Global taxonomic, functional, and phylogenetic diversity of bees in apple orchards.

An essential prerequisite to safeguard pollinator species is characterisation of the multifaceted diversity of crop pollinators and identification of the drivers of pollinator community changes across biogeographical gradients. The extent to which intensive agriculture is associated with the homogenisation of biological communities at large spatial scales remains poorly understood. In this study, we investigated diversity drivers for 644 bee species/morphospecies in 177 commercial apple orchards across 33 countries and four global biogeographical biomes. Our findings reveal significant taxonomic dissimilarity among biogeographical zones. Interestingly, despite this dissimilarity, species from different zones share similar higher-level phylogenetic groups and similar ecological and behavioural traits (i.e. functional traits), likely due to habitat filtering caused by perennial monoculture systems managed intensively for crop production. Honey bee species dominated orchard communities, while other managed/manageable and wild species were collected in lower numbers. Moreover, the presence of herbaceous, uncultivated open areas and organic management practices were associated with increased wild bee diversity. Overall, our study sheds light on the importance of large-scale analyses contributing to the emerging fields of functional and phylogenetic diversity, which can be related to ecosystem function to promote biodiversity as a key asset in agroecosystems in the face of global change pressures.

Treating disease progression with osimertinib in EGFR-mutated non-small-cell lung cancer: novel targeted agents and combination strategies.

A precision medicine approach has been successfully applied in medical oncology for the treatment of non-small-cell lung cancer (NSCLC) through the identification of targetable driver molecular aberrations; activating mutations of epidermal growth factor receptor (EGFR) are the most common. Osimertinib, a third-generation, wild-type sparing, irreversible EGFR tyrosine kinase inhibitor (TKI), originally showed a striking activity after progression to first- and second-generation EGFR-TKIs when T790M resistance mutation was identified. Thereafter, upfront use of osimertinib became the standard of care based on overall survival benefit over first-generation TKIs erlotinib and gefitinib as reported in the FLAURA trial. For patients progressing on osimertinib, identification of resistance mechanisms is crucial to develop novel targeted therapeutic approaches. Moreover, innovative drugs or combination therapies are being developed for cases in which a specific resistance mechanism is not identifiable. In this review, the post-osimertinib treatment options for EGFR-mutated NSCLC are analyzed, with an outlook to ongoing clinical trials. An algorithm to guide clinicians in managing progression on osimertinib is proposed.

Toxicity of the insecticide sulfoxaflor alone and in combination with the fungicide fluxapyroxad in three bee species.

The sulfoximine insecticide sulfoxaflor is regarded as a potential substitute for neonicotinoids that were recently banned in the EU due to their side effects on bees. Like neonicotinoids, sulfoxaflor acts as a competitive modulator of nicotinic acetylcholine receptors. In agricultural environments, bees are commonly exposed to combinations of pesticides, and neonicotinoids are known to interact synergistically with fungicides. The objective of our study is to assess the acute oral toxicity of sulfoxaflor alone and in combination with a single dose of fluxapyroxad, a succinate dehydrogenase inhibitor (SDHI) fungicide, in three bee species: Apis mellifera, Bombus terrestris and Osmia bicornis. Because synergism may be dose-dependent, we tested a range of sulfoxaflor doses. Synergistic effects were assessed using three different approaches: Bliss criterion of drugs independence, ratio test comparing LD50s and model deviation ratio. Osmia bicornis was the most sensitive species to sulfoxaflor and both O. bicornis and A. mellifera showed significant synergism between the insecticide and the fungicide. For the most part, these synergistic effects were weak and only occurred at early assessment times and intermediate sulfoxaflor doses. The potential ecological relevance of these effects should be confirmed in field and/or cage studies. Overall, our laboratory results demonstrate that sulfoxaflor is somewhat less toxic than the recently banned neonicotinoids imidacloprid, thiamethoxam and clothianidin, but much more toxic than other neonicotinoids (acetamiprid, thiacloprid) still in use in the EU at the time this study was conducted.

Female volatiles as sex attractants in the invasive population of Vespa velutina nigrithorax.

Due to its huge invasion potential and specialization in honeybee predation, the invasive hornet Vespa velutina nigrithorax represents a high-concern species under both an ecological and economical perspective. In light of the development of specific odorant attractants to be used in sustainable control strategies, we carried out both behavioural assays and chemical analyses to investigate the possibility that, in the invasive population of V. velutina nigrithorax, reproductive females emit volatile pheromones to attract males, as demonstrated in a Chinese non-invasive population. We focused on the secretions produced by sternal and venom glands; because of the volatility and complexity of their composition, both of them could potentially allow an attraction and a species-specific response, decreasing therefore non-target species by-catches. Results of chemical analyses and behavioural assays showed that venom volatiles, although population-specific, are unlikely candidates as male attractants since they do not differ in composition or in quantity between reproductive females and workers and do not attract males. Conversely, sternal gland secretion differs between female castes for the presence of some ketoacids exclusive of gynes already reported as sex pheromones for the non-invasive subspecies V. velutina auraria. Despite such a difference, males are attracted by the sternal gland secretion of both workers and gynes. These results provide a first step to understand the reproductive biology of V. velutina nigrithorax in its invasive range and to develop effective and sustainable management strategies for the species.

Effects of nonprotein amino acids on survival and locomotion of Osmia bicornis.

To investigate the effects of two nectar nonprotein amino acids, ß-alanine and γ-aminobutyric acid (GABA), on Osmia bicornis survival and locomotion, two groups of caged bees were fed with sugar syrup enriched with ß-alanine and GABA, respectively. A further control group was fed with sugar syrup. Five behavioural categories were chosen according to the principle of parsimony and intrinsic unitary consistency from start to end, and recorded by scan sampling: two states (remaining under paper or in tubes) and three events (walking on net, feeding from flower and flying). We also analysed the amino acid content of haemolymph sampled from an additional 45 bees fed the same diets (15 per diet type). Bees fed with ß-alanine had a significantly shorter survival time than those fed with the control and GABA diets. The GABA diet induced higher levels of locomotion than ß-alanine. The former nonprotein amino acid was only detected in the haemolymph of bees fed GABA. The results suggest that insects consuming nonprotein amino-acid-rich diets absorb and transfer these substances to the haemolymph and that nonprotein amino acids affect survival and locomotion. Ecological consequences are discussed in the framework of plant reproductive biology.

Seasonal and annual variations in the pollination efficiency of a pollinator community of Dictamnus albus L.

The interplay between insect and plant traits outlines the patterns of pollen transfer and the subsequent plant reproductive fitness. We studied the factors that affect the pollination efficiency of a pollinator community of Dictamnus albus L. by evaluating insect behaviour and morphological characteristics in relation to flowering phenology. In order to extrapolate the pollinator importance of single taxa and of the whole pollinator guild, we calculated an index distinguishing between potential (PPI) and realized (RPI) pollinator importance. Although the pollinator species spectrum appeared rather constant, we found high intra- and inter-annual variability of pollinator frequency and importance within the insect community. Flower visitation rate strictly depended on insect abundance and on the overlap between their flying period and flower blooming. All the pollinators visited flowers from the bottom to the top of the racemes, excluding intra-plant geitonogamous pollination, and most of them showed high pollen fidelity. Only medium large-sized bees could contact the upward bending stiles while feeding on nectar, highlighting a specialisation of the plant towards bigger pollinators. Moreover, we found evidence of functional specialisation, since all pollinators were restricted to a single taxonomic group (order: Hymenoptera; superfamily: Apoidea). Both the PPI and RPI indices indicate Habropoda tarsata as the most important pollinator of D. albus. Following hand cross-pollination experiments we revealed the presence of pollination limitation in 1 of the 3 years of field study. We discuss this result in relation to flowering abundance and to possible mismatches of phenological periods between plants and insects.

Reproductive cloning in humans and therapeutic cloning in primates: is the ethical debate catching up with the recent scientific advances?

After years of failure, in November 2007 primate embryonic stem cells were derived by somatic cellular nuclear transfer, also known as therapeutic cloning. The first embryo transfer for human reproductive cloning purposes was also attempted in 2006, albeit with negative results. These two events force us to think carefully about the possibility of human cloning which is now much closer to becoming a reality. In this paper we tackle this issue from two sides, first summarising what scientists have achieved so far, then discussing some of the ethical arguments in favour and against human cloning which are debated in the context of policy making and public consultation. Therapeutic cloning as a means to improve and save lives has uncontroversial moral value. As to human reproductive cloning, we consider and assess some common objections and failing to see them as conclusive. We do recognise, though, that there will be problems at the level of policy and regulation that might either impair the implementation of human reproductive cloning or make its accessibility restricted in a way that could become difficult to justify on moral grounds. We suggest using the time still available before human reproductive cloning is attempted successfully to create policies and institutions that can offer clear directives on its legitimate applications on the basis of solid arguments, coherent moral principles, and extensive public consultation.

Sleeve resections and bronchoplastic procedures in typical central carcinoid tumours.

BACKGROUND: Typical carcinoids are low grade malignant neuroendocrine neoplasms, mostly located centrally in the tracheobronchial tree. The aim of our study was to analyse the long-term survival and surgical treatment outcome in patients submitted to parenchyma-sparing resections for typical central carcinoid tumours. METHODS: We retrospectively reviewed the data of 70 patients who underwent sleeve resections or bronchoplastic procedures. We performed 21 sleeve lobectomies, 9 sleeve resections of the main bronchus, 25 bronchoplasties associated with lung resections and 15 isolated wedge bronchoplasties. Nine patients (12.8%) had nodal metastases. RESULTS: There was no operative mortality; postoperative complications occurred in one patient (1.4%) who presented an empyema. At long-term follow-up evaluation, we were able to report good results: all patients were alive and nobody manifested recurrence; one patient had a late cicatricial bronchial stenosis, which was treated with laser therapy. CONCLUSIONS: This series of central typical bronchial carcinoids, treated with sleeve or bronchoplastic resection, demonstrated an excellent outcome. Our results suggest that, in experienced and skilled hands, conservative procedures must be considered the treatment of choice for the management of these tumours.

The surgeon and the oncologist in non-small cell lung cancer (NSCLC).

A strict collaboration is necessary between the oncologist and the surgeon, both must know the respective problematic and competences and must contribute together to all phases of clinical management of patients affected by NSCLC.

Animal rights, animal minds, and human mindreading.

Do non-human animals have rights? The answer to this question depends on whether animals have morally relevant mental properties. Mindreading is the human activity of ascribing mental states to other organisms. Current knowledge about the evolution and cognitive structure of mindreading indicates that human ascriptions of mental states to non-human animals are very inaccurate. The accuracy of human mindreading can be improved with the help of scientific studies of animal minds. However, the scientific studies do not by themselves solve the problem of how to map psychological similarities (and differences) between humans and animals onto a distinction between morally relevant and morally irrelevant mental properties. The current limitations of human mindreading-whether scientifically aided or not-have practical consequences for the rational justification of claims about which rights (if any) non-human animals should be accorded.

Low-pathogenicity avian influenza (LPAI) in Italy (2000-01): epidemiology and control.

In 1999-2000, Italy was affected by the most severe avian influenza (AI) epidemic that has ever occurred in Europe. The epidemic was caused by a type A influenza virus of the H7N1 subtype, which originated from the mutation of a low-pathogenicity (LP) AI virus of the same subtype. From August to November 2000, 4 months after the eradication of the highly pathogenic (HP) AI virus, the LPAI strain re-emerged and infected 55 poultry farms mainly located in the southern area of Verona province (Veneto region). To supplement disease control measures already in force, an emergency vaccination program against the disease was implemented in the area. Vaccination was carried out using an inactivated heterologous vaccine (A/chicken/Pakistan/1995-H7N3). In order to establish whether LPAI infection was circulating in the area, regular serological testing of sentinel birds in vaccinated flocks and a discriminatory test able to distinguish the different types of antineuraminidase antibodies (anti-N1 and anti-N3) were performed. Shortly after the beginning of the vaccination campaign (December 2000 to March 2001), the H7N1 LPAI virus emerged again, infecting 23 farms. Among these, only one vaccinated flock was affected, and infection did not spread further to other vaccinated farms. The data reported in the present paper indicate that the combination of biosecurity measures, official control, and vaccination can be considered successful for the control of LPAI infections in densely populated poultry areas.

Surgical results for multiple primary lung cancers.

OBJECTIVE: The development of a multiple primary lung cancer (MPLC) is not rare in long-term survivors after curative resections. We analysed our experience in order to verify surgical results and long-term survival in our patients. METHODS: From 1971 to 1999, 80 patients with MPLC (two tumours each, total 160) were treated at the Division of Thoracic Surgery of the University of Padua. Our criteria for the definition of a synchronous or metachronous cancer are those proposed by Martini and Melamed. We had 19 patients with a synchronous tumour and 61 patients with a metachronous tumour. We performed 95 lobectomies, 5 completion pneumonectomies and 53 segmentectomies. Of 160 MPLCs, 60 were squamous carcinomas, 78 adenocarcinomas, 8 small cell lung cancers, 9 large cell lung cancers and 5 other tumours. Of 160 MPLCs, 140 were N0 disease (87.5%) and 20 were N1 or N2 disease (12.5%). RESULTS: The overall 30-day mortality was 2.5% (2 patients). Eighteen patients (22.5%) had postoperative complications. Survival at 5 and 10 years for all patients was 72% and 58%, respectively. Five-year survival for patients with metachronous and synchronous disease from the time of initial diagnosis of cancer was 85% and 20% (P=0.001), and 10-year survival was 58% and 0% (P=0.001), respectively. Survival after the development of a metachronous lesion was 51% at 5 years and 20% at 10 years. The 5-year survival of patients with metachronous tumours undergoing standard surgical procedures of the second tumour was 52%; the 5-year survival of patients undergoing atypical or segmental resections was 55%. CONCLUSIONS: Careful follow-up is recommended in all patients surviving curative resection. More accurate selection criteria for MPLC is required. An aggressive surgical approach is justified in patients with MPLC and offers the greatest chance for long-term survival even in the case of limited resection.

The role of surgery in integrated therapies for non-small-cell lung cancer.

Surgery represents the best treatment for early-stage non-small-cell lung cancer (NSCLC). In selected cases, even locally-advanced cancers may be suitable for surgical treatment. The combination of chemotherapy (with or without radiotherapy) and surgery has proved potentially useful in improving survival, but pre-operative treatment may represent a risk factor for the onset of post-operative complications. Studies performed to date indicate the need for further multidisciplinary research with a view to identifying more advantageous treatment modalities, particularly for locally-advanced NSCLC.

Morbidity, mortality, and survival after bronchoplastic procedures for lung cancer.

OBJECTIVE: Bronchoplastic procedures represent an effective surgical therapy for benign lesions, tumors of low-grade malignancy and also bronchogenic carcinoma in patients with a limited pulmonary function. We analyzed our experience in order to verify the mortality, morbidity, and long term survival in our patients. METHODS: From 1980 to 1994, 217 patients underwent bronchoplastic procedures. We performed 92 bronchoplasties, 94 bronchial sleeves, and 31 tracheo-bronchial sleeves. Histologic examination revealed 133 epidermoid carcinomas, 28 adenocarcinomas, 11 small cells lung cancers, 5 large cells carcinomas, 2 adenosquamous carcinomas, 29 bronchial carcinoids, 6 adenoidocistic carcinomas, and 3 mucoepidermoid tumors. Regarding nodal status, 99 patients had N0 disease, 64 patients had N1 disease, and 54 patients had N2 disease. Thirty-six patients had preoperative irradiation and 181 patients had no preoperative irradiation. In 63 patients we used a perianastomotic pedicled flap; in 154 we did not use it. We considered all the 217 patients for the analysis of 30-day mortality and morbidity; of the 217 patients we analyzed long-term survival only in 179 because we excluded 38 patients with low grade malignant neoplasm. RESULTS: Twenty-seven patients (12.5%) had postoperative complications. The 30-day mortality was 6.2% (14 patients). Survival at 5 and 10 years for all patients but those with low grade malignant neoplasm was 49 and 38%, respectively. For patients with N0 status 5- and 10-year survival was 72.4 and 59.4%; for patients with N1 status these rates were 35.7 and 26.8%; for patients with N2 status, 5- and 10-year survival was 22 and 14.4%. Postoperative complication rates for patients with or without pedicled flap are not significantly different; however, the rates for patients with or without preoperative irradiation are significantly different. CONCLUSIONS: Bronchoplastic procedures are a safe and effective therapy for selected patients with pulmonary malignancy. Tracheo-bronchial sleeves are associated with high postoperative mortality and complication rates and these procedures should be limited to patients without N2 disease. Preoperative irradiation increases significantly the mortality and morbidity. A multivariate analysis shows that only the nodal status affects long-term survival (P = 0.0002).

A dose-escalating study of carboplatin combined with vinorelbine in non-small-cell lung cancer.

Platinum compounds and vinorelbine have been demonstrated to be active in non-small-cell lung cancer (NSCLC). The aims of the study were to assess tolerability and feasibility of increasing doses of carboplatin (level 1: 300 mg/ m2 on day 1, level 2: 350 mg/m2 on day 1, level 3: 400 mg/m2 on day 1) in combination with a fixed dose of vinorelbine (25 mg/m2 on days 1 and 8) in advanced NSCLC. Forty-two patients entered the study and were evaluable for toxicity and response. The patients were not treated using systemic chemotherapy, had TNM stage IIIB-IV, performance status ECOG 0-2, and their median age was 62 (range 41-70) years. The number of patients evaluable for each dose level was 14. A total of 138 (median 3) courses was administered. Nonhematologic side effects included grade I-II mucositis (9%), neurotoxicity (6%), and infections (4%). Myelotoxicity was manageable and generally of short duration, with 19% of the patients having grade III-IV neutropenia. No significant difference was observed for the three treatment groups. No drug-related death was observed. An objective remission was observed in 10 patients (24% response rate; 95% confidence interval 12-39%), with 5 responses in 14 patients treated with the 400-mg/m2 dose. In conclusion, the combination of carboplatin at a dose of 400 mg/m2 on day 1 and vinorelbine at a dose of 25 mg/m2 on days 1 and 8 can be safely administered as first-line cytotoxic therapy in advanced NSCLC and warrants further evaluation.

Surgery followed by intracavitary plus systemic chemotherapy in malignant pleural mesothelioma.

AIMS AND BACKGROUND: Malignant mesothelioma is associated with a median survival of 4 to 12 months. Data from the literature indicate that single modality treatment (surgery or intrapleural and/or systemic chemotherapy) does not significantly affect survival. METHODS: We therefore evaluated a combined approach consisting of surgery (pleurectomy + diaphragmatic or pericardial resection), intrapleural chemotherapy with cisplatin (100 mg/m2) and cytarabine (1,000 mg/m2) for 4 h immediately after pleurectomy, and systemic chemotherapy consisting of epirubicin (60 mg/m2) and mitomycin-C (10 mg/m2) day 1 every 4 weeks for 4 cycles. RESULTS: Twenty patients were enrolled in the study and were evaluable. Thirteen cases had residual gross disease after pleurectomy and 7 patients only minimal disease. Median time to disease progression was 7.4 months, and median survival was 11.5 months (range, 2-25+). No treatment-related death have been observed. Side effects after intracavitary chemotherapy included renal toxicity, anaemia and pain. Myelosuppression and alopecia were recorded during systematic chemotherapy. CONCLUSIONS: The results of the study indicate that the schedule is feasible, with encouraging results in terms of survival for patients with minimal residual disease after surgery.

Carcinoma of the superior pulmonary sulcus. Results of irradiation and radical resection.

Fifty-six patients with superior sulcus syndrome were evaluated at the First Surgical Department of the University of Padua between 1981 and 1990. Forty-two patients with the characteristic of Pancoast's tumor received preoperative irradiation and then en bloc resection of the tumor, chest wall, and adjacent structures. Seven lobectomies and 35 segmentectomies or wedge resections were performed. There was one early postoperative death. Median survival was 14 months, and actuarial survival was 25% at 5 years. Patients with pain relief had better 5-year survival (36.4%) than patients without pain relief (9%). We have no patients with vertebral invasion who survived more than 1 year. Of the five patients with subclavian artery invasion, only one survived more than 1 year. Of five patients with N2 disease, only one survived more than 1 year. Our results suggest that pain relief after irradiation is a good prognostic factor, whereas N2 involvement and vertebral body and great vessel invasion are ominous factors. Another ominous prognostic factor is the Claude Bernard-Horner syndrome even if it is not a contraindication to resection.