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Self-folding is an emerging paradigm for the inverse design of three-dimensional structures. While most efforts have concentrated on the shape of the net, our approach introduces a new design dimension-bond specificity between the edges. We transform this design process into a Boolean satisfiability problem to derive solutions for various target structures. This method significantly enhances the yield of the folding process. Furthermore, by linearly combining independent solutions, we achieve designs for shape-shifting nets wherein the dominant structure evolves with varying external conditions. This approach is demonstrated through coarse-grained simulations on two examples of triangular and square nets capable of folding into multiple target shapes.
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INTRODUCTION: Venous thromboembolism (VTE) includes pulmonary embolism (PE), deep vein thrombosis (DVT) in lower limbs, and thrombosis in rare locations. VTE is a common cardiovascular disease, being the leading preventable cause of in-hospital death. Both surgical and acute medical patients have an elevated risk of developing VTE. VTE risk assessment is essential to identify patients who might benefit from VTE prophylaxis accurately. Clinical data on risk factors and prophylaxis in Portugal are scarce. We aimed to determine the proportion of at-risk patients who received prophylaxis and the incidence of bleeding events. We also intended to study the rate of VTE in a cohort of medical and surgical patients during the hospitalization period and three months after discharge. METHODS: During one week in 2020, adults admitted for more than 72hr to a medical or surgical ward were included. The study excluded patients with a diagnosis of VTE three months before hospitalization and who were either chronically receiving anticoagulation therapy or had started it 48 hours after admission. Risk assessments were based on the Padua Prediction Score (PPS) for medical patients and the Caprini Risk Assessment Model (CRAM) for surgical patients. We used CHEST guidelines, 9th edition, to determine the adequacy of the prophylactic method. RESULTS: A total of 123 patients were analyzed, 18.7% of which tested positive for SARS-CoV-2. VTE risk in surgical patients was categorized as very low or low (16.6%), moderate (37.5%), and high (43.8%), according to the CRAM. Risk in medical patients was categorized as low (60.0%) or high (40.0%) according to the PPS. We estimated that VTE chemoprophylaxis was overused in about 30.0% of patients vs. 7.0% who were at risk and did not receive appropriate chemoprophylaxis. The rate of thromboembolic events was 4.1% (n=5), 2 of which happened after discharge. Two of these patients were under VTE prophylaxis during hospitalization. Major bleeding occurred in 2.4% of patients (n=3). DISCUSSION: A significant number of hospitalized patients are deemed to be at risk for VTE, making appropriate prophylaxis essential. The results emphasize the insufficient management of VTE prophylaxis.
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Sarcomatous carcinoma of the bile duct is tremendously uncommon and aggressive. Herein, we report a case of a male who presented with jaundice. The thoraco-abdominopelvic tomography scan revealed a lesion within the common bile duct highly suspicious of malignancy. After laparoscopic pancreaticoduodenectomy, histological examination revealed a sarcomatous carcinoma. Two years after the initial diagnosis, the patient remains without signs of recurrence. Additional research about this rare condition is needed to improve care and prognosis.
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BACKGROUND: This study aimed to compare brain asymmetry in patients with schizophrenia (SCZ), bipolar disorder (BPD), and healthy controls to test whether asymmetry patterns could discriminate and set boundaries between two partially overlapping severe mental disorders. METHODS: We applied a fully automated voxel-based morphometry (VBM) approach to assess structural brain hemispheric asymmetry in magnetic resonance imaging (MRI) anatomical scans in 60 participants (SCZ = 20; BP = 20; healthy controls = 20), all right-handed and matched for gender, age, and education. RESULTS: Significant differences in gray matter asymmetry were found between patients with SCZ and BPD, between SCZ patients and healthy controls (HC), and between BPD patients and HC. We found a higher asymmetry index (AI) in BPD patients when compared to SCZ in Brodmann areas 6, 11, and 37 and anterior cingulate cortex and an AI higher in SCZ patients when compared to BPD in the cerebellum. CONCLUSION: Our study found significant differences in brain asymmetry between patients with SCZ and BPD. These promising results could be translated to clinical practice, given that structural brain changes detected by MRI are good candidates for exploration as biological markers for differential diagnosis, besides helping to understand disease-specific abnormalities.
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The control over the self-assembly of complex structures is a long-standing challenge of material science, especially at the colloidal scale, as the desired assembly pathway is often kinetically derailed by the formation of amorphous aggregates. Here, we investigate in detail the problem of the self-assembly of the three Archimedean shells with five contact points per vertex, i.e., the icosahedron, the snub cube, and the snub dodecahedron. We use patchy particles with five interaction sites (or patches) as model for the building blocks and recast the assembly problem as a Boolean satisfiability problem (SAT) for the patch-patch interactions. This allows us to find effective designs for all targets and to selectively suppress unwanted structures. By tuning the geometrical arrangement and the specific interactions of the patches, we demonstrate that lowering the symmetry of the building blocks reduces the number of competing structures, which in turn can considerably increase the yield of the target structure. These results cement SAT-assembly as an invaluable tool to solve inverse design problems.
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Nucleation in systems with a metastable liquid-gas critical point is the prototypical example of a two-step nucleation process in which the appearance of the critical nucleus is preceded by the formation of a liquid-like density fluctuation. So far, the majority of studies on colloidal and protein crystallization have focused on one-component systems, and we are lacking a clear description of two-step nucleation processes in multicomponent systems, where critical fluctuations involve coupled density and concentration inhomogeneities. Here, we examine the nucleation process of a binary mixture of patchy particles designed to nucleate into a diamond lattice. By combining Gibbs-ensemble simulations and direct nucleation simulations over a wide range of thermodynamic conditions, we are able to pin down the role of the liquid-gas metastable phase diagram on the nucleation process. In particular, we show that the strongest enhancement of crystallization occurs at an azeotropic point with the same stoichiometric composition of the crystal.
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"Watch and wait" is becoming a common treatment option for patients with locally advanced rectal cancer (LARC) submitted to neoadjuvant treatment. However, currently, no clinical modality has an acceptable accuracy for predicting pathological complete response (pCR). The aim of this study was to assess the clinical utility of circulating tumor DNA (ctDNA) in predicting the response and prognosis in these patients. We prospectively enrolled a cohort of three Iberian centers between January 2020 and December 2021 and performed an analysis on the association of ctDNA with the main response outcomes and disease-free survival (DFS). The rate of pCR in the total sample was 15.3%. A total of 24 plasma samples from 18 patients were analyzed by next-generation sequencing. At baseline, mutations were detected in 38.9%, with the most common being TP53 and KRAS. Combination of either positive magnetic resonance imaging (MRI) extramural venous invasion (mrEMVI) and ctDNA increased the risk of poor response (p = 0.021). Also, patients with two mutations vs. those with fewer than two mutations had a worse DFS (p = 0.005). Although these results should be read carefully due to sample size, this study suggests that baseline ctDNA combined with mrEMVI could potentially help to predict the response and baseline ctDNA number of mutations might allow the discrimination of groups with different DFS. Further studies are needed to clarify the role of ctDNA as an independent tool in the selection and management of LARC patients.
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The Brownian motion of a single particle is a paradigmatic model of the nonequilibrium dynamics of dissipative systems. In the system-plus-reservoir approach, one can derive the particle's equations of motion from the reversible dynamics of the system coupled to a bath of oscillators representing its thermal environment. However, extending the system-plus-reservoir approach to multiple particles in a collective environment is not straightforward, and conflicting models have been proposed to that end. Here, we set out to reconcile some aspects of the nonlinear and the bilinear models of two Brownian particles. We show how the nonlinear dissipation originally derived from exponential system-reservoir couplings can alternatively be obtained from the bilinear Lagrangian, with a modified spectral function that explicitly depends on the distance between the particles. We discuss applications to the contexts of anomalous diffusion and of hydrodynamic interactions. Our results thus broaden the applicability of the bilinear model.
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INTRODUCTION: Pre-exposure prophylaxis (PrEP) has gained relevance as a method of prevention for HIV in certain people and settings. Following the publication of the guideline on PrEP prescribing in Portugal, we aimed to assess the knowledge of Portuguese Medical Students about PrEP. MATERIAL AND METHODS: An online survey was sent to Medical students of Portuguese Medical Schools. We conducted a descriptive analysis of the results and an analytic cross-sectional study to identify factors associated with "knowing about PrEP", "having had one class about PrEP" and "identifying eligible groups correctly". RESULTS: Of the 796 students that responded to the survey, 64.6% were aware of what PrEP is. Of these, 34.44% acquired this knowledge during their training. Out of the total amount of respondents, 4.77% could identify correctly and completely the eligible groups for PrEP. As the training years went by, the probability of being aware of PrEP, having had one class about PrEP, and identifying the eligible groups correctly, increased. Of the sixth-year students, 43.48% had had one class about PrEP and among the students that were aware of PrEP, 28% identified what the eligible groups were. After adjusting for the school year, we found differences between Medical Schools regarding the outcomes. The association between the different ways of learning about PrEP and the ability to correctly identify eligible groups for PrEP was not statistically significant. CONCLUSION: The differences between Medical Schools could be harmonized through changes in the medical curricula that would allow this topic to be addressed more often.
Introdução: A profilaxia pré-exposição (PrEP) ganhou relevância como método de prevenção do VIH em determinados indivíduos e contextos. Após a entrada em vigor das normas para prescrição em Portugal, pretendemos aferir o conhecimento em relação à PrEP entre os estudantes de Medicina em Portugal.Material e Métodos: Foi enviado um questionário online aos estudantes de Medicina das escolas médicas portuguesas. Foi feita uma análise descritiva dos resultados e um estudo transversal analítico para identificar fatores associados a "conhecer a PrEP", "ter tido uma aula de PrEP", e "identificar grupos elegíveis corretamente".Resultados: Dos 796 estudantes que responderam, 64,6% sabiam o que era a PrEP. Destes, 34,44% obteve conhecimento sobre a mesma durante a sua formação. Entre os respondentes, 4,77% identificaram correta e completamente os grupos elegíveis. Com o avançar do ano letivo, a probabilidade de conhecer a PrEP, ter tido uma aula de PrEP e identificar os grupos corretamente aumentava. No sexto ano, 43,48% tinham tido uma aula sobre PrEP e entre os que conheciam a PrEP, 28% identificaram os grupos elegíveis. Existem diferenças entre as escolas médicas após ajustamento para o ano letivo em relação aos resultados obtidos. A forma como se tomou conhecimento da PrEP não alterou de forma estatisticamente significativa a capacidade de identificar corretamente grupos elegíveisConclusão: As diferenças entre as escolas médicas poderão ser harmonizadas. Esta temática poderá ser reforçada nos respetivos currículos.
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HIV Infections , Pre-Exposure Prophylaxis , Cross-Sectional Studies , Curriculum , HIV , HIV Infections/prevention & control , Health Knowledge, Attitudes, Practice , Humans , Portugal , Surveys and QuestionnairesABSTRACT
BACKGROUND: The management of locally advanced rectal cancer (LARC) requires a multidisciplinary approach, with an increasing interest for non-operative strategies. Liquid biopsy for obtaining circulating tumor DNA (ctDNA) can provide information on neoadjuvant chemoradiotherapy (nCRT) pathological response and cancer-specific prognosis, and therefore might be a promising guide for these treatments. METHODS: A systematic review of the studies available in literature has been performed to assess the role of ctDNA as a predictive and prognostic biomarker in LARC patients. RESULTS: We retrieved 21 publications, of which 17 full-text articles and 4 abstracts. Results have been labelled into two groups: predictive and prognostic. Data about the usefulness of liquid biopsy in this setting is still inconclusive. However, baseline higher levels of longer fragments of cell-free DNA and integrity index, tumor-specific mutations and certain methylated genes could predict non-responders. Also, undetectable baseline ctDNA and decrease of common rectal cancer mutations throughout treatment (dynamic monitoring) were predictive factors of pathological complete response. The continuous detection of ctDNA in different timepoints of treatment (minimal residual disease) was consistently associated with worse prognosis. CONCLUSIONS: ctDNA is a promising biomarker that could assist predicting treatment response to nCRT and prognosis in patients with LARC. The ideal methods and timings for the liquid biopsy still have to be defined.
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Carcinoma/therapy , Chemoradiotherapy , Circulating Tumor DNA/blood , Proctectomy , Rectal Neoplasms/therapy , Carcinoma/blood , Carcinoma/pathology , Humans , Liquid Biopsy , Mesentery/surgery , Neoadjuvant Therapy , Prognosis , Rectal Neoplasms/blood , Rectal Neoplasms/pathologyABSTRACT
The availability of wearable devices (WDs) to collect biometric information and their use during activities of daily living is significantly increasing in the general population. These small electronic devices, which record fitness and health-related outcomes, have been broadly utilized in industries such as medicine, healthcare, and fitness. Since they are simple to use and progressively cheaper, they have also been used for numerous research purposes. However, despite their increasing popularity, most of these WDs do not accurately measure the proclaimed outcomes. In fact, research is equivocal about whether they are valid and reliable methods to specifically evaluate physical activity and health-related outcomes in older adults, since they are mostly designed and produced considering younger subjects' physical and mental characteristics. Additionally, their constant evolution through continuous upgrades and redesigned versions, suggests the need for constant up-to-date reviews and research. Accordingly, this article aims to scrutinize the state-of-the-art scientific evidence about the usefulness of WDs, specifically on older adults, to monitor physical activity and health-related outcomes. This critical review not only aims to inform older consumers but also aid researchers in study design when selecting physical activity and healthcare monitoring devices for elderly people.
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We explore the role a non-Markovian memory kernel plays on information exchange and entropy production in the context of a external work protocol. The Jarzynski equality is shown to hold for both the harmonic and the nonharmonic models. We observe the memory function acts as an information pump, recovering part of the information lost to the thermal reservoir as a consequence of the nonequilibrium work protocol. The pumping action occurs for both the harmonic and nonharmonic cases. Unexpectedly, we found that the harmonic model does not produce entropy, regardless of the work protocol. The presence of even a small amount of nonlinearity recovers the more normal entropy producing behavior, for out-of-equilibrium protocols.
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The structure and dynamics of tissue cultures depend strongly on the physical and chemical properties of the underlying substrate. Inspired by previous advances in the context of inorganic materials, the use of patterned culture surfaces has been proposed as an effective way to induce space-dependent properties in cell tissues. However, cells move and diffuse, and the transduction of external stimuli to biological signals is not instantaneous. Here, we show that the fidelity of patterns to demix tissue cells depends on the relation between the diffusion (τD) and adaptation (τ) times. Numerical results for the self-propelled Voronoi model reveal that the fidelity decreases with τ/τD, a result that is reproduced by a continuum reaction-diffusion model. Based on recent experimental results for single cells, we derive a minimal length scale for the patterns in the substrate that depends on τ/τD and can be much larger than the cell size.
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DiffusionABSTRACT
Background and objectives: The long-term outcome of endodontic microsurgery (EMS) performed on root-filled teeth affected by post-treatment apical periodontitis (AP) has been a matter of debate, re-launched by the introduction of novel root-end filling materials which have been proven to improve the short-term outcome of EMS. The purpose of this systematic review and meta-analysis is to evaluate the clinical and radiographic long-term outcome of endodontic microsurgery in teeth diagnosed with secondary AP through radiographic evaluation. Materials and Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion and exclusion criteria were defined a priori to select the best longitudinal evidence. Only randomized clinical trials (RCT) and prospective clinical studies (PCS), with a follow-up ≥ 2-year, and exhibiting well-established clinical and radiographic outcome criteria, were selected. Results: A total of 573 articles were obtained, from which 10 fulfill inclusion criteria: 6 PCS and 4 RCT. Meta-analysis showed a pooled proportion of success rate of 91.3%, from an overall amount of 453 treated teeth included in RCT; from overall 839 included teeth in PCS, a pooled success rate of 78.4% was observed, with the follow-up time ranging from 2 to 13-years. Survival rate outcomes varied from 79 to 100% for the same follow-up period. Five prognostic factors with influence on the outcome were disclosed: smoking habits, tooth location and type, absence/presence of dentinal defects, interproximal bone level, and root-end filling material. Conclusions: High success rates and predictable results can be expected when EMS is performed by trained endodontists, allowing good prognosis and preservation of teeth affected by secondary AP.
Subject(s)
Endodontics , Microsurgery , Humans , Prognosis , Prospective Studies , Root Canal Filling Materials , Treatment OutcomeABSTRACT
Mesenchymal stromal cells (MSCs) have been widely exploited for the treatment of several conditions due to their intrinsic regenerative and immunomodulatory properties. MSC have demonstrated to be particularly relevant for the treatment of ischemic diseases, where MSC-based therapies can stimulate angiogenesis and induce tissue regeneration. Regardless of the condition targeted, recent analyses of MSC-based clinical trials have demonstrated limited benefits indicating a need to improve the efficacy of this cell product. Preconditioning MSC ex vivo through microenvironment modulation was found to improve MSC survival rate and thus prolong their therapeutic effect. This workstudy aims at enhancing the in vitro angiogenic capacity of a potential MSC-based medicinal product by comparing different sources of MSC and culture conditions. MSC from three different sources (bone marrow [BM], adipose tissue [AT], and umbilical cord matrix [UCM]) were cultured with xenogeneic-/serum-free culture medium under static conditions and their angiogenic potential was studied. Results indicated a higher in vitro angiogenic capacity of UCM MSC, compared with cells derived from BM and AT. Physicochemical preconditioning of UCM MSC through a microcarrier-based culture platform and low oxygen concentration (2% O2 , compared with atmospheric air) increased the in vitro angiogenic potential of the cultured cells. Envisaging the clinical manufacturing of an allogeneic, off-the-shelf MSC-based product, preconditioned UCM MSC maintain the angiogenic gene expression profile upon cryopreservation and delivery processes in the conditions of our study. These results are expected to contribute to the development of MSC-based therapies in the context of angiogenesis.
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Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/physiology , Neovascularization, Physiologic , Adipose Tissue/cytology , Bone Marrow Cells/cytology , Cell Differentiation , Cell Proliferation , Cell Separation , Cells, Cultured , Cellular Microenvironment/physiology , Cryopreservation , Culture Media, Serum-Free , Humans , Immunophenotyping , In Vitro Techniques , Neovascularization, Physiologic/genetics , Oxygen , Transcriptome , Umbilical Cord/cytologyABSTRACT
Time has been an elusive concept to grasp. Although we do not yet understand it properly, there have been advances made in regard to how we can explain it. One such advance is the Page-Wootters mechanism. In this mechanism, time is seen as an inaccessible coordinate and the apparent passage of time arises as a consequence of correlations between the subsystems of a global state. Here we propose a measure that captures the relational character of the mechanism, showing that the internal coherence is the necessary ingredient for the emergence of time in the Page-Wootters model. Also, we connect it to results in quantum thermodynamics, showing that it is directly related to the extractable work from quantum coherence.
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Mesenchymal stromal cells (MSC) hold great promise for tissue engineering applications and cell-based therapies. Large cell doses (>1 × 106 cells kg-1 ) and Good Manufacturing Practices (GMP)-compliant processes are however required for clinical purposes. Here, a serum- and xenogeneic-free (S/XF) microcarrier-based culture system is established for the expansion of human umbilical cord matrix (UCM)- and adipose tissue (AT)-derived MSC using the Vertical-Wheel system (PBS-0.1 MAG; PBS Biotech). UCM and AT MSC are expanded to maximum cell densities of 5.3 ± 0.4 × 105 cell mL-1 (n = 3) and 3.6 ± 0.7 × 105 cell mL-1 (n = 3), respectively, after 7 days of culture, while maintaining their identity, according to standard criteria. An economic evaluation of the process transfer from T-flasks to PBS-0.1 MAG shows a reduction in the costs associated with the production of a dose for an average 70 kg adult patient (i.e., 70 million cells). Costs decrease from $17.0 K to $11.1 K for UCM MSC and from $21.5 K to $11.1 K for AT MSC, proving that the transition to Vertical-Wheel reactors provides a cost-effective alternative for MSC expansion. The present work reports the establishment of a scalable and cost-effective culture platform for the manufacturing of UCM and AT MSC in a S/XF microcarrier-based system.
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Bioreactors , Cell Culture Techniques/economics , Cell Culture Techniques/instrumentation , Mesenchymal Stem Cells , Cell Culture Techniques/methods , HumansABSTRACT
ABSTRACT Background and objectives: Surgery for Crohn disease has a wide range of factors that are being studied as possible risk factors for postoperative complications. The later are a major problem in those patients and are associated with longer hospital stays and increased mortality and morbidity. Despite the debate regarding the influence of patients' characteristics, preoperative and operative details, the risk factors are not fully identified. The debate has been focused on the new medical therapy and the time of surgery. Our goal was to help identify and confirm risk factors for postoperative complications. Materials and methods: A retrospective cohort study including all patients operated due to Crohn disease in São João Hospital Center from 2010 to 2015. We analyzed patient, preoperative and surgical characteristics. For postoperative complications data only those occurring within 30 days were included. Results: Neither age at diagnosis or previous corticotherapy/anti-TNF/ustekinumab was significantly associated with an increased risk in postoperative complications. Only age at surgery >40 years (Montreal Classification A1 + A2 vs. A3; OR = 4.12; p < 0.05) and the group others (occlusion vs. others [combination of intestinal perforation, mesenteric ischemia and postoperative complications] vs. fistula/abscess as indication for surgery; OR = 4.12; p < 0.05) remained as independent risk factors after multivariable regression analysis. Conclusions: We described clear associations between age at surgery >40 years and the group others (intestinal perforation, mesenteric ischemia and postoperative complications) and overall postoperative complications in Crohn disease. These results may suggest that surgery does not need to be delayed and, in some cases, should be anticipated.
RESUMO Introdução e objetivos: Vários fatores têm sido estudados como possíveis fatores de risco para complicações pós-operatórias na doença de Crohn. Estas complicações estão associadas a estadias mais prolongadas no hospital e a um aumento da mortalidade. Apesar do debate relativo à influência das características dos pacientes, pré-operatórias e operatórias, os fatores de risco ainda não estão completamente identificados. Atualmente, o debate centra-se nos avanços da terapia médica e no melhor momento para realizar a operação. O objetivo era identificar os fatores de risco para complicações pós- operatórias. Materiais e métodos: Realizamos um estudo retrospectivo incluindo todos os pacientes operados devido à doença de Crohn no Hospital São João desde 2010 até 2015. Analisamos as características dos doentes, as pré e as pós-operatórias. Apenas foram incluídos os dados relativos a complicações no período de 30 dias após a cirurgia. Resultados: A idade ao diagnóstico e o uso prévio de corticoterapia/anti-TNF/ustekinumab não foram associados a um aumento no risco de complicações pós-operatórias. Apenas a idade na cirurgia superior aos 40 anos (Classificação de Montreal A1 + A2 vs. A3; OR = 4.12; p < 0.05) e o grupo 'outros' (oclusão vs. outros [combinação de perfuração intestinal, isquemia mesentérica e complicações pós-operatórias] vs. fistula/abscesso como indicação para cirurgia; OR = 4.12; p < 0.05) são fatores de risco independentes. Conclusões: Descrevemos uma associação clara entre a idade na cirurgia superior aos 40 anos e o grupo 'outros' e a existência de complicações pós-operatórias na doença de Crohn. A cirurgia não deve ser adiada e, em alguns casos, seria benéfico antecipá-la.
Subject(s)
Humans , Male , Female , Postoperative Complications , Crohn Disease/surgery , Risk Factors , Crohn Disease/complications , Retrospective Studies , Age FactorsABSTRACT
An extension of the random sequential adsorption model has been proposed recently, motivated by the coverage of oil droplets by DNA-functionalized colloidal particles. Particles arrive to a flat substrate with a uniform flux F but they can only adsorb on patches. Patches diffuse on the substrate with a diffusion coefficient D if they are free and they remain immobile when attached to an adsorbed particle. The adsorption is considered irreversible and particles cannot adsorb on top of each other. Thus, the system reaches a jammed state, consisting of a monolayer where no more particles can adsorb. We performed Monte Carlo simulations to study the adsorption kinetics and jammed-state morphology on a one-dimensional lattice. We show that, while the time-dependence of the coverage depends on F and D, the jammed-state coverage depends solely on the ratio F/D. This result is grasped by a simple mean-field calculation. We also report two different regimes for the functional dependence of the jammed-state coverage on the size of the particles, for low and high density of patches.