| 1. |
- Coquery, N, et al.
(author)
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Locomotion and eating behavior changes in Yucatan minipigs after unilateral radio-induced ablation of the caudate nucleus
- 2019
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 17082-
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Journal article (peer-reviewed)abstract
- The functional roles of the Caudate nucleus (Cd) are well known. Selective Cd lesions can be found in neurological disorders. However, little is known about the dynamics of the behavioral changes during progressive Cd ablation. Current stereotactic radiosurgery technologies allow the progressive ablation of a brain region with limited adverse effects in surrounding normal tissues. This could be of high interest for the study of the modified behavioral functions in relation with the degree of impairment of the brain structures. Using hypofractionated stereotactic radiotherapy combined with synchrotron microbeam radiation, we investigated, during one year after irradiation, the effects of unilateral radio-ablation of the right Cd on the behavior of Yucatan minipigs. The right Cd was irradiated to a minimal dose of 35.5 Gy delivered in three fractions. MRI-based morphological brain integrity and behavioral functions, i.e. locomotion, motivation/hedonism were assessed. We detected a progressive radio-necrosis leading to a quasi-total ablation one year after irradiation, with an additional alteration of surrounding areas. Transitory changes in the motivation/hedonism were firstly detected, then on locomotion, suggesting the influence of different compensatory mechanisms depending on the functions related to Cd and possibly some surrounding areas. We concluded that early behavioral changes related to eating functions are relevant markers for the early detection of ongoing lesions occurring in Cd-related neurological disorders.
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| 2. |
- Goedecke, J H, et al.
(author)
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Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women
- 2015
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 39:2, s. 303-311
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Journal article (peer-reviewed)abstract
- Background: Black women have lower visceral adipose tissue (VAT) but are less insulin sensitive than white women; the mechanisms responsible are unknown.Objective: The study aimed to test the hypothesis that variation in subcutaneous adipose tissue (SAT) sensitivity to glucocorticoids might underlie these differences.Methods: Body fatness (dual energy X-ray absorptiometry) and distribution (computerized tomography), insulin sensitivity (SI, intravenous and oral glucose tolerance tests), and expression of 11β-hydroxysteroid dehydrogenase-1 (11HSD1), hexose-6-phosphate dehydrogenase and glucocorticoid receptor-α (GRα), as well as genes involved in adipogenesis and inflammation were measured in abdominal deep SAT, superficial SAT and gluteal SAT (GLUT) depots of 56 normal-weight or obese black and white premenopausal South African (SA) women. We used a combination of univariate and multivariate statistics to evaluate ethnic-specific patterns in adipose gene expression and related body composition and insulin sensitivity measures.Results: Although 11HSD1 activity and mRNA did not differ by ethnicity, GRα mRNA levels were significantly lower in SAT of black compared with white women, particularly in the GLUT depot (0.52±0.21 vs 0.91±0.26 AU, respectively, P<0.01). In black women, lower SAT GRα mRNA levels were associated with increased inflammatory gene transcript levels and abdominal SAT area, and reduced adipogenic gene transcript levels, VAT/SAT ratio and SI. Abdominal SAT 11HSD1 activity associated with increased VAT area and decreased SI in white, but not in black women.Conclusions: In black SA women, downregulation of GRα mRNA levels with obesity and reduced insulin sensitivity, possibly via increased SAT inflammation, is associated with reduced VAT accumulation.
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| 3. |
- O’Reilly, Catherine M., et al.
(author)
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Rapid and highly variable warming of lake surface waters around the globe
- 2015
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In: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 42:24
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Journal article (peer-reviewed)abstract
- In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade−1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors—from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade−1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade−1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes.
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| 4. |
- Pressler, Ronit M., et al.
(author)
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Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO) : an open-label, dose finding, and feasibility phase 1/2 trial
- 2015
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In: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 14:5, s. 469-477
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Journal article (peer-reviewed)abstract
- Background Predinical data suggest that the loop-diuretic bumetanide might be an effective treatment for neonatal seizures. We aimed to assess dose and feasibility of intravenous bumetanide as an add-on to phenobarbital for treatment of neonatal seizures. Methods In this open-label, dose finding, and feasibility phase 1/2 trial, we recruited full-term infants younger than 48 h who had hypoxic ischaemic encephalopathy and electrographic seizures not responding to a loading-dose of phenobarbital from eight neonatal intensive care units across Europe. Newborn babies were allocated to receive an additional dose of phenobarbital and one of four bumetanide dose levels by use of a bivariate Bayesian sequential dose-escalation design to assess safety and efficacy. We assessed adverse events, pharmacokinetics, and seizure burden during 48 h continuous electroencephalogram (EEG) monitoring. The primary efficacy endpoint was a reduction in electrographic seizure burden of more than 80% without the need for rescue antiepileptic drugs in more than 50% of infants. The trial is registered with ClinicalTrials.gov, number NCT01434225. Findings Between Sept 1, 2011, and Sept 28, 2013, we screened 30 infants who had electrographic seizures due to hypoxic ischaemic encephalopathy. 14 of these infants (10 boys) were included in the study (dose allocation: 0.05 mg/kg, n=4; 0.1 mg/kg, n=3; 0. 2 mg/kg, n=6; 0.3 mg/kg, n=1). All babies received at least one dose of bumetanide with the second dose of phenobarbital; three were withdrawn for reasons unrelated to bumetanide, and one because of dehydration. All but one infant also received aminoglycosides. Five infants met EEG criteria for seizure reduction (one on 0.05 mg/kg, one on 0.1 mg/kg and three on 0.2 mg/kg), and only two did not need rescue antiepileptic drugs (ie, met rescue criteria; one on 0.05 mg/kg and one on 0.3 mg/kg). We recorded no short-term dose-limiting toxic effects, but three of 11 surviving infants had hearing impairment confirmed on auditory testing between 17 and 108 days of age. The most common non-serious adverse reactions were moderate dehydration in one, mild hypotension in seven, and mild to moderate electrolyte disturbances in 12 infants. The trial was stopped early because of serious adverse reactions and limited evidence for seizure reduction. Interpretation Our findings suggest that bumetanide as an add-on to phenobarbital does not improve seizure control in newborn infants who have hypoxic ischaemic encephalopathy and might increase the risk of hearing loss, highlighting the risks associated with the off-label use of drugs in newborn infants before safety assessment in controlled trials.
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| 5. |
- Sharma, Sapna, et al.
(author)
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A global database of lake surface temperatures collected by in situ and satellite methods from 1985–2009
- 2015
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In: Scientific Data. - : Macmillan Publishers Limited. - 2052-4463. ; 2
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Journal article (peer-reviewed)abstract
- Global environmental change has influenced lake surface temperatures, a key driver of ecosystem structure and function. Recent studies have suggested significant warming of water temperatures in individual lakes across many different regions around the world. However, the spatial and temporal coherence associated with the magnitude of these trends remains unclear. Thus, a global data set of water temperature is required to understand and synthesize global, long-term trends in surface water temperatures of inland bodies of water. We assembled a database of summer lake surface temperatures for 291 lakes collected in situ and/or by satellites for the period 1985–2009. In addition, corresponding climatic drivers (air temperatures, solar radiation, and cloud cover) and geomorphometric characteristics (latitude, longitude, elevation, lake surface area, maximum depth, mean depth, and volume) that influence lake surface temperatures were compiled for each lake. This unique dataset offers an invaluable baseline perspective on global-scale lake thermal conditions as environmental change continues.
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| 6. |
- Stokes, Chris R., et al.
(author)
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On the reconstruction of palaeo-ice sheets : Recent advances and future challenges
- 2015
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In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 125, s. 15-49
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Research review (peer-reviewed)abstract
- Reconstructing the growth and decay of palaeo-ice sheets is critical to understanding mechanisms of global climate change and associated sea-level fluctuations in the past, present and future. The significance of palaeo-ice sheets is further underlined by the broad range of disciplines concerned with reconstructing their behaviour, many of which have undergone a rapid expansion since the 1980s. In particular, there has been a major increase in the size and qualitative diversity of empirical data used to reconstruct and date ice sheets, and major improvements in our ability to simulate their dynamics in numerical ice sheet models. These developments have made it increasingly necessary to forge interdisciplinary links between sub-disciplines and to link numerical modelling with observations and dating of proxy records. The aim of this paper is to evaluate recent developments in the methods used to reconstruct ice sheets and outline some key challenges that remain, with an emphasis on how future work might integrate terrestrial and marine evidence together with numerical modelling. Our focus is on pan-ice sheet reconstructions of the last deglaciation, but regional case studies are used to illustrate methodological achievements, challenges and opportunities. Whilst various disciplines have made important progress in our understanding of ice-sheet dynamics, it is clear that data-model integration remains under-used, and that uncertainties remain poorly quantified in both empirically-based and numerical ice-Sheet reconstructions. The representation of past climate will continue to be the largest source of uncertainty for numerical modelling. As such, palaeo-observations are critical to constrain and validate modelling. State-of-the-art numerical models will continue to improve both in model resolution and in the breadth of inclusion of relevant processes, thereby enabling more accurate and more direct comparison with the increasing range of palaeo-observations. Thus, the capability is developing to use all relevant palaeo-records to more strongly constrain deglacial (and to a lesser extent pre-LGM) ice sheet evolution. In working towards that goal, the accurate representation of uncertainties is required for both constraint data and model outputs. Close cooperation between modelling and data-gathering communities is essential to ensure this capability is realised and continues to progress.
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| 7. |
- Woolway, R. Iestyn, et al.
(author)
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Diel Surface Temperature Range Scales with Lake Size
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
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Journal article (peer-reviewed)abstract
- Ecological and biogeochemical processes in lakes are strongly dependent upon water temperature. Long-term surface warming of many lakes is unequivocal, but little is known about the comparative magnitude of temperature variation at diel timescales, due to a lack of appropriately resolved data. Here we quantify the pattern and magnitude of diel temperature variability of surface waters using high-frequency data from 100 lakes. We show that the near-surface diel temperature range can be substantial in summer relative to long-term change and, for lakes smaller than 3 km(2), increases sharply and predictably with decreasing lake area. Most small lakes included in this study experience average summer diel ranges in their near-surface temperatures of between 4 and 7 degrees C. Large diel temperature fluctuations in the majority of lakes undoubtedly influence their structure, function and role in biogeochemical cycles, but the full implications remain largely unexplored.
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