Laparoscopic and robotic pyeloplasty as minimally invasive alternatives to the open approach for the treatment of uretero-pelvic junction obstruction in infants: a multi-institutional comparison of outcomes and learning curves.

BACKGROUND: Since the development of minimally invasive surgery (MIS), laparoscopic and robotic approaches have been widely adopted. However, little has been published detailing the learning curve of MIS, especially in infants. OBJECTIVE: To quantify the learning curve of laparoscopic (LP) and robot-assisted laparoscopic pyeloplasty (RAL-P) for treatment of uretero-pelvic junction obstruction (UPJO) in infants evidenced by number of cases, operative time, success and complications. PATIENTS AND METHODS: Between 2009 and 2017, we retrospectively reviewed pyeloplasty cases for treatment of UPJO in infants at three academic institutions. The primary outcome was success. Secondary outcomes were UPJO recurrence, complications, and operative time as a surrogate of skill acquisition. Continuous variables were analyzed by t test, Welch-test, and one-way ANOVA. Non-continuous variables were analyzed by Chi-squared test or Fisher's exact test. Learning curves (LC) were studied by r-to-z transformation and CUSUM. RESULTS: Thirty-nine OP, 26 LP, and 39 RAL-P had mean operative times (OT) of 106, 121, and 151 min, respectively. LCs showed plateau in OT after 18 and 13 cases for LP and RAL-P, respectively. RAL-P showed a second phase of further improvements after 37 cases. At 16 months follow-up, there were similar rates of success and complications between the three groups. CONCLUSIONS: Despite different duration of learning phases, proficiency was achieved in both LP and RAL-P as evidenced by stabilization of operative time and similar success rates and complications to OP. Before and after achievement of proficiency, LP and RAL-P can be safely learned and implemented for treatment of UPJO in infants.

Localized Nanoresonator Mode in Plasmonic Microcavities.

Submicron-thick hexagonal boron nitride crystals embedded in noble metals form planar Fabry-Perot half-microcavities. Depositing Au nanoparticles on top of these microcavities forms previously unidentified angle- and polarization-sensitive nanoresonator modes that are tightly laterally confined by the nanoparticle. Comparing dark-field scattering with reflection spectroscopies shows plasmonic and Fabry-Perot-like enhancements magnify subtle interference contributions, which lead to unexpected redshifts in the dark-field spectra, explained by the presence of these new modes.

Long Spin Diffusion Length in Few-Layer Graphene Flakes.

We report a spin valve with a few-layer graphene flake bridging highly spin-polarized La_{0.67}Sr_{0.33}MnO_{3} electrodes, whose surfaces are kept clean during lithographic definition. Sharp magnetic switching is verified using photoemission electron microscopy with x-ray magnetic circular dichroism contrast. A naturally occurring high interfacial resistance ∼12 MΩ facilitates spin injection, and a large resistive switching (0.8 MΩ at 10 K) implies a 70-130 µm spin diffusion length that exceeds previous values obtained with sharp-switching electrodes.

Electroluminescence in single layer MoS2.

We detect electroluminescence in single layer molybdenum disulfide (MoS2) field-effect transistors built on transparent glass substrates. By comparing the absorption, photoluminescence, and electroluminescence of the same MoS2 layer, we find that they all involve the same excited state at 1.8 eV. The electroluminescence has pronounced threshold behavior and is localized at the contacts. The results show that single layer MoS2, a direct band gap semiconductor, could be promising for novel optoelectronic devices, such as two-dimensional light detectors and emitters.

Graphene field-effect transistors as room-temperature terahertz detectors.

The unique optoelectronic properties of graphene make it an ideal platform for a variety of photonic applications, including fast photodetectors, transparent electrodes in displays and photovoltaic modules, optical modulators, plasmonic devices, microcavities, and ultra-fast lasers. Owing to its high carrier mobility, gapless spectrum and frequency-independent absorption, graphene is a very promising material for the development of detectors and modulators operating in the terahertz region of the electromagnetic spectrum (wavelengths in the hundreds of micrometres), still severely lacking in terms of solid-state devices. Here we demonstrate terahertz detectors based on antenna-coupled graphene field-effect transistors. These exploit the nonlinear response to the oscillating radiation field at the gate electrode, with contributions of thermoelectric and photoconductive origin. We demonstrate room temperature operation at 0.3 THz, showing that our devices can already be used in realistic settings, enabling large-area, fast imaging of macroscopic samples.

The shear mode of multilayer graphene.

The quest for materials capable of realizing the next generation of electronic and photonic devices continues to fuel research on the electronic, optical and vibrational properties of graphene. Few-layer graphene (FLG) flakes with less than ten layers each show a distinctive band structure. Thus, there is an increasing interest in the physics and applications of FLGs. Raman spectroscopy is one of the most useful and versatile tools to probe graphene samples. Here, we uncover the interlayer shear mode of FLGs, ranging from bilayer graphene (BLG) to bulk graphite, and suggest that the corresponding Raman peak measures the interlayer coupling. This peak scales from ~43 cm(-1) in bulk graphite to ~31 cm(-1) in BLG. Its low energy makes it sensitive to near-Dirac point quasiparticles. Similar shear modes are expected in all layered materials, providing a direct probe of interlayer interactions.

Measurement of filling-factor-dependent magnetophonon resonances in graphene using Raman spectroscopy.

We perform polarization-resolved Raman spectroscopy on graphene in magnetic fields up to 45 T. This reveals a filling-factor-dependent, multicomponent anticrossing structure of the Raman G peak, resulting from magnetophonon resonances between magnetoexcitons and E(2g) phonons. This is explained with a model of Raman scattering taking into account the effects of spatially inhomogeneous carrier densities and strain. Random fluctuations of strain-induced pseudomagnetic fields lead to increased scattering intensity inside the anticrossing gap, consistent with the experiments.

Global longitudinal strain for prediction of mortality in ST-segment elevation myocardial infarction and aortic stenosis patients: two sides of the same coin.

OBJECTIVE: Global longitudinal strain (GLS) predicts major adverse events in ST-segment elevation myocardial infarction (STEMI) and aortic stenosis (AS). Different cut-off values and different end-points have been proposed for prognostic stratification. We aimed to verify whether a single GLS cut-off value can be used to identify increased risk of all-cause death in STEMI and AS. PATIENTS AND METHODS: One-hundred- seventeen successfully treated first STEMI (age 63.8±12.5 yrs, 70% men) and 64 AS (age 80.3±6.9 yrs, 44% men) patients, undergoing echocardiography before discharge and before AS treatment, respectively, were retrospectively analyzed. GLS was analyzed, together with pulmonary artery systolic pressure (PASP), Killip class and Genereux stage. End-point was all-cause death at 6-month follow-up. RESULTS: All-cause death occurred in 4 (3.4%) STEMI and 5 (7.8%) AS patients (p=ns). AS patients who died had GLS similar to died STEMI patients (9.7±2.1 vs. 11.3±1.7, p=ns). GLS cut-off ≤12% predicted death with 89% sensitivity and 70% specificity (AUC 0.84, p=0.001): STEMI and AS patients with GLS ≤12% had worse survival than STEMI and AS patients with GLS >12% (log-rank p=0.001). At multivariate Cox regression analysis, lower GLS values independently predicted death (HR 0.667, 95% CI 0.451-0.986, p=0.042), and the prediction model was improved when GLS was added to old age, significant comorbidities, PASP and Killip/Genereux stage (χ2 6.691 vs. 1.364, p=0.010). CONCLUSIONS: Died patients with STEMI and AS show similar values of GLS. A unique cut-off value of GLS can reliably be used to stratify the risk of all-cause death at 6-month follow-up in both two clinical settings.

CORAL: QSAR models for acute toxicity in fathead minnow (Pimephales promelas).

CORrelation And Logic (CORAL) is a software that generates quantitative structure activity relationships (QSAR) for different endpoints. This study is dedicated to the QSAR analysis of acute toxicity in Fathead minnow (Pimephales promelas). Statistical quality for the external test set is a complex function of the split (into training and test subsets), the number of epochs of the Monte Carlo optimization, and the threshold that is a criterion for dividing the correlation weights into two classes rare (blocked) and not rare (active). Computational experiments with three random splits (data on 568 compounds) indicated that this approach can satisfactorily predict the desired endpoint (the negative decimal logarithm of the 50% lethal concentration, in mmol/L, pLC50). The average correlation coefficients (r2) are 0.675 ± 0.0053, 0.824 ± 0.0242, 0.787 ± 0.0101 for subtraining, calibration, and test set, respectively. The average standard errors of estimation (s) are 0.837 ± 0.021, 0.555 ± 0.047, 0.606 ± 0.049 for subtraining, calibration, and test set, respectively. The CORAL software together with three random splits into subtraining, calibration, and test sets can be downloaded on the Internet (http://www.insilico.eu/coral/).

Role of first pass and delayed enhancement in assessment of segmental functional recovery after acute myocardial infarction.

PURPOSE: Assessing myocardial viability is crucial in decision making and prognostic restratification after acute myocardial infarction (MI). A number of noninvasive imaging modalities have been employed in viability identification, but contrast-enhanced magnetic resonance (MR) imaging has been shown to be extremely accurate because of its transmural resolution and precise definition of microvascular obstruction. Our purpose was to assess functional recovery after acute MI, with special focus on the role of infarct transmurality and microvascular obstruction. MATERIALS AND METHODS: Forty-six consecutive patients with first acute MI, reperfused by primary percutaneous transluminal coronary angioplasty (PTCA) (n=40) or fibrinolysis (n=6), underwent MR imaging within the first week to assess oedema, microvascular obstruction, function and viability and then again after 4-6 months to assess functional recovery and scar. RESULTS: At first MR examination, postcontrast images were analysed according to three patterns, based on a combination of first-pass and delayed-enhancement data: pattern 1 (normal first pass and late hyperenhancement <50% thickness) identified viable myocardium, whereas pattern 2 (late hyperenhancement >50% thickness, with or without first-pass perfusion defect) and pattern 3 (perfusion defect at first pass and late hypoenhancement) recognised nonviable myocardium, with 93% sensitivity, 75% specificity, 92% positive predictive value and 78% negative predictive value for identifying viable tissue. Furthermore, by dividing pattern 2 into two subpatterns, 2A and 2B, based on absence or presence of microvascular obstruction in >50% transmural infarcts, we were able to better identify the segments without recovery or that were nonviable with a 1.39 relative risk of failed recovery. CONCLUSIONS: After acute MI, not all infarcts with transmurality >50% can be considered nonviable; microvascular obstruction detected at first pass can help to better stratify these cases.

Correlation between clinical presentation and delayed-enhancement MRI pattern in myocarditis.

PURPOSE: The exact incidence of myocarditis is unknown, as the diagnosis is frequently delayed or missed. Clinical presentation and disease course are extremely variable, as there may be acute onset with acute coronary syndrome, or cardiogenic shock, or progressive heart failure or arrhythmias. The purpose of this study was to identify prognostic factors on magnetic resonance imaging (MRI) performed in patients with bioptically proven myocarditis at presentation and after 6 months. MATERIALS AND METHODS: Fifty-six consecutive patients with different presentations of myocarditis (20 with acute coronary syndrome, 20 with heart failure, 16 with arrhythmias) were enrolled. All patients underwent B-mode echocardiography (echo) and tissue Doppler imaging, coronarography, ventriculography, endomyocardial biopsy and contrast-enhanced MRI examination, as well as clinical and echo follow-up at 6 months. RESULTS: At 6-month follow-up, patients were divided in two groups according to values of end-systolic volume and ejection fraction: patients with negative remodelling and those with positive remodelling. Late enhancement was found to be an independent predictor of negative remodelling. CONCLUSIONS: Contrast-enhanced MRI is useful both in the diagnosis and as a prognostic indicator in the clinical suspicion of myocarditis.

Quantifying defects in graphene via Raman spectroscopy at different excitation energies.

We present a Raman study of Ar(+)-bombarded graphene samples with increasing ion doses. This allows us to have a controlled, increasing, amount of defects. We find that the ratio between the D and G peak intensities, for a given defect density, strongly depends on the laser excitation energy. We quantify this effect and present a simple equation for the determination of the point defect density in graphene via Raman spectroscopy for any visible excitation energy. We note that, for all excitations, the D to G intensity ratio reaches a maximum for an interdefect distance ∼3 nm. Thus, a given ratio could correspond to two different defect densities, above or below the maximum. The analysis of the G peak width and its dispersion with excitation energy solves this ambiguity.

A combined approach to investigate the toxicity of an industrial landfill's leachate: chemical analyses, risk assessment and in vitro assays.

Solid wastes constitute an important and emerging problem. Landfills are still one of the most common ways to manage waste disposal. The risk assessment of pollutants from landfills is becoming a major environmental issue in Europe, due to the large number of sites and to the importance of groundwater protection. Furthermore, there is lack of knowledge for the environmental, ecotoxicological and toxicological characteristics of most contaminants contained into landfill leacheates. Understanding leachate composition and creating an integrated strategy for risk assessment are currently needed to correctly face the landfill issues and to make projections on the long-term impacts of a landfill, with particular attention to the estimation of possible adverse effects on human health and ecosystem. In the present study, we propose an integrated strategy to evaluate the toxicity of the leachate using chemical analyses, risk assessment guidelines and in vitro assays using the hepatoma HepG2 cells as a model. The approach was applied on a real case study: an industrial waste landfill in northern Italy for which data on the presence of leachate contaminants are available from the last 11 years. Results from our ecological risk models suggest important toxic effects on freshwater fish and small rodents, mainly due to ammonia and inorganic constituents. Our results from in vitro data show an inhibition of cell proliferation by leachate at low doses and cytotoxic effect at high doses after 48 h of exposure.

Effects of kaolin on Ophelimus maskelli (Hymenoptera: Eulophidae) in laboratory and nursery experiments.

Although recent research has demonstrated that clays provide satisfactory control of some agricultural insect pests, the effect of clays on gall wasps that damage forest trees has not been previously reported. The aim of the current study is to evaluate the effectiveness of the clay kaolin in the laboratory and in the field in reducing the damage caused by the eulophid Ophelimus maskelli (Ashmead) on seedlings of eucalyptus (Eucalyptus L'Hér.) species. In the laboratory, kaolin + wetting agent significantly reduced the percentage of infested leaves and the number of galls per leaf. In the nursery, gall number per leaf was not correlated with leaf area with kaolin + wetting agent but was related to leaf area for all other treatments (wetting agent alone, imidacloprid, and untreated control). In the nursery, gall number per leaf was lower with kaolin + wetting agent and with imidacloprid than with the other two treatments. Overall, kaolin effectively reduced eulophid infestations, and its effect was more persistent than that of imidacloprid. Although application of kaolin might not be feasible on large forested areas, kaolin could represent a valuable control method in nurseries, where the repeated application with more toxic chemicals can result in high concentrations of residual pesticides in the soil.

Pediatric robotic-assisted laparoscopic ureterocalycostomy: Salient tips and technical modifications for optimal repair.

Introduction: Ureterocalycostomy is a necessary option for renal salvage in cases where conventional reconstructions have failed or as a primary option in anatomic situations such as intrarenal pelvis, malrotated, or horseshoe kidney. The primary principle of this procedure is to allow for dependent drainage. Ureterocalycostomy is often difficult due to extensive scar tissue and may be complicated by bleeding in the setting of a normal functioning lower pole cortex, compared to thin renal cortex and poor renal function as seen in end-spectrum of the obstruction. Identification of a dependent calyx and hemostasis can be difficult when there is a normal cortical thickness. Though the vascular control of hilum is an option, we suggest some simple tips to avoid this step and optimize surgical results. We present our experience and salient technical tips with pediatric robotic-assisted laparoscopic ureterocalycostomy and provide a step-by-step video. Methods: Four patients underwent robotic-assisted laparoscopic ureterocalycostomy between the years 2012 and 2016 by a single surgeon. Perioperative outcomes measured included operative time, hospital stay, pain relief, degree of hydronephrosis on postoperative ultrasound at 3 months, and renal scintigraphy as needed. We describe the operative procedure and provide tips on identifying a dependent lower pole calyx with flexible nephroscopy and needle puncture, the use of harmonic scalpel for incision of the lower pole cortex, and anastomosis by pre-placement of interrupted sutures as the urothelium of the renal calyces is thin and friable. Results: Patients ranged in age between 11 months and 14 years old. Three of four patients had one prior pyeloplasty, and one patient had two prior pyeloplasties. Mean operative time (incision to closure) was 208 minutes. No Clavien-Dindo 30-day complications were encountered and no patients required blood transfusion. Anatomic success was reported in all patients with a mean follow-up of 4.46 years; however, one patient ultimately required nephrectomy despite patent anastomosis, which would not drain due to a capacious pelvis. Conclusions: Robotic-assisted laparoscopic ureterocalycostomy is feasible in re-operative cases with extensive scaring and in patients with normal lower pole renal cortex. We offer tips to allow for safe and proficient performance of this procedure.

The Monte Carlo method to build up models of the hydrolysis half-lives of organic compounds.

The hydrolysis of organic chemicals such as pesticides, pollutants, or drugs can affect the fate and behaviour of environmental contaminants, so it is of interest to evaluate the stability of substances in water for various purposes. For the registration of organic compounds in Europe, information on hydrolysis must be presented. However, the experimental measurements of all chemicals would require enormous resources, and computational models may become attractive. Applying the CORAL software (http://www.insilico.eu/coral) quantitative structure-property relationships (QSPRs) were built up to model hydrolysis. The 2D-optimal descriptor is calculated with so-called correlation weights for attributes of simplified molecular input-line entry systems (SMILES). The correlation weights are obtained as results of the special Monte Carlo optimization. The nature of (five- and six-member) rings is an important component of this approach. Another important component is the atom pair proportions for nitrogen, oxygen, and sulphur. The statistical quality of the best model is: n = 44, r2 = 0.74 (training set); n = 14, r2 = 0.75 (calibration set); and n = 12, r2 = 0.80 (validation set).

Choice architecture-based prescribing tool for TB preventive therapy: a pilot study in South Africa.

BACKGROUND: All people with HIV who screen negative for active tuberculosis (TB) should receive isoniazid preventive therapy (IPT). IPT implementation remains substantially below the 90% WHO target. This study sought to further understanding of IPT prescription by piloting a simplified prescribing approach. SETTING: Primary care clinics in Matlosana, South Africa. DESIGN: This was a mixed-methods implementation study. METHODS: Nine providers were recruited and underwent training on 2018 WHO guidelines. A simplified prescribing tool containing antiretroviral therapy (ART) and IPT prescriptions was introduced into the workflow for 2 weeks. Prescription data were collected from file review. Interviews were conducted with prescribers. RESULTS: During the study period, 41 patients were evaluated for ART initiation; 34 (83%) files used the simplified prescribing tool. Thirty-seven (90%) patients were eligible for same-day ART and IPT initiation, of whom 36 (97%) received IPT prescription. Qualitative interviews identified the following barriers to IPT prescription: cognitive burden, extensive documentation, limited management support, paucity of training, stock-outs, and patient-related factors. Provider acceptability of the tool was favorable, with unanimous recommendation to colleagues on the basis of streamlining documentation and reminding to prescribe. CONCLUSIONS: This simplified prescribing device for IPT was feasible to implement. Streamlining documentation and reminding providers to prescribe can reduce work-flow barriers to IPT provision.

Duchenne muscular dystrophy: preliminary experience with sacubitril-valsartan in patients with asymptomatic left ventricular dysfunction.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an inherited X-linked recessive neuromuscular disease caused by mutations of the dystrophin gene, leading to early and progressive muscle deterioration and dilated cardiomyopathy. The aim of this investigation was to assess whether treatment with sacubitril/valsartan (S/V) is well tolerated and may have beneficial effects in DMD patients with left ventricle (LV) dysfunction. PATIENTS AND METHODS: We administered S/V to 3 DMD patients (19-29 yeard old) with LV ejection fraction <35% at echocardiography but no symptoms of heart failure. All patients were on optimal medical therapy. S/V was initiated at a very low dose of 12/13 mg/die, after withdrawal of angiotensin-converting enzyme inhibitor therapy, and slowly titrated to the dose of 49/51 mg twice daily or the maximally tolerated dose. Clinical and echocardiographic follow-up was performed after 3, 6 and 12 months. RESULTS: At baseline, the LV ejection fraction was 32±1%. A significant improvement of LV ejection fraction was observed at 3 months (44.0±6.0%; p<0.05), which was maintained at 6 (45.7±5.0%) and 12 (43.3±3.2%) months (p<0.05 for both). No relevant side effects were reported throughout the period of the study. CONCLUSIONS: Our preliminary data suggest that, in DMD patients with reduced LV ejection fraction, S/V is safe and may improve LV function.

QSAR models for biocides: The example of the prediction of Daphnia magna acute toxicity.

Biocides are multi-component products used to control undesired and harmful organisms able to affect human or animal health or to damage natural and manufactured products. Because of their widespread use, aquatic and terrestrial ecosystems could be contaminated by biocides. The environmental impact of biocides is evaluated through eco-toxicological studies with model organisms of terrestrial and aquatic ecosystems. We focused on the development of in silico models for the evaluation of the acute toxicity (EC50) of a set of biocides collected from different sources on the freshwater crustacean Daphnia magna, one of the most widely used model organisms in aquatic toxicology. Toxicological data specific for biocides are limited, so we developed three models for daphnid toxicity using different strategies (linear regression, random forest, Monte Carlo (CORAL)) to overcome this limitation. All models gave satisfactory results in our datasets: the random forest model showed the best results with a determination coefficient r2 = 0.97 and 0.89, respectively, for the training (TS) and the validation sets (VS) while linear regression model and the CORAL model had similar but lower performance (r2 = 0.83 and 0.75, respectively, for TS and VS in the linear regression model and r2 = 0.74 and 0.75 for the CORAL model).

Mild ring 17 syndrome shares common phenotypic features irrespective of the chromosomal breakpoints location.

Ring 17 syndrome is a rare disorder with clinical features influenced by the presence or deletion of the Miller-Dieker critical region (MDCR). Presence of the MDCR is associated with a mild phenotype, including growth delay (GD), mental retardation (MR), seizures, cafè au lait skin (CALS) spots and minor facial dysmorphisms. Previous studies have been mainly focused on this locus providing poor information about the role of other genes located on the p- and q-arms. Here, we used bacterial artificial chromosome (BAC)/P1 artificial chromosome (PAC) and fosmid clones as fluorescence in situ hybridization (FISH) probes to perform a cyto-molecular analysis of a ring 17 case and found that the breakpoints were close to the telomeric ends. METRNL is the sole gene located on the q-arm terminal end, whereas two open reading frames and the RPH3AL gene are located on the terminal p-arm. To detect possibly unrevealed small deletions involving the transcription units, we used subcloned FISH probes obtained by long-range polymerase chain reaction (PCR), which showed that the investigated regions were preserved. Comparing our findings with other reports, it emerges that different breakpoints, involving (or not) large genomic deletions, present overlapping clinical aspects. In conclusion, our data suggest that a mechanism based on gene expression control besides haploinsufficiency should be considered to explain the common phenotypic features found in the mild ring 17 syndrome.