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Screening programs may be useful to reduce the rate of undetected glaucoma. Compass (CMP, CenterVue, Padova, Italy) Standard Suprathreshold strategy (SST) analyses the visual function at 52 retinal locations. A new Quick Suprathreshold strategy (QST) reduces the number of tested locations to 24. With both tests, the CMP also provides an image of the central retina and a detail of the optic nerve head. The aim of this paper is to measure the performances of SST and QST compared with clinical diagnosis. 63 consecutive healthy subjects and 60 consecutive patients with perimetric defects from glaucoma in both eyes were recruited. They received one test per eye (SST or QST in randomized order), results were classified into normal, suspect and abnormal according to a global index provided in the report and called SupraThreshold Response (STR). Agreement between clinical diagnosis and test output were calculated, and test time was also measured. The agreement with the clinical diagnosis was 95.7% for SST and 95.1% for QST. When two suspect tests were excluded, agreement for QST increased to 96.7%. Test duration was 164 ± 82 s for SST and 71 ± 41 s for QST (p &lt, 0.0001). Such a difference was similar in both glaucoma patients (respectively 231 ± 65 s vs 105 ± 33 s, p&nbsp, &lt, 0.0001) and normal subjects (98 ± 17 and 39 ± 9 s, p &lt, 0.0001). In conclusion, SST and QST showed similar, high agreement with clinical judgement. Morphological analysis is potentially helpful in further improving the clinical usefulness of suprathreshold tests. QST is characterized by a strong time saving compared with SST.

Glaucoma is a progressive optic neuropathy with characteristic changes to the optic nerve head and the visual field (VF). Detecting progression of VF damage with Standard Automated Perimetry (SAP) is of paramount importance for clinical care. One common approach to detecting progression is to compare each new VF test to a baseline SAP test (event analysis). This comparison is made difficult by the test–retest variability of SAP, which increases with the level of VF damage, and the limited range of measurement, meaning that damage cannot be assessed below a certain level. We performed a prospective international multi-centre data collection of SAP data on 90 eyes from 90 people with glaucoma and different levels of VF damage over a short period of time (6 tests in 60 days). Data were collected using a fundus tracked perimeter (Compass, CenterVue). We used these data (minus the first test) to develop an improved event analysis that accounts for both the change in variability with damage and the lower bound on the measurement imposed by SAP. Using simulations, we show that our approach is more sensitive compared to previously developed methods, especially in the case of advanced glaucoma, while retaining similar specificity.

Orientador: Maria Helena Robert Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecanica Resumo: Neste trabalho são investigados os efeitos de parâmetros de processo na eficiência de incorporação do reforço carboneto de silício na forma de partículas, na liga AA7075 e na sua distribuição na estrutura do compósito produzido. O tipo de processamento utilizado foi por compofundição, ou seja, a adição do reforço na matriz metálica em estado semi-sólido reofundido. Para isto, foi projetado e construído um equipamento, não disponível no mercado, para a obtenção de estruturas pastosas reofundidas e a adição de partículas de reforço a esta, obtendo-se assim, os materiais compósitos desejados. Os lingotes reofundidos e compofundidos então obtidos atestam a eficiência do equipamento projetado e construído. Os efeitos de parâmetros de processo observados foram: a redução da temperatura de processamento aumenta a esfericidade dos glóbulos obtidos e diminui significativamente a quantidade de fase líquida na pasta, aumentando a sua viscosidade, resultando em melhor incorporação do reforço, com menor porosidade causada devido ao processo de adição, porém, não leva à desejada distribuição da fase reforçante pelo lingote. Maiores temperaturas levam à melhor distribuição das fases sólida/líquida pelo volume do lingote, conseqüentemente melhor distribuição da fase reforçante, porém, com pior incorporação desta, devido à maior porosidade associada ao processo de adição. O aumento do tempo de processamento leva à separação das trações líquidas e sólidas na pasta, o que produz acentuadas heterogeneidades macro e microestrutural. O aumento da velocidade de agitação leva à melhor distribuição das trações sólida e líquida na pasta, melhorando a distribuição da fase reforçante e possibilitando maior quantidade de reforço adicionada à pasta sem problemas. Maiores quantidades de reforço adicionadas auxiliam a obtenção de estrutura globular devido à maior tração sólida total da pasta, porém, introduzem maior porosidade no produto compofundido devido ao processo de adição do reforço Abstract: The effects of process parameters in the efficiency of incorporation and distribution of silicon carbide particulate in AA7075 alIoy are investigated. The composites were produced by compocasting. It was necessary to design and build an equipament based on mechanical stirring of the liquid alIoyduring its solidification, to produce rheocast slurries and composites. The observed effects of process parameters in the compocast ingots were: reducing temperature leads to improvement in the espherical morphology of primary phase in the slurry; reduces the liquid the liquid content; increases the viscosity, resulting in better incprporation of the reinforcement, less porosity and not uniform final distribution of silicon carbide in the matrix. On the oposite, processing at higher temperature leads to higher liquid content and better distribution of silicon carbide particles. However, more gases can be associated damaging incorporation. Increasing stirring time leads to separation of liquidlsolid phases in the slurry, promoting heterogeneities in the macro and microstructures. Increasing stirring speed promotes better distribution of liquid/solid phases and silicon carbide particles in the ingot. Higher speeds also allow higher content of reinforcement to be added. Higher reinforcement content helps to produce globular solid phase in the matrix Mestrado Materiais e Processos de Fabricação Mestre em Engenharia Mecânica

Background A large proportion of patients with coronavirus disease 2019 (COVID-19) develop severe respiratory failure requiring admission to the intensive care unit (ICU) and about 80% of them need mechanical ventilation (MV). These patients show great complexity due to multiple organ involvement and a dynamic evolution over time; moreover, few information is available about the risk factors that may contribute to increase the time course of mechanical ventilation. The primary objective of this study is to investigate the risk factors associated with the inability to liberate COVID-19 patients from mechanical ventilation. Due to the complex evolution of the disease, we analyzed both pulmonary variables and occurrence of non-pulmonary complications during mechanical ventilation. The secondary objective of this study was the evaluation of risk factors for ICU mortality. Methods This multicenter prospective observational study enrolled 391 patients from fifteen COVID-19 dedicated Italian ICUs which underwent invasive mechanical ventilation for COVID-19 pneumonia. Clinical and laboratory data, ventilator parameters, occurrence of organ dysfunction, and outcome were recorded. The primary outcome measure was 28 days ventilator-free days and the liberation from MV at 28 days was studied by performing a competing risks regression model on data, according to the method of Fine and Gray; the event death was considered as a competing risk. Results Liberation from mechanical ventilation was achieved in 53.2% of the patients (208/391). Competing risks analysis, considering death as a competing event, demonstrated a decreased sub-hazard ratio for liberation from mechanical ventilation (MV) with increasing age and SOFA score at ICU admission, low values of PaO2/FiO2 ratio during the first 5 days of MV, respiratory system compliance (CRS) lower than 40 mL/cmH2O during the first 5 days of MV, need for renal replacement therapy (RRT), late-onset ventilator-associated pneumonia (VAP), and cardiovascular complications. ICU mortality during the observation period was 36.1% (141/391). Similar results were obtained by the multivariate logistic regression analysis using mortality as a dependent variable. Conclusions Age, SOFA score at ICU admission, CRS, PaO2/FiO2, renal and cardiovascular complications, and late-onset VAP were all independent risk factors for prolonged mechanical ventilation in patients with COVID-19. Trial registration NCT04411459

PURPOSE: To analyze the comparative safety and efficacy of two techniques of corneal neurotization (CN) (direct corneal neurotization [DCN] vs indirect corneal neurotization [ICN] for the treatment of neurotrophic keratopathy (NK).DESIGN: Multicenter Interventional Prospective Comparative Case Series.METHODS: Setting: ASST Santi Paolo e Carlo University Hospital, Milan; S.Orsola-Malpighi University Hospital, Bologna; Santa Maria alle Scotte University Hospital, Siena.STUDY POPULATION: Consecutive patients with NK undergoing CN between November 2014 and October 2019; Intervention Procedures: DCN was performed by transferring contralateral supraorbital and supratrochlear nerves; ICN was performed using sural nerve graft.MAIN OUTCOME MEASURES: NK healing; corneal sensitivity; corneal nerve fiber length (CNFL) measured by in vivo confocal microscopy (IVCM); complication rate.RESULTS: 26 eyes of 25 patients were included: 16 were treated with DCN and 10 with ICN. After surgery, NK healed in all patients after a mean period of 3.9 months without differences between DCN and ICN. Mean corneal sensitivity improved significantly 1 year after surgery (from 3.07 to 22.11 mm; p

A chiral NHC-catalyzed dearomatizing reaction of activated N-alkylpyridinium salts with aliphatic aldehydes is described. The resulting acylated 1,4-dihydropyridines have been obtained with complete C4 regioselectivity and enantioselectivities in the range 52-78% ee. The (4R)-absolute configuration of the synthesized compounds has been determined by the TD-DFT simulation of the electronic circular dichroism spectra.

Orientadores : Maria Helena Robert, Jose Manuel Torralba Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Mecanica Resumo: o processo de moagem de alta energia submete as partículas do pó à sucessivos processos de deformação, soldagem e fratura, utilizando-se para tal um moinho de bolas de alta energia. Este trabalho estuda o processo de fabricação de materiais compósitos de matriz de alumínio AA6061 reforçados com S~N4, A1N e ZrB2, através da moagem de alta energia, compactação e extrusão. Os resultados obtidos permitem relacionar as distintas etapas do processo de moagem de alta energia com as características dos pós produzidos: sua morfologia, densidade aparente, compactabilidade e extrudabilidade. Inicialmente, devido à esfericidade das partículas da liga metálica, a densidade aparente e a extrudabilidade são altas e a compactabilidade é baixa. Após início do processo de moagem, quando predomina a deformação, partículas esféricas se transformam em partículas laminares, diminuindo a densidade aparente e a extrudabilidade e aumentando a compactabilidade. Após um tempo mais longo de processo, quando passa a predominar a fratura, as partículas passam a apresentar morfologia equiaxial, aumentando a densidade aparente e extrudabilidade e diminuindo a compactabilidade. Observa-se que a presença de partículas de reforço acelera o processo, do ponto de vista morfológico e microestrutural, aumentando a deformação produzida na matriz metálica durante a moagem, favorecendo tanto a soldagem quanto a fratura das partículas; entre os tipos de reforços analisados, o S~N 4 é o que mais acelera o processo. O processo de moagem de alta energia confere, após extrusão, aumentos em tomo a 100 % no limite de resistência à tração e na dureza da liga metálica sem reforço e dos compósitos, devido à microestrutura extremamente refinada produzida, com uma fina e homogênea dispersão de óxido e carboneto de alumínio, à diminuição do tamanho e ao arredondamento das partículas de reforço Abstract: a high-energy ball milling. This work investigates the use of this technique to produce aluminium AA6061 matrix composite reinforced with S~N4, AlN e Zr~. The results correlate the stages of mechanical alloying with the powder characteristics: its morphology, apparent density, compatibility and extrudability. First, due to the spherical morphology of as received aluminium powder, the apparent density and the extrudability are high and the compatibility is low. After short times of milling, the powder morphology changes to a flattened one, due to the predominance of deformation, decreasing the apparent density and extrudability and an increasing of the compatibility. After longer milling times, the powder morphology chan~s to an equiaxial one, due to the predominance of fracture, increasing the apparent density and extrudability and decreasing the compatibility. The presence of brittle particles of reinforcements accelerate the process, from the morphological and microestrutural point of view, increasing the matrix deformation, enhancing the welding and the fracture of particles; for the analysed reinforcements, the silicon nitride provide the most expressive acceleration. The mechanical alloying provides of about 100 % in the ultimate tensile strength and hardness, due to the refined microstructure produced, with a homogeneous distribution of aluminium oxides and carbides, the decreasing of particle size and rounding particle shape of the reinforcements Doutorado Materiais e Processos de Fabricação Doutor em Engenharia Mecânica

This study aimed to analyze macular structure by using spectral-domain optical coherence tomography (SD-OCT) in a cohort of patients affected by autosomal recessive retinitis pigmentosa and Usher syndrome, due to genetic variants in USH2A gene, and to correlate optical coherence tomography (OCT) parameters with functional and genetic data.The subjects of this study were 92 patients, 46 syndromic (Usher syndrome type IIa [Ush2]) and 46 nonsyndromic (autosomal recessive RP [arRP]), with clinical and genetic diagnosis of USH2A-related retinal dystrophy, who underwent a complete ophthalmic examination and spectral-domain OCT analysis. The study focused on evaluating the differences between the 2 groups in the following parameters: best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, presence of epiretinal membrane (ERM), and cystic macular lesions (CMLs). Variants in USH2A gene were divided into 3 categories, according to the expected impact (low/high) at protein level of the different variants on each allele.BCVA and EZ width were significantly lower in Ush2 than in arRP patients (p0.0001 and p = 0.001). ERM was detected in 34.8% (16/46) of arRP patients and in 65.2% (30/46) of Ush2 patients (p = 0.003). CML was detected in 17.4% (8/46) of arRP patients and 30.4% (14/46) of Ush2 patients (p = 0.14). The allelic distribution was statistically different (p = 0.0003) by dividing the 2 diseases: for Ush2 patients it was 45.7% (high/high), 39.1% (low/high) and 15.2% (low/low); for arRP patients it was 8.7% (high/high), 56.5% (low/high), and 34.8% (low/low). The severity class of the variants significantly affected visual acuity and EZ width parameters (p = 0.004 and p = 0.002, respectively).Retinal disease, as evaluated by means of SD-OCT, shows more advanced degeneration signs in the syndromic than the nonsyndromic form of retinal dystrophy related to USH2A gene. Variant types and allelic profiles are determining factors for the onset of syndromic features. However, since the 3 allelic profiles can be found in both Usher and RP patients, other factors must necessarily play a determining role.

PURPOSE: To evaluate the ability of additional central testing locations to improve detection of macular visual field (VF) defects in glaucoma. \ud \ud DESIGN: Prospective cross-sectional study. \ud \ud PARTICIPANTS: Four hundred forty healthy people and 499 patients with glaucomatous optic neuropathy (GON) were tested with a fundus tracked perimeter (CMP; CenterVue) using a 24-2 grid with 12 additional macular locations (24-2+). \ud \ud METHODS: Glaucomatous optic neuropathy was identified based on expert evaluation of optic nerve head photographs and OCT scans, independently of the VF. We defined macular defects as locations with measurements outside the 5% and 2% normative limits on total deviation (TD) and pattern deviation (PD) maps within the VF central 10°. Classification was based on the total number of affected macular locations (overall detection) or the largest number of affected macular locations connected in a contiguous cluster (cluster detection). Criteria based on the number of locations and cluster size were used to obtain equivalent specificity between the 24-2 grid and the 24-2+ grids, calculated using false detections in the healthy cohort. Partial areas under the receiver operating characteristic curve (pAUCs) were also compared at specificities of 95% or more. \ud \ud MAIN OUTCOME MEASURES: Matched specificity comparison of the ability to detect glaucomatous macular defects between the 24-2 and 24-2+ grids. \ud \ud RESULTS: At matched specificity, cluster detection identified more macular defects with the 24-2+ grid compared with the 24-2 grid. For example, the mean increase in percentage of detection was 8% (95% confidence interval, 5%-11%) and 10% (95% confidence interval [CI], 7%-13%) for 5% TD and PD maps, respectively, and 5% (95% CI, 2%-7%) and 6% (95% CI, 4%-8%) for the 2% TD and PD maps, respectively. Good agreement was found between the 2 grids. The improvement measured by pAUCs was also significant but generally small. The percentage of eyes with macular defects ranged from about 30% to 50%. Test time for the 24-2+ grid was longer (21% increase) for both cohorts. Between 74% and 98% of defects missed by the 24-2 grid had at least 1 location with sensitivity of < 20 dB. \ud \ud CONCLUSIONS: Visual field examinations with additional macular locations can improve the detection of macular defects in GON modestly without loss of specificity when appropriate criteria are selected.

In the homeostasis of the ocular surface, vitamins play a critical role in regulating inflammatory responses and promoting cell differentiation, development and correct function. Systemic vitamin supplementation has been available for many decades; in recent years, thanks to pharmacological advancements, topical vitamin delivery has also become available in an attempt to better treat ocular surface disease (OSD) and dry eye disease (DED). In this paper, we reviewed the current evidence on the role of vitamin supplementation in OSD and DED. We originally searched the PubMed archive, inspected the references and restricted the search to pertinent papers. The body of evidence was evaluated using the amelioration of both signs and symptoms as the outcome, when available. We found that in patients with vitamin deficiency, systemic supplementation of Vitamin A is effective in treating OSD, reducing both DED signs and symptoms. Additionally, systemic supplementation of vitamin D is useful in reducing DED symptoms and increasing tear volume. Vitamin A is also effective in reducing DED signs and symptoms when administered locally. The efficacy of supplementation with other vitamins is still not fully proven. In conclusion, the inclusion of vitamins into the treatment strategies for OSD and DED allows for better treatment customization and better outcomes in these patients.

Mechanical ventilation (MV) is still necessary in many surgical procedures; nonetheless, intraoperative MV is not free from harmful effects. Protective ventilation strategies, which include the combination of low tidal volume and adequate positive end expiratory pressure (PEEP) levels, are usually adopted to minimize the ventilation-induced lung injury and to avoid post-operative pulmonary complications (PPCs). Even so, volutrauma and atelectrauma may co-exist at different levels of tidal volume and PEEP, and therefore, the physiological response to the MV settings should be monitored in each patient. A personalized perioperative approach is gaining relevance in the field of intraoperative MV; in particular, many efforts have been made to individualize PEEP, giving more emphasis on physiological and functional status to the whole body. In this review, we summarized the latest findings about the optimization of PEEP and intraoperative MV in different surgical settings. Starting from a physiological point of view, we described how to approach the individualized MV and monitor the effects of MV on lung function.

Photoexcited TiO2 dispersed in a de-aerated acetonitrile/2-propanol (CH3CN/2-PrOH) reaction mixture catalyzes the quick and selective reduction of 5-nitrosalicylic acid methyl ester to the corresponding aniline, an immediate precursor of the drug mesalazine. The transformation is selective also when the starting concentration of nitro compound is increased by orders of magnitude and occurs at room temperature and atmospheric pressure. The photocatalyst can be reused. The photocatalytic reaction can be carried out also under aerated conditions without any loss in selectivity and efficiency. All these factors point out the feasibility of this important synthesis under mild conditions.

Coagulation disorders and thrombocytopenia are common in patients with septic shock, but only few studies have focused on platelet variables beyond platelet count. The aim of this study was to evaluate whether platelets reactivity predicts sepsis-induced thrombocytopenia in patients with septic shock. We therefore enrolled consecutive patients with septic shock and platelets count >150*103/μL on the day of the diagnosis. Platelets reactivity tests were performed daily from the diagnosis of septic shock until day five; platelet volume distribution and mean platelet volume were also recorded daily. Sepsis-induced thrombocytopenia was defined as a platelet count

Purpose To describe a multimodal imaging diagnosis of retinopathy in dermatomyositis. Case presentation A 21-year-old white woman with a history of fatigue and a cutaneous rash complained of visual impairment in her left eye. A funduscopic examination showed multiple confluent cotton-wool spots in both eyes. Swept source-optical coherence tomography presented macular edema in both eyes; optical coherence tomography angiography revealed superficial and deep capillary occlusion in all areas affected by cotton-wool spots; and fluorescein angiography showed vascular walls enhancement, veins dilatation, and capillary leakage. After large doses of intravenously administered glucocorticoid therapy, followed by a cyclophosphamide regimen, best corrected visual acuity returned to 20/20 in both eyes. Conclusions This case report presents optical coherence tomography angiography clinical findings in a rare case of dermatomyositis-associated retinopathy, remarking the importance of a multi-imaging approach for a correct diagnosis and treatment of eye injuries, in order to avoid serious complications and permanent sequelae.

Objective.To analyze the effect of a risk-stratified disease-modifying antirheumatic drug (DMARD)–tapering algorithm based on multibiomarker disease activity (MBDA) score and anticitrullinated protein antibodies (ACPA) on direct treatment costs for patients with rheumatoid arthritis (RA) in sustained remission.Methods.The study was a posthoc retrospective analysis of direct treatment costs for 146 patients with RA in sustained remission tapering and stopping DMARD treatment, in the prospective randomized RETRO study. MBDA scores and ACPA status were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and direct treatment costs were evaluated every 3 months. MBDA and ACPA status were used as predictors creating a risk-stratified tapering algorithm based on relapse rates.Results.RA patients with a low MBDA score (< 30 units) and negative ACPA showed the lowest relapse risk (19%), while double-positive patients showed high relapse risk (61%). In ACPA-negative and MBDA-negative (< 30 units), and ACPA or MBDA single-positive (> 30 units) groups, DMARD tapering appears feasible. Considering only patients without flare, direct costs for synthetic and biologic DMARD in the ACPA/MBDA-negative and single positive groups (n = 41) would have been €372,245.16 for full-dose treatment over 1 year. Tapering and stopping DMARD in this low-risk relapse group allowed a reduction of €219,712.03 of DMARD costs. Average reduction of DMARD costs per patient was €5358.83.Conclusion.Combining MBDA score and ACPA status at baseline may allow risk stratification for successful DMARD tapering and cost-effective use of biologic DMARD in patients in deep remission as defined by the 28-joint count Disease Activity Score using erythrocyte sedimentation rate.