Defect Detection and Thickness Mapping of Passivation Layers on Integrated Circuits Using Energy Dispersive X-Ray Analysis and Image Processing Techniques

The relative thickness of passivation layers has been mapped for integrated circuits by utilizing the penetration voltage method, in conjunction with energy dispersive x-ray analysis (EDXA) and a scanning electron microscope (SEM), to detect defects and map film thickness. The thickness mapping technique was evaluated for area coverage and correlated to size of defective areas. The purpose of this study was to determine optimal operational conditions for fast and accurate defect detection on an integrated circuit for failure analysis and non-destructive process evaluation. Image processing was required to enhance the acquired map and to obtain a calibrated image for relative comparison of thickness non-uniformity. Once the defect is detected, linescan and spot measurements can be used to obtain more accurate characterization of the defect areas. Considerable improvement in the detection and characterization of thickness and hole defects in the passivation layers on integrated circuit devices can be obtained with the use of this method

Measurement of Film Thickness on Integrated Circuits using Energy Dispersive X-Ray Analysis (EDXA)

The need for a rapid, non-destructive failure analysis of complex integrated circuits has led to the use of energy dispersive x-ray analysis (EDXA), to measure the localized thickness of Si02 and Al films on integrated circuits, by detecting the penetration threshold of the electron beam through the film. The accuracy (10%-20%) is determined by actual Scanning Electron Microscope (SEM) measurements, traceable to a secondary length standard, of the film thicknesses of sectioned samples. In contrast, another SEM based thickness measurement technique, such as Yakowitz-Newbury method, gave results that were 50-100% larger, required higher accelerating voltage that would damage the integrated circuit and took longer to setup/perform measurement. Typically, the thickness of the films range from 0.3 to 1.5 microns and thee-beam energy varies from 4 keV to 20 keV

Polimorfismi biochimici nel sangue e nel latte della capra sarda

The Authors, in a study on 990 individual samples of blood and milk collected from Sardinian goats, have found the presence of polymorphism at the loci Hb, Tf, X protein, β- Lg, αs-Cn, while the loci Alb, CA, SOD, α-La, β-Cn were monomorphic

Toxicity of oxaliplatin rechallenge in metastatic colorectal cancer.

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Challenging chemoresistant metastatic colorectal cancer: Therapeutic strategies from the clinic and from the laboratory

As survival has improved for patients with metastatic colorectal cancer (mCRC), there is an increasing need for effective and well-tolerated third-line and subsequent-lines of treatment. Despite recent advances with the development of new-targeted therapies in this setting, there remains an unmet need to exploit oncogenic drivers of colorectal cancer and overcome acquired resistance. Potential treatment strategies include revisiting old targets such as human epidermal growth factor receptor 2, RAS, and BRAF and investigating new targets such as c-MET, the PI3 kinase, and Wnt pathways, and also the use of immune-checkpoint inhibitors. Here, we review recent phase III trials exploring approved agents, early trials investigating new drugs for chemorefractory mCRC, and the potential of capturing tumour dynamics during its evolution by liquid biopsy analysis

Characteristics of Submucous Myomas and the Risk of Anemia

Background and Objectives: Uterine fibroids still represent the most common indication for hysterectomy for benign pathologies. In the United States, more than 479,000 hysterectomies are performed annually, 46.6% for myomas and 47.7% in women aged from 18 to 44 years. By applying appropriateness criteria to this procedure, it has been estimated that overuse ranges from 16 to 70%. One of the main reasons that induce patients and gynecologists to consider hysterectomy is represented by severe anemia. Materials and Methods: This is a retrospective cohort study of 202 patients with uterine fibroids diagnosed by transvaginal ultrasound who underwent a hysteroscopic procedure. Myoma grade, size, location, and number were assessed by transvaginal scan and office hysteroscopy and correlated to the pre-treatment hemoglobin level. Results: Univariate analysis showed that anemia does not have a statistically significant association with myoma number and with age considered as a numerical predictor. In the patients with myoma type 0, there is a possibility of 81% having anemia regardless of menorrhagia. On the contrary, in patients with myoma type 1 or type 2, the possibility of having anemia varies according to the presence or absence of menorrhagia. If there is menorrhagia, the risk of moderate anemia is only present for myomas >60 mm. Conclusions: The results of this study may contribute to defining objective criteria for the management of submucous myomas and anemia. Our data suggest that submucosal myomas type 0 >10 mm should always be treated, putting patients at risk for anemia. Myomas type 2 and 3 should be treated for the risk of anemia in the presence of menorrhagia episodes or if > of 60 mm. Adequate management of anemia and myomas could reduce the rate of unnecessary hysterectomies

Pelvic floor function after third and fourth degree perineal lacerations: a case-control study on quality of life

Background: The primary aim of this study was to compare the quality of life between women with obstetric anal sphincter injury (OASI) and women with intact perineum or minor vaginal tears following their first vaginal birth through a validated urogynaecological questionnaire. As a secondary aim, we wanted to identify the specific symptoms for pelvic floor dysfunction after a vaginal birth. Methods: One hundred thirty-three cases (III- and IV-degree vaginal tears) and 133 controls (intact perineum or I- and II-degree vaginal tear) were asked to fill the PFDI-20 condition-specific and quality of life survey at three and 12 months after vaginal delivery. The survey evaluates pelvic floor dysfunction symptoms through three subsections: the Pelvic Organ Prolapse Distress Inventory (POPDI), the Colorectal-Anal Distress Inventory (CRADI), and Urinary Distress Inventory, (UDI). The scoring system ranges from 0 (no distress) to 100 (maximum distress) for each subsection, subsequently summed up to obtain the summary score (0 to 300). The patients recruited were asked to complete the survey at 3- and 12-months follow-up visit. Accordingly, data collection started. Categorical variables were subjected to Chi-square test or Fisher’s Exact test. Quantitative variables were compared through Student’s t-test or Mann-Whitney test. Results: All surveys have shown statistically significant differences when comparing the cases to the control group. Consequently, PFDI-20 has shown a strong correlation between III- and IV-grade lacerations and pelvic floor dysfunction persistence at 12 months after delivery. Intestinal symptoms were the most reported disturbances among women with previous OASI. Conclusions: Major vaginal tears have demonstrated to have a strong impact on women’s quality of life up to a follow-up of 12 months. The use of PFDI-20 questionnaire is a useful and valid tool in the diagnosis and follow-up of genital prolapse, fecal and urinary incontinence in primiparous women with a history of OASI. Thus, its application in clinical practice can help offering the most adequate rehabilitative treatment

Mechanisms of immune escape and resistance to checkpoint inhibitor therapies in mismatch repair deficient metastatic colorectal cancers

SIMPLE SUMMARY: A subset of colorectal cancers (CRCs) is characterized by a mismatch repair deficiency that is frequently associated with microsatellite instability (MSI). The compromised DNA repair machinery leads to the accumulation of tumor neoantigens affecting the sensitivity of MSI metastatic CRC to immune checkpoint inhibitors (CPIs), both upfront and in later lines of treatment. However, up to 30% of MSI CRCs exhibit primary resistance to frontline immune based therapy, and an additional subset develops acquired resistance. Here, we first discuss the clinical and molecular features of MSI CRCs and then we review how the loss of antigenicity, immunogenicity, and a hostile tumor microenvironment could influence primary and acquired resistance to CPIs. Finally, we describe strategies to improve the outcome of MSI CRC patients upon CPI treatment. ABSTRACT: Immune checkpoint inhibitors (CPIs) represent an effective therapeutic strategy for several different types of solid tumors and are remarkably effective in mismatch repair deficient (MMRd) tumors, including colorectal cancer (CRC). The prevalent view is that the elevated and dynamic neoantigen burden associated with the mutator phenotype of MMRd fosters enhanced immune surveillance of these cancers. In addition, recent findings suggest that MMRd tumors have increased cytosolic DNA, which triggers the cGAS STING pathway, leading to interferon-mediated immune response. Unfortunately, approximately 30% of MMRd CRC exhibit primary resistance to CPIs, while a substantial fraction of tumors acquires resistance after an initial benefit. Profiling of clinical samples and preclinical studies suggests that alterations in the Wnt and the JAK-STAT signaling pathways are associated with refractoriness to CPIs. Intriguingly, mutations in the antigen presentation machinery, such as loss of MHC or Beta-2 microglobulin (B2M), are implicated in initial immune evasion but do not impair response to CPIs. In this review, we outline how understanding the mechanistic basis of immune evasion and CPI resistance in MMRd CRC provides the rationale for innovative strategies to increase the subset of patients benefiting from CPIs

Pasta consumption and connected dietary habits: Associations with glucose control, adiposity measures, and cardiovascular risk factors in people with type 2 diabetes—TOSCA.IT study

Background: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. Methods: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. Results: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. Conclusions: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors