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Background: Gas in the renal excretory system is described as a consequence of recent procedures but it can be a sign of severe conditions such as fistulas or infections; however, gas-containing renal stones are only rarely encountered., Purpose: To describe the association of gas-containing renal stones and urinary tract infection., Material and Methods: We performed a retrospective evaluation of the clinical and imaging findings in a series of six patients with gas-containing renal stones and compared our findings with those of patients with gas-containing renal stones reported in the literature. Urine and stone cultures were used as a diagnostic standard for urinary tract infection., Results: Including the present series, there is a total of 21 patients with gas-containing renal stones in the literature. Based on clinical presentation, urinary tract infection could be suspected in 10 (57%) patients, while urine and/or stone cultures showed infection in 18 of 19 (95%) patients, with only one case with no bacterial growth in both (5%); in the remaining patient the information was not available., Conclusion: Gas-containing renal stones are a rarely reported entity usually diagnosed with computed tomography. They are a radiological sign often associated with urinary tract infection that can also be encountered in patients with non-specific renal symptoms.

Monocular polyplopia (ghost or multiple images) is a serious visual impediment for some people who report seeing two (diplopia), three (triplopia) or even more images. Polyplopia is expected to appear if the point spread function (PSF) has multiple intensity cores (a dense concentration of a large portion of the radiant flux contained in the PSF) relatively separated from each other, each of which contributes to a distinct image. We present a theory that assigns these multiple PSF cores to specific features of aberrated wavefronts, thereby accounting optically for the perceptual phenomenon of monocular polyplopia. The theory provides two major conclusions. First, the most likely event giving rise to multiple PSF cores is the presence of hyperbolic, or less probably elliptical, umbilic caustics (using the terminology of catastrophe optics). Second, those umbilic caustics formed on the retinal surface are associated with certain points of the wave aberration function, called cusps of Gauss, where the gradient of a curvature function vanishes. However, not all cusps of Gauss generate those umbilic caustics. We also provide necessary conditions for those cusps of Gauss to be fertile. To show the potential of this theoretical framework for understanding the nature and origin of polyplopia, we provide specific examples of ocular wave aberration functions that induce diplopia and triplopia. The polyplopia effects in these examples are illustrated by depicting the multi-core PSFs and the convolved retinal images for clinical letter charts, both through computer simulations and through experimental recording using an adaptive optics set-up. The number and location of cores in the PSF is thus a potentially useful metric for the existence and severity of polyplopia in spatial vision. These examples also help explain why physiological pupil constriction might reduce the incidence of ghosting and multiple images of daily objects that affect vision with dilated pupils. This mechanistic explanation suggests a possible role for optical phase-masking as a clinical treatment for polyplopia and ghosting., (© 2022 The Authors. Ophthalmic and Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Multifocal and/or extended depth-of-focus designs are widely used in many optical applications. In most of them, the optical configuration has axial symmetry. A usual design strategy consists of exploring the optimal wavefronts that emerging out of the optical system would provide the desired multifocal properties. Those properties are closely related to light concentration on caustic surfaces. We present a systematic analysis of how to obtain those multifocal wavefronts given some prescriptions on the locations of caustics. In particular, we derive several multifocal wavefronts under archetypical prescriptions in the sagittal caustic alone, or combined with the tangential one at certain points, with some emphasis on visual optics applications.

A soluble mesothelin-related peptide (SMRP) is the only FDA-approved biomarker for diagnosis of pleural mesothelioma (PM) and the most used for monitoring treatment. Radiological assessment of PM, based on modified RECIST (mRECIST) criteria, is challenging. This pilot study was designed to evaluate whether SMRP levels correlated over time with mRECIST score. Serial serum samples from PM patients were collected and SMRP levels were measured and compared with the mRECIST score obtained through centralized CT scans by blinded review. The within-patient SMRP-mRECIST relationship over time was estimated through a normal random-effects regression approach applied to the log-transformed mRECIST score. Overall, 58 PM patients were included (46 males and 12 females) with a median age at diagnosis of 67 years (min-max = 48-79), 44 (76%) with epithelioid and 14 (24%) with non-epithelioid histology. The total number of SMRP measurements and CT scans considered for analysis was 183. There was a statistically significant correlation between SMRP and mRECIST score in the 2 cohorts considered both separately and jointly. These results, although exploratory, suggest that SMRP measurement might be considered as an adjunct to monitor PM patients in order to delay CT scans time interval, thus warranting further investigation.

A breakpoint in a portable near-infrared spectroscopy (NIRS) derived deoxygenated haemoglobin (deoxy[Hb]) signal during an incremental VO2max running test has been associated with the second ventilatory threshold (VT2) in healthy participants. Thus, the aim was to examine the association between this breakpoint (NIRS) and VT 2 in well-trained runners. Gas exchange and NIRS data were collected during an incremental VO 2max running test for 10 well-trained runners. The breakpoint calculated in oxygen saturation (StO 2 ) and the VT 2 were determined and compared in terms relative to %VO 2max , absolute speed, VO 2 , and maximum heart rate (HRmax). There were no significant differences (p>0.05) between the breakpoint in StO 2 and VT 2 relative to %VO 2max (87.00±6.14 and 88.28 ± 3.98 %), absolute speed (15.70±1.42 and 16.10±1.66 km·h -1 ), VO 2 (53.71±15.17 and 54.66±15.57 ml·kg -1 ·min -1 ), and%HRmax (90.90±4.17 and 91.84±3.70%). There were large and significant correlations between instruments relative to%VO 2max (r=0.68, p<0.05), absolute speed (r=0.86, p<0.001), VO 2 (r=0.86, p<0.001), and %HR max (r=0.69; p<0.05). A Bland and Altman analysis of agreement between instruments resulted in a mean difference of - 1.27±4.49%, -0.40±0.84 km·h -1 ,-0.90±3.07 ml·kg -1 ·min -1 , and - 0.94±3.14 for %VO 2max , absolute speed, VO 2, and %HR max , respectively. We conclude that a portable NIRS determination of the StO 2 breakpoint is comparable with VT 2 using gas exchange and therefore appropriate for use in determining exercise training above VT 2 intensity. This is the first study to analyze the validity with the running mode using a NIRS portable device., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Multifocal lenses comprising progressive power surfaces are commonly used in contact and intraocular lens designs. Given a visual performance metric, a wavefront engineering approach to design such lenses is based on searching for the optimal wavefront at the exit pupil of the eye. Multifocal wavefronts distribute the energy along the different foci thanks to having a varying mean curvature. Therefore, a fundamental step in the wavefront engineering approach is to generate the wavefront from a prescribed mean curvature function. Conventionally, such a thing is done by superimposing spherical wavefront patches and maybe adding a certain component of spherical aberration to each spherical patch in order to increase the depth-of-field associated with each focus. However, such a procedure does not lead to smooth wavefront solutions and also restricts the type of available multifocal wavefronts. We derive a new, to the best of our knowledge, mathematical method to uniquely construct multifocal wavefronts from mean curvature functions (depending on radial and angular coordinates) under certain numerically justified approximations and restrictions. Additionally, our procedure leads to a particular family of wavefronts (line-umbilical multifocal wavefronts) described by 2 conditions: (1) to be smooth multiplicative separable functions in the radial and angular coordinates; (2) to be umbilical along a specific segment connecting the circle center with its edge. We provide several examples of multifocal wavefronts belonging to this family, including a smooth variant of the so-called light sword element.

A 45-year-old man presents with 48-hour status of high temperature, cough and dyspnoea. In the context of pandemic, the patient is initially diagnosed with COVID-19 syndrome. Later, the laboratory and ultrasound study supported acute appendicitis diagnosis. Appendicectomy was performed. The histopathology study confirmed eosinophilic appendicitis and that a parasitic infection was suspected. The stool sample was positive for Strongyloides stercoralis The diagnosis of a S stercoralis is a rare finding in Spain. S. stercoralis simulates clinical findings of inflammatory bowel disease or eosinophilic gastroenteritis, which may lead to the wrong therapeutic choice. Since in inflammatory diseases corticosteroid treatments are considered the initial choice in many cases, in the case of S. stercoralis infection, the administration of this therapy can be fatal. In Spain, the number of diagnoses is much lower than in the past decade, although it is highly probable that the infection has been underdiagnosed due to low clinical awareness among Spanish population., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The zinc-containing histone deacetylase enzyme HDAC7 is emerging as an important regulator of immunometabolism and cancer. Here, we exploit a cavity in HDAC7, filled by Tyr303 in HDAC1, to derive new inhibitors. Phenacetyl hydroxamates and 2-phenylbenzoyl hydroxamates bind to Zn 2+ and are 50-2700-fold more selective inhibitors of HDAC7 than HDAC1. Phenylbenzoyl hydroxamates are 30-70-fold more potent HDAC7 inhibitors than phenacetyl hydroxamates, which is attributed to the benzoyl aromatic group interacting with Phe679 and Phe738. Phthalimide capping groups, including a saccharin analogue, decrease rotational freedom and provide hydrogen bond acceptor carbonyl/sulfonamide oxygens that increase inhibitor potency, liver microsome stability, solubility, and cell activity. Despite being the most potent HDAC7 inhibitors to date, they are not selective among class IIa enzymes. These strategies may help to produce tools for interrogating HDAC7 biology related to its catalytic site.

Background: Intravenous thrombolysis (IVT)-ineligible patients undergoing direct thrombectomy tended to have poorer functional outcome as compared with IVT-eligible patients undergoing bridging therapy. We aimed to assess radiological and functional outcomes in large vessel occlusion-related stroke patients receiving direct thrombectomy in the presence of absolute exclusion criteria for IVT vs relative exclusion criteria for IVT and vs non-exclusion criteria for IVT., Methods: A cohort study on prospectively collected data from 2282 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke cohort for treatment with direct thrombectomy (n = 486, absolute exclusion criteria for IVT alone; n = 384, absolute in combination with relative exclusion criteria for IVT; n = 777, relative exclusion criteria for IVT alone; n = 635, non-exclusion criteria for IVT)., Results: After adjustment for unbalanced variables (model 1), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.595, 95% CI 1.042-2.440) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.235, 95% CI 1.014-1.504). After adjustment for predefined variables (model 2: age, sex, pre-stroke mRS ≤ 1, NIHSS, occlusion in the anterior circulation, onset-to-groin time, and procedure time), ORs for 3-month death was higher in the presence of absolute exclusion criteria for IVT alone (vs relative exclusion criteria for IVT alone) (1.235, 95% CI 1.014-1.504) and in the presence of absolute exclusion criteria for IVT alone (vs non-exclusion criteria for IVT) (1.246, 95% CI 1.039-1.495). No significant difference was found between the groups as regards any type of intracerebral hemorrhage and parenchymal hematoma within 24 h, successful and complete recanalization after procedure, and modified Rankin Scale score 0-2 at 3 months. After adjustment for predefined variables of model 2, ORs for death were higher in the presence of recent administration of IV heparin (OR: 2.077), platelet count < 100,000/mm 3 (OR: 4.798), bacterial endocarditis (OR: 15.069), neoplasm with increased hemorrhagic risk (OR: 6.046), and severe liver disease (OR: 6.124)., Conclusions: Radiological outcomes were similar after direct thrombectomy in patients with absolute, relative, and non- exclusion criteria for IVT, while an increase of fatal outcome was observed in the presence of some absolute exclusion criterion for IVT.

Progressive addition lenses (PALs) contain a surface of spatially varying curvature, which supplies variable optical power for different viewing areas over the lens. We derive complete compatibility equations providing the exact magnitude of a cylinder along lines of curvature on any arbitrary PAL smooth surface. These equations reveal that, contrary to current knowledge, the cylinder and its derivative depend not only on the principal curvature and its derivatives along the principal line but also on the geodesic curvature and its derivatives along the line orthogonal to the principal line. We quantify the relevance of the geodesic curvature through numerical computations. We also derive an extended and exact Minkwitz theorem restricted only to be applied along lines of curvature, but excluding umbilical points.

Eosinophilic colitis (EC) is a rare entity. It is part of eosinophilic gastroenteritis, a rare inflammatory disorder characterised by eosinophilic infiltration of tissues that can affect any segment of the digestive tract. The diagnosis is established by the presence of an increased eosinophilic infiltrate in the colon wall in symptomatic patients. There is no characteristic clinical picture of EC. It can be associated with abdominal pain, changes in bowel movements, diarrhoea and rectal bleeding. Biopsies are mandatory if EC is suspected and despite visualising a normal mucosa. Although there are no protocol guidelines in this regard, steroid treatment is the first option in controlling the disease. Increasing the knowledge of clinicians and pathologists of this disorder and the recording its real incidence and population impact, could improve the understanding and treatment of the disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

In this paper, we show a strategy to modify salphen-type Schiff base ligands with naphtol (SYML1) and pyrocathecol (2,3-dihydroxyphenyl) groups (SYML2), or a combination of both (ASYML). Each of these ligands can be used to obtain polynuclear metal complexes following two different strategies. One relies on using metals that are either too large for the N 2 O 2 cavity or not fond of coordination number 4 and the other one relies on forcing the polynuclear species by adding functional groups to the hydroxybenzaldehayde in order to have extra coordination sites in the ligand. We report and characterize the mononuclear complexes SYML1-Cu and SYML1-Ce, along with the dinuclear complex SYML1-Fe and the tetranuclear species SYML2-Mn. The asymmetric ligand ASYML routinely hydrolyzes into the symmetric ligands in the reaction mixtures. SYML1-Fe displays a nearly linear Fe-O-Fe bridge with very strong antiferromagnetic coupling between the Fe(III) ions., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Introduction: Since Hirschsprung's disease (HSCR) already proved to benefit from robotic surgery, we aimed at describing a wider series of patients with this rare disease who were operated on with a robotic approach., Patients and Methods: All consecutive HSCR patients who underwent totally robotic soave pull-through (TRSPT), between October 2015 and June 2019, have been included. Ethical Committee approval was obtained. Data regarding clinical features, technical details, complications, hospital stay, and functional outcome have been prospectively collected for each patient., Results: Eleven patients have been included. Mean age at surgery was 29 months. Median length of surgery was 420 min. Median console time was 180 min. Six patients suffered from rectosigmoid aganglionosis, three from long HSCR (extending up to the hepatic flexure), two from total colonic aganglionosis. No major intraoperative complications occurred. Four patients (three of whom carrying a stoma) experienced minor mucosal tearing during dissection. One anastomotic stricture required dilatation under general anesthesia and two cuff strictures required cuff release (both occurring in patients who experienced intraoperative mucosal tearing). Follow-up lasted a median of 12 months. One patient experienced mild postoperative enterocolitis. Continence scored excellent-to-good in all patients who could be assessed on that regard (7 out of 11)., Conclusions: Provided a number of technical key points are respected, the outcome of TRSPT for HSCR is promising. Younger patients, particularly those carrying a stoma, proved to be technically demanding and deserve a longer learning curve. Accurate preoperative bowel preparation, correct trocar placement and patient positioning proved to be crucial aspects of treatment. To conclude, TRSPT is particularly suitable for older HSCR patients, even those requiring a redo, and represents a valid alternative to available surgical option for this delicate subgroup of HSCR patients.

Objective: This paper presents an integrated device, based on smart glasses, for the pattern-reversal visual evoked potential (PR-VEP) clinical test., Methods: Smart glasses are used to generate the checkerboard changing pattern, with its related red fixation point through an Android application. Electroencephalographic signals, for monitoring the stimulus generated by PR-VEP, were amplified close to the scalp and then transmitted wirelessly to a PC. A MATLAB real-time algorithm processed the incoming signals to extract the final PR-VEP signal., Methods: In total, 40 eyes (from 20 subjects, 12 males and 8 females between 24 and 28 years old) were tested and results were compared, with a commercial device for VEP clinical exam, to test the reproducibility and the efficacy of the proposed solution., Results: PR-VEPs generated by smart glasses showed typical triphasic waveforms: We observed promising results and components in moderate agreement with those obtained using commercial PR-VEP recorder, with potential for improvements after further refinement works., Significance: The proposed device leads the way for a portable and low-cost solution.

The important role of morality in the transgressive behavior which occurs within peer groups, such as bullying, has often been observed. However, little attention has been paid to this kind of violence in the initial stages of primary education. This study aims to analyze the attribution of moral emotions (self and other) to victims in different bullying types (verbal, physical, relational, and exclusion) and roles (aggressor and victim). An ad hoc questionnaire with supporting stick-figure cartoons was used. In total, 1150 schoolchildren between the ages of 6 and 11 years took part in the study (50.3% girls). The results showed that over 80% of schoolchildren had been involved in any type of aggressive behavior, and that there were significant differences by gender, year, and involvement in self- and other-attributed moral emotions. Aggressors showed less shame in general. In self-attribution situations, there was a greater indifference in aggressors. Victims had less shame and greater indifference in self-attributions for verbal and physical aggression. Girls recognized higher percentages of guilt in victims. The main moral emotion in the first stage was shame. This tendency changed to guilt as the children got older in both situations. Results support the need for the study of moral emotions development of victims and aggressors. How the experience of being involved in bullying biases the moral interpretation toward from the feelings of the victim is discussed.

Background: Tuberculosis (TB) infection was responsible for an estimated 1.3 million deaths in 2017. Better diagnostic tools are urgently needed. We sought to determine whether accurate TB antigen detection in blood or urine has the potential to meet the WHO target product profiles for detection of active TB., Materials and Methods: We developed Electrochemiluminescence (ECL) immunoassays for Lipoarabinomannan (LAM) and ESAT-6 detection with detection limits in the pg/ml range and used them to compare the concentrations of the two antigens in the urine and serum of 81 HIV-negative and -positive individuals with presumptive TB enrolled across diverse geographic sites., Results: LAM and ESAT-6 overall sensitivities in urine were 93% and 65% respectively. LAM and ESAT-6 overall sensitivities in serum were 55% and 46% respectively. Overall specificity was ≥97% in all assays. Sensitivities were higher in HIV-positive compared to HIV-negative patients for both antigens and both sample types, with signals roughly 10-fold higher on average in urine than in serum. The two antigens showed similar concentration ranges within the same sample type and correlated., Conclusions: LAM and ESAT-6 can be detected in the urine and serum of TB patients, regardless of the HIV status and further gains in clinical sensitivity may be achievable through assay and reagent optimization. Accuracy in urine was higher with current methods and has the potential to meet the WHO accuracy target if the findings can be transferred to a point-of-care TB test., Competing Interests: TB, CMD and EM are employed by FIND (Geneva, Switzerland), a nonprofit organization that collaborates with industry partners. GBS, MT, AM, TP, DB, and SB are employed by Meso Scale Diagnostics LLC (Rockville, USA) and received funding from FIND and NIH. MK and KK are employed by Otsuka Pharmaceutical Co., Ltd (Tokyo, Japan). FIND, MSD, and Otsuka provided support in the form of salaries for authors [TB, CMD, EM, GBS, MT, AM, TP, DB, SB, MK and KK], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. TB and AP report patents in the field of LAM detection. The interests of authors do not alter the adherence to PLOS ONE policies on sharing data and materials. (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests) All other authors declare no competing interests.

In this work, inverse supercritical fluid chromatography was applied to characterize the surface of four silica materials (three commercial Kromasils and one silica aerogel) from chromatographic retention data. Retention factors at various pressures (150-300 bar), temperatures (25-60 °C) and modifier concentrations (5-20 vol.% methanol in CO 2 ) for a set of representative 17 solutes were correlated with the solute properties by the linear solvation energy relationships (LSER). Two types of the LSER models were identified based on different criteria. Firstly, a generally valid model with two descriptors concerning dipolarity/polarizability and solute hydrogen-bonding acceptor ability was constructed. Secondly, a group of specific models for each particular silica material was proposed. According to the statistical analysis of the modeling results, the acid-basic interactions were demonstrated to have a major contribution to the retention for all studied silicas. The intensity of these interactions decreases with increasing methanol concentration in the mobile phase, possibly due to the mixed mechanism of competitive adsorption of the modifier on silanol groups and modification of mobile phase property. Moreover, retention factors measured under constant conditions (p, T, methanol concentration) for a pair of the materials were found to be proportional in logarithmic scale implying the transferability of the adsorption free energies and the adsorption constants across four studied silica materials., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Radial Refractive Gradient (RRG) spectacles are lenses specifically designed to minimize peripheral hyperopic defocus typically found in conventional spectacles. Our goals were: (1) to demonstrate a method to design such lenses; and (2) to quantify the exact foveal vision power errors induced by them., Methods: The design procedure was based on a point-by-point sequential surface construction algorithm that designs a front aspheric surface (back surface is spherical) to achieve a given overall tangential focal length of the lens. A peripheral refraction model was built based on average peripheral refractive errors from a set of eyes. We designed four negative lenses with optical powers: -2.5, -5.0, -7.5 and -10.0 D, so that the tangential focal length of the lens matches the retinal conjugate surface., Results: The lenses induce very small sagittal power errors in a wide range of off-axis field angles (30°), solving the problem of peripheral hyperopic defocus. However, such designs introduce non-negligible mean power errors (above 0.25 D from 7°, 6.8°, 7.1° and 7.8° for the -2.5, -5.0, -7.5 and -10.0 D lenses, respectively) for foveal vision in a rotating eye., Conclusion: Our results show the unavoidable errors introduced by RRG spectacles when used for dynamic foveal vision. The described method offers valuable information towards determining the best trade-off between controlling power errors for peripheral and foveal vision., (© 2018 The Authors Ophthalmic & Physiological Optics © 2018 The College of Optometrists.)

We present a comprehensive procedure to simulate real-world scenes viewed through ophthalmic lenses. Such a method enables us to anticipate the effects on image formation of the following combined undesired optical defects typically found in ophthalmic lenses: blur, distortion, and chromatic aberration. Additionally, it helps in comparing the expected scenes seen with different lens designs. The procedure is based on the following steps: (1) to calculate the distortion and local dioptric matrix associated with a set of different gaze directions; (2) to estimate point spread functions (PSF) associated with these matrices; (3) to compute the joint action of distortion, chromatic aberration, and PSF field on the scenes. We illustrate this procedure with two +5D spherical lenses: a moderately good performance lens and a highly degrading one. The method is suitable to evaluate ophthalmic lenses in a virtual reality framework.

For the management of a (micro)-smart grid it is important to know the patters of the load profiles and of the generators. In this article the power consumption data obtained through a monitoring activity developed on a micro-smart grid in an agro-industrial test-site are presented. In particular, this reports the synthesis of the monitoring results of 5 loads (5 industrial machineries for crop micronization, corncob crashing and other similar processes). How these data were used within a monitoring and managing scheme of a micro-smart grid can be found in (E. Fabrizio, V. Branciforti, A. Costantino, M. Filippi, S. Barbero, G. Tecco, P. Mollo, A. Molino, 2017) [1]. The data can be useful for other researchers in order to create benchmarks of energy use input appropriate energy demand values in optimization tools for the industrial sector.

Many women have incorrect knowledge about nutrition in pregnancy owing to false beliefs derived from popular practices. More than 90% of our cohort of pregnant women during early pregnancy (<12 weeks of gestational age) gave at least one incorrect answer to the five questions relative to common myths about nutrition in pregnancy. Education was inversely associated with the percentage of incorrect answers, and the lowest percentage of any mistakes was found in the small number of women who received nutritional information by a dietician. In conclusion, the usual sources of information about nutrition in pregnancy are not adequate to overcome the false beliefs acquired by traditions.

Vulvar tumors are not very common and account for about 4% of all cancers affecting the female genital organs. Frequently, malignant neoplasia of this site have squamous phenotype and the rare cases of metastasization are reported in the locoregional lymph nodes and in the surrounding organs. We report a case of metastasization of a vulvar squamous cell carcinoma in an unusual place such as the parietal pleura, in a relapsing patient that was submitted to a surgical vulvectomy the previous year., (© Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Purpose: Non-uniform magnification (distortion) and dioptric blur are two major undesired optical defects affecting vision when looking through progressive addition lenses (PALs) and studying them is potentially very valuable for PAL design. The major purpose of this paper is to analyse the relationship between dioptric power and magnification and, additionally, to evaluate the expected values of distortion and dioptric blur typically present in PALs. This has not been carefully and rigorously analysed to date., Methods: We computed the local dioptric and magnification matrices (using a two-ray differential method) for different gaze directions in an archetypical model of a PAL. We used four different maps: scalar magnification and anamorphic distortion, to describe magnification, and mean power and astigmatism, to describe dioptric power., Results: There is a good correlation between scalar magnification and mean power on the one hand, and anamorphic distortion and astigmatism on the other hand. Changes of 1 D in mean power are associated with variations in scalar magnification of around 3%. Also, 3% of anamorphic distortion is associated with increasing astigmatism up to 1 D. The directions of maximal power and maximal magnification are quite similar, though not equal (differences up to ± 1.5°). These directions strongly change from close to isotropic at the intermediate corridor to around 45° of oblique inclination for a few degrees of horizontal eye rotation. In typical PALs the level of distortion, which is unavoidably present when dioptric blurring appears, is small for usable vision zones (below 1 D of astigmatism)., Conclusion: The combined analysis of dioptric power and magnification in PALs helps to understand their limitations as a visual aid. On the one hand, the potentials of including distortion magnitude as a target in the metric function being optimised in the PAL design are reduced; on the other hand, it seems worthwhile to explore adding the degradation orientation as an additional target., (© 2016 The Authors Ophthalmic & Physiological Optics © 2016 The College of Optometrists.)

This paper presents an integrated empirical methodology for assessing the amount of sediment transported from slopes to the main river in absence of a sediment transport monitoring system. The amount of transported sediment is calculated through the characterization of the sediment source areas including the identification of the slope phenomena responsible for the sediment propagation to the main river: shallow landslides, channelized debris flows and deep-seated rotational slides. On this basis, several scenarios related to the climatic conditions are defined: they indicate the number of possible slope phenomena and potential volumes of mobilized unconsolidated material from sediment source areas to the main river. This methodology was finalized and tested in the Maira River basin (south-western Italian Alps) with quite good results., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: To propose geodesic curvature as a metric to characterise how an optical surface locally differs from axial symmetry. To derive equations to evaluate geodesic curvatures of arbitrary surfaces expressed in polar coordinates., Methods: The concept of geodesic curvature is explained in detail as compared to other curvature-based metrics. Starting with the formula representing a surface as function of polar coordinates, an equation for the geodesic curvature is obtained depending only on first and second radial and first order angular derivatives of the surface function. The potential of the geodesic curvature is illustrated using different surface tests., Results: Geodesic curvature reveals local axial asymmetries more sharply than other types of curvatures such as normal curvatures., Conclusion: Geodesic curvature maps could be used to characterise local axial asymmetries for relevant optometry applications such as corneal topography anomalies (keratoconus) or ophthalmic lens metrology., (© 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.)

Blur and non-uniform magnification are two related undesired effects affecting vision when looking through eyeglasses. We propose a geometrical framework to study the relationship between both effects. Magnification and blur are locally characterized by dioptric and magnification matrices, respectively, which we compute here by using a novel two-ray numerical method. We propose a set of geometrical entities associated with the dioptric and magnification local matrices, which are analyzed in several examples. We prove that there is a strong correlation between such entities (e.g., astigmatism and anamorphic distortion), which, to a certain extent, is maintained even in highly asymmetric lenses. We also show the somewhat anti-intuitive result that the axis of maximal blurring is sometimes close to orthogonal to the axis of maximal distortion. The results provide useful clues for ophthalmic lens design.

In a previous contribution [Appl. Opt.51, 8599 (2012)], a coauthor of this work presented a method for reconstructing the wavefront aberration from tangential refractive power data measured using dynamic skiascopy. Here we propose a new regularized least squares method where the wavefront is reconstructed not only using tangential but also sagittal curvature data. We prove that our new method provides improved quality reconstruction for typical and also for highly aberrated wavefronts, under a wide range of experimental error levels. Our method may be applied to any type of wavefront sensor (not only dynamic skiascopy) able to measure either just tangential or tangential plus sagittal curvature data.

In the medical field, the attention to the environmental impact of industrial processes and products is still limited. In recent years there has been an increased sensitivity towards the environment; meanwhile, the economic burden of hazardous waste disposal is becoming evident. Dialysis is a "big producer" of waste and it has been estimated that disposal costs can be up to 10-40% of the cost of disposables. So there are several reasons of interest on "ecodialysis": the high amount of waste defined as "potentially hazardous", which requires a very expensive management and the recyclability potential of the non-contaminated waste, that has not yet been fully explored in dialysis. This primary study has been performed in collaboration with the Politecnico di Torino. Its aim has been to define a schedule of activities by a few brainstorming sessions. This schedule is to be readily performed or it should be developed in detail to optimize, by reducing and recycling, the waste production during the dialysis session. The discussion identified seven basic points for the eco-sustainability of haemodialysis to: [1] reduce packaging; [2] facilitate separation of materials, and [3] their discharge; [4] differentiate materials; [5] clearly highlight the potentially hazardous materials; [6] improve the recyclability of plastic products; [7] propose a path of recovery and reuse. Although a full optimization requires a close cooperation with the manufacturers and is achievable only in the long term, the reduction of one pound of potentially contaminated materials could presently lead, on a national scale, to a saving of several million euros, which can be better employed in investments to improve our treatments.

Presbyopia, understood as the age-related loss of ability to clearly see near objects, was known to ancient Greeks. However, few references to it can be found in ancient manuscripts. A relevant discussion on presbyopia appears in a book called Symposiacs written by Lucius Mestrius Plutarchus around 100 A.C. In this work, Plutarch provided four explanations of presbyopia, associated with different theories of vision. One of the explanations is particularly interesting as it is based on a binocular theory of vision. In this theory, vision is produced when visual rays, emanating from the eyes, form visual cones that impinge on the objects to be seen. Visual rays coming from old people's eyes, it was supposed, are weaker than those from younger people's eyes; so the theory, to be logically coherent, implies that this effect is compensated by the increase in light intensity due to the overlapping, at a certain distance, of the visual cones coming from both eyes. Thus, it benefits the reader to move the reading text further away from the eyes in order to increase the fusion area of both visual cones. The historical hypothesis taking into consideration that the astronomer Hipparchus of Nicaea was the source of Plutarch's explanation of the theory is discussed., (© 2013 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

A widespread type of multifocal intraocular lens (MIOL) is based on expanding the depth of focus with specific amounts of spherical aberration. However, knowing the optimal wavefront aberration for multifocality does not directly provide a MIOL geometry. To overcome this issue, we present a new strategy to design MIOLs. The method optimizes directly the IOL surface geometries (aspheres with aspherical coefficients up to tenth order) using a multisurface pseudophakic eye model and a multiconfiguration approach, where the merit function jointly considers the optical quality at different object plane locations. An example of MIOL [22 diopters (D) far distance correction] was designed. For this design, the ocular modulator transfer function (MTF) at 50 cycles per millimeter remained above 0.47 for all object locations. The design provides high optical quality performance for far and intermediate distances and peak optical performance at near distances (MTF>0.57). Additionally, the design shows good performance against pupil changes (3-5 mm pupil diameter range). Finally, when the MIOL was tested on pseudophakic eye models with corneal spherical aberrations within a typical population range, the high multifocal performance was maintained in almost 40% of potential patients (ignoring asymmetric aberrations effects).

We describe the case of a patient evaluated for the incidental finding of a suspected paracardiac mass. A computed tomography examination demonstrated two giant coronary aneurysms, containing endoluminal thrombi, involving both coronary arteries. Coronary angiography confirmed the diagnosis. The patient underwent surgical treatment because of the high risk of spontaneous rupture of the masses, owing to the early compressive effect especially on the right ventricular free wall.

Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target.

Procaspase-8, the zymogen form of the apoptosis-initiator caspase-8, undergoes phosphorylation following integrin-mediated cell attachment to an extracellular matrix substrate. Concordant with cell attachment to fibronectin, a population of procaspase-8 becomes associated with a peripheral insoluble compartment that includes focal complexes and lamellar microfilaments. Phosphorylation of procaspase-8 both impairs its maturation to the proapoptotic form and can promote cell migration. Here we show that the cytoskeletal adaptor protein CrkL promotes caspase-8 recruitment to the peripheral spreading edge of cells, and that the catalytic domain of caspase-8 directly interacts with the SH2 domain of CrkL. We show that the interaction is abolished by shRNA-mediated silencing of Src, in Src-deficient MEFs, and by pharmacologic inhibitors of the kinase. The results provide insight into how tyrosine kinases may act to coordinate the suppression caspase-8 mediated apoptosis, while promoting cell invasion.

The aim of this work was to study, using numerical simulations, the attainable level of accuracy to reconstruct the wavefront aberrations from tangential refractive power data measured with dynamic skiascopy. Two mathematical methods have been implemented. The first one is based on curve integration of the curvature data, previously interpolated with cubic splines. The second one reconstructs the three-dimensional wavefront surface, represented by a Zernike polynomial expansion, using a two-step least-squares method. The different factors affecting the reconstruction--noise, sampling, and wavefront patterns--were quantified. The results provide useful information to design more efficient experimental setups based on spatial dynamic skiascopy.

The accuracy of the reconstruction of the Gradient Refractive Index (GRIN) of the crystalline lens from optimization methods was evaluated. Different input data, including direction cosines of deflected rays, ray impacts obtained from ray tracing and optical path differences from Optical Coherence Tomography (OCT) were studied. Three different GRIN models were analyzed. The experimental errors of the different experimental input data were estimated from comparisons of measurements and simulations using artificial lenses of known geometries. The experimental errors in the surfaces shape measurement and the influence of the number of rays were also considered. OCT-based input data produced the most accurate GRIN reconstructions. We found that optimization methods (combining global and local search algorithms) allow GRIN reconstructions with acceptable accuracies for moderate noise level., (© 2011 Optical Society of America)

Power-adjustable spectacle lenses, based on the Alvarez-Lohmann principle, can be used to provide affordable spectacles for subjective refractive errors measurement and its correction. A new mechanical frame has been designed to maximize the advantages of this technology. The design includes a mechanism to match the interpupillary distance with that of the optical centers of the lenses. The frame can be manufactured using low cost plastic injection molding techniques. A prototype has been built to test the functioning of this mechanical design.

A new and complete methodology of monofocal intraocular lens (IOL) design is presented aiming at isoplanatism, i.e. IOLs that provide the eye with optimized optical quality over a wide field of view (typically in a range of ten degrees). The methodology uses a merit function considering dimensional and biomechanical constraints, and a geometrical optical quality metric that is evaluated simultaneously at different field angles. As an example, we present new isoplanatic designs based on different commercial IOL platforms. Aspheric isoplanatic designs improve peripheral quality over current aspheric IOLs. Also, isoplanatic designs provide more stable optical quality across the field and across pupil diameter.

Caspase-8 is a key apical sensory protein that governs cell responses to environmental cues, alternatively promoting apoptosis, proliferation, and cell migration. The proteins responsible for integration of these pathways, however, have remained elusive. Here, we reveal that Rab5 regulates caspase-8-dependent signaling from integrins. Integrin ligation leads to Rab5 activation, association with integrins, and activation of Rac, in a caspase-8-dependent manner. Rab5 activation promotes colocalization and coprecipitation of integrins with caspase-8, concomitant with Rab5 recruitment to integrin-rich regions such as focal adhesions and membrane ruffles. Moreover, caspase-8 expression promotes Rab5-mediated internalization and the recycling of beta1 integrins, increasing cell migration independently of caspase catalytic activity. Conversely, Rab5 knockdown prevented caspase-8-mediated integrin signaling for Rac activation, cell migration, and apoptotic signaling, respectively. Similarly, Rab5 was critical for caspase-8-driven cell migration in vivo, because knockdown of Rab5 compromised the ability of caspase-8 to promote metastasis under nonapoptotic conditions. These studies identify Rab5 as a key integrator of caspase-8-mediated signal transduction downstream of integrins, regulating cell survival and migration in vivo and in vitro.

The differentiation and senescence programs of metazoans play key roles in regulating normal development and preventing aberrant cell proliferation, such as cancer. These programs are intimately associated with both the mitotic and apoptotic pathways. Caspase-8 is an apical apoptotic initiator that has recently been appreciated to coordinate non-apoptotic roles in the cell. Most of these functions are attributed to the catalytic domain, however, the amino-terminal death effector domains (DED)s, which belong to the death domain superfamily of proteins, can also play key roles during development. Here we describe a novel role for caspase-8 DEDs in regulating cell differentiation and senescence. Caspase-8 DEDs accumulate during terminal differentiation and senescence of epithelial, endothelial and myeloid cells; genetic deletion or shRNA suppression of caspase-8 disrupts cell differentiation, while re-expression of DEDs rescues this phenotype. Among caspase-8 deficient neuroblastoma cells, DED expression attenuated tumor growth in vivo and proliferation in vitro via disruption of mitosis and cytokinesis, resulting in upregulation of p53 and induction of differentiation markers. These events occur independent of caspase-8 catalytic activity, but require a critical lysine (K156) in a microtubule-binding motif in the second DED domain. The results demonstrate a new function for the DEDs of caspase-8, and describe an unexpected mechanism that contributes to cell differentiation and senescence.

Alvarez and Lohmann lenses are variable focus optical devices based on lateral shifts of two lenses with cubic-type surfaces. I analyzed the optical performance of these types of lenses computing the first order optical properties (applying wavefront refraction and propagation) without the restriction of the thin lens approximation, and the spot diagram using a ray tracing algorithm. I proposed an analytic and numerical method to select the most optimum coefficients and the specific configuration of these lenses. The results show that Lohmann composite lens is slightly superior to Alvarez one because the overall thickness and optical aberrations are smaller.

Caspase-8 is a proapoptotic protease that suppresses neuroblastoma metastasis by inducing programmed cell death. Paradoxically, caspase-8 can also promote cell migration among nonapoptotic cells; here, we show that caspase-8 can promote metastasis when apoptosis is compromised. Migration is enhanced by caspase-8 recruitment to the cellular migration machinery following integrin ligation. Caspase-8 catalytic activity is not required for caspase-8-enhanced cell migration; rather, caspase-8 interacts with a multiprotein complex that can include focal adhesion kinase and calpain 2 (CPN2), enhancing cleavage of focal adhesion substrates and cell migration. Caspase-8 association with CPN2/calpastatin disrupts calpastatin-mediated inhibition of CPN2. In vivo, knockdown of either caspase-8 or CPN2 disrupts metastasis among apoptosis-resistant tumors. This unexpected molecular collaboration provides an explanation for the continued or elevated expression of caspase-8 observed in many tumors.

Wave aberrations in the human eye are usually known with respect to the ideal spherical wavefront in the exit pupil. Using Kirchhoff's diffraction theory, we have derived a diffraction integral to compute the optical field on the retina from the wave aberration data. We have proposed a numerical algorithm based on the Stamnes-Spjelkavik-Pedersen (SSP) method to solve that integral. We have shown which approximations are admissible to reduce the complexity of the diffraction integral. In addition, we have compared our results with those of the conventional procedure used to compute intensities on the retina. We have found significant differences between our results and the conventional ones.

Caspase 8 is a critical upstream initiator of programmed cell death but, paradoxically, has also been shown to promote cell migration. Here, we show that tyrosine 380 in the linker loop of human caspase 8 is a critical switch determining caspase 8 function. Our studies show that, in addition to its cytosolic distribution, caspase 8 is recruited to lamella of migrating cells. Although the catalytic domain of caspase 8 is sufficient for recruitment and promotion of cell migration, catalytic activity per se is not required. Instead, we find that integrin-mediated adhesion promotes caspase 8 phosphorylation on tyrosine 380. Accordingly, mutation of this site compromises localization to the periphery and the potentiation of cell migration. Mechanistically, this linker region of caspase 8 acts as a Src homology 2 binding site. In particular, tyrosine 380 is critical for interaction with Src homology 2 domains. The results identify a novel mechanism by which caspase 8 is recruited to the lamella of a migrating cell, promoting cell migration independent of its protease activity.

Screening for novel anticancer drugs in chemical libraries isolated from marine organisms, we identified the lipopeptide somocystinamide A (ScA) as a pluripotent inhibitor of angiogenesis and tumor cell proliferation. The antiproliferative activity was largely attributable to induction of programmed cell death. Sensitivity to ScA was significantly increased among cells expressing caspase 8, whereas siRNA knockdown of caspase 8 increased survival after exposure to ScA. ScA rapidly and efficiently partitioned into liposomes while retaining full antiproliferative activity. Consistent with the induction of apoptosis via the lipid compartment, we noted accumulation and aggregation of ceramide in treated cells and subsequent colocalization with caspase 8. Angiogenic endothelial cells were extremely sensitive to ScA. Picomolar concentrations of ScA disrupted proliferation and endothelial tubule formation in vitro. Systemic treatment of zebrafish or local treatment of the chick chorioallantoic membrane with ScA resulted in dose-dependent inhibition of angiogenesis, whereas topical treatment blocked tumor growth among caspase-8-expressing tumors. Together, the results reveal an unexpected mechanism of action for this unique lipopeptide and suggest future development of this and similar agents as antiangiogenesis and anticancer drugs.

It is well known that the aberrations of the cornea are partially compensated by the aberrations of the internal optics of the eye (primarily the crystalline lens) in young subjects. This effect has been found not only for the spherical aberration, but also for horizontal coma. It has been debated whether the compensation of horizontal coma is the result of passive mechanism [Artal, P., Benito, A., & Tabernero, J. (2006). The human eye is an example of robust optical design. Journal of Vision, 6 (1), 1-7] or through an active developmental feedback process [Kelly, J. E., Mihashi, T., & Howland, H. C. (2004). Compensation of corneal horizontal/vertical astigmatism, lateral coma, and spherical aberration by internal optics of the eye. Journal of Vision, 4 (4), 262-271]. In this study we investigate the active or passive nature of the horizontal coma compensation using eyes with artificial lenses, where no active developmental process can be present. We measured total and corneal aberrations, and lens tilt and decentration in a group of 38 eyes implanted with two types of intraocular lenses designed to compensate the corneal spherical aberration of the average population. We found that spherical aberration was compensated by 66%, and horizontal coma by 87% on average. The spherical aberration is not compensated at an individual level, but horizontal coma is compensated individually (coefficients of correlation corneal/internal aberration: -0.946, p<0.0001). The fact that corneal (but not total) horizontal coma is highly correlated with angle lamda (computed from the shift of the 1st Purkinje image from the pupil center, for foveal fixation) indicates that the compensation arises primarily from the geometrical configuration of the eye (which generates horizontal coma of opposite signs in the cornea and internal optics). The amount and direction of tilts and misalignments of the lens are comparable to those found in young eyes, and on average tend to compensate (rather than increase) horizontal coma. Computer simulations using customized model eyes and different designs of intraocular lenses show that, while not all designs produce a compensation of horizontal coma, a wide range of aspheric biconvex designs may produce comparable compensation to that found in young eyes with crystalline lenses, over a relatively large field of view. These findings suggest that the lens shape, gradient index or foveal location do not need to be fine-tuned to achieve a compensation of horizontal coma. Our results cannot exclude a fine-tuning for the orientation of the crystalline lens, since cataract surgery seems to preserve the position of the capsule.

We propose a complete methodology to develop custom monofocal Intraocular Lens (IOL) designs and evaluate their performance on-axis based on an analytical formulation. The analytical formulation was based on Gaussian and primary aberration theory applied to custom (individual biometric data) and realistic (multilayer cornea and thick IOL) pseudoaphakic eye models. Gradient-based optimization algorithms were performed to search for optimal designs. Using two parameters, the best design was obtained by directly minimizing the wavefront variance. We showed, in a case example, that custom designs achieved better final performance than generic IOL designs. Tolerances analysis allowed an evaluation of the implications of the manufacturing errors of the different parameters.

Purpose: For many years, poor vascularization of the short rectal stump has been considered the main cause of leakage. The purpose of this study was to evaluate the vascularization of the rectal stump after total mesorectal excision., Methods: We studied the iliac vascularization on 28 volunteers with healthy rectum to have an anatomic basis. Then, we studied the vascularization of the rectal stumps after total mesorectal excision by using angio computed tomography at seven and three months after operating on 22 patients; we validated this technique by studying the vascularization using angio computed tomography in 18 rectal specimens from cadavers., Results: Both in healthy rectums and in rectal stumps after total mesorectal excision, there is good vascularization sustained by middle and inferior rectal arteries. The former is more important and frequent as described in previous literature., Conclusions: The vascularization of the short rectal stump is generally well represented even after total mesorectal excision.