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1.
Oncologist ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886160

RESUMO

A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss therapeutic implications. The patient had been diagnosed with B-cell chronic lymphocytic leukemia (CLL) years prior to the MTB presentation. GIST had been diagnosed 1 month earlier. After structured clinical annotation of the molecular alterations and interdisciplinary discussion, we considered BRAF/KIT co-mutation unlikely in a treatment-naïve GIST. Discordant variant allele frequencies furthermore suggested a second malignancy. NGS of a CLL sample revealed the identical class 2 BRAF alteration, thus supporting admixture of CLL cells in the paragastric mass, leading to the detection of 2 alterations. Following the MTB recommendation, the patient received imatinib and had a radiographic response. Structured annotation and interdisciplinary discussion in specialized tumor boards facilitate the clinical management of complex molecular findings. Coexisting malignancies and clonal hematopoiesis warrant consideration in case of complex and uncommon molecular findings.

2.
JAMA Netw Open ; 6(11): e2343689, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37976064

RESUMO

Importance: Clinical interpretation of complex biomarkers for precision oncology currently requires manual investigations of previous studies and databases. Conversational large language models (LLMs) might be beneficial as automated tools for assisting clinical decision-making. Objective: To assess performance and define their role using 4 recent LLMs as support tools for precision oncology. Design, Setting, and Participants: This diagnostic study examined 10 fictional cases of patients with advanced cancer with genetic alterations. Each case was submitted to 4 different LLMs (ChatGPT, Galactica, Perplexity, and BioMedLM) and 1 expert physician to identify personalized treatment options in 2023. Treatment options were masked and presented to a molecular tumor board (MTB), whose members rated the likelihood of a treatment option coming from an LLM on a scale from 0 to 10 (0, extremely unlikely; 10, extremely likely) and decided whether the treatment option was clinically useful. Main Outcomes and Measures: Number of treatment options, precision, recall, F1 score of LLMs compared with human experts, recognizability, and usefulness of recommendations. Results: For 10 fictional cancer patients (4 with lung cancer, 6 with other; median [IQR] 3.5 [3.0-4.8] molecular alterations per patient), a median (IQR) number of 4.0 (4.0-4.0) compared with 3.0 (3.0-5.0), 7.5 (4.3-9.8), 11.5 (7.8-13.0), and 13.0 (11.3-21.5) treatment options each was identified by the human expert and 4 LLMs, respectively. When considering the expert as a criterion standard, LLM-proposed treatment options reached F1 scores of 0.04, 0.17, 0.14, and 0.19 across all patients combined. Combining treatment options from different LLMs allowed a precision of 0.29 and a recall of 0.29 for an F1 score of 0.29. LLM-generated treatment options were recognized as AI-generated with a median (IQR) 7.5 (5.3-9.0) points in contrast to 2.0 (1.0-3.0) points for manually annotated cases. A crucial reason for identifying AI-generated treatment options was insufficient accompanying evidence. For each patient, at least 1 LLM generated a treatment option that was considered helpful by MTB members. Two unique useful treatment options (including 1 unique treatment strategy) were identified only by LLM. Conclusions and Relevance: In this diagnostic study, treatment options of LLMs in precision oncology did not reach the quality and credibility of human experts; however, they generated helpful ideas that might have complemented established procedures. Considering technological progress, LLMs could play an increasingly important role in assisting with screening and selecting relevant biomedical literature to support evidence-based, personalized treatment decisions.


Assuntos
Neoplasias Pulmonares , Medicina de Precisão , Humanos , Oncologia , Idioma , Comunicação
3.
Medicina (Kaunas) ; 58(9)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36143897

RESUMO

Background and Objectives: Increasing reluctance to perform surgical mitral valve repair or replacement particularly in high-risk patients with poor left-ventricular function is trending. These patients are increasingly treated interventionally, e.g., by MitraClip, but often show only low to moderate improvement. The primary objective of the study was to investigate whether left ventricular ejection fraction (LVEF) influences postoperative mortality. Materials and Methods: The study included 903 patients undergoing mitral valve repair or replacement between 2009 and 2021. Statistical comparison was performed between patients with LVEF ≤ 30% and LVEF > 30%. Finally, statistical analysis was performed according to propensity score matching (1:3 PS matching). Results: No significant difference in in-hospital mortality was found before and after matching regarding LVEF ≤ 30% and LVEF > 30% (Pre: 10.8% vs. 15.1%, p = 0.241, after: 11.6% vs. 18.1%, p = 0.142). After PS matching, the 112 patients with LVEF ≤ 30% compared with 336 patients with LVEF > 30% showed a significantly higher preoperative NT-proBNP (p < 0.001), larger diameters at preoperative left ventricle and atrium (p < 0.001), lower preoperative TAPSE (p = 0.003) and PAP (p = 0.003), and more dilated cardiomyopathy and chronic kidney disease (p < 0.001, p = 0.045). Conclusions: The results of this study demonstrate that poor preoperative LVEF alone does not play a significant role in postoperative outcome and long-term mortality. Prognosis appears to be multifactorial. Poor preoperative LVEF is not a contraindication for surgery and does not justify primary interventional treatment accepting inferior hemodynamic results impeding outcome.


Assuntos
Insuficiência da Valva Mitral , Disfunção Ventricular Esquerda , Humanos , Insuficiência da Valva Mitral/cirurgia , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/cirurgia , Função Ventricular Esquerda
4.
Forensic Sci Int Genet ; 57: 102648, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34896976

RESUMO

Blunt force traumas by footwear can result in severe and even fatal head and upper body injuries. Oftentimes, footwear impressions are only partially available and evidential value is limited. DNA evidence on shoe soles could provide crucial evidence helping to solve crimes by linking target DNA to the activity of interest. Little is known about the persistence and detectability of biological material post such offenses and the interplay of factors affecting the analytical success. In this study, we assessed the persistence of blood on shoe soles under varying parameters such as blood location, different sneakers, weather condition, gait, amount of blood, underground and step count. We applied an optimized DNA/RNA workflow adapted to micro-traces without constraints for the primary DNA pipeline. There is a high probability to link donor DNA to the shoe sole for up to 300-400 steps, regardless of the underground, blood location, and amount of blood. Depending on the sole material and the degree of abrasion of the sole, a longer blood persistence can be observed. Considering blood, 98.2% of the initial DNA amount (1 µl initial blood volume) was lost after 100 steps walked on sole areas that are in constant contact with the ground. Proportion of foreign DNA was marginal (avg. 4.4 alleles), minimizing the probability of unintentional DNA transfer in this context. RNA typing showed high specificity but lower sensitivity than presumptive tests used for body fluid identification (BFI). Luminol is essential for targeted sampling on shoe soles, as latent blood traces (>100-200 steps) provided sufficient biological material for DNA/RNA typing. The generated data help to address the activity of interest and evaluate probabilities about prevalence of target DNA important for casework implications and assessments on activity level.


Assuntos
RNA , Sapatos , DNA , Impressões Digitais de DNA , Humanos , Manejo de Espécimes
5.
Forensic Sci Int Genet ; 56: 102630, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34808489

RESUMO

DNA evidence on shoes can play an important role in solving a variety of crimes. We investigated the transfer, persistence, prevalence and recovery of DNA (DNAtppr) on shoes (sneakers) and their soles in realistic handling scenarios taking into account the shedder status. This study aims to increase the understanding of the expected composition of DNA profiles and their probative value, providing a basis for activity level assessments. Samples were analyzed using a direct lysis method, suggesting its versatility and increasing the DNA typing success compared to previous studies on footwear. The data showed surface-dependent background DNA (bDNA) levels on shoe soles and prevalence of bDNA on the upper parts of the shoe. The owner of the shoe was allocatable to the mixture for almost every shoe and sampling location. Alternating scenarios of shoe handling were simulated through different pairs of shedders to distinguish shoe owner and subsequent user. Secondary users were attributable to DNA mixtures regardless of shedder status after wearing shoes a single time. The influence of the shedder status follows specific trends in this context. However, particularly intermediate shedders show inconsistent results. The prevalence of bDNA appears to have a greater effect on the impact of the shedder status on DNA profile composition than previously reported. The data help researchers to better resolve suspect statements and determine if a person of interest wore the shoes relevant to the investigation.


Assuntos
Impressões Digitais de DNA , DNA , Crime , Humanos , Sapatos , Manejo de Espécimes
6.
Nat Commun ; 12(1): 6609, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34785681

RESUMO

Magmas readily react with their wall-rocks forming metamorphic contact aureoles. Sulphur and possibly metal mobilization within these contact aureoles is essential in the formation of economic magmatic sulphide deposits. We performed heating and partial melting experiments on a black shale sample from the Paleoproterozoic Virginia Formation, which is the main source of sulphur for the world-class Cu-Ni sulphide deposits of the 1.1 Ga Duluth Complex, Minnesota. These experiments show that an autochthonous devolatilization fluid effectively mobilizes carbon, sulphur, and copper in the black shale within subsolidus conditions (≤ 700 °C). Further mobilization occurs when the black shale melts and droplets of Cu-rich sulphide melt and pyrrhotite form at ∼1000 °C. The sulphide droplets attach to bubbles of devolatilization fluid, which promotes buoyancy-driven transportation in silicate melt. Our study shows that devolatilization fluids can supply large proportions of sulphur and copper in mafic-ultramafic layered intrusion-hosted Cu-Ni sulphide deposits.

7.
Forensic Sci Int Genet ; 55: 102570, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34474323

RESUMO

Latest innovations indicate that continuous tools are promising DNA trace assessment methods. In this study, we present the continuous software solution Statistefix 4.0. The software supports DNA experts in deducing DNA profiles for database queries and can help to preselect DNA samples suitable for further processing using advanced probabilistic search engines. The novel tool weights genotype contributions and deduces major contributors from high- and low-quality DNA traces. Peak height, degradation, stutter as well as allelic drop-in/-out events are incorporated in the statistical model. We analyzed reference and casework samples as well as artificially generated mixture samples for software evaluation. The tool offers the completely automated assessment of reference and mixture samples. Deconvolution outcomes of mixtures are compared with EuroForMix, GenoProof Mixture 3 and STRmix™. Data show that Statistefix 4.0 is as successful as analogously tested and implemented software. Deduced DNA profiles from casework samples highlight the potential benefit in routine casework. Statistefix 4.0 is freely available, works with replicates of different autosomal kits and enables bulk sample processing. This inter-laboratory study includes a variety of sample types and indicates a timesaving, robust and easily implemented software that supports DNA analysts in evaluating DNA traces.


Assuntos
Impressões Digitais de DNA , Repetições de Microssatélites , Gerenciamento de Dados , Humanos , Funções Verossimilhança , Software
8.
Forensic Sci Int Genet ; 54: 102542, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34098418

RESUMO

Molecular identification of body fluids and tissues is crucial in order to understand the circumstances of crimes. For that reason, molecular investigations used to identify body fluids/tissues have increasingly been examined recently. Various studies have proved that messenger RNA (mRNA) profiling is a sensitive and robust method for body fluid/tissue identification. The forensically relevant body fluids/tissues blood, semen, saliva, vaginal secretion, menstrual blood and skin have all been detected successfully by applying suitable mRNA assay. However, rectal mucosa, which can be found as evidence in sexual assault cases, has been neglected in forensic investigations. So far there is no mRNA marker to detect rectal mucosa, although anal penetration occurs in a large number of sexual assaults (23.2% of female victims and 50% of male victims). In this study, specific and sensitive mRNA markers for forensically relevant body fluids were adapted and validated in an mRNA multiplex assay for routine casework. This included the implementation of a DNA/RNA re-extraction method for automated extraction that can be integrated into casework without loss of DNA. This re-extraction method and the mRNA multiplex assay were tested using casework samples. PCR-primers were designed for the identification of rectal mucosa and the more effective marker MUC12 was integrated into an extended multiplex assay. The result of our study is a highly specific and sensitive mRNA multiplex assay plus an automated DNA/RNA re-extraction method, that can be integrated into casework and identify rectal mucosa for the first time.


Assuntos
Líquidos Corporais , Genética Forense , Feminino , Humanos , Masculino , Mucosa , Projetos Piloto , RNA Mensageiro/genética , Fluxo de Trabalho
9.
Nat Commun ; 11(1): 4845, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32973148

RESUMO

Herpesviruses encode conserved protein kinases (CHPKs) to stimulate phosphorylation-sensitive processes during infection. How CHPKs bind to cellular factors and how this impacts their regulatory functions is poorly understood. Here, we use quantitative proteomics to determine cellular interaction partners of human herpesvirus (HHV) CHPKs. We find that CHPKs can target key regulators of transcription and replication. The interaction with Cyclin A and associated factors is identified as a signature of ß-herpesvirus kinases. Cyclin A is recruited via RXL motifs that overlap with nuclear localization signals (NLS) in the non-catalytic N termini. This architecture is conserved in HHV6, HHV7 and rodent cytomegaloviruses. Cyclin A binding competes with NLS function, enabling dynamic changes in CHPK localization and substrate phosphorylation. The cytomegalovirus kinase M97 sequesters Cyclin A in the cytosol, which is essential for viral inhibition of cellular replication. Our data highlight a fine-tuned and physiologically important interplay between a cellular cyclin and viral kinases.


Assuntos
Replicação do DNA/fisiologia , Infecções por Herpesviridae/metabolismo , Herpesviridae/metabolismo , Proteínas Quinases/metabolismo , Animais , Ciclina A/genética , Ciclina A/metabolismo , Citomegalovirus/genética , DNA/metabolismo , Células HEK293 , Herpesviridae/enzimologia , Herpesviridae/genética , Infecções por Herpesviridae/virologia , Humanos , Camundongos , Células NIH 3T3 , Sinais de Localização Nuclear/metabolismo , Fosforilação , Mapas de Interação de Proteínas , Proteínas Virais/genética , Proteínas Virais/metabolismo
10.
J Am Coll Surg ; 231(1): 85-96, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32311464

RESUMO

BACKGROUND: Predicting outcomes and response to therapy through biomarkers is a major challenge in cancer research. In previous studies, we suggested that inappropriate "normal" tissue samples used for comparison with tumors, inter-individual heterogeneity in gene expression, and genetic ancestry all influence biomarker expression in tumors. The aim of this study was to investigate these factors in breast cancer using breast tissues from healthy women and normal tissue adjacent to tumor (NAT) with matrix metalloproteinase 7 (MMP7) as a candidate biomarker. STUDY DESIGN: RNA sequencing was performed on primary luminal progenitor cells from healthy breast, NATs, and tumors to identify transcriptomes enriched in NATs and breast cancer. Expression of select genes was validated via quantitative reverse transcription polymerase chain reaction of RNA and via immunohistochemistry of a tissue microarray of normal, NAT, and tumor samples of different genetic ancestry. RESULTS: Twenty-six genes were significantly overexpressed in NATs and tumors compared with healthy controls at messenger RNA level and formed a para-inflammatory network. MMP7 had the greatest expression in tumor cells, with upregulation confirmed by quantitative reverse transcription polymerase chain reaction. Tumor-enriched but not NAT-enriched expression of MMP7 compared with healthy controls was reproduced at protein levels. When stratified by genetic ancestry, tumor-specific increase of MMP7 reached statistical significance in women of European ancestry. CONCLUSIONS: Transcriptome differences across healthy, NAT, and tumor tissue in breast cancer demonstrate an active para-inflammatory network in NATs and indicate unsuitability of NATs as "normal controls" in biomarker discovery. The discordance between transcriptomic and proteomic MMP7 expression in NATs and the influence of genetic ancestry on its protein expression highlight the complexity in developing universally acceptable biomarkers of breast cancer and the importance of genetic ancestry in biomarker development.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Proteômica/métodos , RNA Neoplásico/genética , Transcriptoma/genética , Biomarcadores Tumorais/metabolismo , Mama/patologia , Neoplasias da Mama/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Prognóstico
11.
Forensic Sci Int Genet ; 44: 102191, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756628

RESUMO

Many challenges are encountered in the analysis of micro traces such as touch DNA or telogen hair samples. Although DNA typing methods have become immensely more sensitive over the last years, recovery of the minute amounts of biological material in micro traces requires further enhancement. For example felony cases, where an offender oftentimes only contributes minor amounts of touch DNA, separation of victim and offender DNA poses difficulties. Whereas complete sampling of evidence generates admixed profiles, single particle collection is labor- and time-intensive. Besides optimization of identification and collection of bio particles during this study, a novel sampling strategy for enhanced DNA yield as well as success rate but simultaneous avoidance of mixture creation is proposed for tapings in forensic casework. Improvement of another crucial step in micro trace analysis, DNA extraction, involved evaluation of efficiency and DNA recovery of different extraction methods, namely magnetic bead based Maxwell extraction, Chelex, Casework Direct Kit and Investigator Casework GO! kit. Direct lysis approaches seemed to be most suitable for low template traces. Recently developed commercial kits even allow the presence of inhibitors. Improvement of embraced aspects successfully facilitates processing of micro traces in terms of time and labor.


Assuntos
Impressões Digitais de DNA , DNA/isolamento & purificação , Genética Forense/métodos , Pele/química , Manejo de Espécimes/métodos , Alelos , Corantes , Feminino , Humanos , Masculino , Repetições de Microssatélites , Microscopia , Reação em Cadeia da Polimerase , Pele/citologia , Manejo de Espécimes/instrumentação , Coloração e Rotulagem , Tato , Azul Tripano
12.
Stud Health Technol Inform ; 216: 604-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26262122

RESUMO

In this study we have developed a rule-based natural language processing (NLP) system to identify patients with family history of pancreatic cancer. The algorithm was developed in a Unstructured Information Management Architecture (UIMA) framework and consisted of section segmentation, relation discovery, and negation detection. The system was evaluated on data from two institutions. The family history identification precision was consistent across the institutions shifting from 88.9% on Indiana University (IU) dataset to 87.8% on Mayo Clinic dataset. Customizing the algorithm on the the Mayo Clinic data, increased its precision to 88.1%. The family member relation discovery achieved precision, recall, and F-measure of 75.3%, 91.6% and 82.6% respectively. Negation detection resulted in precision of 99.1%. The results show that rule-based NLP approaches for specific information extraction tasks are portable across institutions; however customization of the algorithm on the new dataset improves its performance.


Assuntos
Registros Eletrônicos de Saúde/classificação , Armazenamento e Recuperação da Informação/métodos , Anamnese/métodos , Processamento de Linguagem Natural , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Algoritmos , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Anamnese/estatística & dados numéricos , Registro Médico Coordenado , Neoplasias Pancreáticas/epidemiologia
13.
J Am Coll Surg ; 213(5): 677-82, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21880513

RESUMO

BACKGROUND: A significant increase in industry support of professional medical associations coupled with data suggesting that gifts from industry have significant clinical influence have prompted calls from the Institute of Medicine and physician leaders to identify and manage conflicts of interest that stem from financial support of professional medical associations by industry. STUDY DESIGN: A joint task force of members appointed by the Association for Academic Surgery and the Society of University Surgeons was convened in July 2009. Recommendations were developed regarding management of all potential conflicts of interest that can arise within the context of an academic surgical society, with specific focus on relationships with industry. Task force members reached consensus around each recommendation and the guidelines were subsequently adopted by the Executive Councils of both societies. RESULTS: The committee identified 4 primary areas of need for transparent and definitive management of conflict of interest: 1) individual society activities, including general budget support, society endorsements, and journal affiliation; 2) individual personnel conflicts such as society leadership and standards for disclosure of conflict; 3) meeting activities including budgetary support, program committee associations, and abstract review process; and 4) foundation support and research and travel awards. The resulting guidelines aim to protect the societies and their membership from undue bias that may undermine the credibility and mission of these associations. CONCLUSIONS: Policy guidelines to mitigate conflict of interest are necessary to protect the integrity of the work of academic surgical societies and their fiduciary duty to members and patients. Guidelines created and adopted by the Association for Academic Surgery and Society of University Surgeons form an effective model for academic surgical societies and their members.


Assuntos
Conflito de Interesses , Sociedades Médicas/ética , Sociedades Médicas/normas , Especialidades Cirúrgicas , Comitês Consultivos , Conferências de Consenso como Assunto , Ética Médica , Apoio Financeiro , Humanos , Relações Interpessoais , Liderança , Política Organizacional , Sociedades Médicas/economia , Sociedades Médicas/tendências , Revelação da Verdade , Estados Unidos
14.
Clin Gastroenterol Hepatol ; 9(8): 635-48, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21397725

RESUMO

Cystic pancreatic tumors (CPTs) have more frequently been identified in the last decade because of increased use of cross-sectional abdominal imaging. Although serous CPTs follow an indolent course and do not necessarily require surgical resection or long-term follow-up, mucinous CPTs (mucinous cystic neoplasms and intraductal papillary mucinous neoplasms) have a greater risk for malignancy. Although most CPTs are initially detected with imaging modalities such as computed tomography or magnetic resonance imaging, these tests alone rarely permit an accurate clinical diagnosis. Endoscopic ultrasound and endoscopic ultrasound-guided, fine-needle aspiration allow real-time examination and biopsy analysis of CPTs, which increases diagnostic accuracy because cytopathology features and tumor markers in cyst fluid can be analyzed. Management of patients with mucinous CPTs by surgery or imaging surveillance is controversial, partially because of limited information about disease progression and the complexities of surgical resection. We review approaches to diagnosis and management of common CPTs.


Assuntos
Cistadenoma Mucinoso/diagnóstico , Cistadenoma Mucinoso/cirurgia , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Biópsia por Agulha Fina , Técnicas Citológicas , Endossonografia , Humanos , Imageamento por Ressonância Magnética , Radiografia Abdominal , Tomografia Computadorizada por Raios X
15.
Nature ; 472(7342): 209-12, 2011 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-21441908

RESUMO

Very low seismic velocity anomalies in the Earth's mantle may reflect small amounts of melt present in the peridotite matrix, and the onset of melting in the Earth's upper mantle is likely to be triggered by the presence of small amounts of carbonate. Such carbonates stem from subducted oceanic lithosphere in part buried to depths below the 660-kilometre discontinuity and remixed into the mantle. Here we demonstrate that carbonate-induced melting may occur in deeply subducted lithosphere at near-adiabatic temperatures in the Earth's transition zone and lower mantle. We show experimentally that these carbonatite melts are unstable when infiltrating ambient mantle and are reduced to immobile diamond when recycled at depths greater than ∼250 kilometres, where mantle redox conditions are determined by the presence of an (Fe,Ni) metal phase. This 'redox freezing' process leads to diamond-enriched mantle domains in which the Fe(0), resulting from Fe(2+) disproportionation in perovskites and garnet, is consumed but the Fe(3+) preserved. When such carbon-enriched mantle heterogeneities become part of the upwelling mantle, diamond will inevitably react with the Fe(3+) leading to true carbonatite redox melting at ∼660 and ∼250 kilometres depth to form deep-seated melts in the Earth's mantle.

16.
AMIA Annu Symp Proc ; 2010: 237-41, 2010 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-21346976

RESUMO

We sought to determine the accuracy of two electronic methods of identifying pancreatic cancer in a cohort of pancreatic cyst patients, and to examine the reasons for identification failure. We used the International Classification of Diseases, 9(th) Edition (ICD-9) codes and natural language processing (NLP) technology to identify pancreatic cancer in these patients. We compared both methods to a human-validated gold-standard surgical database. Both ICD-9 codes and NLP technology achieved high sensitivity for identifying pancreatic cancer, but the ICD-9 code method achieved markedly lower specificity and PPV compared to the NLP method. The NLP method required only slightly greater expenditures of time and effort compared to the ICD-9 code method. We identified several variables influencing the accuracy of ICD-9 codes to identify cancer patients including: the identification algorithm, kind of cancer to be identified, presence of other conditions similar to cancer, and presence of conditions that are precancerous.


Assuntos
Classificação Internacional de Doenças , Processamento de Linguagem Natural , Algoritmos , Codificação Clínica , Humanos , Neoplasias Pancreáticas , Sensibilidade e Especificidade
17.
Nature ; 462(7270): 209-12, 2009 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-19907492

RESUMO

Magmatic production on Earth is dominated by asthenospheric melts of basaltic composition that have mostly erupted at mid-ocean ridges. The timescale for segregation and transport of these melts, which are ultimately responsible for formation of the Earth's crust, is critically dependent on the permeability of the partly molten asthenospheric mantle, yet this permeability is known mainly from semi-empirical and analogue models. Here we use a high-pressure, high-temperature centrifuge, at accelerations of 400g-700g, to measure the rate of basalt melt flow in olivine aggregates with porosities of 5-12 per cent. The resulting permeabilities are consistent with a microscopic model in which melt is completely connected, and are one to two orders of magnitude larger than predicted by current parameterizations. Extrapolation of the measurements to conditions characteristic of asthenosphere below mid-ocean ridges yields proportionally higher transport speeds. Application of these results in a model of porous-media channelling instabilities yields melt transport times of approximately 1-2.5 kyr across the entire asthenosphere, which is sufficient to preserve the observed (230)Th excess of mid-ocean-ridge basalts and the mantle signatures of even shorter-lived isotopes such as (226)Ra (refs 5,11-14).

18.
HPB (Oxford) ; 10(6): 491-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19088938

RESUMO

Middle segment pancreatectomy (MSP) is a new operation where the advantages of parenchymal preservation are counterbalanced by a high postoperative complication rate and unease among surgeons with adopting a new technique. This study reviews our experience incorporating MSP into our clinical practice focusing on the initial 34 consecutive patients operated on by one surgeon at a single institution between 1998 and 2007. Patients were divided into early (initial 17 operations) and late (subsequent 17 operations) groups for analysis. Thirty-one reconstructions were by Roux-en-y pancreaticojejunostomy and three were by pancreaticogastrostomy. Using multiple linear regression and logistic regression, we found no significant differences in performance outcomes (operative time, blood loss, tumor size, margin negative resection rate, pancreatic fistula rate, hospital length of stay, postoperative complications, and hospital readmission rate) between our early and late experience even after adjusting for potential confounding variables (patient demographics, co-morbidities, neoplasm, pancreatitis). The pancreatic fistula rate in this series was 29.4% (10/34) and they were all International Study Group on Pancreatic Fistula (ISGPF) Grade A (60%) or B (40%). In summary, MSP is an operation with a flat learning curve and acceptable morbidity rate that can be safely incorporated as a parenchymal preserving option by pancreatic surgeons in their clinical practice.

19.
Ann Surg ; 248(3): 438-46, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18791364

RESUMO

OBJECTIVES: To compare perioperative outcomes of laparoscopic left-sided pancreatectomy (LLP) with traditional open left-sided pancreatectomy (OLP) in a multicenter experience. SUMMARY AND BACKGROUND DATA: LLP is being performed more commonly with limited data comparing results with outcomes from OLP. METHODS: Data from 8 centers were combined for all cases performed between 2002-2006. OLP and LLP cohorts were matched by age, American Society of Anesthesiologists, resected pancreas length, tumor size, and diagnosis. Multivariate analysis was performed using binary logistic regression. RESULTS: Six hundred sixty-seven LPs were performed, with 159 (24%) attempted laparoscopically. Indications were solid lesion in 307 (46%), cystic in 295 (44%), and pancreatitis in 65 (10%) cases. Positive margins occurred in 51 (8%) cases, 335 (50%) had complications, and significant leaks occurred in 108 (16%). Conversion to OLP occurred in 20 (13%) of the LLPs. In the matched comparison, 200 OLPs were compared with 142 LLPs. There were no differences in positive margin rates (8% vs. 7%, P = 0.8), operative times (216 vs. 230 minutes, P = 0.3), or leak rates (18% vs. 11%, P = 0.1). LLP patients had lower average blood loss (357 vs. 588 mL, P < 0.01), fewer complications (40% vs. 57%, P < 0.01), and shorter hospital stays (5.9 vs. 9.0 days, P < 0.01). By MVA, LLP was an independent factor for shorter hospital stay (P < 0.01, odds ratio 0.33, 95% confidence interval 0.19-0.56). CONCLUSIONS: In selected patients, LLP is associated with less morbidity and shorter LOS than OLP. Pancreatic fistula rates are similar for OLP and LLP. LLP is appropriate for selected patients with left-sided pancreatic pathology.


Assuntos
Pancreatectomia/métodos , Pancreatopatias/cirurgia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Fístula Pancreática/etiologia , Estudos Retrospectivos
20.
Science ; 316(5829): 1323-5, 2007 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-17540900

RESUMO

The evolution of the martian core is widely assumed to mirror the characteristics observed for Earth's core. Data from experiments performed on iron-sulfur and iron-nickel-sulfur systems at pressures corresponding to the center of Mars indicate that its core is presently completely liquid and that it will not form an outwardly crystallizing iron-rich inner core, as does Earth. Instead, planetary cooling will lead to core crystallization following either a "snowing-core" model, whereby iron-rich solids nucleate in the outer portions of the core and sink toward the center, or a "sulfide inner-core" model, where an iron-sulfide phase crystallizes to form a solid inner core.


Assuntos
Evolução Planetária , Marte , Cristalização , Ferro , Pressão , Sulfetos , Enxofre , Temperatura
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