Assessing the phenomenology of the Cretan Sea shelf area using coupling modelling techniques

International audienceIn this work the ability of nesting two hydrodynamical models, the high-resolution Cretan Sea shelf model and the lower resolution regional ALERMO model, was investigated. A new database was developed by objectively analysing raw climatological data from the MODB database enriched with in situ measurements collected by the Institute of Marine Biology of Crete. Prior to nesting with the ALERMO model, the Cretan Sea model was integrated using this new hydrological database, in order to investigate the capability of the model setup to describe the phenomenology of the Cretan Sea. Results show that the model can successfully reproduce the complex general circulation characteristics of the area, such as the dipole of a cyclone and an anticyclone, and the flow reversal between winter and summer. As a next step, the shelf-model was one-way nested with the ALERMO model and was integrated on a climatological basis. The evolution of the circulation characteristics of the Cretan Sea was compared, qualitatively and quantitatively, against the results of the regional model, and proved that the nesting between the two models can provide reliable information while overcoming at the same time the computational constraints imposed by high-resolution models

A rare case of zolendronate infusion complication leading to glaucoma filtration surgery

Zolendronic acid is a nitrogenous biphosphonate commonly used as an intravenous infusion for the management of Paget’s disease, osteoporosis, and hypercalcemia of malignancy. We report a rare and challenging complication of zolendronate infusion: unilateral acute anterior uveitis followed by persistently raised intraocular pressure despite being on four different classes of antiglaucoma medication. The challenge was that the patient required topical steroid to treat her uveitis in the background of known glaucoma with corresponding steroid response. She eventually underwent a left phacotrabeculectomy augmented with 5-fluorouracil. Four weeks postoperatively she developed an encapsulated bleb and underwent needling with 5-fluorouracil. This case highlights the importance of having a high index of suspicion for anterior uveitis in patients with a red and painful eye after initiating biphosphonate therapy. Caution should also be exercised when prescribing biphosponates to glaucoma patients

Recharging mitochondrial batteries in old eyes. Near infra-red increases ATP.

Progressive accumulation of age related mitochondrial DNA mutations reduce ATP production and increase reactive oxygen species output, leading to oxidative stress, inflammation and degradation. The pace of this is linked to metabolic demand. The retina has the greatest metabolic demand and mitochondrial density in the body and displays progressive age related inflammation and marked cell loss. Near infra-red (670nm) is thought to be absorbed by cytochrome c oxidase (COX), a key element in mitochondrial respiration and it has been demonstrated that it improves mitochondrial membrane potentials in aged eyes. It also significantly reduces the impact of experimental pathology and ameliorates age related retinal inflammation. We show ATP decline with ageing in mouse retina and brain. Also, in these tissues that ATP is significantly increased by 670nm exposure in old mice. In the retina this was associated with increased COX and reduced acrolein expression. Acrolein, being a free radical marker of retinal oxidative stress, is up regulated in Alzheimer's and retinal degeneration. This is the first demonstration of ATP manipulation in vivo and may provide a simple non-invasive route to combating age related tissue decline

Characterizing, modelling and understanding the climate variability of the deep water formation in the North-Western Mediterranean Sea

Observing, modelling and understanding the climate-scale variability of the deep water formation (DWF) in the North-Western Mediterranean Sea remains today very challenging. In this study, we first characterize the interannual variability of this phenomenon by a thorough reanalysis of observations in order to establish reference time series. These quantitative indicators include 31 observed years for the yearly maximum mixed layer depth over the period 1980–2013 and a detailed multi-indicator description of the period 2007–2013. Then a 1980–2013 hindcast simulation is performed with a fully-coupled regional climate system model including the high-resolution representation of the regional atmosphere, ocean, land-surface and rivers. The simulation reproduces quantitatively well the mean behaviour and the large interannual variability of the DWF phenomenon. The model shows convection deeper than 1000 m in 2/3 of the modelled winters, a mean DWF rate equal to 0.35 Sv with maximum values of 1.7 (resp. 1.6) Sv in 2013 (resp. 2005). Using the model results, the winter-integrated buoyancy loss over the Gulf of Lions is identified as the primary driving factor of the DWF interannual variability and explains, alone, around 50 % of its variance. It is itself explained by the occurrence of few stormy days during winter. At daily scale, the Atlantic ridge weather regime is identified as favourable to strong buoyancy losses and therefore DWF, whereas the positive phase of the North Atlantic oscillation is unfavourable. The driving role of the vertical stratification in autumn, a measure of the water column inhibition to mixing, has also been analyzed. Combining both driving factors allows to explain more than 70 % of the interannual variance of the phenomenon and in particular the occurrence of the five strongest convective years of the model (1981, 1999, 2005, 2009, 2013). The model simulates qualitatively well the trends in the deep waters (warming, saltening, increase in the dense water volume, increase in the bottom water density) despite an underestimation of the salinity and density trends. These deep trends come from a heat and salt accumulation during the 1980s and the 1990s in the surface and intermediate layers of the Gulf of Lions before being transferred stepwise towards the deep layers when very convective years occur in 1999 and later. The salinity increase in the near Atlantic Ocean surface layers seems to be the external forcing that finally leads to these deep trends. In the future, our results may allow to better understand the behaviour of the DWF phenomenon in Mediterranean Sea simulations in hindcast, forecast, reanalysis or future climate change scenario modes. The robustness of the obtained results must be however confirmed in multi-model studies

Relationships between retinal layer thickness and brain volumes in the UK Biobank cohort

BACKGROUND: Current methods to diagnose neurodegenerative diseases are costly and invasive. Retinal neuroanatomy may be a biomarker for more neurodegenerative processes and can be quantified in vivo using optical coherence tomography (OCT), which is inexpensive and noninvasive. We examined the association of neuroretinal morphology with brain MRI image derived phenotypes (IDPs) in a large cohort of healthy older people. METHODS: UK Biobank participants aged 40 to 69 years old underwent comprehensive examinations including ophthalmic and brain imaging assessments. Macular retinal nerve fibre layer (mRNFL), ganglion cell-inner plexiform layer (mGCIPL), ganglion cell complex (mGCC) and total macular thicknesses were obtained from OCT. MRI IDPs assessed included total brain, grey-matter, white-matter and hippocampal volume. Multivariable linear regression models were used to evaluate associations between retinal layers thickness and brain MRI IDPs, adjusting for demographic factors and vascular risk factors. RESULTS: A total of 2,131 participants (mean age 55 years; 51% women) with both gradable OCT images and brain imaging assessments were included. In multivariable regression analysis, thinner mGCIPL, mGCC, and total macular thickness were all significantly associated with smaller total brain (p<0.001), grey-matter and white-matter volumes (p<0.01), and grey-matter volume in the occipital pole (p<0.05). Thinner mGCC and total macular thicknesses were associated with smaller hippocampal volume (p<0.02). No association was found between mRNFL and the MRI IDPs. CONCLUSION: Markers of retinal neurodegeneration are associated with smaller brain volumes. Our findings suggest that retinal structures may be a biomarker providing information about important brain structures in healthy, older adults

Mediterranean Sea response to climate change in an ensemble of twenty first century scenarios

The Mediterranean climate is expected to become warmer and drier during the twenty-first century. Mediterranean Sea response to climate change could be modulated by the choice of the socio-economic scenario as well as the choice of the boundary conditions mainly the Atlantic hydrography, the river runoff and the atmospheric fluxes. To assess and quantify the sensitivity of the Mediterranean Sea to the twenty-first century climate change, a set of numerical experiments was carried out with the regional ocean model NEMOMED8 set up for the Mediterranean Sea. The model is forced by air–sea fluxes derived from the regional climate model ARPEGE-Climate at a 50-km horizontal resolution. Historical simulations representing the climate of the period 1961–2000 were run to obtain a reference state. From this baseline, various sensitivity experiments were performed for the period 2001–2099, following different socio-economic scenarios based on the Special Report on Emissions Scenarios. For the A2 scenario, the main three boundary forcings (river runoff, near-Atlantic water hydrography and air–sea fluxes) were changed one by one to better identify the role of each forcing in the way the ocean responds to climate change. In two additional simulations (A1B, B1), the scenario is changed, allowing to quantify the socio-economic uncertainty. Our 6-member scenario simulations display a warming and saltening of the Mediterranean. For the 2070–2099 period compared to 1961–1990, the sea surface temperature anomalies range from +1.73 to +2.97 °C and the SSS anomalies spread from +0.48 to +0.89. In most of the cases, we found that the future Mediterranean thermohaline circulation (MTHC) tends to reach a situation similar to the eastern Mediterranean Transient. However, this response is varying depending on the chosen boundary conditions and socio-economic scenarios. Our numerical experiments suggest that the choice of the near-Atlantic surface water evolution, which is very uncertain in General Circulation Models, has the largest impact on the evolution of the Mediterranean water masses, followed by the choice of the socio-economic scenario. The choice of river runoff and atmospheric forcing both have a smaller impact. The state of the MTHC during the historical period is found to have a large influence on the transfer of surface anomalies toward depth. Besides, subsurface currents are substantially modified in the Ionian Sea and the Balearic region. Finally, the response of thermosteric sea level ranges from +34 to +49 cm (2070–2099 vs. 1961–1990), mainly depending on the Atlantic forcing

Systemic PTEN-Akt1-mTOR pathway activity in patients with normal tension glaucoma and ocular hypertension: A case series

Glaucoma is the most common optic neuropathy in humans and the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP), while increasing evidence suggests that systemic mitochondrial abnormalities may also be implicated in its pathogenesis. We have recently shown that patients who have not developed glaucoma despite being exposed for many years to high IOP (ocular hypertension - OHT) have more efficient mitochondria, measured in peripheral blood lymphocytes, when compared to age-similar controls and fast progressing normal tension glaucoma (NTG) patients. In this prospective case series we aimed to explore some of the molecular pathways involved in mitochondrial efficiency in glaucoma resistance by measuring the systemic activity (in peripheral blood) of key mitochondrial regulators: the mammalian target of rapamycin (mTOR) and its major upstream regulators and downstream effectors that form the PTEN-Akt1-mTOR signalling pathway. We found no statistically significant difference in the systemic mTOR activity between the three groups (control, NTG and OHT). In line with the mTOR results, there was no significant difference in the activity of both the two major upstream mTOR regulators (PTEN and Akt1) and its two main downstream effectors (S6K and 4EBP1). In a single NTG patient, with history of Raynaud's, significantly higher mTOR activity was noted. We conclude that the PTEN-Akt1-mTOR pathway does not appear to play a central role in mitochondrial efficiency in OHT

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

Background: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. Methods: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. Findings: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28–0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. Interpretation: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period