Coupling of Photonic Waveguides to Integrated Detectors Using 3D Inverse Tapering

We report on the design, fabrication, and characterization of a Silicon Nitride (SiN)-based integrated photonic chip in which the dielectric waveguides are coupled to photodetectors integrated homogeneously into the Silicon substrate. The photonic-electronic coupling was realized by a 3D inverse tapering of SiN waveguides. The novelty of our approach consists in tapering the waveguide in the vertical direction by means of an engineered wet chemical etching. This allows for a smooth transition from a full-height to an arbitrarily thin waveguide thickness at the detector location, expanding adiabatically the optical mode towards the latter. The measured chips showed a responsivity $R\approx 109~\mu$A/mW and a corresponding quantum efficiency of $16\%$ at an excitation wavelength of $850$~nm. Our technological solution offers a versatile method for a top-down monolithic integration of lightwave circuitries with substrate-located photon sensing devices

Rubber hand illusion induced by touching the face ipsilaterally to a deprived hand: evidence for plastic "somatotopic" remapping in tetraplegics

Background: Studies in animals and humans indicate that the interruption of body-brain connections following spinal cord injury (SCI) leads to plastic cerebral reorganization.Objective: To explore whether inducing the Rubber Hand Illusion (RHI) via synchronous multisensory visuo-tactile bodily stimulation may reveal any perceptual correlates of plastic remapping in SCI.Methods: In 16 paraplegic, 16 tetraplegic and 16 healthy participants we explored whether RHI may be induced by tactile stimuli involving not only the left hand but also the left hemi-face. Touching the participants actual hand or face was either synchronous or asynchronous with tactile stimuli seen on a rubber hand. We assessed two components of the illusion, namely perceived changes in the real hand in space (indexed by proprioceptive drift) and ownership of the rubber hand (indexed by subjective responses to an ad-hoc questionnaire).Results: Proprioceptive drift and ownership were found in the healthy group only in the condition where the left real and fake hand were touched simultaneously. In contrast, no drift was found in the SCI patients who, however, showed ownership after both synchronous and asynchronous hand stroking. Importantly, only tetraplegics showed the effect also after synchronous face stroking.Conclusions: RHI may reveal plastic phenomena in SCI. In hand representation-deprived tetraplegics, stimuli on the face (represented contiguously in the somatic and motor systems), drive the sense of hand ownership. This hand-face remapping phenomenon may be useful for restoring a sense of self in massively deprived individuals

Sutureless aortic valve replacement in high risk patients neutralizes expected worse hospital outcome: A clinical and economic analysis

Background: Aortic valve replacement (AVR) by sutureless prostheses is changing surgeon options, although which patients benefit most, as well as their possible economic impact is still to be defined. Methods: Perceval-S prosthesis (LivaNova) is reserved, at the documented Institution, for patients at perceived high surgical risk. This retrospective analysis of outcome and resource consumption compared Perceval with other tissue valves. To clarify the comparison, only patients respecting ‘instructions-for- use’ of Perceval were reviewed. Inclusion criteria: > 65 years, +/– coronary artery bypass grafting, patent foramen ovale closure or myectomy. Exclusion criteria: bicuspid, combined valve or aortic sur- gery. Costs were calculated per patient on a daily basis including preoperative tests, operating costs (hourly basis), disposables, drugs, blood components and personnel. Results: The sutureless group (SU-AVR) had a higher risk profile than the sutured group (ST-AVR). Cardiopulmonary bypass (CPB) and cross-clamp times were significantly shorter in SU-AVR (isolated AVR: cross-clamp 52.9 ± 12.6 vs. 69 ± 15.3 min, p < 0.001; CPB 79.4 ± 20.3 vs. 92.7 ± 18.2 min, p < 0.001). Hospital mortality was 0.9% in SU-AVR and nil in ST-AVR, p = 0.489; intubation 7 (IQR 5–10.7) and 7 h (IQR 5–9), p = 0.785; intensive care unit 1 (IQR 1–1) and 1 day (IQR 1–1), p = 0.258; ward stay 5.5 (IQR 4–7) and 5 days (IQR 4–6), p = 0.002; pacemaker 5.7% (6/106) and 0.9% (1/109), p = 0.063, respectively. Hospital costs (excluding the prosthesis) were $12,825 (IQR 11,733–15,334) for SU-AVR and$12,386 (IQR 11,217–14,230) in ST-AVR, p = 0.055. Conclusions: Despite higher operative risks in SU-AVR, hospital mortality, morbidity and resource consumption did not differ. Operative times were shorter with the sutureless device and this improve- ment, along with more frequent ministernotomy, may have improved many postoperative aims.

one step high throughput assay for quantitative detection of β galactosidase activity in intact gram negative bacteria yeast and mammalian cells

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Biological heterogeneity of putative bladder cancer stem-like cell populations from human bladder transitional cell carcinoma samples.

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells, the cancer stem-like cells (CSCs) or tumor initiating cells. We report on the isolation and biological characterization of putative bladder CSC populations from primary TCCs. Isolated cells were induced to proliferate in stem cell culture conditions (serum-free medium containing mitogenic growth factors). The proliferating cells formed spheroids (urospheres) and their abilities for extensive proliferation and self-renewal were assayed. Their positivity for several stem cell markers (CD133, Oct-3/4, nestin, and cytokeratins) was also assessed by immunofluorescence tests and they could have the potential to differentiate in the presence of serum. In stem cell culture conditions they gradually showed loss of proliferation, adherence to the substrate, and morphological changes, which might reflect their progressive acquisition of differentiative capacity and loss of self-renewal ability. To evaluate if effective cell selection occurred after isolation, conventional cytogenetic studies on fresh chromosome spreads immediately after isolation and after culture were carried out. In addition, a molecular cytogenetic study by UroVysion assay was carried out on paraffin-embedded tissue sections and on fresh and after culture nuclei preparations. The data collected indicated important karyotype changes and a positive selection for hypo- or near-diploid cells, losing the complexity present in fresh tumors

Surgeon volume and body mass index influence positive surgical margin risk after robot-assisted radical prostatectomy: Results in 732 cases

Objectives: To evaluate clinicopathological and perioperative factors associated with the risk of focal and non-focal positive surgical margins (PSMs) after robot-assisted radical prostatectomy (RARP).Patients and methods: The study was retrospective and excluded patients who were under androgen-deprivation therapy or had prior treatments. The population included: negative SM cases (control group), focal and non-focal PSM cases (study groups). PSMs were classified as focal when the linear extent of cancer invasion was <= 1 mm and non-focal when >1 mm. The independent association of factors with the risk of focal and non-focal PSMs was assessed by multinomial logistic regression.Results: In all, 732 patients underwent RARP, from January 2013 to December 2017. An extended pelvic lymph node dissection was performed in 342 cases (46.7%). In all, 192 cases (26.3%) had PSMs, which were focal in 133 (18.2%) and non-focal in 59 (8.1%). Independent factors associated with the risk of focal PSMs were body mass index (odds ratio [OR] 0.914; P = 0.006), percentage of biopsy positive cores (BPC; OR 1.011; P = 0.015), pathological extracapsular extension (pathological tumour stage [pT]3a; OR 2.064; P = 0.016), and seminal vesicle invasion (pT3b; OR 2.150; P = 0.010). High surgeon volume was a protective factor in having focal PSM (OR 0.574; P = 0.006). Independent predictors of non-focal PSMs were BPC (OR 1,013; P = 0,044), pT3a (OR 4,832; P < 0.001), and pT3b (OR 5,153; P = 0.001).Conclusions: In high-volume centres features related to host, tumour and surgeon volume are factors that predict the risk of focal and non-focal PSMs after RARP

Blood pressure variability, heart functionality, and left ventricular tissue alterations in a protocol of severe hemorrhagic shock and resuscitation

Autonomic control of blood pressure (BP) and heart rate (HR) is crucial during bleeding and hemorrhagic shock (HS) to compensate for hypotension and hypoxia. Previous works have observed that at the point of hemodynamic decompensation a marked suppression of BP and HR variability occurs, leading to irreversible shock. We hypothesized that recovery of the autonomic control may be decisive for effective resuscitation, along with restoration of mean BP. We computed cardiovascular indexes of baroreflex sensitivity and BP and HR variability by analyzing hemodynamic recordings collected from five pigs during a protocol of severe hemorrhage and resuscitation; three pigs were sham-treated controls. Moreover, we assessed the effects of severe hemorrhage on heart functionality by integrating the hemodynamic findings with measures of plasma high-sensitivity cardiac troponin T and metabolite concentrations in left ventricular (LV) tissue. Resuscitation was performed with fluids and norepinephrine and then by reinfusion of shed blood. After first resuscitation, mean BP reached the target value, but cardiovascular indexes were not fully restored, hinting at a partial recovery of the autonomic mechanisms. Moreover, cardiac troponins were still elevated, suggesting a persistent myocardial sufferance. After blood reinfusion all the indexes returned to baseline. In the harvested heart, LV metabolic profile confirmed the acute stress condition sensed by the cardiomyocytes. Variability indexes and baroreflex trends can be valuable tools to evaluate the severity of HS, and they may represent a more useful end point for resuscitation in combination with standard measures such as mean values and biological measures. NEW & NOTEWORTHY Autonomic control of blood pressure was highly impaired during hemorrhagic shock, and it was not completely recovered after resuscitation despite global restoration of mean pressures. Moreover, a persistent myocardial sufferance emerged from measured cardiac troponin T and metabolite concentrations of left ventricular tissue. We highlight the importance of combining global mean values and biological markers with measures of variability and autonomic control for a better characterization of the effectiveness of the resuscitation strategy

Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects

Sirolimus (SRL) and everolimus (EVR) are mammalian targets of rapamycin inhibitors (mTOR-I) largely employed in renal transplantation and oncology as immunosuppressive/antiproliferative agents. SRL was the first mTOR-I produced by the bacterium Streptomyces hygroscopicus and approved for several medical purposes. EVR, derived from SRL, contains a 2-hydroxy-ethyl chain in the 40th position that makes the drug more hydrophilic than SRL and increases oral bioavailability. Their main mechanism of action is the inhibition of the mTOR complex 1 and the regulation of factors involved in a several crucial cellular functions including: protein synthesis, regulation of angiogenesis, lipid biosynthesis, mitochondrial biogenesis and function, cell cycle, and autophagy. Most of the proteins/enzymes belonging to the aforementioned biological processes are encoded by numerous and tightly regulated genes. However, at the moment, the polygenic influence on SRL/EVR cellular effects is still not completely defined, and its comprehension represents a key challenge for researchers. Therefore, to obtain a complete picture of the cellular network connected to SRL/EVR, we decided to review major evidences available in the literature regarding the genetic influence on mTOR-I biology/pharmacology and to build, for the first time, a useful and specific "SRL/EVR genes-focused pathway", possibly employable as a starting point for future in-depth research projects

Comparison between invasive breast cancer with extensive peritumoral vascular invasion and inflammatory breast carcinoma: a clinicopathologic study of 161 cases.

Objectives: Extensive peritumoral neoplastic lymphovascular invasion (ePVI) is a marker of aggressiveness in invasive breast carcinoma (BC). Methods: We explored the impact of ePVI on different BC subtypes. In a total of 2,116 BCs, 91 ePVI-BCs, 70 inflammatory breast carcinomas (IBCs), and 114 casual BCs as a control group (CG-BC) were recruited. Results: Patients affected by ePVI-BC were younger, had larger tumors, higher histologic grade, elevated Ki-67 score, Her2/neu overexpressed, and more lymph node metastases compared with CG-BC ( P < .001). Interestingly, only younger mean age at diagnosis differentiated patients with ePVI-BC from patients affected by IBC. ePVI-BC showed a clinical outcome intermediate between the prognoses of IBC and CG-BC. Conclusions: Results suggest that ePVI-BC and IBC may share some pathologic processes, providing a novel perspective on the heterogeneity of BC. Epidemiologic data and molecular studies on gene expression features are needed to rationally classify these tumors into their identified subtypes