Moored observations of turbulent mixing events in deep Lake Garda (I)

Deep water circulation and mixing processes in deep lakes are largely unknown, although they are responsible for the transport of matter, nutrients and pollutants. Such a lack of knowledge cannot be reliably provided by numerical hydrodynamic modelling studies because detailed observations are typically not available to validate them. To overcome some of these deficiencies, a dedicated yearlong mooring comprising 100 high-resolution temperature sensors and a single current meter were located in the deeper half of the 344 m deepest point of the subalpine Lake Garda (Italy). The observations show peaks and calms of turbulent exchange, besides ubiquitous internal wave activity. In late winter, northerly winds activate episodic deep convective overturning, the dense water being subsequently advected along the lake-floor. Besides deep convection, such winds also set-up seiches and inertial waves that are associated with about 100 times larger turbulence dissipation rates than that by semidiurnal internal wave breaking observed in summer. In the lower 60 m above the lake-floor however, the average turbulence dissipation rate is approximately constant in value year-around, being about 10 times larger than open-ocean values, except during deep convection episodes.Comment: 42 pages, 10 figure

Wind variability and Earth’s rotation as drivers of transport in a deep, elongated subalpine lake: The case of Lake Garda

The effects of wind forcing and Earth’s rotation on the transport processes in Lake Garda, Italy, are investigated for the first time under different thermal stratification conditions and typical diurnal wind cycles. Numerical simulations are performed by means of a modeling chain composed of a meteorological (WRF) and a hydrodynamic (Delft3D) model. Transport processes are studied through the combined analysis of the residual (time averaged) flow field and the trajectories of Lagrangian particles. Results show that strong currents develop in winter under the forcing of synoptic northerly Föhn winds, especially in the elongated northern region, where winds are channeled by the steep orography. Significant water volumes are displaced laterally by Ekman transport, producing intense downwelling and upwelling along the steep shores. Instead summer patterns are controlled by the diurnal cycle of local breezes, alternately blowing along the main axis of the lake. The resulting circulation reveals counterclockwise gyres in the northern part, driven by the alternating wind direction and affected by Coriolis force. The analysis suggests that complex circulations can develop in lakes with relatively simple geometries, like the narrow trunk region of Lake Garda, where the effect of Earth’s rotation unexpectedly influences the transport patterns

Deep-mixing and deep-cooling events in Lake Garda: Simulation and mechanisms

A calibrated three-dimensional numerical model (Delft3D) and in-situ observations are used to study the relation between deep-water temperature and deep mixing in Lake Garda (Italy). A model-observation comparison indicates that the model is able to adequately capture turbulent kinetic energy production in the surface layer and its vertical propagation during unstratified conditions. From the modeling results several processes are identified to affect the deep-water temperature in Lake Garda. The first process is thermocline tilting due to strong and persistent winds, leading to a temporary disappearance of stratification followed by vertical mixing. The second process is turbulent cooling, which acts when vertical temperature gradients are nearly absent over the whole depth and arises as a combination of buoyancy-induced turbulence production due to surface cooling and turbulence production by strong winds. A third process is differential cooling, which causes cold water to move from the shallow parts of the lake to deeper parts along the sloping bottom. Two of these processes (thermocline tilting and turbulent cooling) cause deep-mixing events, while deep-cooling events are mainly caused by turbulent cooling and differential cooling. Detailed observations of turbulence quantities and lake temperature, available at the deepest point of Lake Garda for the year 2018, indicate that differential cooling was responsible for the deep-water cooling at that location. Long-term simulations of deep-water temperature and deep mixing appear to be very sensitive to the applied wind forcing. This sensitivity is one of the main challenges in making projections of future occurrences of episodic deep mixing and deep cooling under climate change

Systematic versus on-demand early palliative care: results from a multicentre, randomised clinical trial

Background Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating EPC has yet to be defined. Methods This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive ‘standard cancer care plus on-demand EPC’ (n = 100) or ‘standard cancer care plus systematic EPC’ (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. Findings The mean changes in TOI score and HCS score between T0 and T1 were −4.47 and −0.63, with a difference between groups of 3.83 (95% confidence interval [CI] 0.10–7.57) (p = 0.041), and −2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40–4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. Interpretations Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC

Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

BACKGROUND: As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. METHODS: Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. RESULTS: Two hundred sixty-seven GBM patients (median age, 64 y; range, 29-84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2-12.4). The 139 patients 64aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0-18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248-0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388-0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328-0.986; P = .0446). CONCLUSIONS: The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged 6470 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Abstract Introduction Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects

What makes an elongated lake ‘large’? Scales from wind-driven steady circulation on a rotating Earth

When investigating wind-induced steady circulation, the effect of the acceleration due to Earth's rotation is often neglected in narrow lakes, but the argument behind this assumption is blurred. Commonly, when the horizontal dimension is smaller than the Rossby radius, the Coriolis force is considered unimportant, but this is correct only for inertial currents and barotropic and baroclinic waves. In this work, we revisit the classical Ekman transport solution for wind stress acting along the main axis of an elongated lake in steady-state conditions. We demonstrate that a secondary circulation develops and that the resulting crosswise volume transport, constrained in the closed domain, produces downwelling and upwelling that cannot be predicted by the standard Ekman formulas. We claim that the Rossby radius does not play any role in this process, which on the contrary is governed by the ratio between the actual depth and the thickness of the Ekman layer. The theoretical analysis is supported by numerical experiments to show the dependence on latitude, width, depth and turbulence closure