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Depressive disorders are heterogeneous diseases, and the complexity of symptoms has led to the formulation of several aethiopathological hypotheses. This heterogeneity may account for the following open issues about antidepressant therapy: (i) antidepressants show a time lag between pharmacological effects, within hours from acute drug administration, and therapeutic effects, within two-four weeks of subchronic treatment; (ii) this latency interval is critical for the patient because of the possible further mood worsening that may result in suicide attempts for the seemingly ineffective therapy and for the apparent adverse effects; (iii) and only 60–70 % of treated patients successfully respond to therapy. In this review, the complexity of the biological theories that try to explain the molecular mechanisms of these diseases is considered, encompassing (i) the classic “monoaminergic hypothesis” alongside the updated hypothesis according to which long-term therapeutical action of antidepressants is mediated by intracellular signal transduction pathways and (ii) the hypothalamic–pituitary-adrenal axis involvement. Although these models have guided research efforts in the field for decades, they have not generated a compelling and conclusive model either for depression pathophysiology or for antidepressant drugs’ action. So, other emerging theories are discussed: (iii) the alterations of neuroplasticity and neurotrophins in selective vulnerable cerebral areas; (iv) the involvement of inflammatory processes; (v) and the alterations in mitochondrial function and neuronal bioenergetics. The focus is put on the molecular and theoretical links between all these hypotheses, which are not mutually exclusive but otherwise tightly correlated, giving an integrated and comprehensive overview of the neurobiology of depressive disorders.

Research into fault diagnosis in machines with a wide range of variable loads and speeds, such as wind turbines, is of great industrial interest. Analysis of the power signals emitted by wind turbines for the diagnosis of mechanical faults in their mechanical transmission chain is insufficient. A successful diagnosis requires the inclusion of accelerometers to evaluate vibrations. This work presents a multi-sensory system for fault diagnosis in wind turbines, combined with a data-mining solution for the classification of the operational state of the turbine. The selected sensors are accelerometers, in which vibration signals are processed using angular resampling techniques and electrical, torque and speed measurements. Support vector machines (SVMs) are selected for the classification task, including two traditional and two promising new kernels. This multi-sensory system has been validated on a test-bed that simulates the real conditions of wind turbines with two fault typologies: misalignment and imbalance. Comparison of SVM performance with the results of artificial neural networks (ANNs) shows that linear kernel SVM outperforms other kernels and ANNs in terms of accuracy, training and tuning times. The suitability and superior performance of linear SVM is also experimentally analyzed, to conclude that this data acquisition technique generates linearly separable datasets.

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) conditioning or high-dose nontransplant chemotherapy. VOD/SOS with multi-organ dysfunction (MOD) is associated with a mortality rate of > 80%. Defibrotide (25 mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States and to treat severe hepatic VOD/SOS in patients > 1 month of age in the European Union. A random effects model was used for pooling data from 17 systematically chosen defibrotide studies. For patients in these reports (n = 2598), and those in the subset of 10 reports of patients treated with ~ 25 mg/kg/day (n = 1691), estimated Day + 100 survival rates were 54% and 56%, respectively. Among those patients treated with ~ 25 mg/kg/day, estimated Day + 100 survival was 44% among patients with MOD and 71% in patients without MOD; survival was 41% and 70%, respectively, for the population of patients receiving any dose of defibrotide. Safety results were not pooled owing to differences in reporting methodology but were generally consistent with the known tolerability profile of defibrotide. This analysis provides the largest assessment of survival in patients treated with defibrotide for VOD/SOS with or without MOD.

The possibility to accelerate electron beams to ultra-relativistic velocities over short distances by using plasma-based technology holds the potential for a revolution in the field of particle accelerators 1 – 4 . The compact nature of plasma-based accelerators would allow the realization of table-top machines capable of driving a free-electron laser (FEL) 5 , a formidable tool to investigate matter at the sub-atomic level by generating coherent light pulses with sub-ångström wavelengths and sub-femtosecond durations 6 , 7 . So far, however, the high-energy electron beams required to operate FELs had to be obtained through the use of conventional large-size radio-frequency (RF) accelerators, bound to a sizeable footprint as a result of their limited accelerating fields. Here we report the experimental evidence of FEL lasing by a compact (3-cm) particle-beam-driven plasma accelerator. The accelerated beams are completely characterized in the six-dimensional phase space and have high quality, comparable with state-of-the-art accelerators 8 . This allowed the observation of narrow-band amplified radiation in the infrared range with typical exponential growth of its intensity over six consecutive undulators. This proof-of-principle experiment represents a fundamental milestone in the use of plasma-based accelerators, contributing to the development of next-generation compact facilities for user-oriented applications 9 . Using a compact, particle-beam-driven plasma-based accelerator to accelerate high-quality electron beams that are completely characterized in the six-dimensional phase space, free-electron lasing  is observed with narrow-band amplified radiation in the infrared range.

The presence of undesirable biofilms on food processing contact surfaces may lead to: (1) transmission of diseases; (2) food spoilage; (3) shortened time between cleaning events; (4) contamination of product by nonstarter bacteria; (5) metal corrosion in pipelines and tanks; (6) reduced heat transfer efficacy or even obstruction of the heat equipment. Despite the significant problems caused by biofilms in the food industry, biofilm formation in these environments is still poorly understood and effective control of biofilms remains challenging. Although it is understood that cell attachment and biofilm formation are influenced by several factors, including type of strain, chemical–physical properties of the surface, temperature, growth media and the presence of other microorganisms, some conflicting statements can be retrieved from the literature and there are no general trends yet that allow us to easily predict biofilm development. It is likely that still unexplored interaction of factors may be more critical than the effect of a single parameter. New alternative biofilm control strategies, such as biocontrol, use of enzymes and phages and cell-to-cell communication interference, are now available that can reduce the use of chemical agents. In addition, as preventing biofilm formation is a more efficient strategy than controlling mature biofilm, the use of surface-modified materials have been suggested. These strategies may better reveal their beneficial potential when the ecological complexity of biofilms in food environments is addressed.

Background Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS), which may go undiagnosed and can significantly impair a patient’s health-related quality of life (HRQOL). This qualitative research examined timing and reasons patients sought medical care for their EDS and OSA symptoms, and the impact of EDS on HRQOL. Methods Focus groups were conducted in 3 US cities with 42 participants currently experiencing EDS with OSA. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. Results Over three-fifths of study participants ( n  = 26, 62%) were currently using a positive airway pressure (PAP) or dental device; one-third ( n  = 14, 33%) had previously used a positive airway pressure (PAP) or dental device, and the remainder had either used another treatment (n = 1, 2%) or were treatment naïve (n = 1, 2%). Twenty-two participants (52%) reported experiencing OSA symptoms for ≥1 year, with an average duration of 11.4 (median 8.0, range 1–37) years before seeking medical attention. Several ( n  = 7, 32%) considered their symptoms to be “normal,” rather than signaling a serious medical condition. Thirty participants (71%) discussed their reasons for ultimately seeking medical attention, which included: input from spouse/partner, another family member, or friend ( n  = 20, 67%); their own concern about particular symptoms (n = 7, 23%); and/or falling asleep while driving ( n  = 5, 17%). For all 42 participants, HRQOL domains impacted by EDS included: physical health and functioning ( n  = 40, 95%); work productivity ( n  = 38, 90%); daily life functioning ( n  = 39, 93%); cognition (n = 38, 90%); social life/relationships ( n  = 37, 88%); and emotions ( n  = 30, 71%). Conclusions Findings suggest that patients may be unaware that their symptoms could indicate OSA requiring evaluation and treatment. Even following diagnosis, EDS associated with OSA can continue to substantially affect HRQOL and daily functioning. Further research is needed to address diagnostic delays and unmet treatment needs for patients with EDS associated with OSA.

This research demonstrates the use of an unmanned aerial vehicle (UAV) to characterize the gaseous (CO2) and particle (10–500 nm) emissions of a ship at sea. The field study was part of the research voyage “The Great Barrier Reef as a significant source of climatically relevant aerosol particles” on board the RV Investigator around the Australian Great Barrier Reef. Measurements of the RV Investigator exhaust plume were carried out while the ship was operating at sea, at a steady engine load of 30 %. The UAV system was flown autonomously using several different programmed paths. These incorporated different altitudes and distances behind the ship in order to investigate the optimal position to capture the ship plume. Five flights were performed, providing a total of 27 horizontal transects perpendicular to the ship exhaust plume. Results show that the most appropriate altitude and distance to effectively capture the plume was 25 m a.s.l. and 20 m downwind. Particle number emission factors (EFPNs) were calculated in terms of number of particles emitted (no.) per weight of fuel consumed (kgfuel). Fuel consumption was calculated using the simultaneous measurements of plume CO2 concentration. The calculated EFPN was 7.6±1.4×1015no. kgfuel-1 which is in line with those reported in the literature for ship emissions ranging from 0.2 to 6.2×1016 no. kgfuel-1. This UAV system successfully assessed ship emissions to derive EFPN under real world conditions. This is significant as it provides a novel, relatively inexpensive and accessible way to assess ship EFPN at sea.

Next-generation plasma-based accelerators can push electron bunches to gigaelectronvolt energies within centimetre distances1,2. The plasma, excited by a driver pulse, generates large electric fields that can efficiently accelerate a trailing witness bunch3–5, enabling the realization of laboratory-scale applications ranging from high-energy colliders6 to ultrabright light sources7. So far, several experiments have demonstrated large accelerations8–10 but the resulting beam quality, particularly the energy spread, is still far from state-of-the-art conventional accelerators. Here we show the results of a beam-driven plasma acceleration experiment where we used an electron bunch as a driver followed by an ultrashort witness bunch. By setting a positive energy chirp on the witness bunch, its longitudinal phase space is rotated during acceleration, resulting in an ultralow energy spread that is even lower than the spread at the plasma entrance. This result will significantly impact the optimization of the plasma acceleration process and its implementation in forthcoming compact machines for user-oriented applications.In a beam-driven plasma wakefield accelerator, the energy spread of an electron bunch is reduced with respect to the plasma entrance, which is achieved through setting a positive energy chirp that rotates the bunches’ longitudinal phase space.

Two optical configurations are commonly used in single-molecule fluorescence microscopy: point-like excitation and detection to study freely diffusing molecules, and wide field illumination and detection to study surface immobilized or slowly diffusing molecules. Both approaches have common features, but also differ in significant aspects. In particular, they use different detectors, which share some requirements but also have major technical differences. Currently, two types of detectors best fulfil the needs of each approach: single-photon-counting avalanche diodes (SPADs) for point-like detection, and electron-multiplying charge-coupled devices (EMCCDs) for wide field detection. However, there is room for improvements in both cases. The first configuration suffers from low throughput owing to the analysis of data from a single location. The second, on the other hand, is limited to relatively low frame rates and loses the benefit of single-photon-counting approaches. During the past few years, new developments in point-like and wide field detectors have started addressing some of these issues. Here, we describe our recent progresses towards increasing the throughput of single-molecule fluorescence spectroscopy in solution using parallel arrays of SPADs. We also discuss our development of large area photon-counting cameras achieving subnanosecond resolution for fluorescence lifetime imaging applications at the single-molecule level.

Achieving food security in a ‘perfect storm’ scenario is a grand challenge for society. Climate change and an expanding global population act in concert to make global food security even more complex and demanding. As achieving food security and the millennium development goal (MDG) to eradicate hunger influences the attainment of other MDGs, it is imperative that we offer solutions which are complementary and do not oppose one another. Sustainable intensification of agriculture has been proposed as a way to address hunger while also minimizing further environmental impact. However, the desire to raise productivity and yields has historically led to a degraded environment, reduced biodiversity and a reduction in ecosystem services (ES), with the greatest impacts affecting the poor. This paper proposes that the ES framework coupled with a policy response framework, for example Driver-Pressure-State-Impact-Response (DPSIR), can allow food security to be delivered alongside healthy ecosystems, which provide many other valuable services to humankind. Too often, agro-ecosystems have been considered as separate from other natural ecosystems and insufficient attention has been paid to the way in which services can flow to and from the agro-ecosystem to surrounding ecosystems. Highlighting recent research in a large multi-disciplinary project (ASSETS), we illustrate the ES approach to food security using a case study from the Zomba district of Malawi.