Life-history of Palaeoloxodon antiquus reveals Middle Pleistocene glacial refugium in the Megalopolis basin, Greece.

The Balkans are considered a major glacial refugium where flora and fauna survived glacial periods and repopulated the rest of Europe during interglacials. While it is also thought to have harboured Pleistocene human populations, evidence linking human activity, paleoenvironmental indicators and a secure temporal placement to glacial periods is scant. Here, we present the first intra-tooth multi-isotope analysis for the European straight-tusked elephant Palaeoloxodon antiquus, on an adult male individual excavated in association with lithic artefacts at the MIS 12 site Marathousa 1 (Megalopolis basin, Greece). The studied find also exhibits anthropogenic modifications, providing direct evidence of hominin presence. We employed strontium, carbon and oxygen isotope analysis on enamel bioapatite to investigate its foraging and mobility behaviour, using a sequential sampling strategy along the tooth growth axis of the third upper molar, to assess ecological changes during the last decade of life. We found a geographically restricted range, in a C3-dominated open woodland environment, and relatively stable conditions over the examined timeframe. Our results show that, despite the severity of the MIS 12 glacial, the Megalopolis basin sustained a mesic habitat, sufficient plant cover and limited seasonal fluctuations in resource availability, pointing to its role as a glacial refugium for both fauna and hominins.

First record of Macaca (Cercopithecidae, Primates) in the Middle Pleistocene of Greece.

In this article, we describe an almost complete macaque mandible from the Middle Pleistocene locality Marathousa 1 in the Megalopolis Basin of southern Greece. The mandible belonged to a male individual of advanced ontogenetic age and of estimated body mass ∼13 kg. Comparative metric analysis of its teeth permits its attribution to the Barbary macaque Macaca sylvanus, a species that was geographically widely distributed in Western Eurasia during the Plio-Pleistocene. The dental dimensions of the Marathousa 1 macaque fit better within the variation of the Early Pleistocene M. s. florentina and the Middle to Late Pleistocene M. s. pliocena rather than with the extant representative M. s. sylvanus. Moreover, principal component analysis reveals a better match with M. s. pliocena. However, because no clear-cut diagnostic criteria have been defined to differentiate these European fossil subspecies, we attribute the Marathousa 1 specimen to M. s. cf. pliocena, in agreement with the chronology of the locality. Previously known only from the Early Pleistocene of Greece by some isolated teeth, this is the first record of Macaca in the Middle Pleistocene of the country and one of very few in the eastern sector of the peri-Mediterranean region. We discuss the presence of macaques in the paleolake environment of Marathousa 1, as well as their predation risks from both carnivores and hominins present at the locality.

Age constraints for the Trachilos footprints from Crete.

We present an updated time frame for the 30 m thick late Miocene sedimentary Trachilos section from the island of Crete that contains the potentially oldest hominin footprints. The section is characterized by normal magnetic polarity. New and published foraminifera biostratigraphy results suggest an age of the section within the Mediterranean biozone MMi13d, younger than ~ 6.4 Ma. Calcareous nannoplankton data from sediments exposed near Trachilos and belonging to the same sub-basin indicate deposition during calcareous nannofossil biozone CN9bB, between 6.023 and 6.727 Ma. By integrating the magneto- and biostratigraphic data we correlate the Trachilos section with normal polarity Chron C3An.1n, between 6.272 and 6.023 Ma. Using cyclostratigraphic data based on magnetic susceptibility, we constrain the Trachilos footprints age at ~ 6.05 Ma, roughly 0.35 Ma older than previously thought. Some uncertainty remains related to an inaccessible interval of ~ 8 m section and the possibility that the normal polarity might represent the slightly older Chron C3An.2n. Sediment accumulation rate and biostratigraphic arguments, however, stand against these points and favor a deposition during Chron C3An.1n.

Topotecan and pegylated liposomal doxorubicin combination as palliative treatment in patients with pretreated advanced malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive disease with poor or modest responses to chemotherapy and dismal prognosis. In most of the cases the scope of the treatment is only palliative. In the current study, the combination of i.v. topotecan and pegylated liposomal doxorubicin (PLD) in advanced multi-treated MPM was tested. Primary objective was palliation of the symptoms, with the secondary ones being the establishment of the regimen's safety and efficacy. PATIENTS AND METHODS: Nine patients were enrolled (7 males/2 females, median age 57.5 years, ECOG performance status ≤ 2), having progressed after 2 or 3 lines of chemotherapy including pemetrexed and cisplatin. Main symptoms were dyspnea, cough, chest pain, fatigue, and anorexia. The treatment included topotecan 1.2 mg/m2 i.v. on Days 1 - 3 and PLD 40 mg/m2 on Day 4, every 28 days. The patients received 4 - 8 chemotherapy cycles (median 5.8). RESULTS: In all cases, symptoms were significantly improved after the 2nd treatment cycle. Respiratory function tests showed considerable enhancement, while cough and pain were drastically reduced. All patients had objective clinical benefit, 1 patient achieving partial response and 8 stable disease. Median time to progression and overall survival was 7 and 9 months, respectively. The chosen dose of the topotecan/ PLD combination was well-tolerated with no Grade 3/4 toxicities. Quality of life, as it was evaluated by the QLQ-C30 and QLQLC13 questionnaires, had improved scores especially the ones referring symptomatology. CONCLUSION: The current study shows a significant palliative effect of the topotecan/ PLD combination in pretreated patients with advanced MPM.

A guideline for the management of women at substantially increased risk of breast cancer development.

The aim of this guideline is to provide a potential management strategy of women at high risk for breast cancer development. A summary of the available evidence is presented, including genetic risk assessment, chemoprevention, risk-reducing surgery and radiological screening, based on risk assessment of the individual. Recent progress in the diagnostic methods and therapeutic options for breast cancer does not prevent the death of at least one third of these patients from their disease. The focus on breast cancer prevention, especially for the group of women that is designated as high-risk, may reduce mortality. The determination of the group of women who are more likely to develop breast cancer will allow a targeted specific counselling and the application of preventative measures. All Cancer Centres and Units should develop an integrated network of breast cancer care using common clinical guidelines, management protocols and strategies of care (Recommendation grade D). All Breast Units should have a protocol for the management of women at high risk (Recommendation grade D).