Hereditary alpha-tryptasemia (HαT) is an autosomal dominant disorder estimated to affect 5% of the population. High baseline tryptase level is a consistent finding, but there is a great variability ...of clinic manifestations, including no symptoms at all. We describe a case of HαT in a 5 years 8 months old girl manifesting with idiopathic anaphylaxis and elevated baseline tryptase level. As more cases of HαT are described, a better understanding of the clinical phenotype will be acquired.
A novel coronavirus (MERS-CoV) is causing severe disease in the Middle East. In this report on a hospital outbreak of MERS-CoV infection, 23 confirmed cases and evidence of person-to-person ...transmission were identified. The median incubation period was 5.2 days.
Respiratory viruses are an emerging threat to global health security and have led to worldwide epidemics with substantial morbidity, mortality, and economic consequences. Since the severe acute respiratory syndrome (SARS) pandemic in 2003–2004,
1
–
3
two additional human coronaviruses — HKU-1 and NL-63 — have been identified, both of which cause mild respiratory infection and are distributed worldwide.
4
,
5
In September 2012, the World Health Organization (WHO) reported two cases of severe community-acquired pneumonia caused by a novel human β-coronavirus, subsequently named the Middle East respiratory syndrome coronavirus (MERS-CoV).
6
–
8
Since then, MERS-CoV has been identified as the cause of pneumonia . . .
In this phase 3 trial, among children with later-onset spinal muscular atrophy, those who received nusinersen had improvement in motor-function scores and those who underwent a sham procedure did not.
We present the first results from a high sampling rate, multimonth reverberation mapping campaign undertaken primarily at MDM Observatory with supporting observations from telescopes around the ...world. The primary goal of this campaign was to obtain either new or improved H Delta *b reverberation lag measurements for several relatively low luminosity active galactic nuclei (AGNs). We feature results for NGC 4051 here because, until now, this object has been a significant outlier from AGN scaling relationships, e.g., it was previously a ~2-3 Delta *s outlier on the relationship between the broad-line region (BLR) radius and the optical continuum luminosity-the R BLR-L relationship. Our new measurements of the lag time between variations in the continuum and H Delta *b emission line made from spectroscopic monitoring of NGC 4051 lead to a measured BLR radius of R BLR = 1.87+0.54 -0.50 light days and black hole mass of M BH = (1.73+0.55 -0.52) X 106 M. This radius is consistent with that expected from the R BLR-L relationship, based on the present luminosity of NGC 4051 and the most current calibration of the relation by Bentz et al.. We also present a preliminary look at velocity-resolved H Delta *b light curves and time delay measurements, although we are unable to reconstruct an unambiguous velocity-resolved reverberation signal.
Being smart about SMART environmental targets Maxwell, S. L.; Milner-Gulland, E. J.; Jones, J. P. G. ...
Science (American Association for the Advancement of Science),
03/2015, Letnik:
347, Številka:
6226
Journal Article
Recenzirano
Odprti dostop
Focus on the negotiation process, not just the end target
Global progress toward meeting the Convention on Biological Diversity (CBD) Aichi targets has recently been found wanting (
1
). The Aichi ...targets were intended to be SMART (specific, measurable, ambitious, realistic, and time-bound), partly in response to the perception that failure to meet the preceding global biodiversity targets resulted from their lack of SMART-ness (
2
). Negotiations are building toward the September 2015 United Nations meeting on Sustainable Development Goals (SDGs), which will influence government and business development priorities for decades. Some argue that scientists must engage with the SDG negotiation process to ensure that the environmental targets (e.g., sustainable food production and water-use efficiency) are not vague, modest, or lacking in detailed quantification (
3
). We caution against focusing only on ensuring that environmental targets are SMART and call for greater attention on the processes that lead to a target being set and met.
Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. ...Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC) method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut) had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A summary of the technical advances that are incorporated in the fourth major release of the Q-Chem quantum chemistry program is provided, covering approximately the last seven years. These include ...developments in density functional theory methods and algorithms, nuclear magnetic resonance (NMR) property evaluation, coupled cluster and perturbation theories, methods for electronically excited and open-shell species, tools for treating extended environments, algorithms for walking on potential surfaces, analysis tools, energy and electron transfer modelling, parallel computing capabilities, and graphical user interfaces. In addition, a selection of example case studies that illustrate these capabilities is given. These include extensive benchmarks of the comparative accuracy of modern density functionals for bonded and non-bonded interactions, tests of attenuated second order Møller-Plesset (MP2) methods for intermolecular interactions, a variety of parallel performance benchmarks, and tests of the accuracy of implicit solvation models. Some specific chemical examples include calculations on the strongly correlated Cr
2
dimer, exploring zeolite-catalysed ethane dehydrogenation, energy decomposition analysis of a charged ter-molecular complex arising from glycerol photoionisation, and natural transition orbitals for a Frenkel exciton state in a nine-unit model of a self-assembling nanotube.
The forests of Central Africa contain some of Earth's few remaining intact forests. These forests are increasingly threatened by infrastructure development, agriculture, and unsustainable extraction ...of natural resources (e.g. minerals, bushmeat, and timber), all of which is leading to deforestation and forest degradation, particularly defaunation, and hence causing declines in biodiversity and a significant increase in carbon emissions. Given the pervasive nature of these threats, the global importance of Central African forests for biodiversity conservation, and the limited resources for conservation and sustainable management, there is a need to identify where the most important areas are to orientate conservation efforts. We developed a novel approach for identifying spatial priorities where conservation efforts can maximize biodiversity benefits within Central Africa's most intact forest areas. We found that the Democratic Republic of Congo has the largest amount of priority areas in the region, containing more than half, followed by Gabon, the Republic of Congo and Cameroon. We compared our approach to one that solely prioritizes forest intactness and one that aims to achieve only biodiversity representation objectives. We found that when priorities are only based on forest intactness (without considering biodiversity representation), there are significantly fewer biodiversity benefits and vice versa. We therefore recommend multi-objective planning that includes biodiversity representation and forest intactness to ensure that both objectives are maximized. These results can inform various types of conservation strategies needed within the region, including land-use planning, jurisdictional REDD + initiatives, and performance related carbon payments, protected area expansion, community forest management, and forest concession plans.
Asthma and chronic obstructive pulmonary disease (COPD) are common chronic inflammatory respiratory diseases, which impose a substantial burden on healthcare systems and society. Fixed-dose ...combinations (FDCs) of inhaled corticosteroids (ICS) and long-acting β2 agonists (LABA), often administered using dry powder inhalers (DPIs), are frequently prescribed to control persistent asthma and COPD. Use of DPIs has been associated with poor inhalation technique, which can lead to increased healthcare resource use and costs.
A model was developed to estimate the healthcare resource use and costs associated with asthma and COPD management in people using commonly prescribed DPIs (budesonide + formoterol Turbuhaler(®) or fluticasone + salmeterol Accuhaler(®)) over 1 year in Spain, Sweden and the United Kingdom (UK). The model considered direct costs (inhaler acquisition costs and scheduled and unscheduled healthcare costs), indirect costs (productive days lost), and estimated the contribution of poor inhalation technique to the burden of illness.
The direct cost burden of managing asthma and COPD for people using budesonide + formoterol Turbuhaler(®) or fluticasone + salmeterol Accuhaler(®) in 2015 was estimated at €813 million, €560 million, and €774 million for Spain, Sweden and the UK, respectively. Poor inhalation technique comprised 2.2-7.7 % of direct costs, totalling €105 million across the three countries. When lost productivity costs were included, total expenditure increased to €1.4 billion, €1.7 billion and €3.3 billion in Spain, Sweden and the UK, respectively, with €782 million attributable to poor inhalation technique across the three countries. Sensitivity analyses showed that the model results were most sensitive to changes in the proportion of patients prescribed ICS and LABA FDCs, and least sensitive to differences in the number of antimicrobials and oral corticosteroids prescribed.
The cost of managing asthma and COPD using commonly prescribed DPIs is considerable. A substantial, and avoidable, contributor to this burden is poor inhalation technique. Measures that can improve inhalation technique with current DPIs, such as easier-to-use inhalers or better patient training, could offer benefits to patients and healthcare providers through improving disease outcomes and lowering costs.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Our aim was to explore change in kyphosis and vertebral fracture incidence following 8 months of high-intensity resistance and impact training (HiRIT) or machine-based isometric axial ...compression (IAC) training in men with osteopenia and osteoporosis. HiRIT and IAC improved posture. HiRIT participants did not experience progression or incident vertebral fracture. IAC participants did experience progression and incident vertebral fracture.
Introduction
The Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR-M) trial examined efficacy and safety of an eight-month, supervised, high-intensity progressive resistance and impact training (HiRIT) program compared with machine-based isometric axial compression (IAC) training in middle-aged and older men with low areal bone mineral density (aBMD). The primary purpose of the current work was to explore change in thoracic kyphosis and incident fracture from vertebral morphology following eight-months of HiRIT or IAC training. The secondary purpose was to explore change in clinical kyphosis measures for HiRIT, IAC and a non-randomized, matched control group.
Methods
Men (≥ 45 yrs), with low aBMD, were recruited and randomized to HiRIT or IAC, or designated control. Clinical measures of thoracic kyphosis with inclinometry were determined. Cobb angle of kyphosis and vertebral fracture assessment using the Genant semi-quantitative method were determined from lateral thoracolumbar DXA (Medix DR, Medilink, France). Per-protocol (
n
= 40) and intention-to-treat (
n
= 93) analyses were conducted.
Results
Forty participants (HiRIT
n
= 20, IAC
n
= 20; 66.1 ± 7.8 yrs.; lumbar spine T-score − 0.1 ± 0.8; femoral neck T-score − 1.5 ± 0.5) underwent clinical kyphosis measures and thoracolumbar DXA at baseline and follow-up. No between-group differences were detected in kyphosis change, however, within-group improvements in neutral (HiRIT − 2.3 ± 0.8°; IAC − 2.5 ± 0.8°) and ‘standing tall’ (HiRIT − 2.4 ± 0.8°; IAC − 2.0 ± 0.8°) postures were observed (
p
< 0.05). HiRIT improved Cobb angle (− 3.5 ± 1.5°,
p
= 0.027) from baseline. Over the 8 months, no incident vertebral fractures nor progression of prevalent vertebral fractures occurred for HiRIT participants. Five incident fractures of thoracic vertebrae occurred for IAC and one wedge fracture progressed. Ninety-three participants underwent clinical kyphosis measures at both time-points (HiRIT
n
= 34, IAC
n
= 33, control
n
= 26). HiRIT exhibited a reduction in ‘standing tall’ kyphosis compared to control (− 2.3 ± 0.6° versus 1.4 ± 0.7°,
p
< 0.05), but no other between-group differences were detected.
Conclusions
Although there was no difference in change between intervention groups, thoracic kyphosis appeared to improve in both HiRIT and IAC with exercise exposure. HiRIT improved 'standing tall' posture in comparison to usual activities. HiRIT was not associated with vertebral fracture progression or incident vertebral fracture, but for some IAC participants there was evidence of progression of vertebral fracture severity and incident vertebral fractures, in our small sample. Larger trials are required to confirm the observations of the current work, which was exploratory in nature.
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