Heavy inertial particles in rotating turbulence: Distribution of particles in flow and evolution of Lagrangian trajectories.

We revisit the problem of heavy particles suspended in homogeneous box turbulence flow subjected to rotation along the vertical axis, which introduces anisotropy along the vertical and horizontal planes. We investigate the effects of the emergent structures due to rotation, on the spatial distribution and temporal statistics of the particles. The distribution of particles in the flow are studied using the joint probability distribution function (JPDFs) of the second and third principle invariants of the velocity gradient tensor, Q and R. At high rotation rates, the JPDFs of Lagrangian Q-R plots show remarkable deviations from the well-known teardrop shape. The cumulative probability distribution functions for times during which a particle remains in vortical or straining regions show exponentially decaying tails except for the deviations at the highest rotation rate. The average residence times of the particles in vortical and straining regions are also affected considerably due to the addition of rotation. Furthermore, we compute the temporal velocity autocorrelation and connect it to the Lagrangian anisotropy in presence of rotation. The spatial and temporal statistics of the particles are determined by a complex competition between the rotation rate and inertia of the particle.

Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India.

Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.

Diagnostic and prognostic utility of SF-1 in adrenal cortical tumours.

Background and Aims: Superior imaging techniques have increased the recognition of adrenal pathology. Distinguishing benign from malignant adrenocortical tumors is not always easy. Several criteria and immunohistochemical markers have been discovered which help to differentiate between adrenocortical adenoma (ACA) and adrenocortical carcinoma (ACC). Our aim here was to evaluate the diagnostic and prognostic role of steroidogenic factor-1 (SF-1) in adult adrenocortical tumors (ACT) diagnosed using the Weiss criteria. In this cohort, we have also analyzed Ki67 and p53 expression and the extent of agreement between SF-1 and Ki-67. Methodology: This was a retrospective, observational study comprising 24 cases of adult ACT over 10 years. Immunohistochemical staining for SF-1, Ki67, and p53 was done in all the cases, and the results correlated with the morphological diagnosis made using Weiss criteria. Results: SF-1 was 100% sensitive and 80% specific as a marker of malignancy. Increased SF-1 expression correlated with worse survival. There was a moderate degree of agreement between Ki-67 labeling-index and SF-1 as a marker of malignancy with the kappa coefficient being 0.75. The sensitivity of p53 was lower than Ki67 in diagnosing ACC. Conclusion: In adult ACTs, SF-1 has diagnostic significance and prognostic implication. SF-1 is a crucial, dosage-dependent survival factor in ACC. There is a moderate extent of agreement between Ki-67 and SF-1 as a marker of malignancy.

Comparison of Frozen Section and Squash Cytology as Intra-Operative Diagnostic Tool in Pediatric CNS Tumors.

Background: Pediatric central nervous system (CNS) tumors have a different histological spectrum as compared to adults with the infantile group having even more varied and distinct histological profiles. Intra-operative diagnosis is especially important as it guides the neurosurgeon to tailor an approach which is best suited for a particular case. The aim of the study was to evaluate the diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value of frozen section (FS) and squash cytology and to find out the degree of correlation (kappa value) between the two procedures. Materials and Methods: A prospective study was conducted on 55 pediatric patients with clinicoradiologically diagnosed CNS lesions for a period of 2.5 years. Intra-operative squash smears and FS were made and stained with hematoxylin and eosin stain. Diagnosis made subsequently on paraffin embedded sections was taken as the gold standard. Results: Although the specificity (90%) and positive predictive value (96%) were comparable between the two procedures, sensitivity (91.4%) and negative predictive value (75%) of FS was more as compared to squash cytology. Both the diagnostic modalities showed substantial agreement (k = 0.728). Conclusion: Even though the histological spectrum of pediatric CNS tumors is more varied than adults, FS gives a reasonable intra-operative diagnosis and better results when compared to squash alone.

Large-scale flow in a cubic Rayleigh-Bénard cell: long-term turbulence statistics and Markovianity of macrostate transitions.

We investigate the large-scale circulation (LSC) in a turbulent Rayleigh-Bénard convection flow in a cubic closed convection cell by means of direct numerical simulations at a Rayleigh number Ra = 106. The numerical studies are conducted for single flow trajectories up to 105 convective free-fall times to obtain a sufficient sampling of the four discrete LSC states, which can be summarized to one macrostate, and the two crossover configurations which are taken by the flow in between for short periods. We find that large-scale dynamics depends strongly on the Prandtl number Pr of the fluid which has values of 0.1, 0.7, and 10. Alternatively, we run an ensemble of 3600 short-term direct numerical simulations to study the transition probabilities between the discrete LSC states. This second approach is also used to probe the Markov property of the dynamics. Our ensemble analysis gave strong indication of Markovianity of the transition process from one LSC state to another, even though the data are still accompanied by considerable noise. It is based on the eigenvalue spectrum of the transition probability matrix, further on the distribution of persistence times and the joint distribution of two successive microstate persistence times. This article is part of the theme issue 'Mathematical problems in physical fluid dynamics (part 1)'.

Clinicopathological study and immunohistochemical analysis of expression of annexin A5 and apelin in human placentae of gestational diabetes mellitus.

BACKGROUND AND AIMS: Gestational diabetes mellitus (GDM) is one of the commonest medical complications of pregnancy. Annexin A5 (ANXA5) is a protein, found in apical surfaces of syncytiotrophoblasts, which prevents fetal and placental vascular thrombosis in GDM. Apelin is a bioactive peptide which has been linked to GDM. The aim of the present study was to correlate macroscopic as well as microscopic changes and immunohistochemical expression of ANXA5 and apelin in placentae of GDM with maternal and neonatal clinical features and also to compare the results with those in matched controls. METHODS: This prospective observational study was undertaken for a period of one year from April 2020 to March 2021. It comprised of 42 patients of GDM. Gross features, microscopic features and intensity and grade of expression of ANXA5 and Apelin were analyzed in placentae of GDM. RESULTS: Morphological changes detected in GDM placentae included increased immature villi (16 cases, 38%), increased syncytial knots (36, 86%), perivillous fibrin deposition (20, 48%), fibrosis of villous stroma (20, 48%), presence of nucleated red blood cells (12, 28.5%) and hypervascularity (34, 81%). The extent of histopathological changes noted in GDM placentae was significantly higher than that in matched controls. GDM placentae showed significantly reduced expression of ANXA5 and Apelin in terms of grade and intensity when compared with matched controls. Reduced expression (mild intensity) of ANXA5 was noted in 22 GDM cases (52.3%) whereas apelin expression was of weak intensity in 26 (61.9%) cases. Among GDM patients, statistically significant association was noted between ANXA5 intensity and neonatal resuscitation, apelin grade and preterm birth as well as low birth weight and apelin intensity and requirement of treatment in sick neonatal care unit. CONCLUSION: The placental expression of the proteins, ANXA5 and Apelin, is altered in GDM though their exact pathogenetic mechanisms are yet to be understood. They can be targets for development of prophylactic and therapeutic agents in future.

Recurrent Giant Cell Fibroblastoma in an Infant: A Diagnostic Challenge.

Background: Giant cell fibroblastoma (GCF) shows a wide spectrum of morphological patterns which may lead to a misdiagnosis of sarcoma. Case Report: This 14- month- old baby was referred to us for recurrent left scrotal embryonal rhabdomyosarcoma (ERMS), first diagnosed at 8 months, status post chemotherapy. Review of previous histology, cytology (with frequent multinucleated floret type giant cells but without cross striations) and immunohistochemistry resulted in the change of diagnosis to GCF. It was re-excised, recurred at 20 months of age, and was again re-excised. The morphology was the same in both recurrences as the original. Conclusion: Despite chemotherapy, the histology of multiple recurrences for GCF remained the same as the original. Cytologically, identification of the multinucleated floret like giant cells without cross striations was helpful in differentiating this lesion from embryonal rhabdomyosarcoma.

Immunohistochemistry as a Surrogate Marker of Underlying Molecular Derangements in Sporadic Colorectal Carcinoma in Children - A Series of Three Cases.

Background: Colorectal carcinomas (CRCs) are uncommon tumors in children. Here, we elucidate three cases of childhood CRCs with their underlying molecular derangements using immunohistochemistry (IHC) with emphasis on BRAF mutation. Case summary: All three CRCs were sporadic tumors involving the left colon with two of them having a mucinous phenotype. We performed IHC for BRAF, p53 and ß-catenin along with markers of microsatellite instability (MSI) in all three tumors. All the tumors had diffuse strong cytoplasmic BRAF positivity, with focal p53 positivity in two cases and cytoplasmic ß-catenin staining in one case. One case showed CpG island hypermethylation with isolated loss of PMS2 staining. None of the cases had any family history of CRC. Conclusions: IHC can be used as a surrogate marker for determining the underlying molecular derangements in CRC. Sporadic CRCs in children are a cumulative effect of multiple mutations, of which BRAF mutation is significant and critical for planning targeted therapy.

Sex-Cord Tumor with Annular Tubules with Unusual Morphology in an Infant with Peutz-Jeghers Syndrome.

Background Peutz-Jeghers syndrome (PJS) is characterized by hamartomatous gastrointestinal polyposis, mucocutaneous pigmentation and cancer predisposition. The clinical features of PJS manifest in first two decades of life; however, neonatal presentation is uncommon. Case report: We present a five day old girl with PJS that presented with obstructive hamartomatous polyps in the sigmoid colon. At colostomy closure at six months, an incidental ovarian sex-cord tumor with annular tubules (SCTAT) was detected. It showed predominantly a solid pattern with limited tubule formation and was composed of lipid-rich cells. She had no hormonal symptoms. Conclusion: SCTAT can occur as young as six months of age in PJS, and may show histologic overlap with lipid-rich Sertoli cell tumors.

A tale of monoclonal immunoglobulin: Clinicopathological analysis of proliferative glomerulonephritis with monoclonal immunoglobulin deposit.

BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID) is an entity with a variable clinical and histological spectrum, which mimics immune-complex mediated glomerulonephritis on light microscopy. In this article, we aim to describe the clinical and pathological features of six cases of PGNMID that we encountered during our routine practice. MATERIALS AND METHODS: The study was of the prospective type carried out from February 2018 to August 2019. The renal biopsies that we received in our department, were processed for light microscopy, immunofluorescence microscopy, and electron microscopy. Light microscopic findings were carefully re-evaluated by two experienced renal pathologists. Key diagnostic features were 1) Monoclonal staining of glomeruli for one immunoglobulin (Ig) subclass and single light chain, 2) Membranoproliferative glomerulonephritis (MPGN) pattern (rarely membranous or crescentic), 3) Subendothelial and mesangial (rarely subepithelial) deposits. RESULTS: : We diagnosed five cases of IgG PGNMID and one case of IgA PGNMID with a mean age 53 ± 10.33 years. The most common histological pattern, seen in three cases was MPGN. IgG3 deposits were identified in five cases out of which k light chain restriction was present in four cases and λ light chain restriction was present in one case. IgA deposits were identified in one case that had λ light chain restriction. One patient suffered from multiple myeloma. CONCLUSIONS: The renal biopsy especially immunofluorescence analysis is the key modality for diagnosis of PGNMID where it shows staining of the glomerulus for a single heavy-chain subclass and a single light-chain isotype. Electron microscopic evaluation is necessary to differentiate PGNMID from other renal diseases with monoclonal immunoglobulin deposits.

Clinicopathological study of annexin A5 & apelin in pre-eclamptic placentae with emphasis on foetal outcome.

Background & objectives: Pre-eclampsia has remained an elusive disease with serious impacts on both maternal and foetal health. Two novel markers, annexin A5 (ANXA5) and apelin are currently of considerable interest. The present study aimed to determine the placental expression of ANXA5 and apelin in pre-eclamptic placentae and also to elucidate if there is any correlation between the expression of these markers and the clinical features of both, mother and neonate. The comparison between gross and histopathological features of pre-eclamptic placentae and controls was another objective. Methods: A prospective, observational study was undertaken for one year. Placentae of pre-eclamptic patients and matched controls (matched for age, ethnic and socio-economic background) were collected along with the clinical data. Gross and histopathological analyses were done and immunohistochemical study of placental sections with ANXA5 and apelin was also undertaken. Results: 79 pre-eclamptic patients and equal numbers of matched controls were included in the study. The difference in weight and dimensions of placentae between the pre-eclampsia group and matched controls was significant. Histopathological features noted in the pre-eclamptic placentae included decidual vasculopathy, infarction, perivillous fibrin deposition, increased syncytial knots and distal villous hypoplasia. There was a significant reduction in the expression of both ANXA5 and apelin in pre-eclamptic placentae compared to controls. Among pre-eclamptic patients, the intensity of ANXA5 and apelin expression showed a significant association with respect to neonatal resuscitation. Furthermore, the intensity of apelin showed expression a significant correlation with the requirement of sick neonatal care unit treatment. Interpretation & conclusions: The results of the present study suggest that both ANXA5 and apelin levels are reduced in pre-eclamptic placentae. Hence, it is recommended to further explore the impact of these markers on pregnancy outcomes by undertaking randomized controlled trials.

Thyroid Bethesda Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance (AUS/FLUS): A Heterogenous Group.

BACKGROUND: The Bethesda system of reporting thyroid cytopathology (BSRTC) was introduced in 2007. The third category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) poses difficulties for the pathologist, and different papers have been published varying the risks of malignancy. AIMS: (1) Evaluation of the cytological features of thyroid lesions according to BSRTC. (2) After resection, correlation with histopathological report to evaluate the risk of malignancy (ROM) and the risk of neoplasm (RON). (3) Division of category III into six subgroups based on cytological findings and assessment of ROM and RON. MATERIALS AND METHODS: A total of 282 patients with diagnosed thyroid lesions underwent fine-needle sampling under ultrasound guidance. Smears were prepared and stained with May-Grunwald-Giemsa stain and Papanicolaou stain. RESULTS: Of 282 cases, there were 9 cases (3.1%) of category I, 157 cases (55.8%) of category II, 24 cases (8.5%) of category III, 20 cases (7.1%) of category IV, 14 cases (4.8%) of category V, and 58 cases (20.7%) of category VI. The RON was 60, 17.1, 63.1, 77.7, 91.7, and 98.2% and the ROM was 60, 14.3, 26.3, 38.9, 91.7, and 96.3% in categories I, II, III, IV, V, and VI, respectively. The RON was 0, 75, 50, 100, 66.6, and 100% and the ROM was 0, 25, 50, 100, 16.6, and 0% in subgroups 1, 2, 3, 4, 5, and 6, respectively. We have proposed a system of subgrouping AUS/FLUS that may help to dispel the confusion generated by an AUS/FLUS report, and provide with a more exact and reproducible diagnostic and prognostic tool.

Statistics of Lagrangian trajectories in a rotating turbulent flow.

We investigate the Lagrangian statistics of three-dimensional rotating turbulent flows through direct numerical simulations. We find that the emergence of coherent vortical structures because of the Coriolis force leads to a suppression of the "flight-crash" events reported by Xu et al. [Proc. Natl. Acad. Sci. (USA) 111, 7558 (2014)PNASA60027-842410.1073/pnas.1321682111]. We perform systematic studies to trace the origins of this suppression in the emergent geometry of the flow and show why such a Lagrangian measure of irreversibility may fail in the presence of rotation.

Utility of Squash Cytology in Spinal Lesions with Special Reference to Ki67 Immunostain.

BACKGROUND: Squash cytology is of significant importance in intraoperative consultation of central nervous system (CNS) pathology. There are several studies on squash cytology of CNS lesions, and only a few of them deal with spinal lesions alone. AIMS: (1) To evaluate intraoperative squash cytology of spinal lesions. (2) To correlate cytological diagnosis with histopathological diagnosis and assess the diagnostic accuracy. (3) To study Ki67 expression on squash smears and determine whether it can assist in grading spinal tumours on cytology. MATERIALS AND METHODS: A prospective study was conducted on 68 patients with clinico-radiologically diagnosed lesions of the spine. Intraoperative squash smears were stained with haematoxylin-eosin (H&E) stain, Papanicolaou (Pap) stain, and May-Grünwald-Giemsa (MGG) stain. Subsequently, histological diagnosis was made. Ki67 immunostaining was performed on squash smears and histology sections. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of squash cytology in spinal lesions were 84.6, 100, 100, 23.1, and 80.88%, respectively. On immunocytochemistry, the mean Ki67 labelling indices for grade I, II, and III tumours were 0, 0.33 and 9%, respectively. CONCLUSION: Squash smear cytology is a rapid intraoperative technique for diagnosing spinal lesions, with high specificity and high positive predictive value. It is more effective in diagnosing neoplasms than non-neoplastic lesions. Ki67 immunostaining can be done on cytology smears to effectively differentiate between WHO grade I and grade II spinal tumours.

Utility of intraoperative squash cytology in diagnosis of paediatric central nervous system lesions.

BACKGROUND: Role of squash cytology in intraoperative diagnosis of central nervous system lesions has been well established. Intraoperative diagnosis is especially important in paediatric CNS lesions as decision regarding gross total resection or near total resection or subtotal resection is crucial and radiotherapy and chemotherapy are best avoided in this age group. The aim of this study was to evaluate the utility of squash cytology of CNS lesions in paediatric age group and to assess its diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value. MATERIALS AND METHODS: A prospective study was conducted on 42 paediatric patients with clinico-radiologically diagnosed CNS lesions. Intraoperative squash smears were stained with haematoxylin and eosin (H&E) stain. Diagnosis made subsequently on paraffin sections was taken as gold standard. RESULTS: The overall diagnostic accuracy of intraoperative squash cytology of CNS lesions in paediatric age group was 73.80%. The sensitivity, specificity, positive predictive value and negative predictive value of this modality were 92.31%, 87.50%, 96.00% and 77.78%, respectively. CONCLUSIONS: The spectrum of CNS lesions in paediatric age group is different from that in adults. Though the sensitivity and specificity of squash cytology in paediatric tumours are less than that of adults, it is an important tool for intraoperative diagnosis that guides regarding the extent of resection.

Pattern dynamics near inverse homoclinic bifurcation in fluids.

We report the pattern dynamics in the vicinity of an inverse homoclinic bifurcation in an extended dissipative system. We observe, in direct numerical simulations of three dimensional Rayleigh-Bénard convection with stress-free top and bottom plates, a spontaneous breaking of a competition of two mutually perpendicular sets of oscillating cross rolls to one of two possible sets of oscillating cross rolls as the Rayleigh number is raised above a critical value. The time period of the oscillating cross-roll patterns diverges and shows scaling behavior near the bifurcation point. This is an example of a transition from nonlocal to local pattern dynamics near an inverse homoclinic bifurcation. We also present a simple four-mode model that captures the pattern dynamics quite well.