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Since its inception, laparoscopic surgery has evolved and new techniques have been developed due to technological advances. This requires a different and more complex skill set in comparison with open surgery. Reduced working hours, less training time and patient safety factors demand that such skills need to be achieved outside the operating theatre environment. Several studies have been published and have determined the effectiveness of virtual reality training. We aimed to compare virtual reality training with the traditional apprenticeship method of training and determine whether it can supplement or replace the traditional apprenticeship model. We also aimed to perform a meta-analysis of the literature and develop conclusions with respect to the benefits achieved by adding virtual reality training on a regular basis to surgical training programmes. A literature search was carried out on PubMed, MEDLINE, EMBASE and Google Scholar academic search engines using the MESH terms 'randomised controlled trials', 'virtual reality', 'laparoscopy', 'surgical education' and 'surgical training'. All randomised controlled trials published to January 2018 comparing virtual reality training to apprenticeship training were included. Data were collected on improved dexterity, operative performance and operating times. Each outcome was calculated with 95% confidence intervals and with intention-to-treat analysis; 24 randomised controlled trials were analysed. Meta-analytical data were extracted for time, path length, instrument handling, tissue handling, error scores and objective structure assessment of technical skills scoring. There was significant improvement in individual trainee skill in all meta-analyses ( 0.0002). This meta-analysis shows that virtual reality not only improves efficiency in the trainee's surgical practice but also improves quality with reduced error rates and improved tissue handling.

Purinergic signaling is involved in inflammation and cancer. Extracellular ATP accumulates in tumor interstitium, reaching hundreds micromolar concentrations, but its functional role on tumor vasculature and endothelium is unknown. Here we show that high ATP doses (>20 μM) strongly inhibit migration of endothelial cells from human breast carcinoma (BTEC), but not of normal human microvascular EC. Lower doses (1–10 μM) result ineffective. The anti-migratory activity is associated with cytoskeleton remodeling and is significantly prevented by hypoxia. Pharmacological and molecular evidences suggest a major role for P2X7R and P2Y11R in ATP-mediated inhibition of TEC migration: selective activation of these purinergic receptors by BzATP mimics the anti-migratory effect of ATP, which is in turn impaired by their pharmacological or molecular silencing. Downstream pathway includes calcium-dependent Adenilyl Cyclase 10 (AC10) recruitment, cAMP release and EPAC-1 activation. Notably, high ATP enhances TEC-mediated attraction of human pericytes, leading to a decrease of endothelial permeability, a hallmark of vessel normalization. Finally, we provide the first evidence of in vivo P2X7R expression in blood vessels of murine and human breast carcinoma. In conclusion, we have identified a purinergic pathway selectively acting as an antiangiogenic and normalizing signal for human tumor-derived vascular endothelium.

Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.

Liver receptor homolog-1 (LRH-1, NR5A2 ) is an orphan nuclear receptor that has an essential role in cancer progression, notably in breast cancer. Although its role in promoting cancer cell proliferation and migration is well documented, the molecular basis is not completely established. Here, we report that LRH-1 inhibition affects two- and three-dimensional cell proliferation of different types of breast cancer cells, including estrogen receptor α (ERα)-positive and triple-negative cells. This phenotype is accompanied by the upregulation of the cyclin-dependent kinase inhibitor CDKN1A (aka p21 CIP1/WAF1 ) in a p53-independent manner. Chromatin immunoprecipitation analysis shows that LRH-1 cooperates with FOXA1 and binds directly to CDKN1A promoter and a distal regulatory region found at −62 kb from its transcriptional start sites, allowing repression of CDKN1A transcription. LRH-1 or FOXA1 depletion induces CDKN1A upregulation by removing histone deacetylase 2 from the promoter and distal regulatory elements and permitting histone acetylation in these regions. Analysis of breast cancer samples reveals that a high LRH-1 level is inversely correlated with CDKN1A expression in breast cancer patients and is associated with poor prognosis. This study reveals a novel mechanism of control of cell proliferation by LRH-1 regulating CDKN1A transcription in breast cancer cells, independent of ERα and p53 status. Targeting LRH-1 may provide an attractive prospect for treatment of tumors that are resistant to hormonal and targeted therapy.

BackgroundReconstruction of posttraumatic bone defects represents a difficult challenge. The induced membrane technique is an effective two-stage procedure for bone defect reconstruction. To overcome the problems of autologous bone grafting, different graft substitutes have been investigated. The aim of the present study is to evaluate our clinical experience in reconstruction of critical posttraumatic bone defects using an induced membrane technique based on a combination of autologous graft and allograft (cancellous bone) enriched with platelet-rich plasma (PRP) and bone marrow concentrate aspirate (BMCA).Materials and methodsBetween 2009 and 2014, we reconstructed 18 posttraumatic bone defects in 16 patients. Their average length was 6.4 cm (range 1.6–13.2 cm). The defect location was the femur in nine cases (50%), the tibia in eight (44%) cases, and the humerus in one (6%) case. In all cases, we used a combination of autologous and cancellous allograft graft enriched with PRP and BMCA. Bone fixation was achieved using intramedullary nailing in 2 cases (11%), plating in 15 cases (66%), and external fixation in 1 case (6%).ResultsBoth clinical and radiographic union were achieved in 13 (72%) cases (13 patients). Five (28%) cases (four patients) developed nonunion. Nonunion was observed in two of eight (25%) tibial defects and in three (33%) of nine femoral defects (ns). Three of 4 (75%) double defects had delayed union, whereas 2 of 14 (14%) single defects did not heal (p = 0.016). The average length of the 13 defects that united was 6 cm (range 1.6–11.8 cm), while the length of the 5 defects that did not unite was 10.3 cm (range 6–13.2 cm) (p = 0.009).ConclusionsIn this series using an induced membrane technique based on a combination of autograft and allograft enriched with BMCA and PRP, the healing rate was lower than in other series where autologous bone graft alone was employed. Nonunion was more frequent in longer and double defects. Further research aimed at developing effective alternative options to autogenous cancellous bone graft is desirable.Level of evidence: III

The objective of this work was to determine the interference periods of weeds of the bell pepper cultivar ‘Dahra’. Two experiments were conducted during the years 2014/15 (harvest with lower rainfall) and 2015/16 (harvest with higher rainfall). The treatments consisted of 11 growing periods of cohabitation and weed control with ‘Dahra’ bell peppers: 14, 28, 42, 56, 70, 84, 98, 112, 126, 140 and 154 days after transplanting (DAT). For the determination of the interference periods, the productivity data were analyze using the Boltzmann sigmoidal regression model. The main weeds were Eleusine indica, Brachiaria plantaginea, Digitaria nuda and Nicandra physaloides for presenting high biomass and relative density. The concomitance of these weeds caused losses of up to 85.22% (2014/15) and 86.2% (2015/16) in the fruit yield. It was found that, respectively, for the years 2014/15 and 2015/16, the period before the interference was 17 and 11 DAT, and the total interference prevention period of 71 and 89 DAT. Considering a tolerance of 5% in reducing bell pepper yield, it is recommended that weed control be performed from 11 to 89 DAT.

In the last few years, an intense R &D activity on particle detectors for future HEP applications has been carried on with the aim of developing new techniques as well as studying the performance of already existing detectors when operated in a high rate environment. As for Resistive Plate Chamber detectors, the main challenges to face are the improvement of their detection capabilities and longevity at very high-rates, and the search for new eco-friendly gasmixtures free from greenhouse components. Results obtained in the framework of the RPC ECOGas@GIF++ Collaboration on a thin-Resistive Plate Chamber exposed at the CERN Gamma Irradiation Facility and operated with eco-friendly gas mixtures based on Tetrafluoropropene and Carbon dioxide will be discussed in this paper.

Results obtained by the RPC ECOgas@GIF++ Collaboration, using Resistive Plate Chambers operated with new, eco-friendly gas mixtures, based on tetrafluoropropene and carbon dioxide, are shown and discussed in this paper. Tests aimed to assess the performance of this kind of detectors in high-irradiation conditions, analogous to the ones foreseen for the coming years at the Large Hadron Collider experiments, were performed, and demonstrate a performance basically similar to the one obtained with the gas mixtures currently in use, based on tetrafluoroethane, which is being progressively phased out for its possible contribution to the greenhouse effect. Long term aging tests are also being carried out, with the goal to demonstrate the possibility of using these eco-friendly gas mixtures during the whole High Luminosity phase of the Large Hadron Collider.

The outgoing longwave radiation (OLR) emitted to space is a fundamental component of the Earth’s energy budget. There are numerous, entangled physical processes that contribute to OLR and that are responsible for driving, and responding to, climate change. Spectrally resolved observations can disentangle these processes, but technical limitations have precluded accurate space-based spectral measurements covering the far infrared (FIR) from 100 to 667 cm−1 (wavelengths between 15 and 100 μm). The Earth’s FIR spectrum is thus essentially unmeasured even though at least half of the OLR arises from this spectral range. The region is strongly influenced by upper-tropospheric–lower-stratospheric water vapor, temperature lapse rate, ice cloud distribution, and microphysics, all critical parameters in the climate system that are highly variable and still poorly observed and understood. To cover this uncharted territory in Earth observations, the Far-Infrared Outgoing Radiation Understanding and Monitoring (FORUM) mission has recently been selected as ESA’s ninth Earth Explorer mission for launch in 2026. The primary goal of FORUM is to measure, with high absolute accuracy, the FIR component of the spectrally resolved OLR for the first time with high spectral resolution and radiometric accuracy. The mission will provide a benchmark dataset of global observations which will significantly enhance our understanding of key forcing and feedback processes of the Earth’s atmosphere to enable more stringent evaluation of climate models. This paper describes the motivation for the mission, highlighting the scientific advances that are expected from the new measurements.

The presence of weeds may affect both growth and nutrition of agricultural crops due to interference. The objective was to evaluate the interference of weeds in the dry mass distribution and in the accumulation of dry mass and macronutrients in eggplant. The treatments consisted of increasing weed-free and weedy periods (0-14, 0-28, 0-42, 0-56, 0-70, 0-84, 0-98, 0-112, 0-126, 0-140 and 0-154 days after transplanting) in eggplant ‘Nápoli’. The experiment was arranged in a randomized block design with three replicates. Weeds affected the distribution of dry mass between vegetative and reproductive organs of eggplant. There was a significant reduction in the accumulation of dry mass and macronutrients when weeds grew with eggplant crop beyond 42 days after transplanting, reaching the maximum reduction of 79%, 75%, 80%, 82%, 83%, 83% and 80% in the accumulation of dry mass, K, N, Ca, Mg, P and S, respectively. Therefore, the weed community significantly affects the growth and mineral nutrition of eggplant ‘Napoli’, and there should be no weed-crop coexistence beyond 28 days after seedling transplanting.