rasterdiv-An Information Theory tailored R package for measuring ecosystem heterogeneity from space: To the origin and back.

Ecosystem heterogeneity has been widely recognized as a key ecological indicator of several ecological functions, diversity patterns and change, metapopulation dynamics, population connectivity or gene flow.In this paper, we present a new R package-rasterdiv-to calculate heterogeneity indices based on remotely sensed data. We also provide an ecological application at the landscape scale and demonstrate its power in revealing potentially hidden heterogeneity patterns.The rasterdiv package allows calculating multiple indices, robustly rooted in Information Theory, and based on reproducible open-source algorithms.

Bioethics: a challenge and an opportunity for hospital pharmacists.

OBJECTIVES: Traditionally, pharmacy ethics in Europe has held an insignificant place in the scheme of pharmaceutical education. We embraced the idea that bioethics should be an integral part of a pharmacist's education and professional practice, especially in hospital pharmacy where the concept of 'pharmaceutical care' should be revitalised to strengthen the broad-based and patient-oriented responsibilities of the clinical pharmacist. METHODS: We decided to structure a bioethics course tailored to pharmacists who are specialising in hospital pharmacy. We first created a training network partnership between a university and a research hospital to integrate classroom teaching with skill-specific practical experience. Our course pilot project introduces, in two of the four years of the national specialty programme, general topics and practical bioethical issues. RESULTS: A pilot course on ethics for the School of Specialisation in Hospital Pharmacy began at the Padua University in 2014. in February 2017 we contacted the same students again, asking them further questions about their experience. Several students asked to examine more cases and to deal with the few arguments that questioned them on an ethical level. On the whole, through the comments of trainees, the needs of those who are facing an unfamiliar subject, which is perceived as important, emerge. CONCLUSION: Even if we are aware that this is a pilot project and requires more data, dissemination of this experience into a wider network will help us to define an effective educational pathway in collaboration with other Specialty Schools of Hospital Pharmacy.

Egr-1 Maintains NSC Proliferation and Its Overexpression Counteracts Cell Cycle Exit Triggered by the Withdrawal of Epidermal Growth Factor.

In adult mammals, neural stem cells (NSCs) reside in specialized niches at the level of selected CNS regions, such as the subventricular zone (SVZ). The signaling pathways that reg-ulate NSC proliferation and differentiation remain poorly understood. Early growth response protein 1 (Egr-1) is an important transcription factor, widely studied in the adult mammalian brain, mediating the activation of target genes by a variety of extracellular stimuli. In our study, we aimed at testing how Egr-1 regulates adult NSCs derived from mouse SVZ and, in particular, the interplay between Egr-1 and the proliferative factor EGF. We demonstrate that Egr-1 expression in NSCs is induced by growth factor stimulation, and its level decreases after EGF deprivation or by using AG1478, an inhibitor of the EGF/EGFR signaling pathway. We also show that Egr-1 overexpression rescues the cell proliferation decrease observed either after EGF removal or upon treatment with AG1478, suggesting that Egr-1 works downstream of the EGF pathway. To better understand this mechanism, we investigated targets downstream of both the EGF pathway and Egr-1, and found that they regulate genes involved in NSC proliferation, such as cell cycle regulators, cyclins, and cyclin-dependent kinase inhibitors.

Repolarization effects of multiple-cycle chemotherapy and predictors of QTc prolongation: a prospective female cohort study on >2000 ECGs.

PURPOSE: Oncological patients are at increasing risk of QT prolongation, a risk factor for ventricular arrhythmia. We assessed impact and risk factors for corrected QT (QTc) prolongation during multiple-cycle chemotherapy. METHODS: We enrolled 100 outpatients initiating chemotherapy in a university center specializing in female cancer. Clinical, drug, laboratory, and 12-lead ECG data collection at baseline and at each chemotherapy cycle was performed. RESULTS: Enrolled patients were followed for 992 chemotherapy cycles (median 7; interquartile range 6-13); 2438 ECGs were recorded (20; 18-31) 36.8% pre-therapy, 36.8% following chemotherapy, and 22.5% 7-10 days after chemotherapy. Maximum QTc (Max-QTc) was recorded after 4 chemotherapy administrations in >50% of the entire cohort and also within every subset of patients with prolonged QTc (57% 471-480 ms; 54% 481-500 ms; 66% >500 ms). No cumulative effect on QTc was shown. QTc prolongation was comparable among the various protocols. Prophylactic/supportive drugs were not associated with additional QTc prolongation. Variables independently associated with QTc prolongation >470 ms were age (OR 1.056 95% CI 1.006-1.108, p = 0.028) and the baseline-first chemotherapy averaged QTc (BC-QTc) (OR 1.092 95% CI 1.051-1.136), a novel parameter devised for this study. Only BC-QTc maintained significance for QTc >480 ms. BC-QTc >435 ms identified 100 % of patients with Max-QTc >500 ms, 96% with Max-QTc 481-500 ms, and 66% with Max-QTc 471-480 ms. Only 29% of patients with Max-QTc ≤470 ms presented a BC-QTc >435 ms. CONCLUSIONS: Our results confirm the high prevalence of QTc prolongation after chemotherapy. Most of the patients reached Max-QTc after several cycles. BC-QTc may help in stratifying arrhythmic risk in real-world clinical practice.

Solitary Internal Mammary Lymph Node Metastases Detected by F-FDG-PET/CT in Ovarian Cancer.

Internal mammary lymph nodes as solitary site of recurrent ovarian cancer have not been previously described. In this case report, 3 cases of late and very late isolated recurrence in internal mammary lymph nodes are presented. (18)F-FDG-PET/CT allowed the diagnosis which was suspected by the increase of the serum CA-125 level in 2 out of 3 cases. Local treatment, consisting of surgery (in 2 patients) and radiation therapy (in 1 patient), permitted an optimal long-term disease control.

Early (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography may identify a subset of patients with estrogen receptor-positive breast cancer who will not respond optimally to preoperative chemotherapy.

BACKGROUND: A pathologic complete response (pCR) and minimal residual disease (pMRD) after preoperative chemotherapy (PCT) for early stage or locally advanced breast cancer (BC) correlates with a good prognosis. METHODS: Patients who received from 6 to 8 cycles of PCT for BC were monitored by (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET), and the maximal standardized uptake value (SUVmax) was calculated at baseline, after 2 cycles, after 4 cycles, and at the end of PCT. SUVmax percentage changes (Delta-SUV) were compared with the pathologic response rate. Patients who had a pCR or pMRD in the tumor and an absence of cancer cells in ipsilateral axillary lymph nodes were defined as having obtained an optimal pathologic response (pR), whereas all the other conditions were classified as a pathologic nonresponse (pNR). RESULTS: Of 34 patients, 7 (21%) achieved a pR (3 patients had a pCR, and 4 patients had pMRD). After the second cycle, the Delta-SUV threshold with optimal negative predictive value to predict a pR was 50%. Twenty-six patients (76%) had a Delta-SUV >50%, including all 7 patients who had a pR and 19 patients who had a pNR. Conversely, all 8 patients who had a Delta-SUV < or =50% had a pNR. All 8 of those patients had estrogen recepetor-positive tumors. CONCLUSIONS: Early evaluation of metabolic response by (18)F-FDG-PET during PCT was able to identify 30% of patients, all with estrogen receptor-positive tumors, who would not obtain pR after completion of chemotherapy program.

Oestrogen receptor 1 mRNA is a prognostic factor in ovarian cancer patients treated with neo-adjuvant chemotherapy: determination by array and kinetic PCR in fresh tissue biopsies.

Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the context of a neo-adjuvant chemotherapy trial. Study participants had epithelial ovarian or peritoneal carcinoma unsuitable for optimal upfront surgery and were treated with neo-adjuvant platinum-based chemotherapy before surgery. RNA was isolated from frozen tumour biopsies before treatment. RNA expression of ESR1 was determined by microarray and reverse transcriptase kinetic PCR technologies. The prognostic value of ESR1 was tested using univariate and multivariate Cox proportional hazards models, Kaplan-Meier survival statistics and the log-rank test. ESR1 positively correlates with proliferation markers and histopathological grading. ESR1 was a significant predictor of survival as a continuous variable in the univariate Cox regression analysis. In multivariate analysis, elevated baseline ESR1 mRNA levels predicted prolonged progression-free survival (P=0.041) and overall survival (P=0.01) after neo-adjuvant chemotherapy, independently of pathological grade and age. We conclude that pretreatment ESR1 mRNA is associated with tumour growth and is a strong prognostic factor in ovarian cancer, independent of the strongest clinical parameters used in clinical routine. We suggest that ESR1 mRNA status should be considered in order to minimize possible confounding effects in ovarian cancer clinical trials, and that early treatment with anti-hormonal agents based on reliable hormone receptor status determination is worth investigating.

Trastuzumab plus estrogen suppression as salvage treatment in a case of liver failure due to metastatic breast cancer.

BACKGROUND: Liver failure associated with metastatic breast cancer is a short-term survival condition in which standard chemotherapy is almost always contraindicated. CASE REPORT: A 45-year-old premenopausal woman with jaundice, due to extensive metastatic liver involvement from infiltrating ductal carcinoma of the right breast, with positive hormonal receptors (ER 70%, PgR 80%), a high proliferative index (Ki-67 60%) and HER2 overexpressed (immunohistochemical HercepTest 3+) was referred. Metastases were also present in the lymph nodes of the homolateral axilla and in both lungs (T2N2M1). Liver function indices were quite altered, in particular: total bilirubin 12.32 mg/dl (direct 11.49 mg/dl), ammonemia 270 microMoles/l and albumin 2.9 g/dl. Treatment consisted of trastuzumab at a loading dose of 4 mg/kg, followed by weekly doses of 2 mg/kg, Leuprolide at 3.75 mg intramuscularly monthly and Tamoxifen 20 mg daily. RESULTS: The patient presented a rapid and progressive improvement in her clinical conditions and in liver tests. The jaundice was resolved after 1.5 months and after 4 months she had normal liver function tests and an objective partial response was evident. The treatment was optimally tolerated. At this point Taxol, at a dose of 80 mg/m2 weekly, was added. After 10 months, the patient was well with a very important objective remission of all the tumor masses, and is continuing with the combined treatment. CONCLUSION: Trastuzumab plus estrogen suppression can be an effective salvage therapy in patients with liver failure due to metastatic HER2 and ER/PgR-positive breast cancer.

Italian drug policy: ethical aims of essential assistance levels.

In 2001 the Italian Government defined Essential Assistance Levels (LEA), which can be considered as an important step forward in the health care system. The Italian health care system would provide payment of essential and uniform aid services in order to safeguard many values such as human dignity, personal health, equal assistance and good health practices. The Ministry of Health has worked to rationalize the National Formulary and to define evaluation methods for drugs in order to choose what to reimburse without penalizing the rights of the individual and society. This paper describes how this job of rationalization was done and tries to illustrate the choices made in Italy by the use of two meaningful examples (statins and rivastigmine).