Distribution and ecology of <i>Pseudo-nitzschia</i> species (Bacillariophyceae) in surface waters of the Weddell Sea (Antarctica)

The distribution of six Pseudo-nitzschia species and their relationship with environmental conditions were studied for the first time in a vast zone of the Weddell Sea (∼61–77°S, Antarctica). Both qualitative and quantitative phytoplankton samples, collected during summer 2004, were examined using light and scanning electron microscopy. Phytoplankton abundance and composition showed great variability along our study area. Diatoms were the most conspicuous phytoplankton group in the northern area while small flagellates were generally dominant in the southern stations. The genus Pseudo-nitzschia was broadly distributed and significantly contributed to total diatom densities. A marked contrast in Pseudo-nitzschia species distribution was observed in three main zones divided by the Weddell Front (WF) and the Antarctic Slope Front (ASF). P. subcurvata and P. turgiduloides were the most abundant species in the neritic Weddell Sea zone, south of the ASF, mainly near the ice-edge in shallower waters and in conditions of long photoperiod. In contrast, P. prolongatoides and P. lineola dominated north of the ASF; the first was associated with deeper and nutrient-rich waters whereas the latter showed a weak relation with environmental variables examined. Finally, P. turgidula and P. heimii were mostly observed in the Weddell–Scotia Confluence Zone in the warmest and far from ice covered waters, north of the WF. A brief morphological Pseudo-nitzschia species description is given in the Appendix, including morphometrics and pictures.Facultad de Ciencias Naturales y Muse

Paclitaxel, vinorelbine and 5-fluorouracil in breast cancer patients pretreated with adjuvant anthracyclines

We investigated the activity and toxicity of a combination of vinorelbine (VNB), paclitaxel (PTX) and 5-fluorouracil (5-FU) continuous infusion administered as first-line chemotherapy in metastatic breast cancer patients pretreated with adjuvant anthracyclines. A total of 61 patients received a regimen consisting of VNB 25 mg m−2 on days 1 and 15, PTX 60 mg m−2 on days 1, 8 and 15 and continuous infusion of 5-FU at 200 mg m−2 every day. Cycles were repeated every 28 days. Disease response was evaluated by both RECIST and World Health Organization (WHO) criteria. Objective responses were recorded in 39 of 61 patients (64.0%) assessed by WHO and in 36 of 50 patients (72.0%) assessable by RECIST criteria. Complete remission occurred in 15 (24.6%) and 14 patients (28.0%), respectively. The median time to progression and overall survival of entire population was 10.6 and 27.3 months, respectively, and median duration of complete response was 14.8 months. The dose-limiting toxicity was myelosuppression (leucopenia grade 3/4 in 52.5% of patients). Grade 3/4 nonhaematologic toxicities included mucositis/diarrhoea in 13.1%, skin in 3.3% and cardiac in 1.6% of patients. Grade 2/3 neurotoxicity was observed in five patients (7.2%). The VNB, PTX and 5-FU continuous infusion combination regimen was active and manageable. Complete responses were frequent and durable

Observational study of chronic myeloid leukemia italian patients who discontinued tyrosine kinase inhibitors in clinical practice

It is judged safe to discontinue treatment with tyrosine kinase inhibitors (TKI) for chronic myeloid leukemia (CML) in experimental trials on treatment-free remission (TFR). We collected a total of 293 Italian patients with chronic phase CML who discontinued TKI in deep molecular response. Seventy-two percent of patients were on treatment with imatinib, and 28% with second generation TKI at the time of discontinuation. Median duration of treatment with the last TKI was 77 months [Interquartile Range (IQR) 54;111], median duration of deep molecular response was 46 months (IQR 31;74). Duration of treatment with TKI and duration of deep molecular response were shorter with second generation TKI than with imatinib (P&lt;0.001). Eighty-eight percent of patients discontinued as per clinical practice, and reasons for stopping treatment were: toxicity (20%), pregnancy (6%), and shared decision between treating physician and patient (62%). After a median follow up of 34 months (range, 12-161) overall estimated TFR was 62% (95%CI: 56;68). At 12 months, TFR was 68% (95%CI: 62;74) for imatinib, 73% (95%CI: 64;83) for second generation TKI. Overall median time to restart treatment was six months (IQR 4;11). No progressions occurred. Although our study has the limitation of a retrospective study, our experience within the Italian population confirms that discontinuation of imatinib and second generation TKI is feasible and safe in clinical practice

A Generic Bio-Economic Farm Model for Environmental and Economic Assessment of Agricultural Systems

Bio-economic farm models are tools to evaluate ex-post or to assess ex-ante the impact of policy and technology change on agriculture, economics and environment. Recently, various BEFMs have been developed, often for one purpose or location, but hardly any of these models are re-used later for other purposes or locations. The Farm System Simulator (FSSIM) provides a generic framework enabling the application of BEFMs under various situations and for different purposes (generating supply response functions and detailed regional or farm type assessments). FSSIM is set up as a component-based framework with components representing farmer objectives, risk, calibration, policies, current activities, alternative activities and different types of activities (e.g., annual and perennial cropping and livestock). The generic nature of FSSIM is evaluated using five criteria by examining its applications. FSSIM has been applied for different climate zones and soil types (criterion 1) and to a range of different farm types (criterion 2) with different specializations, intensities and sizes. In most applications FSSIM has been used to assess the effects of policy changes and in two applications to assess the impact of technological innovations (criterion 3). In the various applications, different data sources, level of detail (e.g., criterion 4) and model configurations have been used. FSSIM has been linked to an economic and several biophysical models (criterion 5). The model is available for applications to other conditions and research issues, and it is open to be further tested and to be extended with new components, indicators or linkages to other models

AMP-activated protein kinase - not just an energy sensor

Orthologues of AMP-activated protein kinase (AMPK) occur in essentially all eukaryotes as heterotrimeric complexes comprising catalytic α subunits and regulatory β and γ subunits. The canonical role of AMPK is as an energy sensor, monitoring levels of the nucleotides AMP, ADP, and ATP that bind competitively to the γ subunit. Once activated, AMPK acts to restore energy homeostasis by switching on alternate ATP-generating catabolic pathways while switching off ATP-consuming anabolic pathways. However, its ancestral role in unicellular eukaryotes may have been in sensing of glucose rather than energy. In this article, we discuss a few interesting recent developments in the AMPK field. Firstly, we review recent findings on the canonical pathway by which AMPK is regulated by adenine nucleotides. Secondly, AMPK is now known to be activated in mammalian cells by glucose starvation by a mechanism that occurs in the absence of changes in adenine nucleotides, involving the formation of complexes with Axin and LKB1 on the surface of the lysosome. Thirdly, in addition to containing the nucleotide-binding sites on the γ subunits, AMPK heterotrimers contain a site for binding of allosteric activators termed the allosteric drug and metabolite (ADaM) site. A large number of synthetic activators, some of which show promise as hypoglycaemic agents in pre-clinical studies, have now been shown to bind there. Fourthly, some kinase inhibitors paradoxically activate AMPK, including one (SU6656) that binds in the catalytic site. Finally, although downstream targets originally identified for AMPK were mainly concerned with metabolism, recently identified targets have roles in such diverse areas as mitochondrial fission, integrity of epithelial cell layers, and angiogenesis