Man-made activities and morphological changes of Ligurian floodplains (Italy) since modern history to nowadays: an approach through old maps comparison

The Tyrrhenian slope of Liguria extends along the coast, from West to East, for nearly 300 km between Ventimiglia to Marinella di Sarzana: this stretch of territory presents more than a hundred catchments mainly characterized by small-size floodplains, usually less than 1 km2. Ligurian catchments, except for the Roja and the Magra rivers, have common features: by the area they can be distinguished in small basins (less than 15 km2), medium (15-150 km2) and large (150-500 km2). The slopes of the catchment areas are very steep, while the flat alluvial plains are typically narrow and elongated: the largest one are referred to the Entella stream (approximately 4 km long) and the Centa stream (about 7 km in length). On these floodplains are located almost Ligurian urban areas, which represent the expansion of the historical settlements and road connections. Through a comparative mapping it was rebuilt the morphological evolution of Ligurian floodplains in historical times, witnessing the land-use and riverbed changes in the modern era until today, by using: 1) Historical maps of the eighteenth century by Matteo Vinzoni (\u201cPianta delle due riviere della serenissima Repubblica di Genova divise nei commissariati di sanit\ue0\u201d e \u201cIl Dominio della Serenissima Repubblica di Genova in terraferma\u201d); 2) historical topographic maps of the first half of the nineteenth century (\u201cStati Sardi di Terraferma), in different topographic scales: a) 1:50.000, b) 1:20.000 and c) 1:9.450; 3) historical topographic maps of the second half of the nineteenth century until the first half of the twentieth century (\u201cTavolette dell\u2019Istituto Geografico Militare Italiano, Firenze, 1878-1940, 1:25.000); 4) regional maps for the second half of the twentieth century, 1: 10.000 and 1: 25.000, while the current status was assessed with Google Earth Pro platforms; 5) important information was taken by the Map of the historical evolution of urban fabric, 1: 50.000 produced by Liguria Region and obtained by the overlap of urbanized areas in different periods (1855, 1936, 1964 and 1986). The secular human activities have therefore modified the natural landscape through land use changes, either for catchment or for the floodplain. The main channel, and even the minor hydrographic network, have showed major transformations over time. The anthropic action has deeply modified the morphology of Ligurian floodplains, except for the two largest: Albenga (Centa stream) and Chiavari-Lavagna (Entella stream), which still have a portion of soil for agricultural purposes. In many cases it has detected a river-bed covering, especially in the medium-terminal portion, for the purpose of building needs and the road link. Other very widespread changes finally concern: a) deviations and displacements of the riverbed, b) the progradation of the coastline due to fills and embankments

Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial. Italian Chemoprevention Group.

The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 12-month measurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL- and HDL-cholesterol of approximately -9%, -19% and +0.2% in continuous HRT users compared with -9%, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term). We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity

Sentinel lymph node biopsy in microinvasive ductal carcinoma in situ

Background: Microinvasive breast cancer is an uncommon pathological entity. Owing to the rarity of this condition, its surgical axillary management and overall prognosis remain controversial. Methods: A database was analysed to identify patients with microinvasive ductal carcinoma in situ (DCIS) who had surgery for invasive breast cancer at the European Institute of Oncology, Milan, between 1998 and 2010. Women who had undergone axillary staging by sentinel lymph node biopsy were included in the study. Results: Of 257 women with microinvasive breast cancer who underwent sentinel lymph node biopsy (SLNB), 226 (87.9 per cent) had negative sentinel lymph nodes (SLNs) and 31 had metastatic SLNs. Twelve patients had isolated tumour cells (ITCs), 14 had micrometastases and five had macrometastases in sentinel nodes. Axillary lymph node dissection was performed in 16 of the 31 patients with positive SLNs. After a median follow-up of 11 years, only one regional first event was observed in the 15 patients with positive SLNs who did not undergo axillary lymph node dissection. There were no regional first events in the 16 patients with positive SLNs who had axillary dissection. Conclusion: Good disease-free and overall survival were found in women with positive SLNs and microinvasive DCIS. This study is in line with studies showing that SLNB inmicroinvasive DCIS may not be useful, and supports the evidence that less surgery can provide the same level of overall survival with better quality of life

Methodology and Neuromarkers for Cetaceans’ Brains

Cetacean brain sampling may be an arduous task due to the difficulty of collecting and histologically preparing such rare and large specimens. Thus, one of the main challenges of working with cetaceans’ brains is to establish a valid methodology for an optimal manipulation and fixation of the brain tissue, which allows the samples to be viable for neuroanatomical and neuropathological studies. With this in view, we validated a methodology in order to preserve the quality of such large brains (neuroanatomy/neuropathology) and at the same time to obtain fresh brain samples for toxicological, virological, and microbiological analysis (neuropathology). A fixation protocol adapted to brains, of equal or even three times the size of human brains, was studied and tested. Finally, we investigated the usefulness of a panel of 20 antibodies (neuromarkers) associated with the normal structure and function of the brain, pathogens, age-related, and/or functional variations. The sampling protocol and some of the 20 neuromarkers have been thought to explore neurodegenerative diseases in these long-lived animals. To conclude, many of the typical measures used to evaluate neuropathological changes do not tell us if meaningful cellular changes have occurred. Having a wide panel of antibodies and histochemical techniques available allows for delving into the specific behavior of the neuronal population of the brain nuclei and to get a “fingerprint” of their real status

Prevention of Breast cancer with tamoxifen:preliminary findings from the italian randomised trial among hysterectomised women

Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C, Rotmensz N, Boyle P. SourceEuropean Institute of Oncology, Milan, Italy. Abstract BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat. FINDINGS: 5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy

The development of PubMed search strategies for patient preferences for treatment outcomes.

BACKGROUND: The importance of respecting patients' preferences when making treatment decisions is increasingly recognized. Efficiently retrieving papers from the scientific literature reporting on the presence and nature of such preferences can help to achieve this goal. The objective of this study was to create a search filter for PubMed to help retrieve evidence on patient preferences for treatment outcomes. METHODS: A total of 27 journals were hand-searched for articles on patient preferences for treatment outcomes published in 2011. Selected articles served as a reference set. To develop optimal search strategies to retrieve this set, all articles in the reference set were randomly split into a development and a validation set. MeSH-terms and keywords retrieved using PubReMiner were tested individually and as combinations in PubMed and evaluated for retrieval performance (e.g. sensitivity (Se) and specificity (Sp)). RESULTS: Of 8238 articles, 22 were considered to report empirical evidence on patient preferences for specific treatment outcomes. The best search filters reached Se of 100 % [95 % CI 100-100] with Sp of 95 % [94-95 %] and Sp of 97 % [97-98 %] with 75 % Se [74-76 %]. In the validation set these queries reached values of Se of 90 % [89-91 %] with Sp 94 % [93-95 %] and Se of 80 % [79-81 %] with Sp of 97 % [96-96 %], respectively. CONCLUSIONS: Narrow and broad search queries were developed which can help in retrieving literature on patient preferences for treatment outcomes. Identifying such evidence may in turn enhance the incorporation of patient preferences in clinical decision making and health technology assessment

Prioritization of high-cost new drugs for HCV: making sustainability ethical

Hepatitis C virus (HCV) infection is a major health problem worldwide. Chronic HCV infection may in the long run cause cirrhosis, hepatic decompensation and hepatocellular carcinoma, with an ultimate disease burden of at least 350,000 deaths per year worldwide. The new generation of highly effective direct acting antivirals (DAA) to treat HCV infection brings major promises to infected patients in terms of exceedingly high rates of sustained virological response (SVR) but also of tolerability, allowing even the sickest patients to be treated. Even in the face of the excellent safety and efficacy and wide theoretical applicability of these regimens, their introduction is currently facing cost and access issues denying their use to many patients in need. Health systems in all countries are facing a huge problem of distributive justice, since while they should guarantee individual rights, among which the right to health in its broader sense, therefore not limited to healing, but extended to quality of life, they must also grant equal access to the healthcare resources and keep the distribution system sustainable. In the face of a disease with a relatively unpredictable course, where many but not of all chronically infected will eventually die of liver disease, selective allocation of this costly resource is debatable. In most countries the favorite solution has been a stratification of patients for prioritization of treatment, which means allowing Interferon-free DAA treatment only in patients with advanced fibrosis or cirrhosis, while keeping on hold persons with lesser stages of liver disease. In this report, we will perform an ethical assessment addressing the issues linked to access to new therapies, prioritization and eligibility criteria, analyzing the meaning of the term “distributive justice” and the different approaches that can guide us (individualistic libertarianism, social utilitarianism and egalitarianism) on this specific matter. Even if over time the price of new DAA will be reduced through competition and eventual patent expiration, the phenomenon of high drug costs will go on in the next decades and we need adequate tools to face the problems of distributive justice that come with it