Chirp management in silicon-graphene electro absorption modulators.

We study the frequency chirp properties of graphene-on-silicon electro-absorption modulators (EAMs). By experimentally measuring the chirp of a 100 µm long single layer graphene EAM, we show that the optoelectronic properties of graphene induce a large positive linear chirp on the optical signal generated by the modulator, giving rise to a maximum shift of the instantaneous frequency up to 1.8 GHz. We exploit this peculiar feature for chromatic-dispersion compensation in fiber optic transmission thanks to the pulse temporal lensing effect. In particular, we show dispersion compensation in a 10Gb/s transmission experiment on standard single mode fiber with temporal focusing distance (0-dB optical-signal-to-noise ratio penalty) of 60 km, and also demonstrate 100 km transmission with a bit error rate largely lower than the conventional Reed-Solomon forward error correction threshold of 10-3.

Complex effective index in graphene-silicon waveguides.

We report for the first time and characterize experimentally the complex optical conductivity of graphene on silicon photonic waveguides. This permits us to predict accurately the behavior of photonic integrated devices encompassing graphene layers. Exploiting a Si microring add/drop resonator, we show the effect of electrical gating of graphene on the complex effective index of the waveguide by measuring both the wavelength shift of the resonance and the change in the drop peak transmission. Due to electro-refractive effect of graphene a giant (>10-3) change in the effective index is demonstrated for the first time on Si photonics waveguides and this large effect will crucially impact performances and consumption of Si photonics devices. We confirmed the results by two independent experiments involving two different gating schemes: Si gating through the ridge waveguide, and polymer-electrolyte gating. Both the experiments demonstrate a very large phase effect in good agreement with numerical calculations. The reported results validate the Kubo model for the case of graphene-Si photonics interfaces and for propagation in this type of waveguide. This is fundamental for the next design and fabrication of future graphene-silicon photonics devices.

Wide-band polarization controller for Si photonic integrated circuits.

A circuit for the management of any arbitrary polarization state of light is demonstrated on an integrated silicon (Si) photonics platform. This circuit allows us to adapt any polarization into the standard fundamental TE mode of a Si waveguide and, conversely, to control the polarization and set it to any arbitrary polarization state. In addition, the integrated thermal tuning allows kilohertz speed which can be used to perform a polarization scrambler. The circuit was used in a WDM link and successfully used to adapt four channels into a standard Si photonic integrated circuit.

High responsivity SiGe heterojunction phototransistor on silicon photonics platform.

We report on a novel near infrared SiGe phototransistor fabricated by a standard silicon photonics foundry. The device is first investigated by simulations. The fabricated devices are characterized in terms of current-voltage characteristics at different optical power. Typical phototransistors exhibit 1.55µm record responsivity at low optical power exceeding 232A/W and 42A/W at 5V and 1V bias, respectively. A differential detection scheme is also proposed for the dark current cancellation to significantly increase the device sensitivity.

Hemoconcentration induced by exercise: Revisiting the Dill and Costill equation.

The Dill and Costill equation is used to estimate the exercise-induced hemoconcentration. However, this calculation requires drawing an extra whole-blood sample, which cannot be frozen and has to be analyzed with dedicate instrumentation in a relative short time. The aim of the present study was to explore the usefulness of some serum biochemical parameters to estimate hemoconcentration induced by exhaustive exercise. Fourteen healthy male subjects (19-34 years) performed a15-min running test at 110% of anaerobic threshold speed. Hemoglobin, hematocrit, brain natriuretic peptide (BNP), creatinine, gamma-glutamyltransferase (GGT), total-proteins, albumin, total calcium (Ca), K(+), Na(+), and Cl(-) were determined in blood samples taken before, after exercise, and after a 30-min recovery period. Plasma volume loss (ΔPV) was calculated by Dill and Costill equation. At post-exercise and after recovery, the percentage increments of total-proteins, albumin, GGT and Ca correlated significantly with ΔPV. Bland-Altman analyses showed that correcting BNP, creatinine, and K(+) concentration by Ca percentage increments yield biases and limits of agreement that are acceptable when compared with Dill and Costill equation correction. Ca concentration may be used as a hemoconcentration biomarker in high-intensity exercise, which would allow scientists and physicians avoid extra costs, facilitate in-field research, and delayed estimation of hemoconcentration using stored serum samples.

Exercise effects on erythrocyte deformability in exercise-induced arterial hypoxemia.

Exercise-induced arterial hypoxemia (EIAH) is often found in endurance-trained subjects at high exercise intensity. The role of erythrocyte deformability (ED) in EIAH has been scarcely explored. We aimed to explore the role of erythrocyte properties and lactate accumulation in the response of ED in EIAH. ED was determined in 10 sedentary and in 16 trained subjects, both before and after a maximal incremental test, and after recovery, along with mean corpuscular volume (MCV) and red blood cell lactate concentrations. EIAH was found in 6 trained subjects (∆SaO2=-8.25±4.03%). Sedentary and non-EIAH trained subjects showed reduced ED after exercise, while no effect on ED was found in EIAH trained subjects. After exercise, lactate concentrations rose and MCV increased equally in all groups. ED is strongly driven by cell volume, but the different ED response to exercise in EIAH shows that other cellular mechanisms may be implicated. Interactions between membrane and cytoskeleton, which have been found to be O2-regulated, play a role in ED. The drop in SaO2 in EIAH subjects can improve ED response to exercise. This can be an adaptive mechanism that enhances muscular and pulmonary perfusion, and allows the achievement of high exercise intensity in EIAH despite lower O2 arterial transport.

Inconsistency in circulating irisin levels: what is really happening?

The discovery of irisin as a novel and promising peptidic hormone for the treatment of obesity and diabetes has recently been reported. As a result, great hopes have been raised based on this finding, hypothesizing that irisin might provide additional benefits, not only for obesity and diabetes, but also for a wide range of pathological conditions requiring therapeutical and clinical attention. However, controversial results and conclusions on circulating irisin concentrations and correlations with other variables, including its role in metabolism, have recently been reported. Although laboratory assessment of irisin by ELISA is easily available and may provide interesting information for therapeutics and clinical practice, the heterogeneous and often discrepant results published so far, raise serious concerns about its measurement, indicating that it may still not be ready for use or whether irisin really exists. We highlight here some aspects on these discrepancies and contradictions, and put forward their implications.

Multicenter evaluation of the Sepsityper™ extraction kit and MALDI-TOF MS for direct identification of positive blood culture isolates using the BD BACTEC™ FX and VersaTREK(®) diagnostic blood culture systems.

AIMS: (i) Evaluation of delayed time to blood culture extraction by the Sepsityper kit and impact of shipping pellets off-site for MALDI-TOF MS analysis. (ii) Comparison of Sepsityper and laboratory-developed extraction methods from a literature review. METHODS AND RESULTS: Using two blood culture systems (BD BACTEC and VersaTREK), we extracted 411 positive blood cultures using the Sepsityper kit to mimic a potential protocol for institutions without a MALDI-TOF MS. Extracted pellets were shipped and analysed on the Bruker UltraflexIII. Successful extraction of 358 (87·1%) samples was determined by the presence of detectable proteins. MALDI-TOF MS correctly identified 332 (80·8%) samples. CONCLUSIONS: Delayed time to extraction did not affect Sepsityper extraction or MALDI-TOF MS accuracy. The extracted pellets remain stable and provide accurate results by MALDI-TOF MS when shipped at room temperature to off-site reference laboratories. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to show that institutions without a MALDI-TOF MS can take advantage of this innovative technology by shipping a volume of blood to an off-site laboratory for extraction and MALDI-TOF MS analysis. We also performed a literature review to compare various extraction methods.

Idiopathic pulmonary fibrosis clustering based on cilium gene expression: profiling a new paradigm.

Idiopathic pulmonary fibrosis (IPF), the commonest form of the interstitial lung diseases identifies a specific form of chronic, progressive fibrosing interstitial pneumonia, occurring primarily in older adults, and limited to the lungs. IPF represents an unsolved health problem with an urgent medical need due to lack of effective therapies. Although precise IPF etiology remains elusive, during the past decade there has been a shift away from the pathogenetic theory of generalized inflammation progressing to a paradigm of disordered fibroproliferation and alveolar epithelial cell function. A better understanding of the molecular mechanisms driving IPF fibroblasts proliferation is mandatory to provide insights into the pathogenesis, and to identify highly reproducible biomarkers for disease onset and progression. In this review we aim to discuss and analyze the findings recently published by Yang et al. on Thorax, which reported a strong molecular signature as-sociated with the expression of cilium genes that divides IPF/ usual interstitial pneumonia into two subtypes, one with increased cilium gene expression and one with low expression of cilium genes. The study presents a number of methodology limitations, mainly related to samples characterization and to a general overstatement of the conclusions from class clustering analysis. Nevertheless, the study clearly demonstrates ­ for the first time ­ that the cilium apparatus is activated in microscopic honeycombing. In such setting, cilia are likely to act as signaling "machine" which cooperates in promoting proliferative and regenerative cellular processes. Although preliminary, these results sustain a rationale to develop further investigations to confirm the impact of cilium gene expression in IPF with the final perspective of therapeutic intervention.

Post-operative complications of tibial plateau fractures treated with screws or hybrid external fixation.

PURPOSE: To assess the complications and second surgeries rates at 1 year follow-up in a group of patients underwent minimally invasive fixation with screws or hybrid external fixation (HEF) for tibial plateau fractures (TPF). The hypothesis was that low Schatzker (I-IV) TPF would have shown a lower complication rate with respect to high Schatzker (V-VI) TPF. METHODS: 148 patients who underwent minimally invasive surgery with screws or HEF for TPF were included and pooled in two groups: mono-condylar (Schatzker I-IV) and bi-condylar (Schatzker V-VI). The rate of second surgeries and complications, such as stiffness, infection, wound dehiscence and malunion occurred within 1 year, were reported. RESULTS: Statistically significant difference between mono-condylar and bi-condylar groups was found in terms of stiffness (18% vs. 37%, p = 0.01), malunion (4% vs 21%, p = 0.004) and second surgeries (32% vs. 48%, p = 0.049). Associated procedures performed during TPF fixation increased risk of second surgeries (OR 2.1, p < 0.001). No differences in terms of second surgeries and complications were found in bi-condylar group treated with screws and HEF. CONCLUSION: Bi-condylar TPF treated with minimally invasive surgery developed a significantly higher rates of stiffness, malunion and second surgeries within 1 year compared to mono-condylar fractures. Moreover, when an associated procedure was performed, the risk of a reoperation was nearly doubled. Trial registration number PG 0012506 CE AVEC 620/2018/Oss/IOR.

Idiopathic nonspecific interstitial pneumonia: an interstitial lung disease associated with autoimmune disorders?

Recent evidence suggests that idiopathic nonspecific interstitial pneumonia (iNSIP) is a distinct clinical entity amongst other idiopathic interstitial pneumonias, and some data seem to suggest a possible pathogenetic role of autoimmunity. The aim of the present study was to assess if iNSIP might represent an early lung manifestation of an autoimmune disease. After initial review of cases found in the medical records database by searching for the term "NSIP" (n = 63), 37 iNSIP cases were identified, and were re-evaluated using a dynamic integrated multidisciplinary approach. 27 cases with iNSIP were selected for the study. Mean ± sd age at first respiratory symptom was 54.2 ± 8 yrs, 70% were females, and 59% were never-smokers. At follow-up (mean ± sd 59.7 ± 29 months, range 12-138 months), autoimmune diseases occurred in 14 (52%) patients, with seven (26%) cases of autoimmune thyroiditis, six (22%) of undifferentiated connective tissue disease and three (11%) of connective tissue disease. Patients developing autoimmune diseases were older and more frequently never-smoking females. In >50% of patients diagnosed with iNSIP, evidence of autoimmune diseases develops within 2 yrs, suggesting a probable link between the clinical entity of iNSIP and autoimmune disorders.

Prospective evaluation of drug-induced lung toxicity with high-resolution CT and transbronchial biopsy.

PURPOSE: This study compared the results of high-resolution computed tomography (HRCT) and cytohistology after transbronchial biopsy in the evaluation of drug-related interstitial lung disease (DR-ILD). MATERIALS AND METHODS: Patients with a clinical and imaging diagnosis of DR-ILD were prospectively included in a study protocol lasting 5 years. All patients were evaluated by bronchoscopy with transbronchial biopsy or bronchoalveolar lavage (BAL) following an HRCT examination that raised a suspicion of DR-ILD. Two radiologists (one senior and one junior), unaware of the diagnosis, reported the single HRCT findings, their distribution and predominant pattern. In the event of disagreement, the diagnosis was subsequently reached by consensus. Cytohistological examination was considered the gold standard in the diagnosis of DR-ILD. Patients who were unable to undergo the endoscopic procedure were excluded from the study. RESULTS: The study included 42 patients (25 men, 17 women; age range 20-84 years). Transbronchial biopsy was performed in all but four patients (one case of alveolar haemorrhage and three cases of lipoid pneumonia) in whom the diagnosis was established with BAL. Assessment of the HRCT images revealed the following patterns: noncardiogenic pulmonary oedema (n=13); organising pneumonia (OP) (n=9); hypersensitivity pneumonitis (HP) (n=2); alveolar haemorrhage (AH) (n=2); nonspecific interstitial pneumonia (NSIP) (n=5); lipoid pneumonia (LP) (n=1); sarcoid-like pattern (n=1). Cytohistological diagnosis revealed diffuse alveolar damage (DAD) in 11 patients, OP in seven, HP in three, AH in three, chronic interstitial pneumonia (CIP) in eight, LP in three and pseudosarcoidosis in one. Subdivision of the drugs into antineoplastic and nonantineoplastic agents showed that the most common patterns were CIP (n=6), DAD (n=2) and OP (n=2) in the antineoplastic group and DAD (n=9) and OP (n=5) in the nonantineoplastic group. Sensitivity and specificity of the radiological analysis was excellent, especially for patterns such as OP and DAD (sensitivity 0.86 and specificity 0.88 for OP; sensitivity 1 and specificity 0.93 for DAD). CONCLUSIONS: HRCT demonstrated excellent sensitivity and specificity. In cases in which its specificity was low, HRCT was nonetheless useful for biopsy planning and clinical-radiological monitoring after discontinuation of the drug treatment.

Photo thermal effect graphene detector featuring 105 Gbit s-1 NRZ and 120 Gbit s-1 PAM4 direct detection.

One of the main challenges of next generation optical communication is to increase the available bandwidth while reducing the size, cost and power consumption of photonic integrated circuits. Graphene has been recently proposed to be integrated with silicon photonics to meet these goals because of its high mobility, fast carrier dynamics and ultra-broadband optical properties. We focus on graphene photodetectors for high speed datacom and telecom applications based on the photo-thermo-electric effect, allowing for direct optical power to voltage conversion, zero dark current, and ultra-fast operation. We report on a chemical vapour deposition graphene photodetector based on the photo-thermoelectric effect, integrated on a silicon waveguide, providing frequency response >65 GHz and optimized to be interfaced to a 50 Ω voltage amplifier for direct voltage amplification. We demonstrate a system test leading to direct detection of 105 Gbit s-1 non-return to zero and 120 Gbit s-1 4-level pulse amplitude modulation optical signals.

High-responsivity graphene photodetectors integrated on silicon microring resonators.

Graphene integrated photonics provides several advantages over conventional Si photonics. Single layer graphene (SLG) enables fast, broadband, and energy-efficient electro-optic modulators, optical switches and photodetectors (GPDs), and is compatible with any optical waveguide. The last major barrier to SLG-based optical receivers lies in the current GPDs' low responsivity when compared to conventional PDs. Here we overcome this by integrating a photo-thermoelectric GPD with a Si microring resonator. Under critical coupling, we achieve >90% light absorption in a ~6 µm SLG channel along a Si waveguide. Cavity-enhanced light-matter interactions cause carriers in SLG to reach ~400 K for an input power ~0.6 mW, resulting in a voltage responsivity ~90 V/W, with a receiver sensitivity enabling our GPDs to operate at a 10-9 bit-error rate, on par with mature semiconductor technology, but with a natural generation of a voltage, rather than a current, thus removing the need for transimpedance amplification, with a reduction of energy-per-bit, cost, and foot-print.

Endobronchial ultrasound in Dieulafoy's disease of the bronchus: an additional application of EBUS.

Dieulafoy's disease is a rare vascular malformation represented by an abnormally enlarged submucosal arterial vessel. This malformation is mostly found in gastrointestinal tract causing spontaneous bleeding although a few cases have been described in the bronchial tree. Recognizing Dieulafoy's malformation is crucial for the bronchoscopist in order to avoid biopsy that can lead to a massive hemoptysis, sometimes fatal. In this case report we show the clinical utility of endobronchial ultrasound (EBUS) in the evaluation of bronchial alteration suspicious for Dieulafoy's malformation.

Vestibular failure managed with osteopathic manipulative treatment: A report of two cases.

INTRODUCTION: Vestibular failure or hypofunction can be generated by pathologies such as vestibular neuritis (VN), causing the onset of rotatory vertigo and the vestibulo-ocular reflex (VOR) hyporeaction. VN is a post-viral inflammation-producing vestibular nerve-axon impairment, which reaches compensation in 70% of cases. Here, we present two cases of vestibular failure that did not respond to pharmacological therapy, but did show modulated vestibular response after an osteopathic manipulative treatment. Dizziness handicap inventory (DHI) was used to assess disability, while VOR was examined by means of video head impulse test (v-HIT). Case 1 showed bilateral VOR areflexia with severe related disability due to chronic vertigo, while case 2 showed sub-acute VN complicated by intense vomiting. After treatment, both cases had a complete remission of symptoms, with a reduction in DHI score of 60 and 70 points respectively, as well as a normalization of the v-HIT exam. CONCLUSION: OMT might work to modulate VOR, through osteopathic manipulation of the fascial-system and interaction with proprioceptive inputs. Further clinical trials should be performed to investigate the OMT clinical efficacy in uncompensated vestibular neuritis.

The role of transbronchial lung biopsy for the diagnosis of diffuse drug-induced lung disease: a case series of 44 patients.

At present, no studies have evaluated the role of bronchoscopic transbronchial lung biopsy (TBLB) in the diagnosis of diffuse drug-induced lung disease (DILD), and there is no consensus for a definite diagnostic workup approach for this rare clinical entity. The aim of the present study was to evaluate the clinical usefulness of TBLB in diffuse DILD. This study was a retrospective analysis of patients with diffuse DILD, who underwent bronchoscopy. The role of TBLB was assessed to determine whether the histological results are useful for the final diagnosis. Over a 5-yr period, 44 patients underwent bronchoscopy, and all had a bronchoalveolar lavage (BAL). Thirty-three of the 44 patients underwent TBLB (75%), and the results of TBLB were diagnostically helpful in 25 (75.7%) of the procedures. No histopathologic abnormality was identified in 6 (18%) of the 33 patients. In 2 patients (6%) the obtained samples were not adequate, since no lung parenchyma was obtained. No severe complications related to bronchoscopic procedures occurred. In conclusion, TBLB is a safe procedure, and is diagnostically helpful in the majority of cases of patients with diffuse DILD. Histological data obtained by TBLB further corroborate clinical, laboratory, radiologic and BAL results for a definitive diagnosis of diffuse DILD.

Significant impact of survivin on myeloma cell growth.

Survivin is a fascinating member of the inhibitor of apoptosis protein (IAP) family with its dual roles in mitosis and apoptosis, and emerges as an attractive target for cancer therapy. Multiple myeloma (MM) is a plasma cell malignancy, characterized by deregulated proliferation, cell-death processes and fatal outcome. We thus investigated survivin expression in myeloma cells and its role in MM biology to evaluate its potential interest as a target in MM treatment. Our results describe the cancer-specific overexpression of survivin in myeloma cells and show a significant correlation between survivin expression at protein level and clinical course of MM. Moreover, survivin knockdown by RNA interference led to growth rate inhibition of myeloma cells related to apoptosis induction and deep cell-cycle disruption. Finally, survivin knockdown sensitized myeloma cells to conventional anti-myeloma agents. Altogether, these data argue for the interest to evaluate survivin antagonists in MM treatment.

Optical coherence tomography findings of incomplete posterior vitreoschisis with vitreomacular traction syndrome and impending macular hole: a case report.

PURPOSE: Vitreomacular traction syndrome is a clinical entity characterized by partial posterior vitreous detachment in combination with persistent macular adherence. Recently, optical coherence tomography (OCT) allowed visualization of incomplete posterior vitreoschisis leading to vitreomacular traction. METHODS: The authors report on a 57-year-old woman with blurred vision in her left eye. RESULTS: OCT scan showed incomplete posterior vitreoschisis with vitreomacular traction syndrome and impending macular hole in her left eye. CONCLUSIONS: The intraoperative findings together with the evidence that the internal limiting membrane (ILM) thickness is thinner than the axial resolution of the Stratus OCT (8 micronm) and a spontaneous ILM detachment has never been demonstrated are likely to support the hypothesis that posterior vitreoschisis exists and can be associated with vitreomacular traction syndrome.