Palaeoclimatic and palaeoenvironmental evolution of the Lower Pleistocene Arda River succession

The Arda River marine succession, cropping out in western Emilia (northern Italy) represents an excellent site to study past ecosystems dynamics in the frame of Early Pleistocene climate change and tectonic activity. This one-day excursion leads the participants to discover the palaeoclimatic and palaeoenvironmental evolution of the Lower Pleistocene Arda River marine section, unraveled through an integrated use of sedimentological, palaeoecological (molluscs and trace fossils) and geochemical tools. Upsection, the succession was deposited in progressively shallower water and colder climate during phases of advance of fan deltas affected by hyperpycnal flows. It culminates at the top with clast supported alluvial conglomerates and freshwater/terrestrial biota indicating a sea level drop and the establishment of a continental environment. It is very rich in fossils: in the marine part molluscs, brachiopods, corals and echinoderms, besides well preserved trace fossils, are abundant; whereas in the continental part a mammal fauna and freshwater/terrestrial molluscs are occasionally found. Sclerochemical analyses undertaken on bivalve shells indicate that seawater temperature seasonality was the main variable of climate change within the study area during the Early Pleistocene. In particular, strong seasonality and low winter palaeotemperatures were assumed to be the main drivers for the widespread establishment of Arctica islandica populations in the palaeo-Adriatic Sea around 1.80 Ma. During the excursion not only fossils are shown, but also interesting biocalcarenitic bodies with a complex geometry cropping out in the town of Castell\u2019Arquato. The excursion is complemented by the visit to the Giuseppe Cortesi geological and palaeontological museum, housing vertebrate and invertebrate fossil collections

Seasonality fluctuations recorded in fossil bivalves during the early Pleistocene: implications for climate change

Understanding the transformations of the climate system may help to predict and reduce the effects of global climate change. The geological record provides a unique archive that documents the long-term fluctuations of environmental variables, such as seasonal change. Here, we investigate how seasonal variation in seawater temperatures varied in the Mediterranean Sea during the early Pleistocene, approaching the Early-Middle Pleistocene Transition (EMPT) and the beginning of precession-driven Quaternary-style glacial–interglacial cycles. We performed whole-shell and sclerochemical stable isotope analyses (δ18O, δ13C) on bivalves, collected from the lower Pleistocene Arda River marine succession (northern Italy), after checking shell preservation. Our results indicate that seawater temperature seasonality was the main variable of climate change in the Mediterranean area during the early Pleistocene, with the Northern Hemisphere Glaciation (NHG) exerting a control on the Mediterranean climate. We show that strong seasonality (14.4–16.0 °C range) and low winter paleotemperatures (0.8–1.6 °C) were likely the triggers leading to the establishment of widespread populations of so called “northern guests” (i.e., cold water taxa) in the Mediterranean Sea around 1.80 Ma. The shells postdating the arrival of the “northern guests” record a return to lower seasonal variations and higher seawater paleotemperatures, with seasonality increasing again approaching the EMPT; the latter, however, is not associated with a corresponding cooling of mean seawater paleotemperatures, showing that the observed seasonality variation represents a clear signal of progressive climate change in the Mediterranean Sea

Aquifer architecture of the Quaternary alluvial succession of the southern lambro basin (Lombardy-Italy)

Aquifer stratigraphy of the sector of the Pleistocene - Holocene alluvial plain of Lombardy, run by the Lambro valley system south of Milan, has been reconstructed on the basis of geological mapping at 1:10.000 and subsurface interpretation and correlation of more than 150 among water wells, boreholes and deep excavations. The Middle (?) - Late Pleistocene sedimentary evolution of this sector includes four major progradation cycles of alluvial depositional systems that migrated from the alpine northern side towards the axial palaeo-Po depositional system. These cycles were governed by Pleistocene glacial cycles, in combination with ramp-folding of the San Colombano - Salerano apenninic anticlines and minor uplift of the alpine side. Every major cycle is soled by an erosion surface, and is shaped by minor fining upward sequences. Both major and minor sequences record at first the advance of coarse-grained units (distal braided alluvial fan or sandy braid plain) which fringe-out south-eastwards into meandering fluvial systems, and are replaced upwards by alluvial plain fines, which close the sequences. Physical stratigraphy and geomorphology, analysis of facies associations, characterisation of gravel composition, radiocarbon dating on 4 peat and plant relic samples and findings of transported artefacts allowed the correlation of the four cycles with the regional evolution. The Post Glacial meandering depositional systems of the deeply entrenched Lambro valley system (Unit 4, Holocene; Unit 5, historical), are cut into the braided stream to meandering depositional systems that developed during L.G.M. times, at present outside the Lambro valley (Unit 3, Late Pleistocene). These represent the uppermost aquifer unit, i.e. the phreatic - non saturated zone. The underlying Unit 2 (Late Pleistocene) can be correlated with the Besnate Allogroup, and therefore developed during the corresponding glaciations. It is formed by three stacked sequences, controlled by glacial cycles, which are deeply scoured into the lowermost succession that could be studied (Unit 1 Middle ? - Late Pleistocene ?). It represents the most important and permeable intermediate aquifer unit, that is only partly confined by the flood-plain fines of the uppermost sub-unit 2C

New indirect evidence of Permian bi-modal volcanism from sediment petrology in the Orobic Basin (Central Southern Alps, Italy)

The Lower Permian Cabianca Volcanite (lower Collio Fm. Auct.), representing the filling of a large caldera, is dominantly acidic, as most coeval volcanics in the Southern Alps: intermediate rocks are rare and nearly irrelevant by volume (only two small andesite breccia pipes outcrop on the flanks of Mt. Cabianca). Subsurface data document the occurrence of an andesite body in the Novazza mine and a diatreme 2 km to the east (crossed by a prospection well), on the left Serio River valley. Out of the moat, Lower Permian pyroclastics outcrop along tens of kilometres, but intermediate rocks are unreported, except for the Val Pradini \u201cporfirite amigdalare\u201d in the west (Ornica). Permian volcanics and Variscan metamorphics are covered by Lower Permian sediments deposited in a transtensional basin, bound by steep faults and fringed by alluvial fans. The alluvial fan conglomerate of Val Sanguigno, north of Novazza, is dominated by andesitic clasts (cobbles-boulders), which reasonably derived from lavas that were outcropping beyond the southern boundary fault of the basin. Investigations of the petrographic composition of the alluvial fan conglomerates carried out east and west of Mt. Cabianca, allowed comparing the composition of the volcanic rocks preserved in the depocentre (Cabianca Caldera) with the volcanic rocks cropping out outside of it, recorded in the clasts of the alluvial fans at the borders of the Orobic Basin. In the eastern (Lake Barbellino) and central (Val Sanguigno) parts of the basin, conglomerates at the southern border of the basin contain abundant intermediate pebbles, and an increasing proportion of basement clasts to the west. Conglomerates from the northern margin of the basin (Ponteranica Conglomerate, Pizzo dei Tre Signori massif) mainly contain pebbles and cobbles of metamorphic basement, acidic welded tuffs and, subordinately, of grey-green volcanics. In both cases, microscope analysis of associated litharenites revealed significant quantities of intermediate to basic volcanic lithic fragments. Visual estimates suggest that basic to intermediate clasts represent 15 to 20% of the bulk volume. Petrographic composition of Lower Permian conglomerates confirms that Permian streams eroded both volcanic rocks and the Variscan basement, but documents that in the source area of the siliciclastics (i.e. highs bordering the basin) intermediate-basic volcanics were more abundant than in the Cabianca Volcanite. The relatively scarcer acidic pebbles in the conglomerate can be partly ascribed to the fact that they were still incoherent and reluctant to produce pebbles transportable over significant distance. Nevertheless, the high amount of basic-intermediate rocks documents that outside of the caldera these rocks were volumetrically abundant. This fact may be explained suggesting the existence of fractures and faults able to drive and trap basic-intermediate lavas documenting a clear bi-modal distribution of extrusives at the surface

Lithostratigraphy and facies architecture of a Lower Permian continental succession in Central Southern Alps (Orobic Basin, Italy)

The Lower Permian Pizzo del Diavolo Fm. of the Orobic Alps (Laghi Gemelli Gr., upper Collio Fm. Auct.) records, along an E-W area more than 50 km long, events that occurred in a complex continental depositional system, during semi-arid climatic condiitons and in a transtensional tectonic setting. This formation postdates intense volcanic activity and overlays parts of a large caldera and its vast surrounding areas, covered by dominating pyroclastic deposits interbedded with rare braid-plain and lacustrine sediments (Cabianca Volcanite). Post-volcanic sediment distribution reflects the existence of connected half-grabens, characterised by transverse sedimentary input (coarse-grained alluvial fans) evolving into fine-grained heterolitic deposits in the depocentre, hosting ephemeral playa-lakes. Field mapping of two marginal sectors of the Orobic Basin (Pizzo dei Tre Signori massif and Lake Barbellino area), coupled with facies analysis of the Pizzo del Diavolo Fm., led to the identification of significantly different sedimentary evolutions. At the eastern and western ends of the basin, the Pizzo del Diavolo Fm. consists of alluvial fan and floodplain facies associations that differ from the previously studied stratigraphic architecture described in the central part of the basin. The southern borders of the studied areas are characterised by coarse-grained, fining-upward alluvial fan deposits (Val Sanguigno Conglomerate) at their base. The petrographic composition of the conglomerates from the northern border of the basin (Ponteranica Conglomerate) indicates differences in the exposed and eroded rocks from the northern and southern highs, with changes along the basin borders, where conglomeratic units with dominating basement clasts (Mt. Aga Conglomerate) occur. Floodplain facies are similar all along the basin, even if with thickness changes (up to 700 metres in the western part). The stratigraphic architecture observed in the eastern and western sectors markedly differs from that described in the central part of the basin (where a well-organised succession of two fining-upward cycles is described), preventing a detailed correlation of the events across the basin. Also the relative abundance of facies in these three sectors of the basin is different: fine-grained sediments dominate in the central part, whereas coarser deposits occur to the west (Pizzo dei Tre Signori massif) and to the east (Lake Barbellino). The complex architecture of the basin, the difficulty in recognising events or trends that can be traced all across the basin and the different petrographic composition of conglomerates along the northern and southern margins of the basin suggest not only that tectonics controlled facies distribution and depositional environments but also the existence of sub-basins characterised by different evolutions within the greater Orobic Basin, further supporting the envisaged role of strike-slip tectonics

Dimethyl carbonate as a green alternative to acetonitrile in reversed-phase liquid chromatography. Part I: Separation of small molecules

: Nowadays, environmental problems are drawing the attention of governments and international organisations, which are therefore encouraging the transition to green industrial processes and approaches. In this context, chemists can help indicate a suitable direction. Beside the efforts focused on greening synthetic approaches, currently also analytical techniques and separations are under observation, especially those employing large volumes of organic solvents, such as reversed-phase liquid chromatography (RPLC). Acetonitrile has always been considered the best performing organic modifier for RPLC applications, due to its chemical features (complete miscibility in water, UV transparency, low viscosity etc); nevertheless, it suffers of severe shortcomings, and most importantly, it does not fully comply with Environmental, Health and Safety (EHS) requirements. For these reasons, alternative greener solvents are being investigated, especially easily available alcohols. In this work, chromatographic performance of the most common solvents used in reversed-phase chromatography, i.e., acetonitrile, ethanol and isopropanol, have been compared to a scarcely used solvent, dimethyl carbonate (DMC). The analytes of interest were two small molecules, caffeine and paracetamol, whose kinetics and retention behaviour obtained with the four solvents have been compared, and all contributions to band broadening have been assessed. Results about kinetic performance are very promising, indicating that a small amount (7 % v/v) of DMC is able to produce the same efficiency as a 2.5-times larger ACN volume (18 % v/v), and larger efficiency than alcohols. This paper reports, for the first time, fundamental studies concerning the mass transfer phenomena when DMC is used as an organic solvent in RPLC, and, together with the companion paper, represents the results of a research whose final aim was to discover whether DMC is suitable for chromatographic applications both in linear and preparative conditions

Sustainability in peptide chemistry: current synthesis and purification technologies and future challenges.

Developing greener synthesis processes is an inescapable necessity to transform the industrial landscape, mainly in the pharmaceutical sector, into a long-term, sustainable reality. In this context, the renaissance of peptides as medical treatments, and the enforcement of more stringent sustainability requirements by regulatory agencies, pushed chemists toward the introduction of sustainable processes to prepare highly pure, active pharmaceutical ingredients (APIs). Innovative upstream (synthesis) and downstream (purification) methodologies have been developed during the last 5 years with the introduction and optimization of several technologies in solid-phase peptide synthesis (SPPS), liquid-phase peptide synthesis (LPPS), chemoenzymatic peptide synthesis (CEPS), and chromatographic procedures. These innovations are also moving toward the introduction of continuous processes that represent one of the most important targets for iterative processes. This overview discusses the most recent efforts in making peptide chemistry greener. The extensive studies that were carried out on green solvents, reaction conditions, auxiliary reagents and purification technologies in the peptide segment can be useful to other fields of organic synthesi

Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses

Our aim was to study the activity and toxicity of the gemcitabine plus vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously untreated patients aged < 70 years, with stage IV or IIIb (not candidates for radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m–2): level I = 1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A feasibility study was performed at each dose-level, followed by a single-stage phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia. Overall, out of 126 patients enrolled in phase II studies, there were one complete and 32 partial responses (response rate 26%: 95% CI 18–34%). Response rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The treatment was well tolerated. Toxicity was less frequent and severe at level I. Overall median survival was 33 weeks (95% CI 28–40). Descriptive quality of life analysis showed that patients with a worse baseline global health status score tended to drop out of the study earlier than those with a better score. Gem Vin is feasible at different doses. It is sufficiently active and well tolerated. A phase III study to compare the effect on quality of life of Gem Vin (level I) vs cisplatin-based chemotherapy is ongoing. © 2000 Cancer Research Campaig

Antibodies reacting with Simian virus 40 mimotopes in serum samples from patients with thalassaemia major

Background. Simian virus 40 (SV40) is a small DNA tumour virus. Footprints of the virus have been detected in different humam lymphoproliferative disorders and in blood specimens of blood from healthy blood donors. This study was carried out to verify whether SV40 antibodies can be detected in serum samples from multiply transfused patients with thalassaemia major.Materials and methods. An indirect enzyme-linked immunosorbent assay was employed, using SV40 specific synthetic peptides mimicking the antigens of the viral capsid proteins 1-2-3, to test for the presence of antibodies to SV40 in serum samples taken from patients affected by transfusiondependent thalassaemia major (n=190) and healthy blood donors (n=251).Results. The prevalence of antibodies against SV40 was higher in patients than in controls (24% vs 17%). The prevalence increased and was significantly higher in the older age group of patients affected by thalassemia major than in controls (38% vs 20%, p<0.04).Discussion. The higher prevalence of serum antibodies against simian virus 40 in older, multiply transfused patients with thalassamia major than in controls suggests that this virus, or a closely related yet unknown human polyomavirus, could have been transmitted in the past by transfusion with whole blood. At the same time, our data indicate no significant differences in prevalence of SV40 antibodies in patients and controls of younger age thus suggesting that current transfusion methods with leucodepletion and filtered red cells are safe

Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC.</p> <p>Methods</p> <p>Overall, 95 patients received pemetrexed 500 mg/m²i.v. over Day 1 of a 21-day cycle. Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria.</p> <p>Results</p> <p>Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated) reported at least one adverse event: 34 (35.8%) had grade 3 as worst grade and only 5 (5.2%) had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4%) and leukopenia (6.3 %) were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%), fatigue (3.2%) and dyspnea (3.2%) were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade) were pyrexia (11.6%), vomiting, nausea, diarrhea and asthenia (9.5%) and fatigue (8.4%). Tumor Response Rate (CR/PR) in treated patients was 9.2%. The survival at 4.5 months (median follow-up) was 79% and the median PFS was 3.1 months. Twenty patients (21.1%) died mainly because of disease progression.</p> <p>Conclusion</p> <p>Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities.</p