influence on present-day climate. However, our understanding of its complex three-dimensional dynamics and of the impact of its variability on the climate system is rudimentary. The newly constituted, international GoodHope research venture aims to address this knowledge gap by establishing a programme of regular observations across the Southern Ocean between the African and Antarctic continents. The objectives of this programme are fivefold: (1) to improve understanding of Indo-Atlantic inter-ocean exchanges and their impact on the global thermohaline circulation and thus on global climate change; (2) to understand in more detail the influence these exchanges have on the climate variability of the southern African subcontinent; (3) to monitor the variability of the main Southern Ocean frontal systems associated with the Antarctic Circumpolar Current; (4) to study air–sea exchanges and their role on the global heat budget, with particular emphasis on the intense exchanges occurring within the Agulhas Retroflection region south of South Africa, and (5) to examine the role of major frontal systems as areas of elevated biological activity and as biogeographical barriers to the distribution of plankton. We present here preliminary results on the physical and biological structure of the frontal systems using the first GoodHope transect that was completed during February–March 2004

Monitoring the oceanic flow between Africa and Antarctica: report of the first Good Hope cruise

The Southern Ocean plays a major role in the global oceanic circulation, as a component of the Meridional Overturning Circulation, and it is postulated that it has a great influence on present-day climate. However, our understanding of its complex three-dimensional dynamics and of the impact of its variability on the climate system is rudimentary. The newly constituted, international GoodHope research venture aims to address this knowledge gap by establishing a programme of regular observations across the Southern Ocean between the African and Antarctic continents. The objectives of this programme are fivefold: (1) to improve understanding of Indo-Atlantic inter-ocean exchanges and their impact on the global thermohaline circulation and thus on global climate change; (2) to understand in more detail the influence these exchanges have on the climate variability of the southern African subcontinent; (3) to monitor the variability of the main Southern Ocean frontal systems associated with the Antarctic Circumpolar Current; (4) to study air-sea exchanges and their role on the global heat budget, with particular emphasis on the intense exchanges occurring within the Agulhas Retroflection region south of South Africa, and (5) to examine the role of major frontal systems as areas of elevated biological activity and as biogeographical barriers to the distribution of plankton. We present here preliminary results on the physical and biological structure of the frontal systems using the first GoodHope transect that was completed during February-March 2004

Potentiation of thrombus instability: a contributory mechanism to the effectiveness of antithrombotic medications

© The Author(s) 2018The stability of an arterial thrombus, determined by its structure and ability to resist endogenous fibrinolysis, is a major determinant of the extent of infarction that results from coronary or cerebrovascular thrombosis. There is ample evidence from both laboratory and clinical studies to suggest that in addition to inhibiting platelet aggregation, antithrombotic medications have shear-dependent effects, potentiating thrombus fragility and/or enhancing endogenous fibrinolysis. Such shear-dependent effects, potentiating the fragility of the growing thrombus and/or enhancing endogenous thrombolytic activity, likely contribute to the clinical effectiveness of such medications. It is not clear how much these effects relate to the measured inhibition of platelet aggregation in response to specific agonists. These effects are observable only with techniques that subject the growing thrombus to arterial flow and shear conditions. The effects of antithrombotic medications on thrombus stability and ways of assessing this are reviewed herein, and it is proposed that thrombus stability could become a new target for pharmacological intervention.Peer reviewedFinal Published versio

Disorder-Driven Pretransitional Tweed in Martensitic Transformations

Defying the conventional wisdom regarding first--order transitions, {\it solid--solid displacive transformations} are often accompanied by pronounced pretransitional phenomena. Generally, these phenomena are indicative of some mesoscopic lattice deformation that ``anticipates'' the upcoming phase transition. Among these precursive effects is the observation of the so-called ``tweed'' pattern in transmission electron microscopy in a wide variety of materials. We have investigated the tweed deformation in a two dimensional model system, and found that it arises because the compositional disorder intrinsic to any alloy conspires with the natural geometric constraints of the lattice to produce a frustrated, glassy phase. The predicted phase diagram and glassy behavior have been verified by numerical simulations, and diffraction patterns of simulated systems are found to compare well with experimental data. Analytically comparing to alternative models of strain-disorder coupling, we show that the present model best accounts for experimental observations.Comment: 43 pages in TeX, plus figures. Most figures supplied separately in uuencoded format. Three other figures available via anonymous ftp

Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance