Dynamics of Nucleation in Solids: A Self-Consistent Phase Field Approach.

We derive a phase field method for computing rigorously the nucleation rate and the incubation time from the sole knowledge of the free energy of the system in the metastable regime. Our theoretical results are assessed against experimental data relative to demixing of an iron-chromium alloy. Our work clarifies the notions of nucleation rate and incubation time extensively used in classical nucleation theory (CNT) processes in solids. Our work thus emerges as an alternative to CNT but of more general applicability, and enables us to model the nucleation process across the whole range of condition encountered in first order phase transitions, an aspect in which CNT fails.

A systematic review and meta-analysis of germline BRCA mutations in pancreatic cancer patients identifies global and racial disparities in access to genetic testing.

BACKGROUND: Germline BRCA1 and BRCA2 mutations (gBRCAm) can inform pancreatic cancer (PC) risk and treatment but most of the available information is derived from white patients. The ethnic and geographic variability of gBRCAm prevalence and of germline BRCA (gBRCA) testing uptake in PC globally is largely unknown. MATERIALS AND METHODS: We carried out a systematic review and prevalence meta-analysis of gBRCA testing and gBRCAm prevalence in PC patients stratified by ethnicity. The main outcome was the distribution of gBRCA testing uptake across diverse populations worldwide. Secondary outcomes included: geographic distribution of gBRCA testing uptake, temporal analysis of gBRCA testing uptake in ethnic groups, and pooled proportion of gBRCAm stratified by ethnicity. The study is listed under PROSPERO registration number #CRD42022311769. RESULTS: A total of 51 studies with 16 621 patients were included. Twelve of the studies (23.5%) enrolled white patients only, 10 Asians only (19.6%), and 29 (56.9%) included mixed populations. The pooled prevalence of white, Asian, African American, and Hispanic patients tested per study was 88.7%, 34.8%, 3.6%, and 5.2%, respectively. The majority of included studies were from high-income countries (HICs) (64; 91.2%). Temporal analysis showed a significant increase only in white and Asians patients tested from 2000 to present (P < 0.001). The pooled prevalence of gBRCAm was: 3.3% in white, 1.7% in Asian, and negligible (<0.3%) in African American and Hispanic patients. CONCLUSIONS: Data on gBRCA testing and gBRCAm in PC derive mostly from white patients and from HICs. This limits the interpretation of gBRCAm for treating PC across diverse populations and implies substantial global and racial disparities in access to BRCA testing in PC.

Predicting Nonequilibrium Patterns beyond Thermodynamic Concepts: Application to Radiation-Induced Microstructures.

In this work, we derive an analytical model to predict the appearance of all possible radiation-induced steady states and their associated microstructures in immiscible A_{c[over ¯]}B_{1-c[over ¯]} alloys, an example of a nonequilibrium dynamical system. This model is assessed against numerical simulations and experimental results which show that different microstructures characterized by the patterning of A-rich precipitates can emerge under irradiation. We demonstrate that the steady-state microstructure is governed by irradiation conditions and also by the average initial concentration of the alloy c[over ¯]. Such a dependence offers new leverage for tailoring materials with specific microstructures overcoming limitations imposed by the equilibrium thermodynamic phase diagram.

Symmetry Breaking Resulting from Long-Range Interactions in Out of Equilibrium Systems: Elastic Properties of Irradiated AgCu.

This work presents a consistent formulation of the phase-field approach to model the behavior of nonmiscible alloys under irradiation which includes elastic strain fields, an example of a long-range interaction. Simulations show that the spatial isotropy that is characteristic of radiation-induced patterns breaks down as a result of the elastic strain energy. The consequence of this is the emergence of superlattice structures under irradiation liable to modify macroscopic material properties. This approach is assessed against the experimental study of a AgCu alloy under irradiation: we compare our simulation results to measured solubility limits and Young moduli.

A model of defect cluster creation in fragmented cascades in metals based on morphological analysis.

The impacts of ions and neutrons in metals cause cascades of atomic collisions that expand and shrink, leaving microstructure defect debris, i.e. interstitial or vacancy clusters or loops of different sizes. In De Backer et al (2016 Europhys. Lett. 115 26001), we described a method to detect the first morphological transition, i.e. the cascade fragmentation in subcascades, and a model of primary damage combining the binary collision approximation and molecular dynamics (MD). In this paper including W, Fe, Be, Zr and 20 other metals, we demonstrate that the fragmentation energy increases with the atomic number and decreases with the atomic density following a unique power law. Above the fragmentation energy, the cascade morphology can be characterized by the cross pair correlation functions of the multitype point pattern formed by the subcascades. We derive the numbers of pairs of subcascades and observed that they follow broken power laws. The energy where the power law breaks indicates the second morphological transition when cascades are formed by branches decorated by chaplets of small subcascades. The subcascade interaction is introduced in our model of primary damage by adding pairwise terms. Using statistics obtained on hundreds of MD cascades in Fe, we demonstrate that the interaction of subcascades increases the proportion of large clusters in the damage created by high energy cascades. Finally, we predict the primary damage of 500 keV Fe ion in Fe and obtain cluster size distributions when large statistics of MD cascades are not feasible.

What Is the Actual Local Crystalline Structure of Uranium Dioxide, UO2? A New Perspective for the Most Used Nuclear Fuel.

Up to now, uranium dioxide, the most used nuclear fuel, was said to have a Fm3̅m crystalline structure from 30 to 3000 K, and its behavior was modeled under this assumption. However, recently X-ray diffraction experiments provided atomic pair-distribution functions of UO2, in which UO distance was shorter than the expected value for the Fm3̅m space group. Here we show neutron diffraction results that confirm this shorter UO bond, and we also modeled the corresponding pair-distribution function showing that UO2 has a local Pa3̅ symmetry. The existence of a local lower symmetry in UO2 could explain some unexpected properties of UO2 that would justify UO2 modeling to be reassessed. It also deserves more study from an academic point of view because of its good thermoelectric properties that may originate from its particular crystalline structure.

Optical properties of Ar ions irradiated nanocrystalline ZrC and ZrN thin films.

Thin nanocrystalline ZrC and ZrN films (<400 nm), grown on (100) Si substrates at a substrate temperature of 500 °C by the pulsed laser deposition (PLD) technique, were irradiated by 800 keV Ar ion irradiation with fluences from 1 × 1014 at/cm2 up to 2 × 1015 at/cm2. Optical reflectance data, acquired from as-deposited and irradiated films, in the range of 500 - 50000 cm-1 (0.06 - 6 eV), was used to assess the effect of irradiation on the optical and electronic properties. Both in ZrC and ZrN films we observed that irradiation affects the optical properties of the films mostly at low frequencies, which is dominated by the free carriers response. In both materials, we found a significant reduction in the free carriers scattering rate, i.e. possible increase in mobility, at higher irradiation flux. This is consistent with our previous findings that irradiation affects the crystallite size and the micro-strain, but it does not induce major structural changes.

Patterning in systems driven by nonlocal external forces.

This work focuses on systems displaying domain patterns resulting from competing external and internal dynamics. To this end, we introduce a Lyapunov functional capable of describing the steady states of systems subject to external forces, by adding nonlocal terms to the Landau Ginzburg free energy of the system. Thereby, we extend the existing methodology treating long-range order interactions, to the case of external nonlocal forces. By studying the quadratic term of this Lyapunov functional, we compute the phase diagram in the temperature versus external field and we determine all possible modulated phases (domain patterns) as a function of the external forces and the temperature. Finally, we investigate patterning in chemical reactive mixtures and binary mixtures under irradiation, and we show that the last case opens the path toward micro-structural engineering of materials.

Structural Changes in the Local Environment of Uranium Atoms in the Three Phases of U4O9.

The crystal structure of U4O9 remains an enigma because of its differences with U(4+) and U(5+) coordination polyhedral mixtures, as shown in the XANES experimental results. To better understand this crystal structure, its diffraction pattern was measured at seven different temperatures using neutron diffraction before being independently refined by Rietveld's method and pair distribution function analysis. The O cuboctahedron-a structural element consisting of 13 oxygen atoms-is a specific feature of the U4O9 crystal structure. The volume of the cuboctahedron decreases when the temperature increases, whereas the overall volume of the crystal cell increases. This feature can be correlated with the two U4O9 phase transitions that induce sharp changes in the cuboctahedron geometry, suggesting that this structural element has internal dynamics. In particular, these structural modifications in the γ phase suggest that the high-temperature phase can be described as a mixture of U(4+) and U(5+) coordination polyhedra, the latter having U-O distances shorter than 2.2 Å, that are absent in the former. These changes in uranium polyhedra as a function of temperature are tentatively interpreted using steric arguments. They also raise the question of charge localization on the different U ion sites in the low-temperature phases of U4O9.

SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells.

SOX2 (Sex-determining region Y (SRY)-Box2) has important functions during embryonic development and is involved in cancer stem cell (CSC) maintenance, in which it impairs cell growth and tumorigenicity. However, the function of SOX2 in pancreatic cancer cells is unclear. The objective of this study was to analyze SOX2 expression in human pancreatic tumors and determine the role of SOX2 in pancreatic cancer cells regulating CSC properties. In this report, we show that SOX2 is not expressed in normal pancreatic acinar or ductal cells. However, ectopic expression of SOX2 is observed in 19.3% of human pancreatic tumors. SOX2 knockdown in pancreatic cancer cells results in cell growth inhibition via cell cycle arrest associated with p21(Cip1) and p27(Kip1) induction, whereas SOX2 overexpression promotes S-phase entry and cell proliferation associated with cyclin D3 induction. SOX2 expression is associated with increased levels of the pancreatic CSC markers ALDH1, ESA and CD44. Importantly, we show that SOX2 is enriched in the ESA(+)/CD44(+) CSC population from two different patient samples. Moreover, we show that SOX2 directly binds to the Snail, Slug and Twist promoters, leading to a loss of E-Cadherin and ZO-1 expression. Taken together, our findings show that SOX2 is aberrantly expressed in pancreatic cancer and contributes to cell proliferation and stemness/dedifferentiation through the regulation of a set of genes controlling G1/S transition and epithelial-to-mesenchymal transition (EMT) phenotype, suggesting that targeting SOX2-positive cancer cells could be a promising therapeutic strategy.

Refinement of the α-U4O9 crystalline structure: new insight into the U4O9 → U3O8 transformation.

The oxidation reaction of UO(2) into U(3)O(8) is studied as a function of the crystalline distortion of interstitial oxygen clusters, named cuboctahedra, which appear in U(4)O(9) and U(3)O(7) intermediate phases. For that purpose, the refinement of α-U(4)O(9) was performed because this phase undergoes a trigonal distortion from cubic ß-U(4)O(9) when the temperature is decreased. In α-U(4)O(9), the cuboctahedra can be described as crumpled sheets taken from a fragment of U(3)O(8). The manner by which the accumulation of crumpled sheets can lead to the formation of U(3)O(8) is discussed.

Cascade fragmentation under ion beam irradiation: a fractal approach.

Based on the fractal nature of collisions, the fragmentation of displacement cascades is investigated. Introducing the caliper diameter to take into account large displacements of atoms in a collision cascade, it is possible to describe this fragmentation in terms of a threshold energy Ec. From the knowledge of Ec, the number and the volume fraction of subcascades produced is then derived. This last information allows us to classify the efficiency of impinging particles to induce structural changes of solids.

Mesenteric venous collateral vessels mimicking cystic pancreatic neoplasm.

We report an unusual case of intrapancreatic mesenteric venous collateral vessels following partial pancreatic surgical resection resembling pancreatic neoplasm upon greyscale sonographic and unenhanced CT examinations.

Concentration profile distortion under ion beam mixing: an example of Levy flight.

In order to model the evolution of concentration profiles induced by ion beam mixing in thick layers, Monte Carlo simulations were performed to study in detail the transition probability controlling the evolution of this profile within the binary collision approximation. We demonstrate that this transition probability can be factorized in two distinct functions. The first one can be understood as a scale factor. The second one controls the dynamics of ion beam mixing which can be analyzed as a Levy flight. The power law form of the tail of this function closely linked to the cross section of a collision event is responsible for long tails of concentration profiles. We demonstrate that the Levy flight nature of ion beam mixing induces an enhancement of the evolution of the initial concentration profile.

Prevalence of atopy in children with chronic constipation.

OBJECTIVES: To evaluate the prevalence of chronic constipation (CC) in unselected children, its association with atopy and the efficacy of a cow's milk protein (CMP) elimination diet on refractory constipation. STUDY DESIGN: The study was conducted by six primary care paediatricians, serving a population of 5113 children aged from birth through to 12 years; only 2068 children were 6 months to 6 years. During a 3-month period, prevalence of CC was determined for the entire study population, ages 0-12 years. In the second part of the study, all patients aged 6 months to 6 years with CC, and age- and sex-matched controls, were evaluated for atopy and its association with CC. A questionnaire was completed including personal and family history of atopy and bowel-movement characteristics. Patients were tested for atopy by specific serum IgE and/or skin-prick tests. Constipated patients, refractory to osmotic laxatives, underwent a 4-week CMP elimination diet. RESULTS: 91 (1.8%) children had CC, and 69 (3.3%) of the 6 months to 6 years age group fell into the atopy study age range. All 69 constipated children (mean age 34.9 (18.0) months) and 69 controls completed the questionnaire. Twelve of the 69 constipated children (17.3%) and 13 out of the 69 control children (18.8%) had a diagnosis of atopy. Eleven out of 69 (15.9%) constipated children were refractory to constipation treatment, and three (27.3%) of these had atopy. The 4-week trial of dietary elimination did not result in improvement in any of these 11 children. CONCLUSIONS: In our study group, prevalence of atopy among children with CC is similar to that in the general population. The level of refraction of CC does not seem to be related to cow's milk allergy.

Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report.

Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate.

Neutron diffraction study of the size-induced tetragonal to monoclinic phase transition in zirconia nanocrystals.

Accurate neutron powder diffraction experiments at several temperatures allow one to monitor the reconstructive tetragonal to monoclinic phase transition as a function of the size of zirconia nanoparticles. The structure of the tetragonal phase observed in the nanocrystals is identical to that observed in micrometric zirconia above 1400 K. A uniaxial strain depending on grain size is observed. The phase transition occurs above a threshold crystal size. These results are analyzed within the Landau theory and can be understood as a mechanism of size-dependent phase transition where the primary order parameter is altered by the nanoparticle size.

Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin.

BACKGROUND & AIMS: Pancreatic acinar cells from various species express cholecystokinin (CCK) A, CCK-B, or a combination of these CCK receptor subtypes. The presence and functional roles of CCK receptors on human acinar cells remain unclear. METHODS: Acini isolated from human pancreas were treated with CCK receptor agonists, CCK-8 and gastrin, and an agonist for m3 muscarinic acetylcholine receptors (m3 AchR), carbachol. Functional parameters measured included intracellular [Ca(2+)], amylase secretion, and ERK phosphorylation. Binding studies were performed using (125)I-CCK-8. Expression of messenger RNAs (mRNAs) was determined using real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and localized by in situ hybridization. RESULTS: Human acini did not respond to CCK agonists. In contrast, they responded to carbachol with robust increases in each of the functional parameters. Moreover, the cells responded to CCK agonists after adenoviral-mediated gene transfer of CCK-A or CCK-B receptors. A low level of specific and a high level of nonspecific binding of (125)I-CCK-8 were observed. Quantitative RT-PCR indicated that the message levels for CCK-A receptors were approximately 30-fold lower than those of CCK-B receptors, which were approximately 10-fold lower than those of m3 Ach receptors. In situ hybridization indicated the presence of m3 Ach receptor and insulin mRNA but not CCK-A or CCK-B receptor mRNAs in adult human pancreas. CONCLUSIONS: These data indicate that human pancreatic acinar cells do not respond to CCK receptor agonists in terms of expected functional parameters and show that this is due to an insufficient level of receptor expression.

Characterization of the inflammatory infiltrate in peptic oesophagitis.

BACKGROUND: The diagnosis of oesophagitis is mainly based on histology, but interpretation of endoscopic biopsies is often difficult. We performed immunohistochemical studies on oesophageal biopsies to see if better characterization of the inflammatory cell infiltrate would improve the accuracy of the histologic diagnosis of gastro-oesophageal reflux disease. METHODS: The study groups consisted of 40 consecutive children (mean age +/- SD: 79.6 +/- 5l.9 months; 20 boys) with gastro-oesophageal reflux disease and 7 symptomatic children (mean age +/- SD: 52.6 +/- 37.0 months; 3 boys) without gastro-oesophageal reflux disease. All patients underwent upper gastrointestinal endoscopy with oesophageal biopsies. The diagnosis of gastro-oesophageal reflux disease was established by conventional endoscopic and histologic criteria. In each mucosal biopsy specimen, the number of intraepithelial CD3+, CD25+ (IL2 receptor+), ICAM+, HLA-DR+ and mucosal mast cells were determined. RESULTS: Conventional histology was in close agreement with endoscopic findings (p<0.001) and reflected the clinical score even more than endoscopic findings. Conventional histology significantly correlated with each inflammatory immunohistochemical marker (<0.05 for each), but the markers were not predictive of symptom severity. Immunohistochemical markers were always abnormal in the gastro-oesophageal reflux disease patients, even in the mildest cases of oesophagitis. CONCLUSIONS: Although there is a good correlation between symptoms and histology, in a subset of patients, immunohistochemical studies appear useful in supporting the histological diagnosis of gastro-oesophageal reflux disease.

Doctor-patient communication in surgery: attitudes and expectations of general surgery patients about the involvement and education of surgical residents.

BACKGROUND: Education is a major function of academic medical centers. At these teaching institutions residents provide a substantial amount of care on medical and surgical services. The attitudes of patients about the training of surgical residents and the impact of residents on patients' perceptions of care in a surgical setting are unknown. STUDY DESIGN: Patients admitted to the gastrointestinal surgery service completed a 30-item survey designed for this study. Patients included in the study underwent operations and had a postoperative inpatient hospital stay. We analyzed patients' answers to determine frequency and correlations among answers. RESULTS: Two hundred patients participated in the study during a 7-month period between July 1999 and January 2000. A majority of patients were comfortable having residents involved in their care (86%) and felt it was important to help educate future surgeons (91%). Most did not feel inconvenienced by being at a teaching hospital (71%) and felt they received extra attention there (74%). Patients were more willing to participate in resident education if they expected to have several physicians involved in their care, felt that they received extra attention, or if the teaching atmosphere did not inconvenience them. Despite the stated willingness of patients to help with surgical resident education, 32% answered that they would not want residents doing any of their operation. CONCLUSIONS: Surgical resident education is well received and considered important by patients. Patient orientation to the resident education process is vital to patients' perceptions of care and may render patients more willing to participate in educational activities.