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Background Development of distant metastases involves a complex multistep biological process termed the invasion-metastasis cascade, which includes dissemination of cancer cells from the primary tumor to secondary organs. NOTCH developmental signaling plays a critical role in promoting epithelial-to-mesenchymal transition, tumor stemness, and metastasis. Although all four NOTCH receptors show oncogenic properties, the unique role of each of these receptors in the sequential stepwise events that typify the invasion-metastasis cascade remains elusive. Methods We have established metastatic xenografts expressing high endogenous levels of NOTCH3 using estrogen receptor alpha-positive (ERα+) MCF-7 breast cancer cells with constitutive active Raf-1/mitogen-associated protein kinase (MAPK) signaling (vMCF-7Raf-1) and MDA-MB-231 triple-negative breast cancer (TNBC) cells. The critical role of NOTCH3 in inducing an invasive phenotype and poor outcome was corroborated in unique TNBC cells resulting from a patient-derived brain metastasis (TNBC-M25) and in publicly available claudin-low breast tumor specimens collected from participants in the Molecular Taxonomy of Breast Cancer International Consortium database. Results In this study, we identified an association between NOTCH3 expression and development of metastases in ERα+ and TNBC models. ERα+ breast tumor xenografts with a constitutive active Raf-1/MAPK signaling developed spontaneous lung metastases through the clonal expansion of cancer cells expressing a NOTCH3 reprogramming network. Abrogation of NOTCH3 expression significantly reduced the self-renewal and invasive capacity of ex vivo breast cancer cells, restoring a luminal CD44low/CD24high/ERαhigh phenotype. Forced expression of the mitotic Aurora kinase A (AURKA), which promotes breast cancer metastases, failed to restore the invasive capacity of NOTCH3-null cells, demonstrating that NOTCH3 expression is required for an invasive phenotype. Likewise, pharmacologic inhibition of NOTCH signaling also impaired TNBC cell seeding and metastatic growth. Significantly, the role of aberrant NOTCH3 expression in promoting tumor self-renewal, invasiveness, and poor outcome was corroborated in unique TNBC cells from a patient-derived brain metastasis and in publicly available claudin-low breast tumor specimens. Conclusions These findings demonstrate the key role of NOTCH3 oncogenic signaling in the genesis of breast cancer metastasis and provide a compelling preclinical rationale for the design of novel therapeutic strategies that will selectively target NOTCH3 to halt metastatic seeding and to improve the clinical outcomes of patients with breast cancer. Electronic supplementary material The online version of this article (10.1186/s13058-018-1020-0) contains supplementary material, which is available to authorized users.

Objectives Orthodontic mini-implants (OMIs) are a reliable method to provide temporary orthodontic anchorage. We hypothesized that there is an optimal insertion torque (10 Ncm) will decrease the success rate and increase palatal OMI failure was rejected.

Background: Plasmodium falciparum accounts for nearly all severe malaria cases among European travellers, even though, in areas of endemicity, Plasmodium vivax seems to cause severe malaria to a degree which is comparable with P. falciparum. Furthermore, unlike countries at high risk, the incidence of mixed infections among imported cases is very low. We report the case of a man from non-endemic country with a mixed infection diagnosed after a two-year stay in Guinea. Case Presentation: A 43-year-old male Italian patient developed hyperpyrexia and chills the day after his return to Italy. Within 7 days from fever onset, he was found unresponsive with vomiting and seizures. On admission to Emergency Room, the patient was hypotonic with flaccid tetraparesis, with a GCS score of 7. On the basis of personal and working history and clinical features, after exclusion of viral encephalitis, acute pyogenic meningitis, tubercular meningitis and pontine infarct, cerebral malaria infection was suspected. Rapid diagnostic test and peripheral blood smear were positive for plasmodium mixed infection (P. falciparum, P. vivax, Plasmodium ovale). Over the first 30 hours from admission, thrombocyte count dropped, and the patient developed disseminated intravascular coagulation. Renal failure required renal replacement therapy. Death occurred after 48 hours of ICU admission. Conclusion: The fatal course of the severe malaria with related cerebral impairment, lung and kidney failure, disseminated intravascular coagulation, severe acidosis, circulatory collapse with refractory septic shock and subsequent multi organ failure was likely due to delayed medical presentation by the patient and the mixed plasmodium infection. Diagnosis could only be established nine days after onset of symptoms.

European Union (EU) and United States (US) regulations implement different food safety standards, particularly relating to the presence of Listeria monocytogenes in certain ready-to-eat (RTE) meat products. Compared to EU, the US adopt different procedures and methods, and establish zero tolerance limits to ensure consumers protection from Listeria monocytogenes in RTE products. A complete equivalence evaluation of the EU and US food inspection and certification systems has not been carried out yet. This study was funded by the Italian Central Competent Authority in the field of food safety (Ministry of Health) and included a total of 164 Italian establishments, 81 authorized for export of pork meat products to US (“US establishments”) and 83 only authorized for EU internal trade (“EU establishments”). Establishments were stratified according to production volume, type of RTE products manufactured, presentation and processing, in order to include two homogeneous groups (US and EU). Sampling was carried out by NAS (Carabinieri Corps for the prevention of the adulteration of beverages and foodstuffs) without any given notice. Sampling, detection and identification of Listeria monocytogenes and Salmonella spp. took place according to US Food Safety and Inspection Service (FSIS) directives and procedures. All 1124 samples tested negative for Salmonella spp., while 5 samples tested positive for Listeria monocytogenes. Among the latter, 4 samples were collected in 3 US establishments (US products prevalence 4/556 = 0.72%, 95% CL: 0.29–1.83%; US establishments prevalence 3/81 = 3.70%, 95% CL: 1.34–10.32%) and 1 was collected in a EU establishment (EU products prevalence 1/568 = 0.18%, 95% CL: 0.04–0.98%; EU establishment prevalence 1/83 = 1.20%, 95% CL: 0.29–0.46%). Bilateral Fisher's exact test showed no differences between EU and US products and establishments prevalence (P = 0.213 and P = 0.364, respectively), corroborating the existence of equivalent Listeria monocytogenes and Salmonella spp. contamination in the products under these two control systems.

Notwithstanding advances in medical and surgical management of flail chest, its morbidity and mortality rates are still high. Aim of this study is to compare three approaches for parietal thoracic stabilization by analyzing both early and long-term patient outcomes.A retrospective study from January 2006 to January 2018 involving sixty-five surgical flail chest (25 plates,11 struts and 29 wires fixations) was conducted. A mean Abbreviated Injury Scale (AIS) was 2.38±0.82 and a mean Injury Severity Score (ISS) was 32.02±8.21.Struts and plates stabilizations compared with wires fixation showed an immediate restoring of the partial pressure of oxygen (90.56 mmHg vs 91.90 mmHg vs 89.23 mmHg, p = 0.021), the carbon-dioxide levels (36.00 mmHg vs 35.03 mmHg vs 38.98 mmHg, p = 0.000) and the oxygen-blood saturation (97.71% vs 98.21% vs 92.12%, p = 0.000) in the early postoperative period. Furthermore, struts and plates ensured a better recovery of daily activities up to the 3rdmonth (QoL=1.0: p0.001 in lateral flail chest and p0.02 in anterior and antero-lateral flail chest). At the 12thmonth no difference in QoL was found between the different approaches.Plate and strut fixation revealed a lower rate of postoperative morbidity and mortality. Wires stabilization was characterized for a reduction of operative time.

This paper presents the results obtained by the finite elements model co-simulation technique in the transient analysis of an electric drive for advanced traction applications. The case study refers to a 200kW induction motor drive designed for a premium electric vehicle in the frame of the Horizon 2020 “ReFreeDrive” project (Rare earth Free e-Drives featuring low cost manufacturing). The transient performance and the operating limits are evaluated when a field-oriented control strategy based on the lumped parameters model of the machine is used. The co-simulation involves the ANSYS/Simplorer and MATLAB/Simulink environments. The finite element motor model developed in ANSYS is controlled by the rotor flux-oriented controller with axes decoupling built in Simulink. A lumped parameters motor model is also derived to design the control parameters and implemented in Simulink for comparison respect to the co-simulation approach. The results highlight the influence of the controller detuning for the correct prediction of the voltage limit operation at steady state.

Background. Although positron emission tomography/computed tomography, often integrated with 2-deoxy-2-[fluorine-18] fluorine-D-glucose (18F-FDG-PET/CT), is fundamental in the assessment of lung cancer, the relationship between metabolic avidity of different histotypes and maximum standardized uptake value (SUVmax) has not yet been thoroughly investigated. The aim of the study is to establish a reliable correlation between Suvmax and histology in non-small cell lung cancer (NSCLC), in order to facilitate patient management. Methods. We retrospectively assessed the data about lung cancer patients entered in the Italian Registry of VATS Group from January 2014 to October 2019, after establishing the eligibility criteria of the study. In total, 8139 patients undergoing VATS lobectomy were enrolled: 3260 females and 4879 males. The relationship between SUVmax and tumor size was also analyzed. Results. The mean values of SUVmax in the most frequent types of lung cancer were as follows: (a) 4.88 ± 3.82 for preinvasive adenocarcinoma; (b) 5.49 ± 4.10 for minimally invasive adenocarcinoma; (c) 5.87 ± 4.18 for invasive adenocarcinoma; and (d) 8.85 ± 6.70 for squamous cell carcinoma. Processing these data, we displayed a statistically difference (p < 0.000001) of FDG avidity between adenocarcinoma and squamous cell carcinoma. Moreover, by classifying patients into five groups based on tumor diameter and after evaluating the SUVmax value for each group, we noted a statistical correlation (p < 0.000001) between size and FDG uptake, also confirmed by the post hoc analysis. Conclusions. There is a correlation between SUVmax, histopathology outcomes and tumor size in NSCLC. Further clinical trials should be performed in order to confirm our data.

The left atrial appendage (LAA) is a complex cardiovascular structure which can yield to thrombi formation in patients with non-valvular atrial fibrillation (AF). The study of LAA fluid dynamics together with morphological features should be investigated in order to evaluate the possible connection of geometrical and hemodynamics indices with the stroke risk. To reach this goal, we conducted a morphological analysis of four different LAA shapes considering their variation during the cardiac cycle and computational fluid dynamics (CFD) simulations in AF conditions were carried out. The analysis of main geometrical LAA parameters showed a huger ostium and a reduced motility for the cauliflower and cactus shapes, as well as a lower velocity values from the CFD analysis. Such findings are in line with literature and highlight the importance of coupling dynamics imaging data with CFD calculations for providing information not available at clinical level.

Chapter 2 uses autobiographical material to lay out radio/black radio and African American music history, from the 1950s to the present—across the West and East Coasts, the South, and the Midwest—particularly the 1980s generational split in black radio programming, in response to the rise of rap and hip-hop. The chapter also defines and lays out the related R&B-style Quiet Storm radio phenomenon. Tom Joyner’s career and the TJMS’s rise within that history are documented, and its evolving politics and crew members are described. The chapter summarizes the scant public-sphere attention this black radio giant has received.

This chapter details the TJMS reporting and activism during the 2016 presidential election, including interviews with Hillary Clinton, Bernie Sanders, and Barack and Michelle Obama, and crew and audience horrified and enraged reactions to Trump’s election. It lays out their participation in and cheerleading for the Resistance, their fury over the neofascist Charleston protests and the Trump Administration’s failures to aid Americans after Hurricanes Harvey/Maria/Irma, their ongoing and hilariously denigrating anti-Trump reportage, their glee over Fox News commentators’ downfalls over sexual harassment allegations. This chapter also documents their deep involvement in the 2017 and 2018 Democratic triumphs in Virginia and Alabama, their involvement in Brett Kavanaugh’s Supreme Court appointment, the triumphant 2018 midterm elections and protesting ICE’s actions at the border, and their coverage of all of the investigations of Trump&Co, keeping the “woke” flame burning.

The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is being increasingly investigated. HtrA1 overexpression inhibits cell growth and proliferation by influencing apoptosis, invasiveness and migration of tumour cells. In the present study, HtrA1 expression was analysed in 228 colon tissue samples from patients with CRC, adenoma with high-grade dysplasia (AHD), adenoma with low-grade dysplasia (ALD), ulcerative colitis of >10 year duration (UCL), ulcerative colitis of

Because of the growing need for efficient energy production systems, energy policies promoted in recent years have also involved complex structures, like airports. This paper proposes the implementation of an energy management system for a very energy-consuming structure, composed of different power plants and many energy consumers: the Leonardo da Vinci International Airport of Rome. In this study, the examination of historical data related to airport electric power, thermal energy and fuel consumption is discussed, starting with the analysis of the production energy plants, mainly based on a combined heat and power system. Furthermore, pioneering solutions are proposed, not only to cover airport energy requirements, but also to test the safety and reliability of innovative load management systems. For this reason, the choice of the Leonardo da Vinci management company, oriented to install a smart storage in order to manage the bidirectional energy flows by consumers and producers, is justified. Such innovative energy procurement systems are examined, with the goal of achieving greater penetration of renewable sources: mini and micro wind power plants and high concentrator photovoltaic plants.

To any energy flow there is an associated flow of momentum, so that recoil forces arise every time an object absorbs or deflects incoming energy. This same principle governs the operation of macroscopic turbines as well as that of microscopic turbines that use light as the working fluid. However, a controlled and precise redistribution of optical energy is not easy to achieve at the micron scale resulting in a low efficiency of power to torque conversion. Here we use direct laser writing to fabricate 3D light guiding structures, shaped as a garden sprinkler, that can precisely reroute input optical power into multiple output channels. The shape parameters are derived from a detailed theoretical analysis of losses in curved microfibers. These optical reaction micro-turbines can maximally exploit light’s momentum to generate a strong, uniform and controllable torque., Light can be used to rotate micrometric turbines that usually rely on scattering to redistribute optical momentum and generate a mechanical torque. Here, 3D microfabricated light guiding structures can reroute an incoming flow of optical energy to generate a strong, uniform and controllable torque.

The aim of the study was to identify which groups of women contribute to interinstitutional variation of caesarean delivery (CD) rates and which are the reasons for this variation. In this regard, 15,726 deliveries from 11 regional centers were evaluated using the 10-group classification system. Standardized indications for CD in each group were used. Spearman’s correlation coefficient was used to calculate (1) relationship between institutional CD rates and relative sizes/CD rates in each of the ten groups/centers; (2) correlation between institutional CD rates and indications for CD in each of the ten groups/centers. Overall CD rates correlated with both CD rates in spontaneous and induced labouring nulliparous women with a single cephalic pregnancy at term (P=0.005). Variation of CD rates was also dependent on relative size and CD rates in multiparous women with previous CD, single cephalic pregnancy at term (P<0.001). As for the indications, “cardiotocographic anomalies” and “failure to progress” in the group of nulliparous women in spontaneous labour and “one previous CD” in multiparous women previous CD correlated significantly with institutional CD rates (P=0.021,P=0.005, andP<0.001, resp.). These results supported the conclusion that only selected indications in specific obstetric groups accounted for interinstitutional variation of CD rates.

Summary Objective Identification of skeletal maturation phases is of primary importance in terms of individual responsiveness to nearly all dentofacial orthopaedic treatments. In this regard, dentition phase and chronological age are still widely used to define the timing of and responsiveness to orthodontic treatments. Recently, gingival crevicular fluid (GCF) alkaline phosphatase (ALP) activity has been shown to be a reliable biomarker of skeletal maturation in growing subjects. Here, for the first time, circumpubertal dentition phases and chronological age were evaluated for correlations with GCF ALP activity, as a biomarker of skeletal maturation. Materials and methods Eighty-five healthy growing subjects (51 females, 34 males; mean age, 11.7 ± 2.3 years) were enrolled into this double-blind, prospective, cross-sectional-design study. Samples of GCF were collected from each subject at the mesial and distal sites of both of the central incisors, at the maxillary and mandibular arches. Their dentition phases were recorded as intermediate mixed, late mixed, or permanent. GCF ALP enzymatic activity was determined spectrophotometrically. Results The dentition phases showed median GCF ALP activities from 42.0 to 67.5 mU/sample. Although these were slightly greater for the permanent dentition, no significant differences were seen. Also, the chronological age did not correlate significantly with GCF ALP activity, and no significant differences were seen between maxillary and mandibular sites in any of the comparisons. Conclusions Assessment for treatment timing of dentofacial disharmonies in individual patients that require monitoring of their skeletal maturation phases should not rely on their circumpubertal dentition phase and chronological age.

Clinical data suggest that beyond-progression, the blockade of angiogenesis is associated with improved survivals in colorectal cancer. We conducted a systematic review to investigate the therapeutic effects of antiangiogenic drugs administered as later lines of treatment in patients already progressed to a previous anti-VEGF based treatment. An extensive literature search was conducted. Hazard ratios (HR) for progression (PFS) and death (OS) were extracted. An inverse-variance meta-analysis model was implemented. 6 randomized controlled trials were retrieved, including 3407 patients, treated with different antiangiogenic drugs. All of them had progressed during or after a previous line of treatment with bevacizumab. Overall, both PFS (HR=0.63, P P < 0.001) were significantly increased with the use of antiangiogenic drug. No heterogeneity was observed despite different drugs. Protracted inhibition of the VEGF pathway is associated with a significant improvement of both PFS and OS, independently from the antiangiogenic agent used.

Self-propelled bacteria can be integrated into synthetic micromachines and act as biological propellers. So far, proposed designs suffer from low reproducibility, large noise levels or lack of tunability. Here we demonstrate that fast, reliable and tunable bio-hybrid micromotors can be obtained by the self-assembly of synthetic structures with genetically engineered biological propellers. The synthetic components consist of 3D interconnected structures having a rotating unit that can capture individual bacteria into an array of microchambers so that cells contribute maximally to the applied torque. Bacterial cells are smooth swimmers expressing a light-driven proton pump that allows to optically control their swimming speed. Using a spatial light modulator, we can address individual motors with tunable light intensities allowing the dynamic control of their rotational speeds. Applying a real-time feedback control loop, we can also command a set of micromotors to rotate in unison with a prescribed angular speed., Bacteria are able to propel themselves and thus drive systems out of equilibrium. Here the authors aim to control this motion and exploit it in microengineered motors which are powered by genetically modified bacteria and driven by light.

Objective: The objective of this study was to verify the effects of two different training protocols based on Core Stability and Body Balance exercises in subjects with Parkinsons’s Disease. Methods: Eight elderly men with PD (age of 73 ± 9 years, weight 69 ± 16 kg, height 164 ± 13 cm, 2 ± 1 of Disability Score according to Hoehn and Yahr scale). The disability score was evaluated using Hoehn and Yahr scale. This study was 12-month-long organized in 3 blocks of 4 months each. The sample was divided in two groups formed by 4 subjects each group. During the first four months, one group performed core stability exercises (CSG) while the other group exercised itself through a Balance Exercises Program (BG). After this first part of the study both protocols were stopped for the following 4 months. Finally, the group were reversed (counter balance design) for the last 4 months of physical activity. The two groups were measured twice, before (T0) and after the treatment (T1). Both treatments were designed in order to investigate the improvement in core muscles performance in order to grant a better balance control and to reduce the risk of falling. Results: statistically significant variations were found in the flight time of Sit-to-Stand (p < 0.05, +27%) and in the step length (p < 0.05, ?3%). In the CSG group, statistically significant variations were detected in Speed of Steps (p < 0.05, +5%), Step Cadence (p < 0.05, +3%), and Left Stride Duration (p < 0.05, ?3%) (Table 1). Conclusion: Both Body Balance and Core training can be considered two good physical exercise methods for people with PD. This study highlights the positive effects of this training protocol on legs strength improvements and on the balance control while walking.

Swimming bacteria exploit viscous drag forces to generate propulsion in low Reynolds number environments. A rotating helical flagellar bundle can propel the cell body at typical speeds of ten body lengths per second. Not surprisingly, this ability to efficiently swim is preserved even in confining micro-environments which constitute their typical habitat. Quantitative studies would require the ability of fabricating complex environments with controlled geometrical properties. Experimental studies so far were limited to large diameter micro capillaries or 2D confinement. In this last case, E.coli has been shown to swim with an unaltered speed even when the gap size is slightly larger than the cell body thickness. The case of tight 1D confinement is however more challenging requiring 3D fabrication capabilities. Using two-photon polymerization we fabricate 3D microstructures that can confine swimming bacteria in quasi 1D geometries. We observe individual E.coli cells swimming through a sequence of micro-tunnels with progressively decreasing diameters. We demonstrate that E.coli motility is preserved also in tight 1D confinement. Moreover we find that there's an optimal channel diameter for which the increase in flagellar thrust due to 1D confinement can even overcome the increased drag on the cell body resulting in swimming speeds that can be up to 15% larger then the bulk speed.

Scientific Reports 6: Article number: 2329710.1038/srep23297; published online: March222016; updated: May312016 In this Article, Roberto Di Leonardo is incorrectly affiliated with ‘CNR-IMIP, UOS Roma, Dipartimento di Fisica Universita Sapienza, I-00185, Roma, Italy’. The correct affiliation is listed below: NANOTEC-CNR, Institute of Nanotechnology, Soft and Living Matter Laboratory, Roma, Italy.

Video-assisted thoracic surgery (VATS) was considered the gold standard approach in recurrent spontaneous pneumothorax, with unanimous consensus of opinions. The cost-effectiveness analysis in the surgical treatment of recurrence of primary spontaneous pneumothorax (PSP) was carried out comparing VATS with muscle-sparing axillary minithoracotomy (MSAM). Between July 2006 and October 2012 we treated 56 patients with a second episode of PSP by VATS or open approach. Time of intervention, prolonged air leaks, duration of pleural drainage, length of hospitalization, and long-term morbidity were evaluated, establishing the relationship between costs and quality-adjusted life for each technique. The assessment of pain and threshold of tenderness was more favorable in VATS in respect to MSAM during the 5 years of follow-up (p = 0.004 and

Lorenz-Mie scattering theory allows to predict the field scattered by spherical objects illuminated by coherent light. By fitting the fringe pattern resulting from the interference of incident and scattered light, it is possible to track and size colloidal particles with a few nanometer precision. Using digital holographic microscopy (DHM) we extend the applications of Lorenz-Mie theory to hollow spherical structures and to extremely high pressure conditions. On the one hand, we geometrically and optically characterize complex colloids as polymer-shelled microbubbles, with high precision, low costs and short acquisition time. These microbubbles are likely to be unique tools for targeted drug delivery and are currently used as contrast agents for sonography. We measured size, shell thickness and refractive index for hundreds of polymeric microbubbles showing that shell thickness displays a large variation that is strongly correlated with its refractive index and thus with its composition. On the other hand we demonstrate that DHM can be used for accurate 3D tracking and sizing of a holographically trapped colloidal probe in a diamond anvil cell (DAC). Polystyrene beads were trapped in water up to Gigapascal pressures while simultaneously recording in-line holograms at 1 KHz frame rate. This technique may potentially provide a new method for spatially resolved pressure measurements inside a DAC. © (2016) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Background and Objective: In spite of four decades of studies on gingival crevicular fluid, no data have been reported on the repeatability of gingival crevicular fluid collection and the subsequent quantification procedures. The present study reports, for the first time, on the repeatability and method error of gingival crevicular fluid collection and quantification, as determined through its alkaline phosphatase (ALP) activity. Diagnostic considerations are then explored. Material and Methods: Twenty-seven healthy subjects (17 women and 10 men; mean age ± SD, 21.2 ± 4.8 years) with optimal periodontal status were enrolled according to a blind prospective design. The gingival crevicular fluid was collected at baseline, and after 1 d, 1 wk and 3 mo. At each clinical session, two consecutive rounds of gingival crevicular fluid collection were made from each of the four maxillary incisors, allowing the recovery of resting and flow gingival crevicular fluid. The total ALP activities were determined spectrophotometrically, and repeatability and method errors for the resting, flow and overall (resting + flow) gingival crevicular fluid ALP activities were calculated, relative to the corresponding baseline levels. Results: No significant differences were seen over time, although the flow gingival crevicular fluid ALP activity was generally lower than that for the resting gingival crevicular fluid. The method errors ranged from 40 to 58%, with the flow and overall gingival crevicular fluid activities showing the highest and lowest errors, respectively. Conclusion: Reliable use of the gingival crevicular fluid ALP collection and quantification, both in research and diagnosis on an individual basis, should take into account relevant errors, and variations are to be considered as true only above relevant thresholds.

Essential thrombocythemia is a hematological disorder characterized by clonal hemopoiesis in the bone marrow and increased number of circulating platelets. It is usually discovered accidentally at the time of routine blood examinations or can become clinically evident with either thrombotic or hemorrhagic complications. In the present article, we describe the case of a 66-year-old woman with pneumonia due to Pneumocystis carinii, who experienced deep vein thrombosis and pulmonary embolism during hospitalization with a subsequent heparin-induced thrombocytopenia. Bone marrow examination performed after clinical improvement revealed the patient to be affected by essential thrombocythemia.

To compare the operative technique and complications of the Fantoni tracheostomy (TLT) with those of the Ciaglia Blue Rhino tracheostomy (CBR). We also compared the costs of mini-invasive tracheostomy with those of surgical tracheostomy (ST).Between January 1998 and January 2006, 530 patients needed emergency intubation and protracted assisted ventilation in our department. We performed 470 mini-invasive tracheostomies: as TLT in 350 and as CBR in 120. The time between intubation and tracheostomy was 4 +/- 1 days. Interventions were carried out in our intensive care unit (ICU).One hundred and nine patients died within 20 +/- 5 days of intervention, but 361 are still alive after 100 +/- 3 months. TLT and CBR complications were independent of the operative technique (P = 0.74, r = 0.285 vs P = 0.61, r = 0.271) or procedure time (P = 0.95, r = 0.297 vs P = 0.92, r = 0.295). Ciaglia Blue Rhino tracheostomy was noted to have a cost-benefit advantage over TLT and ST (P = 0.0002, P = 0.009, P = 0.22, respectively). The average time until decannulation was 20 +/- 1 days.Mini-invasive tracheostomies are easy, safe, and fast. Ciaglia Blue Rhino tracheostomy took less time to perform and had fewer complications than TLT, because the technique was simpler.

This paper describes techniques for generating and measuring fluid flow in microfluidic devices. The first technique is for the multi-point measurement of fluid flow in microscopic geometries. The flow sensing method uses an array of optically trapped microprobe sensors to map out the fluid flow. The optical traps are alternately turned on and off such that the probe particles are displaced by the flow of the surrounding fluid and then retrapped. The particles' displacements are monitored by digital video microscopy and directly converted into velocity field values. The second is a method for generating flow within a microfluidic channel using an optically driven pump. The optically driven pump consists of two counter-rotating birefringent vaterite particles trapped within a microfluidic channel and driven using optical tweezers. The transfer of spin angular momentum from a circularly polarized laser beam causes the particles to rotate at up to 10 Hz. The pump is shown to be able to displace fluid in microchannels, with flow rates of up to 200 m−3 s−1 (200 fL s−1). In addition a flow sensing method, based upon the technique mentioned above, is incorporated into the system in order to map the magnitude and direction of fluid flow within the channel.

We demonstrate that Digital Holographic Microscopy can be used for accurate 3D tracking and sizing of a colloidal probe trapped in a diamond anvil cell (DAC). Polystyrene beads were optically trapped in water up to Gigapascal pressures while simultaneously recording in-line holograms at 1 KHz frame rate. Using Lorenz-Mie scattering theory to fit interference patterns, we detected a 10% shrinking in the bead’s radius due to the high applied pressure. Accurate bead sizing is crucial for obtaining reliable viscosity measurements and provides a convenient optical tool for the determination of the bulk modulus of probe material. Our technique may provide a new method for pressure measurements inside a DAC.

Several schedules of 5-fluorouracil (FU) and irinotecan (IRI) have been shown to improve overall survival in advanced colorectal cancer (CRC). Preclinical evidence suggests that the sequential administration of IRI and FU produces synergistic activity, although their clinical use has not been fully optimised. We investigated the interaction between short-term exposure to SN-38, the active metabolite of IRI, and prolonged exposure to FU in human CRC HT-29 cells and observed that the synergism of action between the two agents can be increased by extending the time of cell exposure to FU and reducing the interval between administration of the two agents. Based on these findings, we performed a phase I trial in 25 advanced CRC patients using a modified IRI/FU regimen as first-line therapy and evaluated three dose levels of IRI (150-300 mg/m(2)) and two of continuous infusion of FU (800-1000 mg/m(2)) in a 3-weekly schedule. The most severe grade III-IV toxicities were neutropoenia in four cycles and diarrhoea in three. One patient achieved complete response (4%), 12 a partial response (48%), the overall response rate was 52% (+/-20, 95% CI); seven of 25 patients had stable disease (28%), the overall disease control was 80% (+/-16, 95% CI). This modified IRI/FU schedule is feasible and exhibits potentially interesting clinical activity.

Purpose. We performed a case-control study in which we tested the ability of a non-invasive assay to detect telomerase activity and to distinguish between prostatic cancer (Pca) and benign prostatic hyperplasia (BPH) on samples of epithelial cells obtained after prostatic massage. Methods. Telomerase activity was determined by a telomeric repeat amplification protocol (TRAP) assay. We selected 60 patients with histologically proven Pca (30 cases) or BPH (30 cases). Specimens included in this study were from patients who had no suspicious findings on digital rectal examination for cancer, had clinical evidence of lower urinary tract symptoms, had no sonographic signs of Pca at the transrectal ultrasound evaluation, had total PSA values moderately elevated (2.6-15 ng/ml), and had no evidence of other urological cancers. The whole procedure was conducted in double blind between pathologists and molecular biology operators. Results. Telomerase activity was detected in 90% of Pca cases and in 13% of BPH cases. The sensitivity (90%) and specificity (76%) of this method were calculated. The positive predictive value, negative predictive value, and diagnostic efficiency were 87%, 90%, and 88% respectively. Conclusion. Our data indicate that telomerase activity detected by TRAP assay on prostate epithelial cells collected by prostate massage can substantially improve the distinction between Pca and BPH conditions. One of the clinical benefits resulting from the use of this new assay would be to refine the biopsy indication and to avoid for several patients without Pca the unnecessary cost and the complications of prostate biopsy.

The direct conversion of light into work allows the driving of micron-sized motors in a contactless, controllable and continuous way. Light-to-work conversion can involve either direct transfer of optical momentum or indirect opto-thermal effects. Both strategies have been implemented using different coupling mechanisms. However, the resulting efficiencies are always very low, and high power densities, generally obtained by focused laser beams, are required. Here we show that microfabricated gears, sitting on a liquid–air interface, can efficiently convert absorbed light into rotational motion through a thermocapillary effect. We demonstrate rotation rates up to 300 r.p.m. under wide-field illumination with incoherent light. Our analysis shows that thermocapillary propulsion is one of the strongest mechanisms for light actuation at the micron- and nanoscale., The direct conversion of light into work allows the control of micromotors, but typically with low efficiencies and high power density requirements. Here, Maggi et al. demonstrate efficient thermocapillary propulsion of microgears on a liquid–air interface with wide-field, incoherent illumination.

Objective The aim of the study was to evaluate the sympathectomy procedures for primary hyperhidrosis in terms of complications and effectiveness. Methods From January 2010 to September 2012 we performed 130 sympathectomies in 65 patients, 27 males (42%) and 38 females (58%). Electrocoagulation was used in 20 procedures (15%), ultrasonic scalpel in 54 (42%), and radiofrequency dissector in 56 (43%). Seven patients (11%) underwent bilateral sympathectomy in the same surgical session, while in 58 (89%) the right surgical approach was delayed 30 days from the first procedure. Results We noticed 12 complications (9%): (a) chest pain in 6 patients (4 with electrocoagulation, 1 with ultrasonic scalpel, and 1 with radiofrequency dissector), which disappeared in 20 ± 1 day; (b) paresthesias in 3 electrocoagulation patients, was solved in 23 ± 5 days; (c) bradycardia in 1 ultrasonic patient, normalized in 4th postoperative hour; (d) unilateral relapse in 2 electrocoagulation patients after the second side approach, positively treated in 1 patient by resurgery in video-assisted thoracoscopy (VAT). The quality-adjusted life year and the quality of life evaluation revealed a statistically significant improvement (p = 0.02) in excessive sweating and general satisfaction after surgery, with Ultracision and LigaSure showing better findings than electrocoagulation. Conclusion The latest generation devices offered greater efficacy in the treatment of hyperhidrosis, minimizing complications and facilitating the resumption of normal work and social activity of patients.

Background The aim of the study was to analyze the cost-effectiveness outcomes of video-assisted thoracic surgery (VATS) in the treatment of primary spontaneous pneumothorax (PSP), comparing the minimally invasive procedure with pleural drainage (PD). Methods Between July 2006 and October 2012, we treated 122 patients with a first episode of PSP by VATS (61 patients) or pleural drainage (61 patients). We established the relationship between costs and quality-adjusted life (QAL) for both techniques. Results The total cost per patient of minimally invasive procedure was more advantageous than that of chest tube (€2,422.96 vs €4,855.12). The QAL expectancy of VATS was longer than that of PD (57.00 vs 40.80 at 60 months). The QAL year of VATS (.32 at 1st year and .25 at 5th year) was better than that of PD. Incremental cost-effectiveness ratio of VATS versus PD was between €7,600.00 (1st year) and €10,045.00 (5th year), remaining well below the threshold of acceptability. Conclusion VATS as the first-line treatment for PSP allowed low morbidity, short hospitalization, and excellent quality of life.

Background Heart failure (HF) and chronic obstructive pulmonary disease (COPD) share a common organ failure trajectory marked by prognostic uncertainty, which is a barrier to appropriate provision of palliative care. We describe in a prospective cohort from specialist hospital services the epidemiology and late clinical course of these chronic diseases to trace criteria for transition to palliative care in the community. Methods and results Seven centers enrolled 267 patients with advanced HF (n=174) or COPD (n=93) using common (multiple hospitalizations or severely impaired functional status or cachexia) and disease-specific (HF: systolic dysfunction, NYHA classes III–IV, end-organ hypoperfusion; COPD: very severe airflow obstruction, hypoxemia, hypercapnia, or long-term oxygen therapy) entry criteria. These patients represented 7.2% and 13% respectively of the overall HF and COPD population hospitalized during one year. They showed similar symptom burden, functional and quality of life impairment, recurrent hospitalizations, and 6-month mortality (39% and 37%, respectively). Organ failure progression was the cause of death in >75%. In-hospital overall stay during the previous year was the main mortality predictor in both. Disease-specific predictors included anemia, hyponatremia, no beta-blockers in HF; older age, hypercapnia in COPD. Conclusions Patients with advanced HF/COPD represent almost 10% of subjects hospitalized yearly with a primary diagnosis of HF or COPD, have similarly impaired functional status, disabling symptoms and reduced survival. Overall days spent in-hospital during the previous year, a "red flag" in the late clinical course of both diseases, might be used as a simple, reliable screening tool for appropriate transition to palliative care in the community.

The use of individual multimode optical fibers in endoscopy applications has the potential to provide highly miniaturized and noninvasive probes for microscopy and optical micromanipulation. A few different strategies have been proposed recently, but they all suffer from intrinsically low resolution related to the low numerical aperture of multimode fibers. Here, we show that two-photon polymerization allows for direct fabrication of micro-optics components on the fiber end, resulting in an increase of the numerical aperture to a value that is close to 1. Coupling light into the fiber through a spatial light modulator, we were able to optically scan a submicrometer spot (300 nm FWHM) over an extended region, facing the opposite fiber end. Fluorescence imaging with improved resolution is also demonstrated., 5 pages, 3 figures

The sound attenuation in the THz region is studied down to T 16 K in glassy glycerol by inelastic x-ray scattering. At striking variance with the decrease found below 100 K in the GHz data, the attenuation in the THz range does not show any T dependence. This result (i) indicates the presence of two different attenuation mechanisms, active, respectively, in the high- and low-frequency limits, (ii) demonstrates the nondynamic origin of the attenuation of THz sound waves, and confirms a similar conclusion obtained in SiO2 glass by molecular dynamics, and (iii) supports the low-frequency attenuation mechanism proposed by Fabian and Allen [ Phys. Rev. Lett. 82, 1478 (1999)].

Following recent data on multiple myeloma (MM) in the literature, a possible model of myeloma development, involving different cytokine signals, is advanced, and the prognostic significance of two principle staging systems is evaluated. Different therapeutic approaches to MM have been employed, consisting of either treatment with only melphalan and prednisone, or combination chemotherapy, especially in patients with a poor prognosis. However, for the initial therapy, melphalan plus prednisone in doses that compensate for individual variation in drug absorption still appears the best choice in the vast majority of MM patients. The main clinical and hematological features which distinguish Waldenström's macroglobulinemia from MM are described, as are the criteria which should be used in choosing the most appropriate treatment based, when necessary, on chemotherapy with standard alkylating agents, as well as on the new nucleoside analogues, and repeated courses of plasmapheresis.

Digital Holographic Microscopy allows to numerically retrieve three dimensional information encoded in a single 2D snapshot of the coherent superposition of a reference and a scattered beam. Since no mechanical scans are involved, holographic techniques have a superior performance in terms of achievable frame rates. Unfortunately, numerical reconstructions of scattered field by back-propagation leads to a poor axial resolution. Here we show that overlapping the three numerical reconstructions obtained by tilted red, green and blue beams results in a great improvement over the axial resolution and sectioning capabilities of holographic microscopy. A strong reduction in the coherent background noise is also observed when combining the volumetric reconstructions of the light fields at the three different wavelengths. We discuss the performance of our technique with two test objects: an array of four glass beads that are stacked along the optical axis and a freely diffusing rod shaped E.coli bacterium. © 2014 Optical Society of America.

This paper shows how a real-time simulation can be applied for rapid prototyping of an unconventional current regulator in electrical drives. The case study refers to a permanent magnet synchronous motor, with field oriented speed control algorithm arranged in the rotor fixed d-q frame. The novelty introduced in this control scheme is represented by the use of a novel PI current regulator, formerly called multivariable. This regulator has some additional features, like the capability to conduct the machine into the flux-weakening operating area. In the rapid prototyping system, based on the TMS320F2812 microcontroller, the actual motor is replaced by a proper model running on the controller, while the control algorithm is implemented as in the actual application. The case study demonstrates the simplicity of the proposed approach, leading to a sure save of time during the testing and troubleshooting action.

The different therapeutic options that may be employed in the treatment of elderly patients with acute leukemias and myelodysplastic states are considered following an analysis of certain biological features, that have been investigated by cytochemical, cytogenetic and cytokinetic techniques, immunophenotyping, and studies on G-6-PD isoenzymes. These studies imply that in the elderly the pattern of hematological malignancies and the lack of response to conventional treatment derive from intrinsic biological differences between these pathological states in older and younger patients. Treatment in elderly patients has ranged from palliative treatment to intensive chemotherapy, often with disappointing results in both cases. Palliative treatment does not induce remissions, and median survival is short. On the other hand, elderly patients do not tolerate well both induction and post-remission therapy due to the degree of toxicity and the effects of drug-induced pancytopenia. In this scenario, in vitro drug-sensitivity testing and karyotyping assume increasing importance, because they may predict which patients are likely to benefit from intensive therapy. In both acute leukemias and myelodysplasias, treatment ideally should be designed case by case, according to the hematological, clinical and biological features.

Diamond anvil cells can be used to study the behavior of materials at high pressure by compressing small samples up to hundreds of GigaPascals. There is no mechanical access to the sample once the cell is pressurized but it is possible to observe the sample through the diamond windows. Optical tweezers can be used to measure the mechanical properties of fluids, such as viscosity, by trapping and monitoring micron sized spheres suspended in the fluid. We use a diamond anvil cell within a modified optical tweezers instrument to measure the viscosity of water as a function of pressure up to 1:3GPa. Development of this technique will allow investigations of the mechanical changes in biological cells and other soft materials placed under high pressure.

This paper presents a five-phase switched reluctance motor designed to satisfy the requirements of flap actuators in medium size aircrafts, a real example of the more electric aircraft trend. In normal conditions the machine operates with two phases conducting simultaneously but it is designed to satisfy the load specifications also with one or two phases open as consequence of fault remedial strategies. A finite-element study, aiming to predict both the healthy and faulty-mode performance, is presented. The mean torque vs. current capability and the torque ripple are investigated and optimum commutation angles are evaluated in static conditions. Experimental tests on the motor prototype are included, which confirm its capability to satisfy the planned degraded modes of operation and validate the design.

Diamond anvil cells allow the behavior of materials to be studied at pressures up to hundreds of gigapascals in a small and convenient instrument. However, physical access to the sample is impossible once it is pressurized. We show that optical tweezers can be used to hold and manipulate particles in such a cell, confining micron-sized transparent beads in the focus of a laser beam. Here, we use a modified optical tweezers geometry, allowing us to trap through an objective lens with a higher working distance, overcoming the constraints imposed by the limited angular acceptance of the anvil cell. We demonstrate the effectiveness of the technique by measuring water's viscosity at pressures of up to 1.3 GPa. In contrast to previous viscosity measurements in anvil cells, our technique measures absolute viscosity and does not require scaling to the accepted value at atmospheric pressure. This method could also measure the frequency dependence of viscosity as well as being sensitive to anisotropy in the medium's viscosity.

This paper presents an analysis technique of electric motor drives based on transient simulation tools and embedded finite-element motor modeling (co-simulation). A couple of software tools, namely Cedrat Flux and Portunus, are employed suitably interfaced each other. The first one allows the computation of the motor electromagnetic behavior using a finite element model, while the second one allows the dynamic simulation of the control and feeding converter. The interacting use of these tools allows a detailed prediction of the motor transient behavior under a given control strategy and drive scheme. As test case a permanent magnet synchronous motor for biomedical application is considered, driven by field-oriented control. The co-simulation approach is at first compared with the (usual) lumped parameter modeling simulation and then verified by experiments. The results demonstrate that the co-simulation procedure allows taking into account not negligible phenomena, such as cogging and torque ripple, usually not considered in similar studies. Hence, co-simulation analysis represents a significant step for the integrate design of the motor and control, as well as a meaningful tool for electrical drives education.

This paper presents an approach to rapid prototyping of digitally controlled electrical drives based on real-time simulation. The case study refers to an interior permanent magnet synchronous motor drive. A field oriented speed control algorithm is considered, arranged in the rotor fixed d-q frame, with optimization of the torque-to-current ratio and decoupling of the feeding voltages. The real-time simulation platform and the actual drive share the same control hardware, based on the TMS320F2812 digital signal controller. At simulation stage the controlled hardware (motor, converter and transducers) is replaced by proper models running on the digital controller, while the control algorithm is implemented using the same procedures and real-time architecture that will be adopted in the final application. When one backtracks to consider the actual hardware, time and efforts needed for the ultimate controller set-up will be drastically reduced. The case study demonstrates the accuracy, efficiency, and simplicity of the proposed approach which can be easily extended to the prototyping of any kind of control scheme.

The aim of this study was to evaluate the surgical procedures of osteosynthesis and the respective costs in isolated sternal fractures and manubriosternal dislocations.Between January 2006 and July 2011, we treated 47 patients with an isolated fracture and 18 patients with a dislocation of the sternum surgically. In case of sternal fracture, the titanium plate was used in 30 (64%), steel plate in 12 (25%), and steel wire in 5 patients (11%). The stabilization after traumatic luxation was obtained with steel wire in 4 patients (22%) and titanium plate associated with demineralized bone matrix in 14 patients (78%). The quality adjusted life years (QALYs) was analyzed, as well as the incremental cost-effectiveness ratio based on QALYs.In the sternal fractures, titanium plate showed a decreased time of intervention (30 [2] minutes), length of stay (3 [1] days), and total cost (OV0556;2,277.10) compared with steel plate (OV0556;2,667.70) and steel wire (OV0556;2,801.60) procedures, displaying an excellent difference in QALYs (0.825 and 1.615, respectively). In the sternal dislocation, steel wire technique highlighted a poor QALYs, although this approach was less expensive than titanium plate with demineralized bone matrix (OV0556;3,553.60 vs.OV0556;6,047.80). Incremental cost-effectiveness ratio revealed that the titanium plate costs wereOV0556;623.55 more than the steel wire per QALYs gained.The rigid titanium plate application ensured a safe and easy management of traumatic sternal lesions with a good prognosis of patients, justified by the improved QALYs compared with other methods.Therapeutic study, level IV; economic analysis, level IV.

OBJECTIVES: Impaired cardiopulmonary reserve is the main cause of inoperability in non-small-cell lung cancer (NSCLC). This study aims to evaluate the role of a preoperative pulmonary rehabilitation (PPR) programme in the improvement of functional parameters, which can enable an increase in the number of patients eligible for surgery. METHODS: From January 2008 to June 2011, we observed a uniform group of 27 patients with NSCLC and chronic obstructive pulmonary disease (COPD). It showed: (i) a body mass index of 21.5 ± 2 kg/m²; (ii) forced expiratory volume in 1 s (FEV1) of 1.14 ± 0.7 l; (iii) maximal peak of oxygen consumption (VO2max) of 12.9 ± 1.8 ml/kg/min; (iv) carbon monoxide diffusing capacity (DLCO) of 72 ± 3% predicted; (v) stage IB of lung cancer. All patients underwent a 4-week PPR programme, 6 days a week and were re-evaluated before inclusion for surgery. RESULTS: The rehabilitation programme was completed by all patients and extended by 2 weeks in nine patients, in order to obtain a further functional improvement. A statistically significant increase has been in the values of PaO2 (60 ± 10 vs. 82 ± 12 mmHg), of VO2max (12.9 ± 1.8 vs. 19.2 ± 2.1 ml/kg/min, P = 0.00001) and of FEV1 (1.14 ± 0.7 vs. 1.65 ± 0.8 l, P = 0.02). All patients underwent a lobectomy, with a postoperative morbidity of 15%. CONCLUSIONS: A 4 to 6-week PPR programme prepares the NSCLC and COPD patients properly for the surgical approach, reducing the functional limitations of inoperability.