New insights into subsurface imaging of carbon nanotubes in polymer composites via scanning electron microscopy.

Despite many studies of subsurface imaging of carbon nanotube (CNT)-polymer composites via scanning electron microscopy (SEM), significant controversy exists concerning the imaging depth and contrast mechanisms. We studied CNT-polyimide composites and, by three-dimensional reconstructions of captured stereo-pair images, determined that the maximum SEM imaging depth was typically hundreds of nanometers. The contrast mechanisms were investigated over a broad range of beam accelerating voltages from 0.3 to 30 kV, and ascribed to modulation by embedded CNTs of the effective secondary electron (SE) emission yield at the polymer surface. This modulation of the SE yield is due to non-uniform surface potential distribution resulting from current flows due to leakage and electron beam induced current. The importance of an external electric field on SEM subsurface imaging was also demonstrated. The insights gained from this study can be generally applied to SEM nondestructive subsurface imaging of conducting nanostructures embedded in dielectric matrices such as graphene-polymer composites, silicon-based single electron transistors, high resolution SEM overlay metrology or e-beam lithography, and have significant implications in nanotechnology.

Diagnosis of lesions of the acetabular labrum, of the labral-chondral transition zone, and of the cartilage in femoroacetabular impingement: Correlation between direct magnetic resonance arthrography and hip arthroscopy.

OBJECTIVE: To determine the sensitivity and accuracy of direct MR arthrography in the diagnosis of intra-articular lesions associated with femoroacetabular impingement. MATERIAL AND METHODS: We used direct MR arthrography to study 51 patients with femoroacetabular impingement who underwent arthroscopic hip surgery. Surgery demonstrated 37 labral tears, 44 lesions in the labral-chondral transitional zone, and 40 lesions of the articular cartilage. We correlated the findings at preoperative direct MR arthrography with those of hip arthroscopy and calculated the sensitivity, specificity, positive predictive value, negative predictive value, and validity index for direct MR arthrography. RESULTS: The sensitivity and specificity of MR arthrography were 94.5% and 100%, respectively, for diagnosing labral tears, 100% and 87.5%, respectively, for diagnosing lesions of the labral-chondral transition zone, and 92.5% and 54.5%, respectively, for diagnosing lesions of the articular cartilage. The negative predictive value of MR arthrography for lesions of the labral-chondral transitional zone was 100%. MR arthrography accurately defined extensive lesions of the cartilage and the secondary osseous changes (the main factor in poor prognosis), although its diagnostic performance was not so good in small chondral lesions. CONCLUSION: In patients with femoroacetabular impingement, direct MR arthrography can adequately detect and characterize lesions of the acetabular labrum and of the labral-chondral transitional zone as well as extensive lesions of the articular cartilage and secondary osseous changes.

Sarcoidosis-like reactions in cancer patients treated with immune checkpoint inhibitors: experience in a Spanish hospital.

BACKGROUND: Immune checkpoint inhibitors (ICI) have been associated with several immune-related adverse events, including sarcoidosis-like reactions (SLR). SLR, which has a low prevalence but an increasing incidence, is similar to sarcoidosis in terms of histology, and clinical and radiological manifestations. The most commonly affected organs are hilar and mediastinal lymph nodes and skin. SLR is an exclusion diagnosis, so a lymph node biopsy can be useful to distinguish between tumor progression and SLR, particularly in tumors in which nodal involvement is very common. PATIENTS AND METHODS: We performed a retrospective analysis of SLR in all cancer patients receiving ICIs in our institution between January 2016 and June 2020. RESULTS: Among the 1063 treated patients, seven experienced SLR, four of whom were symptomatic (cough, skin lesions, arthralgia), with time to onset ranging from 1.5 to 6.7 months after ICI initiation. All seven patients had bilateral hilar lymphadenopathy, and granulomatous reactions in five of the six patients with lymph node biopsies. SLR improved in all patients, including four patients who continued with ICI. Three patients received corticosteroids and/or stopped ICI therapy. Four of these patients had partial responses at the time SLR was identified. CONCLUSION: Management of SLR lacks a consensus recommendation, although corticosteroids and/or stopping the ICI are generally implemented. The potential consequences of stopping anticancer treatment should be taken into consideration, particularly in the absence of clear management recommendations.

Identification of the products from the reaction of chlorine with the silicon(111)-(7x7) surface.

The various products from the reaction of chlorine (Cl) with the adatom layer of the Si(111)-(7x7) surface have been identified with scanning tunneling microscopy (STM). Initially, a single Cl atom reacts with the adatom dangling bond. At higher surface coverage, additional Cl atoms insert themselves into the Si-Si backbonds between the adatom and rest-atom layers, producing adatoms that have reacted with two or three Cl atoms. These products are characterized by different registries with respect to the underlying rest layer and appear in STM images as adatoms of different sizes, consistent with the breaking of Si-Si backbonds and the formation ofnew Si-Cl bonds.

Blind estimation of general tip shape in AFM imaging.

The use of flared tip and bi-directional servo control in some recent atomic force microscopes (AFM) has made it possible for these advanced AFMs to image structures of general shapes with undercut surfaces. AFM images are distorted representations of sample surfaces due to the dilation produced by the finite size of the tip. It is necessary to obtain the tip shape in order to correct such tip distortion. This paper presents a noise-tolerant approach that can for the first time estimate a general 3-dimensional (3D) tip shape from its scanned image in such AFMs. It extends an existing blind tip estimation method. With the samples, images, and tips described by dexels, a representation that can describe general 3D shapes, the new approach can estimate general tip shapes, including reentrant features such as undercut lines.

Electron beam-based metrology after CMOS.

The magnitudes of the challenges facing electron-based metrology for post-CMOS technology are reviewed. Directed selfassembly, nanophotonics/plasmonics, and resistive switches and selectors, are examined as exemplars of important post-CMOS technologies. Materials, devices, and architectures emerging from these technologies pose new metrology requirements: defect detection, possibly subsurface, in soft materials, accurate measurement of size, shape, and roughness of structures for nanophotonic devices, contamination-free measurement of surface-sensitive structures, and identification of subtle structural, chemical, or electronic changes of state associated with switching in non-volatile memory elements. Electron-beam techniques are examined in the light of these emerging requirements. The strong electron-matter interaction provides measurable signal from small sample features, rendering electron-beam methods more suitable than most for nanometer-scale metrology, but as is to be expected, solutions to many of the measurement challenges are yet to be demonstrated. The seeds of possible solutions are identified when they are available.

General three-dimensional image simulation and surface reconstruction in scanning probe microscopy using a dexel representation.

The ability to image complex general three-dimensional (3D) structures, including reentrant surfaces and undercut features using scanning probe microscopy, is becoming increasing important in many small length-scale applications. This paper presents a dexel data representation and its algorithm implementation for scanning probe microscope (SPM) image simulation (morphological dilation) and surface reconstruction (erosion) on such general 3D structures. Validation using simulations, some of which are modeled upon actual atomic force microscope data, demonstrates that the dexel representation can efficiently simulate SPM imaging and reconstruct the sample surface from measured images, including those with reentrant surfaces and undercut features.

Virtual rough samples to test 3D nanometer-scale scanning electron microscopy stereo photogrammetry.

The combination of scanning electron microscopy for high spatial resolution, images from multiple angles to provide 3D information, and commercially available stereo photogrammetry software for 3D reconstruction offers promise for nanometer-scale dimensional metrology in 3D. A method is described to test 3D photogrammetry software by the use of virtual samples-mathematical samples from which simulated images are made for use as inputs to the software under test. The virtual sample is constructed by wrapping a rough skin with any desired power spectral density around a smooth near-trapezoidal line with rounded top corners. Reconstruction is performed with images simulated from different angular viewpoints. The software's reconstructed 3D model is then compared to the known geometry of the virtual sample. Three commercial photogrammetry software packages were tested. Two of them produced results for line height and width that were within close to 1 nm of the correct values. All of the packages exhibited some difficulty in reconstructing details of the surface roughness.

Residual enzymatic activity as a prognostic factor in patients with Gaucher disease type 1: correlation with Zimran and GAUSS-I index and the severity of bone disease.

BACKGROUND: Gaucher disease (GD) is an autosomal recessive disorder produced by mutations in the glucocerebrosidase gene (GBA), causing storage of glucosylceramide in reticuloendothelial cells in multiple organs. Traditionally, the prediction of the phenotype based on the genotype has been reported to be limited. SUBJECTS AND METHODS: We investigated the correlation between the enzymatic residual activity (ERA) and the phenotype at diagnosis of the disease in 45 GD Spanish patients (44 with type I and 1 with type III GD). The genotype involved two of the following previously expressed proteins: c.517A > C (T134P), 1%; c.721G > A (G202R), 17%; c.1090G > T (G325W), 13.9%; c.1208G > A (S364N), 4.1%; c.1226A > G (N370S), 17.8%; c.1246G > A (G377S), 17.6%; c.1289C > T (P391L), 8.5%; c.1448T > C (L444P), 3%; and c.1504C > T (R463C), 24.5%. Recombinant alleles, deletion of 55 bp in exon 9 and 84GG mutation were considered as mutations with no residual enzymatic activity. RESULTS: The ERA showed a statistically significant correlation with chitotriosidase (P < 0.001), age (P < 0.001), spleen size (P < 0.001), 'Zimran's Severity Score Index' (P < 0.01) and the 'Gaucher Disease Severity Score Index-Type I' (P < 0.0001) at diagnosis of the disorder. Previous to any medical intervention, a comparison between the ERA and bone involvement, demonstrated a statistically significant relationship (P < 0.01) between the two variables. CONCLUSIONS: This study data allowed us to define a new criterion for prognostic assessment of the disease at diagnosis, called Protein Severity Index, which expresses the theoretical severity of the genotype presented by patients, according to the corresponding ERA.

Scanning electron microscope measurement of width and shape of 10nm patterned lines using a JMONSEL-modeled library.

The width and shape of 10nm to 12 nm wide lithographically patterned SiO2 lines were measured in the scanning electron microscope by fitting the measured intensity vs. position to a physics-based model in which the lines' widths and shapes are parameters. The approximately 32 nm pitch sample was patterned at Intel using a state-of-the-art pitch quartering process. Their narrow widths and asymmetrical shapes are representative of near-future generation transistor gates. These pose a challenge: the narrowness because electrons landing near one edge may scatter out of the other, so that the intensity profile at each edge becomes width-dependent, and the asymmetry because the shape requires more parameters to describe and measure. Modeling was performed by JMONSEL (Java Monte Carlo Simulation of Secondary Electrons), which produces a predicted yield vs. position for a given sample shape and composition. The simulator produces a library of predicted profiles for varying sample geometry. Shape parameter values are adjusted until interpolation of the library with those values best matches the measured image. Profiles thereby determined agreed with those determined by transmission electron microscopy and critical dimension small-angle x-ray scattering to better than 1 nm.

Clinicoepidemiologic characteristics, prognostic factors, and survival analysis of patients coinfected with human immunodeficiency virus and Leishmania in an area of Madrid, Spain.

From 1987 to 1995, a retrospective case study was conducted at the Ramon y Cajal Hospital in Madrid, Spain, a public teaching hospital with 1,100 beds, to determine the clinicoepidemiologic characteristics, survival, and prognostic factors of patients with visceral leishmaniasis (VL) and human immunodeficiency virus (HIV) infection. The prevalence of VL in HIV+ patients compared with HIV- patients was studied. Epidemiologic, clinical, and parasitologic characteristics, as well as the effects of treatment, prognosis, and survival in 54 HIV+ patients (90 episodes) with VL were defined. Comparative survival studies among patients with and without acquired immunodeficiency syndrome (AIDS)-defining criteria and multivariate analysis of survival risk factors were performed. The prevalence of VL in patients with AIDS was much higher than in immunocompetent individuals. In spite of a good initial response to treatment for VL, 60.6% of the patients had relapsed by the end of one year. Mortality from the first episode was 18.5%, and 24% died in the first month after diagnosis of any VL episode. The mean survival of the 29 patients who died was 10.27 months. Survival in patients with and without AIDS at the time of the first episode of VL was compared at 30 months: 53.7% versus 20.5% (P = 0.00149). We found no significant difference (P = 0.24) in the survival of HIV+ patients who had died of VL without AIDS at the time of the first episode of VL compared with those of a control group of 413 dead patients with AIDS without VL. A diagnosis of AIDS at the time of the first episode of VL and thrombocytopenia were the only risk factors found related to survival. We conclude that in AIDS patients, VL is a recurrent disease that is highly prevalent and whose clinical course is modified by HIV.

Juvenile chronic lymphocytic leukemia with unusual intracisternal inclusions: an ultrastructural study.

The electron microscopic analysis of intracisternal inclusions in lymphocytes of the bone marrow and peripheral blood in a case of juvenile chronic lymphocytic leukemia is described. These inclusions consist of well-ordered microtubules attached to a central axis. The contribution of electron microscopic analysis in establishing the substructural pattern of these inclusions is discussed.

Algorithms for Scanned Probe Microscope Image Simulation, Surface Reconstruction, and Tip Estimation.

To the extent that tips are not perfectly sharp, images produced by scanned probe microscopies (SPM) such as atomic force microscopy and scanning tunneling microscopy are only approximations of the specimen surface. Tip-induced distortions are significant whenever the specimen contains features with aspect ratios comparable to the tip's. Treatment of the tip-surface interaction as a simple geometrical exclusion allows calculation of many quantities important for SPM dimensional metrology. Algorithms for many of these are provided here, including the following: (1) calculating an image given a specimen and a tip (dilation), (2) reconstructing the specimen surface given its image and the tip (erosion), (3) reconstructing the tip shape from the image of a known "tip characterizer" (erosion again), and (4) estimating the tip shape from an image of an unknown tip characterizer (blind reconstruction). Blind reconstruction, previously demonstrated only for simulated noiseless images, is here extended to images with noise or other experimental artifacts. The main body of the paper serves as a programmer's and user's guide. It includes theoretical background for all of the algorithms, detailed discussion of some algorithmic problems of interest to programmers, and practical recommendations for users.

[Pure red-cell aplasia associated with chronic myeloproliferative syndromes]. / Aplasia pura de serie roja asociada a síndromes mieloproliferativos crónicos.

Pure red cell aplasia is manifested by unregenerative anemia with intense erythroid hypoplasia in the bone marrow and absolute reticulocytopenia. Its association with chronic myeloproliferative syndrome (CMS) is infrequent. The appearance of both processes may or may not be simultaneous and accidental association cannot be ruled out. Two cases of pure red cell aplasia were studied; one associated to Philadelphia positive chronic chromosome myeloid leukemia and the other associated to atypical CMS. In the first case no response was obtained with prednisone alone or associated to cyclophosphamide. In the second patient treatment with danazol was not efficient, however, corticotherapy produced a positive and maintained response. Treatment of pure red cell aplasia associated to CMS must be the same as that employed when this disease is presented as isolated or associated to other processes.

[Von Willebrand disease: characteristics and response to desmopressin. Study of 103 cases]. / Enfermedad de Von Willebrand: características y respuesta a desmopresina. Estudio de 103 casos.

BACKGROUND: To describe the main characteristics and response to desmopressin infusion in 103 patients suffering from von Willebrand disease (vWD). PATIENTS AND METHODS: The criteria for diagnosis were (except for type 2N) the coexistence of von Willebrand factor ristocetin cofactor (vWF:RCo) activity < 50 U/dl with bleeding disease or one of the following data: von Willebrand factor antigen (vWF:Ag) activity < 50 U/dl, factor VIII (FVIII) activity < 50 U/dl or the existence of a increased bleeding time (BT). Multimeric studies of vWF were performed in 51 cases and ristocetin induced platelet aggregation (RIPA) was also performed. RESULTS: Spontaneous bleeding was found in 36 patients, while in 18 cases the diagnosis was done after surgical bleeding. Thirteen patients (6 presenting with mild bleeding) were studied for abnormalities in the routine preanestesic tests. Other 22 patients were diagnosed with vWD by familial studies. There were 3 patients with type 2B, 1 case with type 2N and other patient with type 3. BT was found increased in 26 out of 58 patients. The activities of vWF:CoR and vWF:Ag were 38.4 (9.4) U/dl and 45.8 (23.2) U/dl, respectively, while the activity of FVIII was 49.9 (20.8) U/dl. Prophylactic DDAVP (desmopressin) was infused in 32 patients. After 1 h, basal activities of vWF:CoR and vWF:Ag were increased by 3.1 (3.2) and 3.4 (3.1) times, respectively, and maintained for 3 h. FVIII activity increased 3.6 (2.3) times the basal levels decreasing after 3 h (2.9 [2.1]; p < 0.01). The BT was corrected in 8 out of ten patients. CONCLUSIONS: vWD is a major cause of surgical bleeding. Preanestesic anamnesis and coagulation tests can be useful to identify vWD. Many patients with vWD have normal BT. A failure in the response to desmopressin infusion is unusual.

Evaluation of a minimally aggressive method of patellofemoral osteoarthritis treatment at 10 years minimum follow-up.

BACKGROUND: Knee osteoarthritis mainly affecting the lateral facet of the patella, especially in young patients, is a definite challenge to the surgeon. Our purpose was to investigate the long-term outcome of a simple operation such as the partial lateral facetectomy on middle-aged to elderly patients with predominant lateral patellofemoral osteoarthritis. METHODS: A retrospective, long-term study of 39 knees (28 females, mean aged at surgery 61yearsold) with a minimum follow-up of 10years was performed. Evaluations included preoperative and postoperative questionnaires, physical examinations, and radiographs. RESULTS: The main outcomes included the initial anterior pain relief, with higher scores using the Knee Society Score (that improved in 84% of the knees), and the eventual failure of the technique, including percentage of patients that required secondary total knee replacement (30% of the knees). CONCLUSION: Partial lateral facetectomy aiming to decrease the high pressure in the lateral facet of the patella confirmed frequent pain relief. This surgical procedure being minimally invasive, relatively simple, and effective in selected patients, is a valid early alternative to more complex operations and does not preclude further reconstructive surgery in case of disease progression.

Cytogenetics findings in a histiocytic sarcoma case.

Histiocytic sarcoma (HS) is a neoplasm derived from histiocytes. Its diagnosis was not clear until its immunohistochemistry profile was correctly established. Not much is known about its genetic properties. We report a case of a 48-year-old male patient whose bone marrow was almost completely occupied by monomorphic medium size neoplastic cellularity. Its immunohistochemical profile was CD68(+), CD4(+), CD45(+) with negativity of other dendritic cells, and other lineage markers. Cytogenetic study showed 4 related clones: one with trisomy 8 and extra material on the short arms of chromosome 4; a second line with tetrasomy of chromosome 8, add(4)(p16); the third clone had the same alterations as the previous and deletion of chromosome 3 at q11; the fourth line had tetrasomy 8 and translocation t(3;5)(q25;q35). To our knowledge this is the first HS case showing chromosome 8 trisomy and tetrasomy and the other described alterations.

Sarcoidosis-like reactions in cancer patients treated with immune checkpoint inhibitors: experience in a Spanish hospital

Background Immune checkpoint inhibitors (ICI) have been associated with several immune-related adverse events, including sarcoidosis-like reactions (SLR). SLR, which has a low prevalence but an increasing incidence, is similar to sarcoidosis in terms of histology, and clinical and radiological manifestations. The most commonly affected organs are hilar and mediastinal lymph nodes and skin. SLR is an exclusion diagnosis, so a lymph node biopsy can be useful to distinguish between tumor progression and SLR, particularly in tumors in which nodal involvement is very common. Patients and methods We performed a retrospective analysis of SLR in all cancer patients receiving ICIs in our institution between January 2016 and June 2020. Results Among the 1063 treated patients, seven experienced SLR, four of whom were symptomatic (cough, skin lesions, arthralgia), with time to onset ranging from 1.5 to 6.7 months after ICI initiation. All seven patients had bilateral hilar lymphadenopathy, and granulomatous reactions in five of the six patients with lymph node biopsies. SLR improved in all patients, including four patients who continued with ICI. Three patients received corticosteroids and/or stopped ICI therapy. Four of these patients had partial responses at the time SLR was identified. Conclusion Management of SLR lacks a consensus recommendation, although corticosteroids and/or stopping the ICI are generally implemented. The potential consequences of stopping anticancer treatment should be taken into consideration, particularly in the absence of clear management recommendations (AU)

[The modified "pink test" in the diagnosis of hereditary spherocytosis]. / El "pink test" modificado en el diagnóstico de la esferocitosis hereditaria.

Hereditary spherocytosis is still difficult to diagnose in some situations due to the existence of subclinical expressions and the lack of an accurate test with high sensitivity and specificity. Recently, Vettore et al. described the so-called 'Pink test' as an easy method with the highest reproducibility and sensitivity. Herein, we present our experience with the 'Pink test' in the diagnosis of 16 previously diagnosed hereditary spherocytosis patients comparing the results with those obtained in 96 healthy controls, 41 beta-thalassaemias, 9 autoimmune haemolytic anaemias, 8 chronic hemoproliferative syndromes and 2 patients with pyruvate kinase deficiency. We also present a modification of the original 'Pink test' in which a small sample of blood (200 microL) obtained by finger-prick (or heel puncture in newborns and infants) is mixed with the hemolyzing solution of the 'Pink test' within the first three hours after blood drawing. Elevated correlation coefficients (r = 0.75-0.96) between both methods have been obtained comparing the percentage of final haemolysis in 25 healthy controls, 21 beta-thalassaemia minor and 9 hereditary spherocytosis patients.