Reconstructing with numerical Ice Sheet Models the post-LGM decay of the Eurasian Ice Sheets: data-model comparison and focus on the Storfjorden (Svalbard) ice stream dynamics history

The challenge of reconstructing the growth and decay of palaeo-ice sheets represents a critical task to better understand mechanisms of global climate change and associated sea-level fluctuations in the present and future. The Eurasian palaeo-Ice Sheet (EIS) at its maximum volume and extent (between 21,000 and 20,000 years ago) comprised the Scandinavian (SIS), Svalbard/Barents/Kara seas (SBKSIS), and British-Irish (BIIS) palaeo-ice sheets. The SBKSIS was a so called marine based ice sheet, as it rested several hundreds of meters below the sea level in the Barents and Kara seas. From a bathymetric and topographic point of view, there is a strong similarity between the SBKSIS and the present-day West Antarctic Ice Sheet (WAIS). Consequently, to reconstruct the dynamic processes driving the last deglaciation of the SBKSIS may represent an important task to better understand the WAIS present and future evolution. In this study, the evolution of the EIS during the last deglaciation is reconstructed with two hybrid Shallow-Ice/Shallow-Shelf-Approximation numerical Ice Sheet Models (ISMs), namely PSU and GRISLI. These two ISMs differ mainly in the ice stream parametrization and in the complexity with which grounding line migration is treated. A particular focus in this study is given to the Storfjorden glacial system in the north-western Barents Sea. In fact, several palaeo-data from this area furnish insights on the Storfjorden ice stream dynamics history, providing a good testing ground for ISMs. The ISMs are forced with macro-regional indexes representative of the climate evolution over Siberia/Kara Sea, Svalbard/Barents Sea and Fennoscandia during the last deglaciation. The climate in- dexes are based on TraCE-21ka, a transient climate simulation of the last 21,000 years carried out with the Atmosphere-Ocean General Circulation Model CCSM3. Two different ocean basal melting parametrizations based on ice-ocean heat fluxes are tested. The ocean basal melting parametrizations are forced with time-varying ocean temperature and salinity from TraCE-21ka transient climate simulation. Ocean temperature and salinity representative of Arctic Ocean, Norwegian Sea, north-western and south- western Barents Sea are employed. In order to deal with ISMs poorly constrained model parameters, a statistical approach is adopted. A Latin Hypercube Sampling (LHS) of five GRISLI parameters is performed. Due to large computational costs it is not possible to perform such a statistical approach with PSU ISM. Therefore, a restricted number of simulations performed with PSU ISM employ model parameter values from GRISLI significant simulations. GRISLI-simulated ice streams dynamics has a strong control on the deglaciation of the EIS, in particular in the Southern SIS and in the Western SBKSIS. In terms of total ice volume there is a good agreement between GRISLI simulations, ICE-5G reconstruction and global Eustatic Sea Level data. In contrast, GRISLI-simulated ice sheet extent evolution presents discrepancies with geological observation in the Southern SIS and in the Eastern SBKSIS. The use of different basal melting parametrizations in GRISLI has a strong impact both on the deglaciation of the SBKSIS and on the retreat of Storfjorden ice stream. The Storfjorden ice stream dynamics history in GRISLI simulations is in good agreement with palaeo-data in terms of timing of the ice stream retreat, Grounding Zone Wedges formation and response to Meltwater Pulse 1A. The different treatment in PSU of ice streams and Grounding Line migration has a remarkable effect on the EIS deglaciation. In particular, in PSU the Grounding Line dynamics plays a primary role with respect to ocean basal melting, thus exerting a strong control on the decay of the marine-based SBKSIS. Finally, an inverse-type approach is adopted to match PSU simulations with ICE-5G reconstruction and the other palaeo-data

Optical Modeling of Plasmonic Nanoparticles with Electronically Depleted Layers

Doped metal oxide (MO) nanocrystals (NCs) are well-known for the localized surface plasmon resonance in the infrared range generated by free electrons in the conduction band of the material . Owing to the intimate connection between plasmonic features and t h e NC's carrier density profile, proper modeling can unveil the underlying electronic structure. The carrier density profile in MO NCs is characterized by the presence of an electronically depleted layer as a result of the Fermi level pinning at the surface of the NC. Moreover, the carrier profile can be spatially engineered by tuning the dopant concentrations in core-shell architectures, generating a rich plethora of plasmonic features. In this work, we systematically studied the influence of the simulation parameters used for optical modeling of representative experimental absorption spectra by implementing multilayer models. We highlight in particular the importance of minimizing the fit parameters by support of experimental results and the importance of interparameter relationships. We show that, in all cases investigated, the depletion layer is fundamental to correctly describe the continuous spectra evolution. We foresee that this multilayer model can be used to design the optoelectronic properties of core-shell systems in the framework of energy band and depletion layer engineering

Biomedical research involving patients with disorders of consciousness: ethical and legal dimensions

The directive 2001/20/UE and the research involving patients with docs. Research  involving patients with disorders of consciousness (DOCs) deserves special ethical and  legal attention because of its Janus-faced nature. On the one hand, it raises concerns  about the risk to expose the involved subjects to disproportionate risks not respecting  their individual dignity, particularly their right to be cared for; on the other hand, research  is  an  essential  tool  in  order  to  improve  the  clinical  condition  of  patients  with  DOCs. The present paper concerns the ethical and legal dimensions of biomedical research  involving  patients  with  disorders  of  consciousness.  In  particular,  it  focuses  on  informed consent to experimental treatments, which is a challenging issue both from an  ethical and legal point of view. The first part reads the Directive 2001/20/EU in the light  of the experimentation of patients with DOCs, and suggests a revision in order to better  assess the issue of informed consent.The particular case of informed consent for observational studies of non-communicative patients. The second part presents an informed consent form for studies through  video-recording of patients unable to communicate their own consent. This form has  been elaborated by the bioethics unit of the project “Review of the nosography of vegetative states: application of methods of behavioral analysis to individuals in coma or  vegetative state” developed at the Italian National Institute of Health.Relevance of the suggested form. The paper describes the conceptual framework of  the form for informed consent to studies through video-recoding, which is a relevant  example of what issues should be included in an informed consent for any type of studies  through video-recording of patients unable to express their own consent. The article has  been sent on November the 7th 2013, before the adoption of the Regulation (EU) no.  536/2014 (and consequent abrogation of the Directive 2001/20/EU) and the release of  the new edition of the Italian Code of Medical Ethics. 

Editorial: Primary and acquired resistance in lung cancer

No abstract availabl

Simulated last deglaciation of the Barents Sea Ice Sheet primarily driven by oceanic conditions

The Barents Sea Ice Sheet was part of an interconnected complex of ice sheets, collectively referred to as the Eurasian Ice Sheet, which covered north-westernmost Europe, Russia and the Barents Sea during the Last Glacial Maximum (around 21 ky BP). Due to common geological features, the Barents Sea component of this ice complex is seen as a paleo-analogue for the present-day West Antarctic Ice Sheet. Investigating key processes driving the last deglaciation of the Barents Sea Ice Sheet represents an important tool to interpret recent observations in Antarctica over the multi-millennial temporal scale of glaciological changes. We present results from a perturbed physics ensemble of ice sheet model simulations of the last deglaciation of the Barents Sea Ice Sheet, forced with transient atmospheric and oceanic conditions derived from AOGCM simulations. The ensemble of transient simulations is evaluated against the data-based DATED-1 reconstruction to construct minimum, maximum and average deglaciation scenarios. Despite a large model/data mismatch at the western and eastern ice sheet margins, the simulated and DATED-1 deglaciation scenarios agree well on the timing of the deglaciation of the central and northern Barents Sea. We find that the simulated deglaciation of the Barents Sea Ice Sheet is primarily driven by the oceanic forcing, with prescribed eustatic sea level rise amplifying the ice sheet sensitivity to sub-shelf melting over relatively short intervals. Our results highlight that the sub-shelf melting has a very strong control on the simulated grounding-line flux, showing that a slow, gradual ocean warming trend is capable of triggering sustained grounded ice discharge over multi-millennial timescales, even without taking into account marine ice sheet or ice cliff instability

Growing bone tissue-engineered niches with graded osteogenicity: an in vitro method for biomimetic construct assembly

The traditional bone tissue-engineering approach exploits mesenchymal stem cells ( MSCs) to be seeded once only on three-dimensional (3D) scaffolds, hence, differentiated for a certain period of time and resulting in a homogeneous osteoblast population at the endpoint. However, after achieving terminal osteodifferentiation, cell viability is usually markedly compromised. On the other hand, naturally occurring osteogenesis results from the coexistence of MSC progenies at distinct differentiative stages in the same microenvironment. This diversification also enables long-term viability of the mature tissue. We report an easy and tunable in vitro method to engineer simple osteogenic cell niches in a biomimetic fashion. The niches were grown via periodic reseeding of undifferentiated MSCs on MSC/scaffold constructs, the latter undergoing osteogenic commitment. Timefractioning of the seeded cell number during differentiation time of the constructs allowed graded osteogenic cell populations to be grown together on the same scaffolds (i.e., not only terminally differentiated osteoblasts). In such cell-dynamic systems, the overall differentiative stage of the constructs could also be tuned by varying the cell density seeded at each inoculation. In this way, we generated two different biomimetic niche models able to host good reservoirs of preosteoblasts and other osteoprogenitors after 21 culture days. At that time, the niche type resulting in 40.8% of immature osteogenic progenies and only 59.2% of mature osteoblasts showed a calcium content comparable to the constructs obtained with the traditional culture method (i.e., 100.03 – 29.30 vs. 78.51 – 28.50 pg/cell, respectively; p = not significant), the latter colonized only by fully differentiated osteoblasts showing exhausted viability. This assembly method for tissue-engineered constructs enabled a set of important parameters, such as viability, colonization, and osteogenic yield of the MSCs to be balanced on 3D scaffolds, thus achieving biomimetic in vitro models with graded osteogenicity, which are more complex and reliable than those currently used by tissue engineers

Case report: optic atrophy and nephropathy with m.13513G>A/MT-ND5 mtDNA pathogenic variant

Isolated complex I deficiency represents the most common mitochondrial respiratory chain defect involved in mitochondrial disorders. Among these, the mitochondrial DNA (mtDNA) m.13513G>A pathogenic variant in the NADH dehydrogenase 5 subunit gene (MT-ND5) has been associated with heterogenous manifestations, including phenotypic overlaps of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes, Leigh syndrome, and Leber’s hereditary optic neuropathy (LHON). Interestingly, this specific mutation has been recently described in patients with adult-onset nephropathy. We, here, report the unique combination of LHON, nephropathy, sensorineural deafness, and subcortical and cerebellar atrophy in association with the m.13513G>A variant

MET inhibition sensitizes rhabdomyosarcoma cells to NOTCH signaling suppression

Rhabdomyosarcoma (RMS) is a pediatric myogenic soft tissue sarcoma. The Fusion-Positive (FP) subtype expresses the chimeric protein PAX3-FOXO1 (P3F) while the Fusion-Negative (FN) is devoid of any gene translocation. FP-RMS and metastatic FN-RMS are often unresponsive to conventional therapy. Therefore, novel therapeutic approaches are needed to halt tumor progression. NOTCH signaling has oncogenic functions in RMS and its pharmacologic inhibition through gamma-secretase inhibitors blocks tumor growth in vitro and in vivo. Here, we show that NOTCH signaling blockade resulted in the up-regulation and phosphorylation of the MET oncogene in both RH30 (FP-RMS) and RD (FN-RMS) cell lines. Pharmacologic inhibition of either NOTCH or MET signaling slowed proliferation and restrained cell survival compared to control cells partly by increasing Annexin V and CASP3/7 activation. Co-treatment with NOTCH and MET inhibitors significantly amplified these effects and enhanced PARP1 cleavage in both cell lines. Moreover, it severely hampered cell migration, colony formation, and anchorage-independent growth compared to single-agent treatments in both cell lines and significantly prevented the growth of FN-RMS cells grown as spheroids. Collectively, our results unveil the overexpression of the MET oncogene by NOTCH signaling targeting in RMS cells and show that MET pathway blockade sensitizes them to NOTCH inhibition

The Business Case for Preconception Care: Methods and Issues

Only a limited number of economic evaluations have addressed the costs and benefits of preconception care. In order to persuade health care providers, payers, or purchasers to become actively involved in promoting preconception care, it is important to demonstrate the value of doing so through development of a “business case”. Perceived benefits in terms of organizational reputation and market share can be influential in forming a business case. In addition, it is standard to include an economic analysis of financial costs and benefits from the perspective of the provider practice, payer, or purchaser in a business case. The methods, data needs, and other issues involved with preparing an economic analysis of the likely financial return on investment in preconception care are presented here. This is accompanied by a review or case study of economic evaluations of preconception care for women with recognized diabetes. Although the data are not sufficient to draw firm conclusions, there are indications that such care may yield positive financial benefits to health care organizations through reduction in maternal and infant hospitalizations. More work is needed to establish how costs and economic benefits are distributed among different types of organizations. Also, the optimum methods of delivering preconception care for women with diabetes need to be evaluated. Similar assessments should also be conducted for other forms of preconception care, including comprehensive care