42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

42 CFR 455.101 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., independent clinical laboratory, renal disease facility, rural health clinic, or health maintenance... specified in § 438.2. Indirect ownership interest means an ownership interest in an entity that has an ownership interest in the disclosing entity. This term includes an ownership interest in any entity that has...

The SAPHO syndrome: a clinical and imaging study.

PubMed

Sallés, Meritxell; Olivé, Alejandro; Perez-Andres, Ricard; Holgado, Susana; Mateo, Lourdes; Riera, Elena; Tena, Xavier

2011-02-01

The purpose of this study is to describe the clinical and radiological manifestations of patients with the synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. Retrospective study (1984-2007) was performed in a single center. All patients with the SAPHO syndrome were included. Fifty-two patients were included: 26 male, mean age at diagnosis is 42±12 years. Ostearticular involvement was present before cutaneous involvement in 59.6% of patients and concomitantly in 23.5%. Anterior chest pain was the commonest clinical manifestation, it was present in 38 patients (73%), followed by peripheral arthritis in 17 patients (32%), and sacroliliac pain in 14 patients (26.9%). Cutaneous involvement was present in 33 patients (63.5%). HLA B27 antigen was present in eight patients (17.7%). Bone scintigraphy showed an increased uptake in 42 patients (93.3%). The location of the uptake was mainly in sternoclavicular and manubriosternal joints. CT scan was performed in all "hot joints" showing sclerosis, erosions, hyperostosis, and soft tissue involvement. Refractory patients were treated mainly with pamidronate. Although SAPHO syndrome is an entity that share features that fit into a variety of established disease categories, the present study has a homogenous clinical and radiological pattern that gives support to believe that the SAPHO syndrome is an isolated clinical entity.

Massive ovarian oedema: a misleading clinical entity.

PubMed

Machairiotis, Nikolaos; Stylianaki, Aikaterini; Kouroutou, Paraskevi; Sarli, Polixeni; Alexiou, Nikolaos Konstantinos; Efthymiou, Elias; Maras, Athanasios; Alexiou, Nikolaos Georgios; Nikolaou, Spyridon Evaggelos; Courcoutsakis, Nikolaos; Papakonstantinou, Eleni; Zarogoulidis, Paul; Barbetakis, Nikolaos; Paliouras, Dimitrios; Gogakos, Apostolos; Machairiotis, Christodoulos

2016-02-03

Massive ovarian oedema is a rare non-neoplastic clinicopathologic entity has a higher incidence in women during their second and third life decade. The oedema can be presented in one or both ovaries as a result of partial intermittent torsion of the ovarian pedicle that interferes to the venal and lymphatic drainage of the ovary. We present a clinical case of a 16 year old with massive ovarian oedema and we performed a review of the literature. The pathophysiology of this entity is very complex. We tried to perform a complete review of the literature and focus on the complexity of this entity as far as its pathophysiological backround is concerned and as far as its clinical presentation is concerned. In conclusion, massive ovarian oedema is a rare, multi disease mimicking clinical entity, with an acute or progressive clinical presentation. It has also to be a part of our differential diagnosis in cases of acute abdominal pain and we have to try to treat her conservatively, in order to preserve fertility.

Anatomical Entity Recognition with a Hierarchical Framework Augmented by External Resources

PubMed Central

Xu, Yan; Hua, Ji; Ni, Zhaoheng; Chen, Qinlang; Fan, Yubo; Ananiadou, Sophia; Chang, Eric I-Chao; Tsujii, Junichi

2014-01-01

References to anatomical entities in medical records consist not only of explicit references to anatomical locations, but also other diverse types of expressions, such as specific diseases, clinical tests, clinical treatments, which constitute implicit references to anatomical entities. In order to identify these implicit anatomical entities, we propose a hierarchical framework, in which two layers of named entity recognizers (NERs) work in a cooperative manner. Each of the NERs is implemented using the Conditional Random Fields (CRF) model, which use a range of external resources to generate features. We constructed a dictionary of anatomical entity expressions by exploiting four existing resources, i.e., UMLS, MeSH, RadLex and BodyPart3D, and supplemented information from two external knowledge bases, i.e., Wikipedia and WordNet, to improve inference of anatomical entities from implicit expressions. Experiments conducted on 300 discharge summaries showed a micro-averaged performance of 0.8509 Precision, 0.7796 Recall and 0.8137 F1 for explicit anatomical entity recognition, and 0.8695 Precision, 0.6893 Recall and 0.7690 F1 for implicit anatomical entity recognition. The use of the hierarchical framework, which combines the recognition of named entities of various types (diseases, clinical tests, treatments) with information embedded in external knowledge bases, resulted in a 5.08% increment in F1. The resources constructed for this research will be made publicly available. PMID:25343498

Accommodating Ontologies to Biological Reality—Top-Level Categories of Cumulative-Constitutively Organized Material Entities

PubMed Central

Vogt, Lars; Grobe, Peter; Quast, Björn; Bartolomaeus, Thomas

2012-01-01

Background The Basic Formal Ontology (BFO) is a top-level formal foundational ontology for the biomedical domain. It has been developed with the purpose to serve as an ontologically consistent template for top-level categories of application oriented and domain reference ontologies within the Open Biological and Biomedical Ontologies Foundry (OBO). BFO is important for enabling OBO ontologies to facilitate in reliably communicating and managing data and metadata within and across biomedical databases. Following its intended single inheritance policy, BFO's three top-level categories of material entity (i.e. ‘object’, ‘fiat object part’, ‘object aggregate’) must be exhaustive and mutually disjoint. We have shown elsewhere that for accommodating all types of constitutively organized material entities, BFO must be extended by additional categories of material entity. Methodology/Principal Findings Unfortunately, most biomedical material entities are cumulative-constitutively organized. We show that even the extended BFO does not exhaustively cover cumulative-constitutively organized material entities. We provide examples from biology and everyday life that demonstrate the necessity for ‘portion of matter’ as another material building block. This implies the necessity for further extending BFO by ‘portion of matter’ as well as three additional categories that possess portions of matter as aggregate components. These extensions are necessary if the basic assumption that all parts that share the same granularity level exhaustively sum to the whole should also apply to cumulative-constitutively organized material entities. By suggesting a notion of granular representation we provide a way to maintain the single inheritance principle when dealing with cumulative-constitutively organized material entities. Conclusions/Significance We suggest to extend BFO to incorporate additional categories of material entity and to rearrange its top-level material entity taxonomy. With these additions and the notion of granular representation, BFO would exhaustively cover all top-level types of material entities that application oriented ontologies may use as templates, while still maintaining the single inheritance principle. PMID:22253856

[Rotator cuff repair: single- vs double-row. Clinical and biomechanical results].

PubMed

Baums, M H; Kostuj, T; Klinger, H-M; Papalia, R

2016-02-01

The goal of rotator cuff repair is a high initial mechanical stability as a requirement for adequate biological recovery of the tendon-to-bone complex. Notwithstanding the significant increase in publications concerning the topic of rotator cuff repair, there are still controversies regarding surgical technique. The aim of this work is to present an overview of the recently published results of biomechanical and clinical studies on rotator cuff repair using single- and double-row techniques. The review is based on a selective literature research of PubMed, Embase, and the Cochrane Database on the subject of the clinical and biomechanical results of single- and double-row repair. In general, neither the biomechanical nor the clinical evidence can recommend the use of a double-row concept for the treatment for every rotator cuff tear. Only tears of more than 3 cm seem to benefit from better results on both imaging and in clinical outcome studies compared with the use of single-row techniques. Despite a significant increase in publications on the surgical treatment of rotator cuff tears in recent years, the clinical results were not significantly improved in the literature so far. Unique information and algorithms, from which the optimal treatment of this entity can be derived, are still inadequate. Because of the cost-effectiveness and the currently vague evidence, the double-row techniques cannot be generally recommended for the repair of all rotator cuff tears.

Highly stable families of soliton molecules in fiber-optic systems

NASA Astrophysics Data System (ADS)

Moubissi, A.-B.; Tchofo Dinda, P.; Nse Biyoghe, S.

2018-04-01

We develop an efficient approach to the design of families of single solitons and soliton molecules most suited to a given fiber system. The obtained solitonic entities exhibit very high stability, with a robustness which allows them to propagate over thousands of kilometers and to survive collisions with other solitonic entities. Our approach enables the generation of a large number of solitonic entities, including families of single solitons and two-soliton molecules, which can be distinguished sufficiently by their respective profiles or energy levels, and so can be easily identifiable and detectable without ambiguity. We discuss the possible use of such solitonic entities as symbols of a multi-level modulation format in fiber-optic communication systems.

Follicular vitiligo: A report of 8 cases.

PubMed

Gan, Emily Yiping; Cario-André, Muriel; Pain, Catherine; Goussot, Jean-Francois; Taïeb, Alain; Seneschal, Julien; Ezzedine, Khaled

2016-06-01

Follicular vitiligo, a recently proposed new subtype of vitiligo, has primary involvement of the hair follicle melanocytic reservoir. We sought to characterize follicular vitiligo through a case series of 8 patients. Patients with features of follicular vitiligo who were seen at the vitiligo clinic in the National Center for Rare Skin Disorders in Bordeaux, France, were recruited. A retrospective review of case records and clinical photographs was carried out. There were 8 male patients with a mean age of 48 years. All patients reported significant whitening of their body and, in some, scalp hairs before cutaneous depigmentation. Examination revealed classic generalized depigmented lesions of vitiligo and an impressive presence of leukotrichia, not only in the vitiliginous areas, but also in areas with clinically normal-appearing skin. Punch biopsy specimen of the leukotrichia and vitiligo lesions demonstrated loss of melanocytes and precursors in the basal epidermis and hair follicle. This was a cross-sectional study based on a single-center experience. Follicular vitiligo is a distinct entity within the spectrum of vitiligo. This entity may serve as the missing link between alopecia areata and vitiligo, with probable physiopathological similarities between these conditions. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

26 CFR 1.1502-13 - Intercompany transactions.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., gain, deduction, and loss of members from intercompany transactions. The purpose of this section is to... treatment). For example, S determines its gain or loss from a sale of property to B on a separate entity... of a single corporation (single entity treatment). For example, if S sells land to B at a gain and B...

75 FR 54193 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-03

... other entities. Commission staff estimates that it receives approximately 125 applications per year under the Act. Although each application typically is submitted on behalf of multiple entities, the entities in the vast majority of cases are related companies and are treated as a single respondent for...

78 FR 25324 - Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

... company status, among other entities. Commission staff estimates that it receives approximately 110... entities, the entities in the vast majority of cases are related companies and are treated as a single...-precedented, routine application to approximately $150,000 to prepare a complex and/or novel application. This...

78 FR 41131 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-09

... other entities. Commission staff estimates that it receives approximately 110 applications per year under the Act. Although each application typically is submitted on behalf of multiple entities, the entities in the vast majority of cases are related companies and are treated as a single respondent for...

42 CFR 411.352 - Group practice.

Code of Federal Regulations, 2010 CFR

2010-10-01

... considered to be a single legal entity notwithstanding that it is composed of multiple legal entities... ownership, governance, and operation; and (3) Organization of the group practice into multiple entities is...). (f) Unified business. (1) The group practice must be a unified business having at least the following...

Automatic recognition of disorders, findings, pharmaceuticals and body structures from clinical text: an annotation and machine learning study.

PubMed

Skeppstedt, Maria; Kvist, Maria; Nilsson, Gunnar H; Dalianis, Hercules

2014-06-01

Automatic recognition of clinical entities in the narrative text of health records is useful for constructing applications for documentation of patient care, as well as for secondary usage in the form of medical knowledge extraction. There are a number of named entity recognition studies on English clinical text, but less work has been carried out on clinical text in other languages. This study was performed on Swedish health records, and focused on four entities that are highly relevant for constructing a patient overview and for medical hypothesis generation, namely the entities: Disorder, Finding, Pharmaceutical Drug and Body Structure. The study had two aims: to explore how well named entity recognition methods previously applied to English clinical text perform on similar texts written in Swedish; and to evaluate whether it is meaningful to divide the more general category Medical Problem, which has been used in a number of previous studies, into the two more granular entities, Disorder and Finding. Clinical notes from a Swedish internal medicine emergency unit were annotated for the four selected entity categories, and the inter-annotator agreement between two pairs of annotators was measured, resulting in an average F-score of 0.79 for Disorder, 0.66 for Finding, 0.90 for Pharmaceutical Drug and 0.80 for Body Structure. A subset of the developed corpus was thereafter used for finding suitable features for training a conditional random fields model. Finally, a new model was trained on this subset, using the best features and settings, and its ability to generalise to held-out data was evaluated. This final model obtained an F-score of 0.81 for Disorder, 0.69 for Finding, 0.88 for Pharmaceutical Drug, 0.85 for Body Structure and 0.78 for the combined category Disorder+Finding. The obtained results, which are in line with or slightly lower than those for similar studies on English clinical text, many of them conducted using a larger training data set, show that the approaches used for English are also suitable for Swedish clinical text. However, a small proportion of the errors made by the model are less likely to occur in English text, showing that results might be improved by further tailoring the system to clinical Swedish. The entity recognition results for the individual entities Disorder and Finding show that it is meaningful to separate the general category Medical Problem into these two more granular entity types, e.g. for knowledge mining of co-morbidity relations and disorder-finding relations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

76 FR 20593 - Guidance Under Section 108(a) Concerning the Exclusion of Section 61(a)(12) Discharge of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

... a disregarded entity under this provision is a domestic single member limited liability company that.... Examples of disregarded entities include a domestic single member limited liability company that does not... Federal income tax purposes, all assets, liabilities, and items of income, deduction, and credit of a...

A Complex Multiherbal Regimen Based on Ayurveda Medicine for the Management of Hepatic Cirrhosis Complicated by Ascites: Nonrandomized, Uncontrolled, Single Group, Open-Label Observational Clinical Study.

PubMed

Patel, Manish V; Patel, Kalapi B; Gupta, Shivenarain; Michalsen, Andreas; Stapelfeldt, Elmar; Kessler, Christian S

2015-01-01

Hepatic cirrhosis is one of the leading causes of death worldwide, especially if complicated by ascites. This chronic condition can be related to the classical disease entity jalodara in Traditional Indian Medicine (Ayurveda). The present paper aims to evaluate the general potential of Ayurvedic therapy for overall clinical outcomes in hepatic cirrhosis complicated by ascites (HCcA). In form of a nonrandomized, uncontrolled, single group, open-label observational clinical study, 56 patients fulfilling standardized diagnostic criteria for HCcA were observed during their treatment at the P. D. Patel Ayurveda Hospital, Nadiad, India. Based on Ayurvedic tradition, a standardized treatment protocol was developed and implemented, consisting of oral administration of single and compound herbal preparations combined with purificatory measures as well as dietary and lifestyle regimens. The outcomes were assessed by measuring liver functions through specific clinical features and laboratory parameters and by evaluating the Child-Pugh prognostic grade score. After 6 weeks of treatment and a follow-up period of 18 weeks, the outcomes showed statistically significant and clinically relevant improvements. Further larger and randomized trials on effectiveness, safety, and quality of the Ayurvedic approach in the treatment of HCcA are warranted to support these preliminary findings.

Scientific and industrial challenges of developing nanoparticle-based theranostics and multiple-modality contrast agents for clinical application

NASA Astrophysics Data System (ADS)

Wáng, Yì Xiáng J.; Idée, Jean-Marc; Corot, Claire

2015-10-01

Designing of theranostics and dual or multi-modality contrast agents are currently two of the hottest topics in biotechnology and biomaterials science. However, for single entity theranostics, a right ratio of their diagnostic component and their therapeutic component may not always be realized in a composite suitable for clinical application. For dual/multiple modality molecular imaging agents, after in vivo administration, there is an optimal time window for imaging, when an agent is imaged by one modality, the pharmacokinetics of this agent may not allow imaging by another modality. Due to reticuloendothelial system clearance, efficient in vivo delivery of nanoparticles to the lesion site is sometimes difficult. The toxicity of these entities also remains poorly understood. While the medical need of theranostics is admitted, the business model remains to be established. There is an urgent need for a global and internationally harmonized re-evaluation of the approval and marketing processes of theranostics. However, a reasonable expectation exists that, in the near future, the current obstacles will be removed, thus allowing the wide use of these very promising agents.

78 FR 14914 - Addition of Certain Persons to the Entity List

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

.... This person will be listed on the Entity List under Germany, Russia, and Taiwan. DATES: Effective date... different countries for the person being added to the Entity List, consist of single entries in Russia... one person being listed under three separate entries, T -Platforms, a company headquartered in Russia...

Definition of ALI/ARDS.

PubMed

Raghavendran, Krishnan; Napolitano, Lena M

2011-07-01

Although acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are caused by different injuries and conditions, their similar clinical picture makes a compelling case for them to be studied as a single entity. An array of potential specific targets for pharmacologic intervention can be applied to ALI/ARDS as one disease. Although a working definition of ALI/ARDS that includes pulmonary and extrapulmonary causes can have benefit in standardizing supportive care, it can also complicate assessments of the efficacy of therapeutic interventions. In this article, definitions that have been recently used for ALI/ARDS in various clinical studies are discussed individually. Copyright © 2011 Elsevier Inc. All rights reserved.

5 CFR 890.1003 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... a physician, hospital, clinic, or other individual or entity that, directly or indirectly, furnishes... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL... and equipment; and hospitals, clinics, or other institutional entities that furnish supplies and...

5 CFR 890.1003 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... a physician, hospital, clinic, or other individual or entity that, directly or indirectly, furnishes... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL... and equipment; and hospitals, clinics, or other institutional entities that furnish supplies and...

5 CFR 890.1003 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... a physician, hospital, clinic, or other individual or entity that, directly or indirectly, furnishes... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL... and equipment; and hospitals, clinics, or other institutional entities that furnish supplies and...

5 CFR 890.1003 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... a physician, hospital, clinic, or other individual or entity that, directly or indirectly, furnishes... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL... and equipment; and hospitals, clinics, or other institutional entities that furnish supplies and...

Clinical features and course of refractory anemia with ring sideroblasts associated with marked thrombocytosis

PubMed Central

Broseus, Julien; Florensa, Lourdes; Zipperer, Esther; Schnittger, Susanne; Malcovati, Luca; Richebourg, Steven; Lippert, Eric; Cermak, Jaroslav; Evans, Jyoti; Mounier, Morgane; Raya, José Maria; Bailly, François; Gattermann, Norbert; Haferlach, Torsten; Garand, Richard; Allou, Kaoutar; Besses, Carlos; Germing, Ulrich; Haferlach, Claudia; Travaglino, Erica; Luno, Elisa; Pinan, Maria Angeles; Arenillas, Leonor; Rozman, Maria; Perez Sirvent, Maria Luz; Favre, Bernardine; Guy, Julien; Alonso, Esther; Ahwij, Nuhri; Jerez, Andrés; Hermouet, Sylvie; Maynadié, Marc; Cazzola, Mario; Girodon, François

2012-01-01

Background Refractory anemia with ring sideroblasts associated with marked thrombocytosis was proposed as a provisional entity in the 2001 World Health Organization classification of myeloid neoplasms and also in the 2008 version, but its existence as a single entity is contested. We wish to define the clinical features of this rare myelodysplastic/myeloproliferative neoplasm and to compare its clinical outcome with that of refractory anemia with ring sideroblasts and essential thrombocythemia. Design and Methods We conducted a collaborative retrospective study across Europe. Our database included 200 patients diagnosed with refractory anemia with ring sideroblasts and marked thrombocytosis. For each of these patients, each patient diagnosed with refractory anemia with ring sideroblasts was matched for age and sex. At the same time, a cohort of 454 patients with essential thrombocythemia was used to compare outcomes of the two diseases. Results In patients with refractory anemia with ring sideroblasts and marked thrombocytosis, depending on the Janus Kinase 2 V617F mutational status (positive or negative) or platelet threshold (over or below 600×109/L), no difference in survival was noted. However, these patients had shorter overall survival and leukemia-free survival with a lower risk of thrombotic complications than did patients with essential thrombocythemia (P<0.001) but better survival (P<0.001) and a higher risk of thrombosis (P=0.039) than patients with refractory anemia with ring sideroblasts. Conclusions The clinical course of refractory anemia with ring sideroblasts and marked thrombocytosis is better than that of refractory anemia with ring sideroblasts and worse than that of essential thrombocythemia. The higher risk of thrombotic events in this disorder suggests that anti-platelet therapy might be considered in this subset of patients. From a clinical point of view, it appears to be important to consider refractory anemia with ring sideroblasts and marked thrombocytosis as a distinct entity. PMID:22532522

Peritoneal Lipomatosis: A Case Report of a 12-Year-Old Boy

PubMed Central

Fotis, L.; Koglmeier, J.; Shah, N.

2013-01-01

Peritoneal lipomatosis is a rare disease in childhood with only two cases previously described in children. We report a further case of a 12-year-old boy diagnosed with peritoneal lipomatosis. His main symptoms were abdominal pain, alternating bowel habit, abdominal distension, and melaena. His diagnostic work up included an abdominal MRI, wireless capsule endoscopy and single-balloon enteroscopy. Peritoneal lipomatosis although rare can be diagnosed in childhood. It is a benign clinical entity with variable manifestations. PMID:23762668

The Hæmorrhagic Diathesis

PubMed Central

Tidy, H. Letheby

1928-01-01

The primary purpuras form a single clinical entity. Variations in the number of platelets can occur without the production of hæmorrhages. These variations are the result of the condition of the capillaries and are not the cause of hæmorrhages. The platelets may vary in any form of purpura, primary or secondary. The essential cause of the hæmorrhagic state is a defect or increased permeability of the capillary endothelium. Purpura is allied to urticaria, the Henoch-Schönlein type being an intermediate state. PMID:19986460

Unsupervised Biomedical Named Entity Recognition: Experiments with Clinical and Biological Texts

PubMed Central

Zhang, Shaodian; Elhadad, Nóemie

2013-01-01

Named entity recognition is a crucial component of biomedical natural language processing, enabling information extraction and ultimately reasoning over and knowledge discovery from text. Much progress has been made in the design of rule-based and supervised tools, but they are often genre and task dependent. As such, adapting them to different genres of text or identifying new types of entities requires major effort in re-annotation or rule development. In this paper, we propose an unsupervised approach to extracting named entities from biomedical text. We describe a stepwise solution to tackle the challenges of entity boundary detection and entity type classification without relying on any handcrafted rules, heuristics, or annotated data. A noun phrase chunker followed by a filter based on inverse document frequency extracts candidate entities from free text. Classification of candidate entities into categories of interest is carried out by leveraging principles from distributional semantics. Experiments show that our system, especially the entity classification step, yields competitive results on two popular biomedical datasets of clinical notes and biological literature, and outperforms a baseline dictionary match approach. Detailed error analysis provides a road map for future work. PMID:23954592

A study of machine-learning-based approaches to extract clinical entities and their assertions from discharge summaries.

PubMed

Jiang, Min; Chen, Yukun; Liu, Mei; Rosenbloom, S Trent; Mani, Subramani; Denny, Joshua C; Xu, Hua

2011-01-01

The authors' goal was to develop and evaluate machine-learning-based approaches to extracting clinical entities-including medical problems, tests, and treatments, as well as their asserted status-from hospital discharge summaries written using natural language. This project was part of the 2010 Center of Informatics for Integrating Biology and the Bedside/Veterans Affairs (VA) natural-language-processing challenge. The authors implemented a machine-learning-based named entity recognition system for clinical text and systematically evaluated the contributions of different types of features and ML algorithms, using a training corpus of 349 annotated notes. Based on the results from training data, the authors developed a novel hybrid clinical entity extraction system, which integrated heuristic rule-based modules with the ML-base named entity recognition module. The authors applied the hybrid system to the concept extraction and assertion classification tasks in the challenge and evaluated its performance using a test data set with 477 annotated notes. Standard measures including precision, recall, and F-measure were calculated using the evaluation script provided by the Center of Informatics for Integrating Biology and the Bedside/VA challenge organizers. The overall performance for all three types of clinical entities and all six types of assertions across 477 annotated notes were considered as the primary metric in the challenge. Systematic evaluation on the training set showed that Conditional Random Fields outperformed Support Vector Machines, and semantic information from existing natural-language-processing systems largely improved performance, although contributions from different types of features varied. The authors' hybrid entity extraction system achieved a maximum overall F-score of 0.8391 for concept extraction (ranked second) and 0.9313 for assertion classification (ranked fourth, but not statistically different than the first three systems) on the test data set in the challenge.

Discovery of antitubulin agents with antiangiogenic activity as single entities with multitarget chemotherapy potential.

PubMed

Gangjee, Aleem; Pavana, Roheeth Kumar; Ihnat, Michael A; Thorpe, Jessica E; Disch, Bryan C; Bastian, Anja; Bailey-Downs, Lora C; Hamel, Ernest; Bai, Rouli

2014-05-08

Antiangiogenic agents (AA) are cytostatic, and their utility in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors with antitubulin agents have been particularly successful. We have discovered a novel, potentially important analogue, that combines potent VEGFR2 inhibitory activity (comparable to that of sunitinib) with potent antitubulin activity (comparable to that of combretastatin A-4 (CA)) in a single molecule, with GI50 values of 10(-7) M across the entire NCI 60 tumor cell panel. It potently inhibited tubulin assembly and circumvented the most clinically relevant tumor resistance mechanisms (P-glycoprotein and β-III tubulin expression) to antimicrotubule agents. The compound is freely water-soluble as its HCl salt and afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib, or Temozolomide, without any toxicity.

Clinical manifestations of trisomy 4p syndrome.

PubMed

Patel, S V; Dagnew, H; Parekh, A J; Koenig, E; Conte, R A; Macera, M J; Verma, R S

1995-06-01

Trisomy 4p syndrome is a distinct clinical entity which was noted almost a quarter century ago by Wilson et al. [71] and later was delineated by Gonzalez and colleagues [29]. The variation in the length of duplicated segment usually associated with monosomy of other genetic material which has resulted in confusion and as a result a so-called 4p syndrome could not be recognized without cytogenetic analysis. We wish to draw the attention of clinicians to this subject by presenting the description of over 75 cases including one from our clinic and stress the point that molecular approaches are imperative to characterize this anomaly. After extensive review, it appears that patients retaining at least the distal two-thirds to the entire short arm share an overlapping phenotypic expression that constitutes pure trisomy 4p syndrome which includes prominent glabella, bulbous nose with flat or depressed nasal bridge, retrognathia, pointed chin, short neck with low hairline, enlarged ears with abnormal helix and antihelix, rocker-bottom feet with prominent heel. Arachnodactyly and camptodactyly. Molecular characterization of 4p is imperative. We have also included an extensive bibliography for clinicians who may find it useful as a single reference source for evaluating their future cases. The 4p-syndrome is a distinct entity but without cytogenetic evaluation, the syndrome can not be recognized.

Pellagra-like condition is xeroderma pigmentosum/Cockayne syndrome complex and niacin confers clinical benefit.

PubMed

Hijazi, H; Salih, M A; Hamad, M H A; Hassan, H H; Salih, S B M; Mohamed, K A; Mukhtar, M M; Karrar, Z A; Ansari, S; Ibrahim, N; Alkuraya, F S

2015-01-01

An extremely rare pellagra-like condition has been described, which was partially responsive to niacin and associated with a multisystem involvement. The condition was proposed to represent a novel autosomal recessive entity but the underlying mutation remained unknown for almost three decades. The objective of this study was to identify the causal mutation in the pellagra-like condition and investigate the mechanism by which niacin confers clinical benefit. Autozygosity mapping and exome sequencing were used to identify the causal mutation, and comet assay on patient fibroblasts before and after niacin treatment to assess its effect on DNA damage. We identified a single disease locus that harbors a novel mutation in ERCC5, thus confirming that the condition is in fact xeroderma pigmentosum/Cockayne syndrome (XP/CS) complex. Importantly, we also show that the previously described dermatological response to niacin is consistent with a dramatic protective effect against ultraviolet-induced DNA damage in patient fibroblasts conferred by niacin treatment. Our findings show the power of exome sequencing in reassigning previously described novel clinical entities, and suggest a mechanism for the dermatological response to niacin in patients with XP/CS complex. This raises interesting possibilities about the potential therapeutic use of niacin in XP. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

42 CFR 420.201 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... provider of services, an independent clinical laboratory, a renal disease facility, a rural health clinic..., common supporting staff, or common equipment). Indirect ownership interest means any ownership interest in an entity that has an ownership interest in the disclosing entity. The term includes an ownership...

42 CFR 420.201 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... provider of services, an independent clinical laboratory, a renal disease facility, a rural health clinic..., common supporting staff, or common equipment). Indirect ownership interest means any ownership interest in an entity that has an ownership interest in the disclosing entity. The term includes an ownership...

42 CFR 420.201 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... provider of services, an independent clinical laboratory, a renal disease facility, a rural health clinic..., common supporting staff, or common equipment). Indirect ownership interest means any ownership interest in an entity that has an ownership interest in the disclosing entity. The term includes an ownership...

Named Entity Recognition in Chinese Clinical Text Using Deep Neural Network.

PubMed

Wu, Yonghui; Jiang, Min; Lei, Jianbo; Xu, Hua

2015-01-01

Rapid growth in electronic health records (EHRs) use has led to an unprecedented expansion of available clinical data in electronic formats. However, much of the important healthcare information is locked in the narrative documents. Therefore Natural Language Processing (NLP) technologies, e.g., Named Entity Recognition that identifies boundaries and types of entities, has been extensively studied to unlock important clinical information in free text. In this study, we investigated a novel deep learning method to recognize clinical entities in Chinese clinical documents using the minimal feature engineering approach. We developed a deep neural network (DNN) to generate word embeddings from a large unlabeled corpus through unsupervised learning and another DNN for the NER task. The experiment results showed that the DNN with word embeddings trained from the large unlabeled corpus outperformed the state-of-the-art CRF's model in the minimal feature engineering setting, achieving the highest F1-score of 0.9280. Further analysis showed that word embeddings derived through unsupervised learning from large unlabeled corpus remarkably improved the DNN with randomized embedding, denoting the usefulness of unsupervised feature learning.

Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study.

PubMed

Eddleston, Michael; Eyer, Peter; Worek, Franz; Mohamed, Fahim; Senarathna, Lalith; von Meyer, Ludwig; Juszczak, Edmund; Hittarage, Ariyasena; Azhar, Shifa; Dissanayake, Wasantha; Sheriff, M H Rezvi; Szinicz, Ladislaus; Dawson, Andrew H; Buckley, Nick A

Although more than 100 organophosphorus insecticides exist, organophosphorus poisoning is usually regarded as a single entity, distinguished only by the compound's lethal dose in animals. We aimed to determine whether the three most common organophosphorus insecticides used for self-poisoning in Sri Lanka differ in the clinical features and severity of poisoning they cause. We prospectively studied 802 patients with chlorpyrifos, dimethoate, or fenthion self-poisoning admitted to three hospitals. Blood cholinesterase activity and insecticide concentration were measured to determine the compound and the patients' response to insecticide and therapy. We recorded clinical outcomes for each patient. Compared with chlorpyrifos (35 of 439, 8.0%), the proportion dying was significantly higher with dimethoate (61 of 264, 23.1%, odds ratio [OR] 3.5, 95% CI 2.2-5.4) or fenthion (16 of 99, 16.2%, OR 2.2, 1.2-4.2), as was the proportion requiring endotracheal intubation (66 of 439 for chlorpyrifos, 15.0%; 93 of 264 for dimethoate, 35.2%, OR 3.1, 2.1-4.4; 31 of 99 for fenthion, 31.3%, 2.6, 1.6-4.2). Dimethoate-poisoned patients died sooner than those ingesting other pesticides and often from hypotensive shock. Fenthion poisoning initially caused few symptoms but many patients subsequently required intubation. Acetylcholinesterase inhibited by fenthion or dimethoate responded poorly to pralidoxime treatment compared with chlorpyrifos-inhibited acetylcholinesterase. Organophosphorus insecticide poisoning is not a single entity, with substantial variability in clinical course, response to oximes, and outcome. Animal toxicity does not predict human toxicity since, although chlorpyrifos is generally the most toxic in rats, it is least toxic in people. Each organophosphorus insecticide should be considered as an individual poison and, consequently, patients might benefit from management protocols developed for particular organophosphorus insecticides.

Negation’s Not Solved: Generalizability Versus Optimizability in Clinical Natural Language Processing

PubMed Central

Wu, Stephen; Miller, Timothy; Masanz, James; Coarr, Matt; Halgrim, Scott; Carrell, David; Clark, Cheryl

2014-01-01

A review of published work in clinical natural language processing (NLP) may suggest that the negation detection task has been “solved.” This work proposes that an optimizable solution does not equal a generalizable solution. We introduce a new machine learning-based Polarity Module for detecting negation in clinical text, and extensively compare its performance across domains. Using four manually annotated corpora of clinical text, we show that negation detection performance suffers when there is no in-domain development (for manual methods) or training data (for machine learning-based methods). Various factors (e.g., annotation guidelines, named entity characteristics, the amount of data, and lexical and syntactic context) play a role in making generalizability difficult, but none completely explains the phenomenon. Furthermore, generalizability remains challenging because it is unclear whether to use a single source for accurate data, combine all sources into a single model, or apply domain adaptation methods. The most reliable means to improve negation detection is to manually annotate in-domain training data (or, perhaps, manually modify rules); this is a strategy for optimizing performance, rather than generalizing it. These results suggest a direction for future work in domain-adaptive and task-adaptive methods for clinical NLP. PMID:25393544

Two rare entities in the same palate lesion: hyalinizing-type clear cell carcinoma and necrotizing sialometaplasia.

PubMed

Arpaci, Rabia Bozdoğan; Kara, Tuba; Porgali, Canan; Serinsoz, Ebru; Polat, Ayse; Vayisoglu, Yusuf; Ozcan, Cengiz

2014-05-01

Hyalinizing clear cell carcinoma is a low-grade malignant epithelial neoplasm of the salivary glands. The tumor has epithelial cells and lacks myoepithelial cells. Necrotizing sialometaplasia is a benign, self-limiting lesion of the salivary glands. The clinical and histologic features mimic those of mucoepidermoid carcinoma or squamous cell carcinoma. The importance of these entities are the rarity of both of them and their potential to be misdiagnosed as other lesions. Pathologists and clinicians should be aware of these entities to prevent misdiagnosis. This is the first clinical report of 2 rare and consecutive different entities of the same location on the hard palate to our knowledge.

The continuing search for antitumor agents from higher plants

PubMed Central

Pan, Li; Chai, Heebyung; Kinghorn, A. Douglas

2009-01-01

Plant secondary metabolites and their semi-synthetic derivatives continue to play an important role in anticancer drug therapy. In this short review, selected single chemical entity antineoplastic agents from higher plants that are currently in clinical trials as cancer chemotherapy drug candidates are described. These compounds are representative of a wide structural diversity. In addition, the approaches taken toward the discovery of anticancer agents from tropical plants in the laboratory of the authors are summarized. The successful clinical utilization of cancer chemotherapeutic agents from higher plants has been evident for about half a century, and, when considered with the promising pipeline of new plant-derived compounds now in clinical trials, this augurs well for the continuation of drug discovery research efforts to elucidate additional candidate substances of this type. PMID:20228943

Organizational diagnosis of computer and information learning needs: the process and product.

PubMed

Nelson, R; Anton, B

1997-01-01

Organizational diagnosis views the organization as a single entity with problems and challenges that are unique to the organization as a whole. This paper describes the process of establishing organizational diagnoses related to computer and information learning needs within a clinical or academic health care institution. The assessment of a college within a state-owned university in the U.S.A. is used to demonstrate the process of organizational diagnosis. The diagnoses identified include the need to improve information seeking skills and the information presentation skills of faculty.

[Autoimmune/inflammatory syndrome induced by adjuvants. A new clinical entity?

PubMed

Ferrer-Cosme, Belkis; Téllez-Martínez, Damiana; Batista-Duharte, Alexander

2017-01-01

Recently Shoenfeld and Agmon-Levin proposed a new clinical entity called autoimmune/inflammatory syndrome induced by adjuvants (ASIA), which includes four clinical entities called: 1) siliconosis, 2) Gulf War syndrome, 3) macrophage myofasciitis) and 4) post-vaccination phenomenon associated with adjuvants. They all have a common denominator: a prior exposure to immunoadjuvants, and, in addition, they also share several clinical criteria associated to chronic inflammation and autoimmune reactions. This proposal still needs to be validated by the scientific community, but nowadays is a topic of hot discussion in the literature and in various international conferences. In this revision article, we analyze the characteristics of this syndrome, the current mechanisms possibly involved in the pathogenesis, and the more recent reports regarding ASIA associated to vaccine and some foreign substances.

Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes

PubMed Central

2016-01-01

Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities. PMID:27909577

Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes.

PubMed

González-de-Olano, David; Matito, Almudena; Orfao, Alberto; Escribano, Luis

2016-01-01

Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities.

The role of joint ventures in bridging the gap between research and management

USDA-ARS?s Scientific Manuscript database

No single entity can effectively address conservation planning and actions for migratory bird species that move across continents annually to fulfill their habitat needs. Successful landscape-level conservation requires cooperation and coordination of efforts among individual conservation entities....

Mesomelic skeletal dysplasias.

PubMed

Kaitila, I; Leisti, J T; Rimoin, D L

1976-01-01

Mesomelic shortening of the extremities lends itself as a useful clinical and/or radiologic sign to characterize a group of hereditary bone dysplasias. Table 1 and Figure 4 are presented to facilitate the comparison between the many different types of mesomelic dwarfism. Differential diagnosis between these types is not difficult because of the specific bone changes and extraskeletal malformations present. As in many hereditary syndromes, however, there may be wide clinical variability within a single entity, and meticulous clinical and radiologic examination must be done to arrive at the correct diagnosis. Certain other forms of chondrodystrophies, such as achondroplasia, hypochondroplasia, pseudoachondroplasia and distrophic dwarfism, can be easily differentiated from the mesomelic dysplasias by their clinical features and skeletal radiographs. Nothing is known about the pathogenesis of the various forms of mesomelic dysplasias. There is no available specific treatment, although corrective surgery has benefited selected patients. The correct diagnosis is, however, important both for prognostication and accurate genetic counseling.

CLARA: an integrated clinical research administration system.

PubMed

Bian, Jiang; Xie, Mengjun; Hogan, William; Hutchins, Laura; Topaloglu, Umit; Lane, Cheryl; Holland, Jennifer; Wells, Thomas

2014-10-01

Administration of human subject research is complex, involving not only the institutional review board but also many other regulatory and compliance entities within a research enterprise. Its efficiency has a direct and substantial impact on the conduct and management of clinical research. In this paper, we report on the Clinical Research Administration (CLARA) platform developed at the University of Arkansas for Medical Sciences. CLARA is a comprehensive web-based system that can streamline research administrative tasks such as submissions, reviews, and approval processes for both investigators and different review committees on a single integrated platform. CLARA not only helps investigators to meet regulatory requirements but also provides tools for managing other clinical research activities including budgeting, contracting, and participant schedule planning. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Epigenetic polypharmacology: from combination therapy to multitargeted drugs.

PubMed

de Lera, Angel R; Ganesan, A

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed.

Dysplastic Nevi and Melanoma

PubMed Central

Goldstein, Alisa M.; Tucker, Margaret A.

2013-01-01

Dysplastic nevi (DN) are described as being on a continuum between common acquired nevi and melanoma because they are morphologically and biologically intermediate between these two entities. Since initially being reported as histologic lesions observed in melanoma-prone families, there has been considerable debate about the definition of dysplastic nevi, the histologic and clinical criteria used to define them, and their biological importance. Their role as precursor lesions for melanoma is not their primary role in their relationship to melanoma because of the rarity of transformation of any individual nevus to a melanoma. Although there is still no single universally agreed upon histologic or clinical definition or even name for these nevi, dysplastic nevi should be considered important because of their association with an increased risk for melanoma. PMID:23549396

Clinical Phenotype of Depression Affects Interleukin-6 Synthesis.

PubMed

Zadka, Łukasz; Dzięgiel, Piotr; Kulus, Michał; Olajossy, Marcin

2017-06-01

Major depressive disorder (MDD) is not a single disease, but a number of various ailments that form one entity. Psychomotor retardation, anhedonia, sleep disorders, an increased suicide risk, and anxiety are the main symptoms that often define the clinical diagnosis of depression. Interleukin-6 (IL-6), as one of the proinflammatory cytokines, seems to be overexpressed during certain mental disorders, including MDD. Overexpression of IL-6 in depression is thought to be a factor associated with bad prognosis and worse disease course. IL-6 may directly affect brain functioning and production of neurotransmitters; moreover, its concentration is correlated with certain clinical symptoms within the wide range of depressive symptomatology. Furthermore, there is a strong correlation between IL-6 synthesis and psychosomatic functioning of the patient. This article discusses potential sources and significance of IL-6 in the pathogenesis of depression.

Acquired bilateral telangiectatic macules: a distinct clinical entity.

PubMed

Park, Ji-Hye; Lee, Dong Jun; Lee, Yoo-Jung; Jang, Yong Hyun; Kang, Hee Young; Kim, You Chan

2014-09-01

We evaluated 13 distinct patients with multiple telangiectatic pigmented macules confined mostly to the upper arms to determine if the clinical and histopathological features of these cases might represent a specific clinical entity. We retrospectively investigated the clinical, histopathologic, and immunohistochemical features of 13 patients with multiple telangiectatic pigmented macules on the upper arms who presented between January 2003 and December 2012. Epidermal pigmentation, melanogenic activity, melanocyte number, vascularity, epidermal thickness, and perivascular mast cell number of the specimens were evaluated. Clinically, the condition favored middle-aged men. On histopathologic examination, the lesional skin showed capillary proliferation and telangiectasia in the upper dermis. Histochemical and immunohistochemical analysis revealed basal hyperpigmentation and increased melanogenic activity in the lesional skin (P < .05). No significant difference in epidermal thickness or mast cell number was observed between the normal perilesional skin and the lesional skin. The clinical and histopathologic features of these lesions were relatively consistent in all patients. In addition, the features are quite distinct from other diseases. Based on clinical and histologic features, we suggest the name acquired bilateral telangiectatic macules for this new entity.

Ascending transaqueductal cystoventriculoperitoneal shunting in Dandy-Walker malformation: technical note.

PubMed

Unal, Omer Faruk; Aras, Yavuz; Aydoseli, Aydin; Akcakaya, Mehmet Osman

2012-01-01

The optimal treatment for Dandy-Walker malformation is still controversial. Ventriculoperitoneal shunting, cystoperitoneal shunting or combinations are the most common surgical options in the management of this clinical entity. Endoscopic procedures like ventriculocystostomy, 3rd ventriculostomy or endoscopy-assisted shunt surgeries have become the focus of recent publications. We describe a new transcystic endoscopic technique, with the usage of a single ascending transaqueductal shunt catheter with additional holes, whereby both the posterior fossa cyst and supratentorial ventricular compartments are drained effectively. By using this new technique complications associated with combined shunting can be avoided. In addition, by equalizing the pressure within the supra- and infratentorial compartments, the upward or downward herniations associated with single-catheter shunting can be prevented. Copyright © 2013 S. Karger AG, Basel.

42 CFR 411.352 - Group practice.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false Group practice. 411.352 Section 411.352 Public... Entities Furnishing Designated Health Services § 411.352 Group practice. For purposes of this subpart, a group practice is a physician practice that meets the following conditions: (a) Single legal entity. The...

42 CFR 411.352 - Group practice.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false Group practice. 411.352 Section 411.352 Public... Entities Furnishing Designated Health Services § 411.352 Group practice. For purposes of this subpart, a group practice is a physician practice that meets the following conditions: (a) Single legal entity. The...

75 FR 42174 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-20

... investment advisers, and entities seeking to avoid investment adviser status, among others. [[Page 42175... applicants in the vast majority of cases are related entities and are treated as a single respondent for...-precedented, routine application to approximately $80,000 to prepare a complex or novel application. We...

Lichen planus hypertrophicus of the vulva - a rare entity.

PubMed

Job, Anupa Mary; Kaimal, Sowmya

2017-09-01

Vulvovaginal lichen planus is a type of chronic inflammatory dermatosis of the vulva, usually seen as a part of widespread lichen planus. The common clinical types of vulval lichen planus include papulosquamous, erosive and pigmented types. Hypertrophic lichen planus of the vulva is a rare entity. We report a case of hypertrophic lichen planus of the vulva which clinically simulated genital warts.

Data Entities and Information System Matrix for Integrated Agriculture Information System (IAIS)

NASA Astrophysics Data System (ADS)

Budi Santoso, Halim; Delima, Rosa

2018-03-01

Integrated Agriculture Information System is a system that is developed to process data, information, and knowledge in Agriculture sector. Integrated Agriculture Information System brings valuable information for farmers: (1) Fertilizer price; (2) Agriculture technique and practise; (3) Pest management; (4) Cultivation; (5) Irrigation; (6) Post harvest processing; (7) Innovation in agriculture processing. Integrated Agriculture Information System contains 9 subsystems. To bring an integrated information to the user and stakeholder, it needs an integrated database approach. Thus, researchers describes data entity and its matrix relate to subsystem in Integrated Agriculture Information System (IAIS). As a result, there are 47 data entities as entities in single and integrated database.

Ovarian clear cell carcinoma--bad endometriosis or bad endometrium?

PubMed

Gounaris, Ioannis; Charnock-Jones, D Stephen; Brenton, James D

2011-10-01

It has become increasingly clear that the four main histological subtypes of epithelial ovarian cancer (EOC), high-grade serous, endometrioid, clear cell and mucinous, are entities with different epidemiologies, clinical presentations, responses to treatment, and ultimate outcomes. In fact, for all intents and purposes, they can be considered different diseases, their only common denominator being that they frequently involve the ovary and pelvic organs. However, clinical practice has not caught up with these insights and the treatment of EOC is that of a single disease entity. In part, this is because we lack detailed knowledge of the molecular mechanisms driving the pathogenesis of each disease, which is vital in order to develop therapeutic approaches against common driver events. In the last few years, mutations in ARID1A and PIK3CA have been described in a substantial fraction of cases of ovarian clear cell carcinoma, yet the paper by Yamamoto et al in this issue of The Journal of Pathology reveals that PIK3CA mutations can be detected in precursor endometriosis tissues. These and other recent observations underscore the importance of investigating whether mutations in the eutopic endometrium actually predispose to endometriosis and eventually to malignancy. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The European Society for Medical Oncology Magnitude of Clinical Benefit Scale in daily practice: a single institution, real-life experience at the Medical University of Vienna.

PubMed

Kiesewetter, Barbara; Raderer, Markus; Steger, Günther G; Bartsch, Rupert; Pirker, Robert; Zöchbauer-Müller, Sabine; Prager, Gerald; Krainer, Michael; Preusser, Matthias; Schmidinger, Manuela; Zielinski, Christoph C

2016-01-01

The European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) has been designed to stratify the therapeutic benefit of a certain drug registered for the treatment of cancer. However, though internally validated, this tool has not yet been evaluated for its feasibility in the daily practice of a major center of medical oncology. The practicability of the MCBS for advanced oncological diseases at the Clinical Division of Oncology, Medical University of Vienna, which constitutes one of the largest oncological centres in Europe, was analysed in a three-step approach. First, retrospectively collected data were analysed to gain an overview of treatments in regular use. Second, data were scored by using the MCBS. Third, the ensuing results were evaluated within corresponding programme directorships to assess feasibility in a real-life clinical context. In the majority of tumour entities, the MCBS results reported earlier are consistent with daily clinical practice. Thus, in metastatic breast cancer or advanced lung cancer, there was a high level of clinical benefit for first-line treatment standards, and these results reflected well real-life experience. However, analyses based on the first version of the MCBS are limited if it comes to salvage treatment in tumour entities in which optimal sequencing of potential treatment options is of major importance, as in metastatic colorectal or renal cell cancer. In contrast to this, it is remarkable that certain novel therapies such as nivolumab assessed for heavily pretreated advanced renal cancer reached the highest level of clinical benefit due to prolongation in survival and a favourable toxicity profile. The MCBS clearly underlines the potential benefit of these compounds. The MCBS is an excellent tool for daily clinical practice of a tertiary referral centre. It supports treatment decisions based on the clinical benefit to be expected from a novel approach such as immunotherapy in as yet untested indications.

Clinical Named Entity Recognition Using Deep Learning Models.

PubMed

Wu, Yonghui; Jiang, Min; Xu, Jun; Zhi, Degui; Xu, Hua

2017-01-01

Clinical Named Entity Recognition (NER) is a critical natural language processing (NLP) task to extract important concepts (named entities) from clinical narratives. Researchers have extensively investigated machine learning models for clinical NER. Recently, there have been increasing efforts to apply deep learning models to improve the performance of current clinical NER systems. This study examined two popular deep learning architectures, the Convolutional Neural Network (CNN) and the Recurrent Neural Network (RNN), to extract concepts from clinical texts. We compared the two deep neural network architectures with three baseline Conditional Random Fields (CRFs) models and two state-of-the-art clinical NER systems using the i2b2 2010 clinical concept extraction corpus. The evaluation results showed that the RNN model trained with the word embeddings achieved a new state-of-the- art performance (a strict F1 score of 85.94%) for the defined clinical NER task, outperforming the best-reported system that used both manually defined and unsupervised learning features. This study demonstrates the advantage of using deep neural network architectures for clinical concept extraction, including distributed feature representation, automatic feature learning, and long-term dependencies capture. This is one of the first studies to compare the two widely used deep learning models and demonstrate the superior performance of the RNN model for clinical NER.

Clinical Named Entity Recognition Using Deep Learning Models

PubMed Central

Wu, Yonghui; Jiang, Min; Xu, Jun; Zhi, Degui; Xu, Hua

2017-01-01

Clinical Named Entity Recognition (NER) is a critical natural language processing (NLP) task to extract important concepts (named entities) from clinical narratives. Researchers have extensively investigated machine learning models for clinical NER. Recently, there have been increasing efforts to apply deep learning models to improve the performance of current clinical NER systems. This study examined two popular deep learning architectures, the Convolutional Neural Network (CNN) and the Recurrent Neural Network (RNN), to extract concepts from clinical texts. We compared the two deep neural network architectures with three baseline Conditional Random Fields (CRFs) models and two state-of-the-art clinical NER systems using the i2b2 2010 clinical concept extraction corpus. The evaluation results showed that the RNN model trained with the word embeddings achieved a new state-of-the- art performance (a strict F1 score of 85.94%) for the defined clinical NER task, outperforming the best-reported system that used both manually defined and unsupervised learning features. This study demonstrates the advantage of using deep neural network architectures for clinical concept extraction, including distributed feature representation, automatic feature learning, and long-term dependencies capture. This is one of the first studies to compare the two widely used deep learning models and demonstrate the superior performance of the RNN model for clinical NER. PMID:29854252

Preferred mental models in reasoning about spatial relations.

PubMed

Jahn, Georg; Knauff, Markus; Johnson-Laird, P N

2007-12-01

The theory of mental models postulates that individuals infer that a spatial description is consistent only if they can construct a model in which all the assertions in the description are true. Individuals prefer a parsimonious representation, and so, when a description is consistent with more than one possible layout of entities on the left-right dimension, individuals in our culture prefer to construct models working from left to right. They also prefer to locate entities referred to in the same assertion as adjacent to one another in a model. And, if possible, they tend to chunk entities into a single unit in order to capture several possibilities in a single model. We report four experiments corroborating these predictions. The results shed light on the integration of relational assertions, and they show that participants exploit implicit constraints in building models of spatial relations.

Rethinking cancer nanotheranostics

NASA Astrophysics Data System (ADS)

Chen, Hongmin; Zhang, Weizhong; Zhu, Guizhi; Xie, Jin; Chen, Xiaoyuan

2017-07-01

Advances in nanoparticle synthesis and engineering have produced nanoscale agents affording both therapeutic and diagnostic functions that are often referred to by the portmanteau 'nanotheranostics'. The field is associated with many applications in the clinic, especially in cancer management. These include patient stratification, drug-release monitoring, imaging-guided focal therapy and post-treatment response monitoring. Recent advances in nanotheranostics have expanded this notion and enabled the characterization of individual tumours, the prediction of nanoparticle-tumour interactions, and the creation of tailor-designed nanomedicines for individualized treatment. Some of these applications require breaking the dogma that a nanotheranostic must combine both therapeutic and diagnostic agents within a single, physical entity; instead, it can be a general approach in which diagnosis and therapy are interwoven to solve clinical issues and improve treatment outcomes. In this Review, we describe the evolution and state of the art of cancer nanotheranostics, with an emphasis on clinical impact and translation.

Gene expression profiling in multiple myeloma--reporting of entities, risk, and targets in clinical routine.

PubMed

Meissner, Tobias; Seckinger, Anja; Rème, Thierry; Hielscher, Thomas; Möhler, Thomas; Neben, Kai; Goldschmidt, Hartmut; Klein, Bernard; Hose, Dirk

2011-12-01

Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification. The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore). The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression-based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively. GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities. ©2011 AACR.

Late post-treatment radiographic changes 3 years following chemoradiation for glioma: the importance of histopathology.

PubMed

Galante, Joao R; Rodriguez, Fausto; Grossman, Stuart A; Strowd, Roy E

2017-07-18

Treatment-related changes can mimic brain tumor progression both clinically and radiographically. Distinguishing these two entities represents a major challenge in neuro-oncology. No single imaging modality is capable of reliably achieving such distinction. While histopathology remains the gold standard, definitive pathological criteria are also lacking which can further complicate such cases. We report a patient with high-grade glioma who, after initially presenting with histopathologically confirmed pseudoprogression 10 months following treatment, re-presented 3 years following concurrent chemoradiation with clinical and radiographic changes that were most consistent with progressive disease but for which histopathology revealed treatment effects without active glioma. This case highlights the potential late onset of treatment-related changes and underscores the importance of histopathologic assessment even years following initial therapy.

Recognition of medication information from discharge summaries using ensembles of classifiers.

PubMed

Doan, Son; Collier, Nigel; Xu, Hua; Pham, Hoang Duy; Tu, Minh Phuong

2012-05-07

Extraction of clinical information such as medications or problems from clinical text is an important task of clinical natural language processing (NLP). Rule-based methods are often used in clinical NLP systems because they are easy to adapt and customize. Recently, supervised machine learning methods have proven to be effective in clinical NLP as well. However, combining different classifiers to further improve the performance of clinical entity recognition systems has not been investigated extensively. Combining classifiers into an ensemble classifier presents both challenges and opportunities to improve performance in such NLP tasks. We investigated ensemble classifiers that used different voting strategies to combine outputs from three individual classifiers: a rule-based system, a support vector machine (SVM) based system, and a conditional random field (CRF) based system. Three voting methods were proposed and evaluated using the annotated data sets from the 2009 i2b2 NLP challenge: simple majority, local SVM-based voting, and local CRF-based voting. Evaluation on 268 manually annotated discharge summaries from the i2b2 challenge showed that the local CRF-based voting method achieved the best F-score of 90.84% (94.11% Precision, 87.81% Recall) for 10-fold cross-validation. We then compared our systems with the first-ranked system in the challenge by using the same training and test sets. Our system based on majority voting achieved a better F-score of 89.65% (93.91% Precision, 85.76% Recall) than the previously reported F-score of 89.19% (93.78% Precision, 85.03% Recall) by the first-ranked system in the challenge. Our experimental results using the 2009 i2b2 challenge datasets showed that ensemble classifiers that combine individual classifiers into a voting system could achieve better performance than a single classifier in recognizing medication information from clinical text. It suggests that simple strategies that can be easily implemented such as majority voting could have the potential to significantly improve clinical entity recognition.

Extrapelvic endometriosis: a rare entity or an under diagnosed condition?

PubMed Central

2013-01-01

Endometriosis is a clinical entity characterized by the presence of normal endometrial mucosa abnormally implanted in locations other than the uterine cavity. Endometriosis can be either endopelvic or extrapelvicdepending on the location of endometrial tissue implantation. Despite the rarity of extrapelvic endometriosis, several cases of endometriosis of the gastrointestinal tract, the urinarytract, the upper and lower respiratory system, the diaphragm, the pleura and the pericardium, as well as abdominal scars loci have been reported in the literature. There are several theories about the pathogenesis and the pathophysiology of endometriosis. Depending on the place of endometrial tissue implantation, endometriosis can be expressed with a wide variety of symptoms. The diagnosis of this entity is neither easy nor routine. Many diagnostic methods clinical and laboratory have been used, but none of them is the golden standard. The multipotent localization of endometriosis in combination with the wide range of its clinical expression should raise the clinical suspicion in every woman with periodic symptoms of extrapelvic organs. Finally, the therapeutic approach of this clinical entity is also correlated with the bulk of endometriosis and the locum that it is found. It varies from simple observation, to surgical treatment and treatment with medication as well as a combination of those. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1968087883113362. PMID:24294950

[Childhood scabies: a different entity].

PubMed

Níguez Carbonell, J C; García-Marcos Alvarez, L; Sebastián Raz, J M; García Marcos, V; Guillén Pérez, J J

1988-01-01

Epidemiological, clinical, diagnostic and therapeutic aspects that make scabies a clinical entity with a special personality in the pediatric field, are reviewed. On the epidemiological aspects, a special mention of its unsuspected frequency in this age is made. Scabies is an endemic disease in our country among the more deprived people. On the clinical aspects, the great importance of clinical history and distribution of skin lesions for the early diagnosis is pointed out. Some "alert pointers" are described for this early diagnosis. On the therapeutic field, the importance of the primary care prevention is discussed, and the drug approach for its relieve is commented.

19 CFR 141.58 - Single entry for separately arriving portions of unassembled or disassembled entities.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., third of six portions). If both the carrier and the importer are automated, such adjustments may be made electronically through the CBP Automated Commercial System (ACS). The release of each portion upon arrival as... information for that portion of the ordered entity (for example, detailed packing lists). (f) Examination. CBP...

19 CFR 141.58 - Single entry for separately arriving portions of unassembled or disassembled entities.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., third of six portions). If both the carrier and the importer are automated, such adjustments may be made electronically through the CBP Automated Commercial System (ACS). The release of each portion upon arrival as... information for that portion of the ordered entity (for example, detailed packing lists). (f) Examination. CBP...

19 CFR 141.58 - Single entry for separately arriving portions of unassembled or disassembled entities.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., third of six portions). If both the carrier and the importer are automated, such adjustments may be made electronically through the CBP Automated Commercial System (ACS). The release of each portion upon arrival as... information for that portion of the ordered entity (for example, detailed packing lists). (f) Examination. CBP...

19 CFR 141.58 - Single entry for separately arriving portions of unassembled or disassembled entities.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., third of six portions). If both the carrier and the importer are automated, such adjustments may be made electronically through the CBP Automated Commercial System (ACS). The release of each portion upon arrival as... information for that portion of the ordered entity (for example, detailed packing lists). (f) Examination. CBP...

19 CFR 141.58 - Single entry for separately arriving portions of unassembled or disassembled entities.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., third of six portions). If both the carrier and the importer are automated, such adjustments may be made electronically through the CBP Automated Commercial System (ACS). The release of each portion upon arrival as... information for that portion of the ordered entity (for example, detailed packing lists). (f) Examination. CBP...

Pacific Theater Operations

DTIC Science & Technology

2011-01-01

Pacific theater, the 311th SC (T) is the Army’s IT service provider. They execute the activities associated with network operation , management , and...processes, and infrastructure responsible for the operation , management and health of the network under a single, administrative control entity. The...all other 311th operational entities to execute the NSC operational concept. They are primarily responsible for the technical operation

12 CFR 613.3300 - Participations and other interests in loans to similar entities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... outstanding under paragraph (b) of this section to a single credit risk shall not exceed 10 percent of its... similar entities. 613.3300 Section 613.3300 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT... purchase, sale, or transfer of interests in loans, or other extensions of credit, or other technical and...

[On the benefits to keep using the asperger diagnosis].

PubMed

Delcommenne, M; Francolini, M; Bon, O L

The purpose of this paper is to examine the possible benefits to keep using the diagnosis of Asperger's syndrome. We first describe the evolution of this entity over time and within nomenclature bases such as the ICD- 10, the CFTMEA and the last versions of DSM. Then, we discuss more precisely the impact of the decision made in the DSM-5 to suppress the Asperger syndrome as a differentiated entity within the pervasive developmental disorders (PDD). This disorder chapter by the way also disappears and is replaced by Autism Spectrum Disorder (ASD). We present here three clinical cases encountered in an outpatient general child psychiatry clinic : 1 case was diagnosed as Asperger syndrome, 1 as infantile autism (early infantile autism) and 1 as another pervasive developmental disorder (psychotic disharmony). The objective was to expose the commonali ties and differences between these three entities. We conclude that keeping using the Asperger diagnosis is important for the clinical management of these clinical situations but also for the individual, his or her family and society at large.

Enhancement of Chemical Entity Identification in Text Using Semantic Similarity Validation

PubMed Central

Grego, Tiago; Couto, Francisco M.

2013-01-01

With the amount of chemical data being produced and reported in the literature growing at a fast pace, it is increasingly important to efficiently retrieve this information. To tackle this issue text mining tools have been applied, but despite their good performance they still provide many errors that we believe can be filtered by using semantic similarity. Thus, this paper proposes a novel method that receives the results of chemical entity identification systems, such as Whatizit, and exploits the semantic relationships in ChEBI to measure the similarity between the entities found in the text. The method assigns a single validation score to each entity based on its similarities with the other entities also identified in the text. Then, by using a given threshold, the method selects a set of validated entities and a set of outlier entities. We evaluated our method using the results of two state-of-the-art chemical entity identification tools, three semantic similarity measures and two text window sizes. The method was able to increase precision without filtering a significant number of correctly identified entities. This means that the method can effectively discriminate the correctly identified chemical entities, while discarding a significant number of identification errors. For example, selecting a validation set with 75% of all identified entities, we were able to increase the precision by 28% for one of the chemical entity identification tools (Whatizit), maintaining in that subset 97% the correctly identified entities. Our method can be directly used as an add-on by any state-of-the-art entity identification tool that provides mappings to a database, in order to improve their results. The proposed method is included in a freely accessible web tool at www.lasige.di.fc.ul.pt/webtools/ice/. PMID:23658791

Neutrophilic leukocyte membrane proteins. I. Isolation.

PubMed

Hawkins, D; Sauvé, M

1978-03-01

Rabbit exudate-derived PMN were homogenized and the cell membranes isolated on a two-phase aqueous system. Glycoproteins were extracted from cell membranes with lithium diiodosalicylate. SDS polyacrylamide gel electrophoretic analysis showed a consistent pattern of three major glycoprotein entities. Cells radioiodinated supravitally showed most of the radioactivity associated with larger glycoprotein entities whereas PMN membranes radiolabeled after isolation yielded a single major peak of radioactivity associated with a much smaller protein entity. Heterologous antisera against rabbit PMN, PMN membranes, and membrane glycoproteins were all cytotoxic for PMN in the presence of complement, and all bound to the PMN surface as demonstrated with immunocolloidal gold on electron microscopy. The data suggest that one or more glycoprotein entities are membrane-associated ectoglycoproteins which can be radiolabeled supravitally.

Structured prediction models for RNN based sequence labeling in clinical text.

PubMed

Jagannatha, Abhyuday N; Yu, Hong

2016-11-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies for structured prediction in order to improve the exact phrase detection of various medical entities.

Structured prediction models for RNN based sequence labeling in clinical text

PubMed Central

Jagannatha, Abhyuday N; Yu, Hong

2016-01-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies1 for structured prediction in order to improve the exact phrase detection of various medical entities. PMID:28004040

PTCH1 Germline Mutations and the Basaloid Follicular Hamartoma Values in the Tumor Spectrum of Basal Cell Carcinoma Syndrome (NBCCS).

PubMed

Ponti, Giovanni; Manfredini, Marco; Pastorino, Lorenza; Maccaferri, Monia; Tomasi, Aldo; Pellacani, Giovanni

2018-01-01

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominantly inherited disorder characterized by multiple basal cell carcinomas (BCC), odontogenic tumors and various skeletal anomalies. Basaloid follicular hamartomas (BFHs) constitute rare neoplasms that can be detected in sporadic and familial settings as in the Basaloid Follicular Hamartoma Syndrome (BFHS). Although BFHS shares clinical, histopathological and genetic overlapping with the NBCCS, they are still considered two distinctive entities. The aim of our single-institution study was the analysis of a cohort of PTCH1-mutated patients in order to define clinical and biomolecular relationship between NBCCS and BFHs. In our study we evaluated PTCH1 gene-carrier probands affected by NBCCS to detect the incidence of BFHs and their correlation with this rare syndrome. Among probands we recognized 4 patients with BFHs. We found 15 germline PTCH1 mutations, uniformly distributed across the PTCH1 gene. Six of them had familial history of NBCCS, two of them were novel and have not been described previously. NBCCS and BFHS may be the same genetic entity and not two distinctive syndromes. The inclusion of BFH in the NBCCS cutaneous tumor spectrum might be useful for the recognition of misdiagnosed NBCCS cases that could benefit from tailored surveillance strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

PubMed

Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel

2016-02-25

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Contemporary Patterns of Multiple Organ Dysfunction in Trauma.

PubMed

Shepherd, Joanna M; Cole, Elaine; Brohi, Karim

2017-04-01

Multiple organ dysfunction syndrome (MODS) is associated with poor outcomes for trauma patients. Different forms of MODS may exist and have different consequences. The ability to distinguish them clinically may have implications for prognosis and treatment. We wished to study whether prolonged MODS (PRMODS) could be observed as a distinct clinical entity to early resolving MODS (ERMODS) in critically injured patients. Adult major trauma patients recruited to a prospective observational study at a single major trauma center were eligible for inclusion. MODS was defined as Sequential Organ Failure Assessment (SOFA) score >5; and PRMODS as lasting >7 days. Time to recovery (TTR) was calculated as the number of days before the SOFA fell below the MODS threshold (≤5). Five hundred ninety-five patients were enrolled of whom 285 developed ERMODS (48%) and 184 (31%) PRMODS. Organ dysfunction was more severe and protracted in PRMODS, especially in patients without brain injury (mean SOFA 11 vs. 6, Day 2, P < 0.001; TTR 17 vs. 3 days, P < 0.001). PRMODS exhibited higher rates of hepatic and renal dysfunction (84% vs. 56%; and 78% vs. 47%, P≤0.001). Patterns of recovery were distinct in hepatic, renal, and neurological systems (TTR 15 vs. 4; 20 vs. 3; and 28 vs. 7 days, P < 0.01). PRMODS was associated with higher infection and mortality rates (91% vs. 41%; and 22% vs. 7%, P < 0.001). PRMODS appears common, a distinct clinical entity, and associated with worse patient outcomes. PRMODS may represent an important endpoint for studies evaluating outcomes following trauma.

Ultrasensitive protein detection in blood serum using gold nanoparticle probes by single molecule spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Jiji; Wang, Chungang; Irudayaraj, Joseph

2009-07-01

A one-step rapid and ultrasensitive immunoassay capable of detecting proteins in blood serum is developed using gold nanoprobes and fluorescence correlation spectroscopy (FCS). In this approach we take advantage of the inherent photoluminescence property of gold nanoparticles (GNPs) to develop a fluorophore-free assay to observe binding entities by monitoring the diffusion of bound versus unbound molecules in a limited confocal volume. 40-nm GNPs conjugated separately with rabbit anti-IgG (Fc) and goat anti-IgG (Fab) when incubated in blood serum containing IgG forms a sandwich structure constituting dimers and oligomers that can be differentiated by to detect IgG in blood serum at a limit of detection (LOD) of 5 pg/ml. The novelty of integrating GNPs with FCS to develop a sensitive blood immunoassay brings single molecule methods one step closer to the clinic.

LAND-deFeND - An innovative database structure for landslides and floods and their consequences.

PubMed

Napolitano, Elisabetta; Marchesini, Ivan; Salvati, Paola; Donnini, Marco; Bianchi, Cinzia; Guzzetti, Fausto

2018-02-01

Information on historical landslides and floods - collectively called "geo-hydrological hazards - is key to understand the complex dynamics of the events, to estimate the temporal and spatial frequency of damaging events, and to quantify their impact. A number of databases on geo-hydrological hazards and their consequences have been developed worldwide at different geographical and temporal scales. Of the few available database structures that can handle information on both landslides and floods some are outdated and others were not designed to store, organize, and manage information on single phenomena or on the type and monetary value of the damages and the remediation actions. Here, we present the LANDslides and Floods National Database (LAND-deFeND), a new database structure able to store, organize, and manage in a single digital structure spatial information collected from various sources with different accuracy. In designing LAND-deFeND, we defined four groups of entities, namely: nature-related, human-related, geospatial-related, and information-source-related entities that collectively can describe fully the geo-hydrological hazards and their consequences. In LAND-deFeND, the main entities are the nature-related entities, encompassing: (i) the "phenomenon", a single landslide or local inundation, (ii) the "event", which represent the ensemble of the inundations and/or landslides occurred in a conventional geographical area in a limited period, and (iii) the "trigger", which is the meteo-climatic or seismic cause (trigger) of the geo-hydrological hazards. LAND-deFeND maintains the relations between the nature-related entities and the human-related entities even where the information is missing partially. The physical model of the LAND-deFeND contains 32 tables, including nine input tables, 21 dictionary tables, and two association tables, and ten views, including specific views that make the database structure compliant with the EC INSPIRE and the Floods Directives. The LAND-deFeND database structure is open, and freely available from http://geomorphology.irpi.cnr.it/tools. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Information and organization in public health institutes: an ontology-based modeling of the entities in the reception-analysis-report phases.

PubMed

Pozza, Giandomenico; Borgo, Stefano; Oltramari, Alessandro; Contalbrigo, Laura; Marangon, Stefano

2016-09-08

Ontologies are widely used both in the life sciences and in the management of public and private companies. Typically, the different offices in an organization develop their own models and related ontologies to capture specific tasks and goals. Although there might be an overall coordination, the use of distinct ontologies can jeopardize the integration of data across the organization since data sharing and reusability are sensitive to modeling choices. The paper provides a study of the entities that are typically found at the reception, analysis and report phases in public institutes in the life science domain. Ontological considerations and techniques are introduced and their implementation exemplified by studying the Istituto Zooprofilattico Sperimentale delle Venezie (IZSVe), a public veterinarian institute with different geographical locations and several laboratories. Different modeling issues are discussed like the identification and characterization of the main entities in these phases; the classification of the (types of) data; the clarification of the contexts and the roles of the involved entities. The study is based on a foundational ontology and shows how it can be extended to a comprehensive and coherent framework comprising the different institute's roles, processes and data. In particular, it shows how to use notions lying at the borderline between ontology and applications, like that of knowledge object. The paper aims to help the modeler to understand the core viewpoint of the organization and to improve data transparency. The study shows that the entities at play can be analyzed within a single ontological perspective allowing us to isolate a single ontological framework for the whole organization. This facilitates the development of coherent representations of the entities and related data, and fosters the use of integrated software for data management and reasoning across the company.

A woman with a dangling digit.

PubMed

Roesch, Alexander; Kinner, Bernd; Schaechinger, Ulrich; Obermann, Ellen C; Landthaler, Michael; Hohenleutner, Ulrich

2007-11-01

Ainhum (dactylolysis spontanea) is a distinct clinical and radiological disorder of dark-skinned people characterized by a progressive development of a constricting band encircling the toe which usually results in spontaneous amputation. Ainhum mainly occurs in African natives, but in times of global migration and tourism, Ainhum is likely to be more often encountered outside Africa. Even though the clinical presentation can mimic more common entities such as arthritis and trauma, the correct diagnosis and treatment is easy if one knows this unusual entity.

Psychomedical care in gender identity dysphoria during adolescence.

PubMed

Sánchez Lorenzo, Isabel; Mora Mesa, Juan José; Oviedo de Lúcas, Olga

In the clinical literature, the term gender dysphoria is used to define the perception of rejection that a person has to the fact of being male or female. In children and adolescents, gender identity dysphoria is a complex clinical entity. The result of entity is variable and uncertain, but in the end only a few will be transsexuals in adulthood. METHODOLOGY: RESULTS AND CONCLUSIONS. Copyright © 2015 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

[Epithelioid hemangioendothelioma: an uncommon liver tumor].

PubMed

Pareja, Eugenia; Cortés, Miriam; Rayon, Miguel; Moya, Angel; Mir, Jose

2010-01-01

We report the case of a female patient who was referred to our unit because of a solid liver tumor, suggestive of metastasis. After biopsy, the patient was diagnosed with epithelioid hemangioendothelioma of the liver. Epithelioid hemangioendothelioma is a rare entity with an unpredictable, potentially fatal, clinical course and outcome. Due to its rarity, this entity should be considered when a solitary hepatic lesion is detected and should be included in the differential diagnosis with liver metastases. We highlight the infrequency of this tumor, its presentation as a solitary hepatic lesion and the indication of surgical treatment. We describe the clinical and pathological characteristics of epithelioid hemangioendothelioma of the liver and report a new case of this entity. The distinct therapeutic options are discussed. Copyright 2010 Elsevier España, S.L. All rights reserved.

NMR spectroscopy of single sub-nL ova with inductive ultra-compact single-chip probes

PubMed Central

Grisi, Marco; Vincent, Franck; Volpe, Beatrice; Guidetti, Roberto; Harris, Nicola; Beck, Armin; Boero, Giovanni

2017-01-01

Nuclear magnetic resonance (NMR) spectroscopy enables non-invasive chemical studies of intact living matter. However, the use of NMR at the volume scale typical of microorganisms is hindered by sensitivity limitations, and experiments on single intact organisms have so far been limited to entities having volumes larger than 5 nL. Here we show NMR spectroscopy experiments conducted on single intact ova of 0.1 and 0.5 nL (i.e. 10 to 50 times smaller than previously achieved), thereby reaching the relevant volume scale where life development begins for a broad variety of organisms, humans included. Performing experiments with inductive ultra-compact (1 mm2) single-chip NMR probes, consisting of a low noise transceiver and a multilayer 150 μm planar microcoil, we demonstrate that the achieved limit of detection (about 5 pmol of 1H nuclei) is sufficient to detect endogenous compounds. Our findings suggest that single-chip probes are promising candidates to enable NMR-based study and selection of microscopic entities at biologically relevant volume scales. PMID:28317887

Late-onset hepatic veno-occlusive disease post autologous peripheral stem cell transplantation successfully treated with oral defibrotide.

PubMed

Shah, Mithun S; Jeevangi, Nandish Kumar S; Joshi, Amit; Khattry, Navin

2009-01-01

Hepatic veno-occlusive disease (VOD) remains one of the commonest and most serious complications after myeloablative hematopoietic stem cell transplantation (HSCT). Clinical diagnosis of hepatic VOD is based on the finding of the triad of painful hepatomegaly, hyperbilirubinemia, and unexplained fluid retention occurring within 21 days of the transplant. However, the uncommon clinical entity of late-onset VOD can occur even beyond 20 days and should be considered in the differential diagnosis of any liver disease of more than 3 weeks' duration. While mild cases usually resolve spontaneously, severe VOD is associated with a grim prognosis. Defibrotide, a polydisperse mixture of single-stranded oligonucleotide with antithrombotic and fibrinolytic effects on microvascular endothelium, has emerged as an effective and safe therapy for patients with severe VOD. We describe a patient who presented 55 days post transplant with clinical features suggestive of VOD. Upon treatment with oral defibrotide, he showed complete resolution of the VOD.

Juxta-articular myxoma and intramuscular myxoma are two distinct entities. Activating Gs alpha mutation at Arg 201 codon does not occur in juxta-articular myxoma.

PubMed

Okamoto, Sumika; Hisaoka, Masanori; Meis-Kindblom, Jeanne M; Kindblom, Lars-Gunnar; Hashimoto, Hiroshi

2002-01-01

Juxta-articular myxoma is a rare myxoid tumor of soft tissue that bears a close histologic resemblance to intramuscular myxoma but is distinguished from the latter by its clinical setting and behavior. Activating missense mutations at the Arg 201 codon of the Gs alpha gene ultimately leading to increased levels of cyclic adenosine monophosphate have been implicated in McCune-Albright syndrome and sporadic fibrous dysplasia of bone. Recently, we have demonstrated that the same Gs alpha mutations occur in intramuscular myxomas associated with fibrous dysplasia of bone (Mazabraud's syndrome) as well as in sporadic intramuscular myxoma. The overlapping histologic appearances of juxta-articular myxoma and intramuscular myxoma prompted us to investigate whether there is a relationship between the two entities. We studied this possibility by looking for Gs alpha mutations in juxta-articular myxoma using polymerase chain reaction (PCR) to amplify appropriate genomic DNA fragments extracted from formalin-fixed, paraffin-embedded specimens of five juxta-articular myxomas, followed by single-strand conformation polymorphism analysis. Using these techniques, no aberrant bands were detected in any of the five juxta-articular myxomas, indicating that they lack Gs alpha mutations. Moreover, DNA sequencing of the PCR products of two JAMs showed no abnormalities. We conclude that juxta-articular myxomas, in contrast to intramuscular myxomas, do not involve Arg 201 mutations of the Gs alpha gene, indicating that they represent distinct entities with different underlying molecular mechanisms.

Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward

PubMed Central

Twisk, Frank N.M.

2016-01-01

Myalgic encephalomyelitis (ME), described in the medical literature since 1938, is characterized by distinctive muscular symptoms, neurological symptoms, and signs of circulatory impairment. The only mandatory feature of chronic fatigue syndrome (CFS), introduced in 1988 and redefined in 1994, is chronic fatigue, which should be accompanied by at least four or more out of eight “additional” symptoms. The use of the abstract, polythetic criteria of CFS, which define a heterogeneous patient population, and self-report has hampered both scientific progress and accurate diagnosis. To resolve the “diagnostic impasse” the Institute of Medicine proposes that a new clinical entity, systemic exercise intolerance disease (SEID), should replace the clinical entities ME and CFS. However, adopting SEID and its defining symptoms, does not resolve methodological and diagnostic issues. Firstly, a new diagnostic entity cannot replace two distinct, partially overlapping, clinical entities such as ME and CFS. Secondly, due to the nature of the diagnostic criteria, the employment of self-report, and the lack of criteria to exclude patients with other conditions, the SEID criteria seem to select an even more heterogeneous patient population, causing additional diagnostic confusion. This article discusses methodological and diagnostic issues related to SEID and proposes a methodological solution for the current “diagnostic impasse”. PMID:26861399

The influence of category coherence on inference about cross-classified entities.

PubMed

Patalano, Andrea L; Wengrovitz, Steven M; Sharpes, Kirsten M

2009-01-01

A critical function of categories is their use in property inference (Heit, 2000). However, one challenge to using categories in inference is that most entities in the world belong to multiple categories (e.g., Fido could be a dog, a pet, a mammal, or a security system). Building on Patalano, Chin-Parker, and Ross (2006), we tested the hypothesis that category coherence (the extent to which category features go together in light of prior knowledge) influences the selection of categories for use in property inference about cross-classified entities. In two experiments, we directly contrasted coherent and incoherent categories, both of which included cross-classified entities as members, and we found that the coherent categories were used more readily as the source of both property transfer and property extension. We conclude that category coherence, which has been found to be a potent influence on strength of inference for singly classified entities (Rehder & Hastie, 2004), is also central to category use in reasoning about novel cross-classified ones.

Mosaic generalized neurofibromatosis 1: report of two cases.

PubMed

Hardin, Jori; Behm, Allan; Haber, Richard M

2014-01-01

We report two cases of mosaic generalized neurofibromatosis 1 (NF1) and review the history of the classification of segmental neurofibromatosis (SNF; Ricardi type NF-V). Somatic mutations giving rise to limited disease, such as segmental neurofibromatosis are manifestations of mosaicism. If the mutation occurs before tissue differentiation, the clinical phenotype will be generalized disease. Mutations that occur later in development give rise to disease that is confined to a single region. Segmental neurofibromatosis is caused by a somatic mutation of neurofibromatosis type 1, and should not be regarded as a distinct entity from neurofibromatosis 1. Cases previously referred to as unilateral or bilateral segmental neurofibromatosis are now best referred to as mosaic generalized or mosaic localized neurofibromatosis 1.

A Patient Presenting with Cardiac Tamponade and the Challenges of Finding Its Cause: A Cardiac Angiosarcoma.

PubMed

Habibi, Roshanak; Faramarzi, Negar; Altamirano, Alvaro J; Dadkhah, Shahriar

2018-01-01

Primary malignancies of the heart are so rare that most of the available data come from case reports or large single-center-based studies, with the overall incidence of 0.02% in the United States. Diagnosis in case of an isolated pericardial effusion as presentation is challenging, and determining that an angiosarcoma is even more challenging. Here, we presented a rare case of pericardial angiosarcoma which presented to us with tamponade. The patient eventually was diagnosed through pericardiectomy. A multimodality approach was attempted to treat the cancer. The clinical details of such a unique disease entity inspired us to present it as a case report.

Recurrent Guillain-Barré syndrome presenting stereotypic manifestations, positive antiganglioside antibodies, and rapid recovery.

PubMed

Pyun, So Young; Jeong, Jin-Ho; Bae, Jong Seok

2015-12-01

Recurrent Guillain-Barré syndrome (rGBS) has been described as a rare entity with distinct characteristics. However, little is known about rGBS in Asian group. The aim of this study was to identify the incidence and clinical course of rGBS, and to determine its clinical/pathophysiological implications. The consecutive data of 117 GBS patients were retrieved from a single university-based hospital in Korea and analyzed in terms of clinical, serological, electrophysiological aspects. A thorough review revealed that three (2.6%) of the enrolled patients had experienced more than two definite recurrent attacks of GBS. Interestingly, all three cases exhibited clinically stereotypical features, serum antiganglioside antibodies, and rapid recovery after intravenous immunoglobulin treatment. Clinical, serological, and electrophysiological features of rGBS cases were described in detail. The stereotypic presentation of each attack in this variant suggests the importance of both host and genetic factors for the clinical manifestations. In addition, the simultaneous presence of serum antiganglioside antibodies and rapid recovery implicate reversible nerve conduction failure as the mechanism of rGBS. These features are different from typical monophasic GBS and acute onset of chronic inflammatory demyelinating polyneuropathy. Copyright © 2015 Elsevier B.V. All rights reserved.

A Novel Approach towards Medical Entity Recognition in Chinese Clinical Text

PubMed Central

Yu, Jian

2017-01-01

Medical entity recognition, a basic task in the language processing of clinical data, has been extensively studied in analyzing admission notes in alphabetic languages such as English. However, much less work has been done on nonstructural texts that are written in Chinese, or in the setting of differentiation of Chinese drug names between traditional Chinese medicine and Western medicine. Here, we propose a novel cascade-type Chinese medication entity recognition approach that aims at integrating the sentence category classifier from a support vector machine and the conditional random field-based medication entity recognition. We hypothesized that this approach could avoid the side effects of abundant negative samples and improve the performance of the named entity recognition from admission notes written in Chinese. Therefore, we applied this approach to a test set of 324 Chinese-written admission notes with manual annotation by medical experts. Our data demonstrated that this approach had a score of 94.2% in precision, 92.8% in recall, and 93.5% in F-measure for the recognition of traditional Chinese medicine drug names and 91.2% in precision, 92.6% in recall, and 91.7% F-measure for the recognition of Western medicine drug names. The differences in F-measure were significant compared with those in the baseline systems. PMID:29065612

Identifying Liver Cancer and Its Relations with Diseases, Drugs, and Genes: A Literature-Based Approach

PubMed Central

Song, Min

2016-01-01

In biomedicine, scientific literature is a valuable source for knowledge discovery. Mining knowledge from textual data has become an ever important task as the volume of scientific literature is growing unprecedentedly. In this paper, we propose a framework for examining a certain disease based on existing information provided by scientific literature. Disease-related entities that include diseases, drugs, and genes are systematically extracted and analyzed using a three-level network-based approach. A paper-entity network and an entity co-occurrence network (macro-level) are explored and used to construct six entity specific networks (meso-level). Important diseases, drugs, and genes as well as salient entity relations (micro-level) are identified from these networks. Results obtained from the literature-based literature mining can serve to assist clinical applications. PMID:27195695

77 FR 34958 - Draft Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... the Agency considers your comment on this draft guidance before it begins work on the final version of... the regulated entities under FDA's and OHRP's jurisdiction. The Agencies wish to stress, however, that... other entities involved in the study oversight transfer process. FDA and OHRP will continue to work...

42 CFR 414.902 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... carrier means an entity assigned by CMS to process and pay claims for drugs and biologicals under the CAP... participating CAP physician, in his or her clinical judgment, to require prompt action or attention for purposes... requirements of § 414.906(e) are met. Local carrier means an entity assigned by CMS to process and pay claims...

42 CFR 414.902 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... carrier means an entity assigned by CMS to process and pay claims for drugs and biologicals under the CAP... participating CAP physician, in his or her clinical judgment, to require prompt action or attention for purposes... requirements of § 414.906(e) are met. Local carrier means an entity assigned by CMS to process and pay claims...

42 CFR 414.902 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... carrier means an entity assigned by CMS to process and pay claims for drugs and biologicals under the CAP... participating CAP physician, in his or her clinical judgment, to require prompt action or attention for purposes... requirements of § 414.906(e) are met. Local carrier means an entity assigned by CMS to process and pay claims...

Cystic renal tumors: new entities and novel concepts.

PubMed

Moch, Holger

2010-05-01

Cystic renal neoplasms and renal epithelial stromal tumors are diagnostically challenging and represent some novel tumor entities. In this article, clinical and pathologic features of established and novel entities are discussed. Predominantly cystic renal tumors include cystic nephroma/mixed epithelial and stromal tumor, synovial sarcoma, and multilocular cystic renal cell carcinoma. These entities are own tumor entities of the 2004 WHO classification of renal tumors. Tubulocystic carcinoma and acquired cystic disease-associated renal cell carcinoma are neoplasms with an intrinsically cystic growth pattern. Both tumor types should be included in a future WHO classification as novel entities owing to their characteristic features. Cysts and clear cell renal cell carcinoma frequently coexist within the kidneys of patients with von Hippel-Lindau disease. Sporadic clear cell renal cell carcinomas often contain cysts, usually as a minor component. Some clear cell renal cell carcinomas have prominent cysts, and multilocular cystic renal cell carcinoma is composed almost exclusively of cysts. Recent molecular findings suggest that clear cell renal cancer may develop through cyst-dependent and cyst-independent molecular pathways.

Role of Imaging and Cytogenetics in Evaluation of DiGeorge Syndrome - A Rare Entity in Clinical Practice.

PubMed

Ramachandran, Rajoo; Babu, Sellappan Rajamanickam; Ilanchezhian, Subramanian; Radhakrishnan, Prabhu Radhan

2015-01-01

DiGeorge syndrome is a congenital genetic disorder that affects the endocrine system, mainly the thymus and parathyroid glands. The syndrome produces different symptoms, which vary in severity and character between patients. It manifests with craniofacial dysmorphism and defects in the heart, parathyroid, and thymus. Patients can present with a palatal deformity and nasal speech. This rare entity is caused mainly due to deletion of chromosome 22q11.2. Radiographic evaluation of DiGeorge syndrome is necessary to define aberrant anatomy, evaluate central nervous system, craniofacial abnormalities, musculoskeletal system, and cardiothoracic contents. It also helps in planning surgical procedures and surgical reconstructions. We report a case of DiGeorge syndrome in a 4-month-old neonate and discuss the clinical, imaging, and cytogenetic findings that helped in the diagnosis of this rare entity.

Update on Genetic Conditions Affecting the Skin and the Kidneys

PubMed Central

Reimer, Antonia; He, Yinghong; Has, Cristina

2018-01-01

Genetic conditions affecting the skin and kidney are clinically and genetically heterogeneous, and target molecular components present in both organs. The molecular pathology involves defects of cell–matrix adhesion, metabolic or signaling pathways, as well as tumor suppressor genes. This article gives a clinically oriented overview of this group of disorders, highlighting entities which have been recently described, as well as the progress made in understanding well-known entities. The genetic bases as well as molecular cell biological mechanisms are described, with therapeutic applications. PMID:29552546

[Isotretinoin embryopathy: An entity that can be avoided].

PubMed

Cammarata-Scalisi, Francisco; Nieves, Dairelis; Avendaño, Andrea; Lacruz-Rengel, María A; Alviárez, Karelys; Dávila, Francys; Yavuz, Izzet; Callea, Michele

2018-04-01

Isotretinoin is the most effective drug in the treatment of severe recalcitrant nodulocystic acne. However, treatment with this drug is associated with adverse effects, the most severe being teratogenesis. It has been estimated that 40% of pregnancies exposed to isotretinoin present spontaneous abortion and 35% develop embryopathy. We present the case of a newborn with a history of prenatal exposure to isotretinoin, a clinical entity that can be avoided, with severe congenital defects in the central nervous system and important facial dysmorphisms, with unfavorable clinical course. Sociedad Argentina de Pediatría.

Clinics in diagnostic imaging (178). Wünderlich syndrome and pseudoaneurysm.

PubMed

Chung, Raymond; Chawla, Ashish; Peh, Wilfred Cg

2017-06-01

Wünderlich syndrome is a rare entity characterised by spontaneous retroperitoneal haemorrhage with renal origin. We present a case of Wünderlich syndrome secondary to clotting dyscrasia in a 64-year-old woman. The patient experienced a second Wünderlich haemorrhagic event with metachronous pseudoaneurysm formation, which was likely secondary to the large subcapsular haematoma stripping the renal capsule and tearing the cortical arteries. Selective pseudoaneurysm embolisations were successfully performed on both occasions. This clinical entity, its imaging differential diagnoses and management are discussed. Copyright: © Singapore Medical Association.

The clinical entity of remitting seronegative synovitis with pitting edema (RS3PE syndrome).

PubMed

Triplett, L M; Pfister, A K

2001-01-01

Remitting seronegative symmetrical synovitis with pitting edema is a clinical entity distinct from polymyalgia rheumatica arthritis appearing in elderly patients. Distal pitting edema and tenosynovitis of the digitorum tendons are characteristically seen in this disorder. In contrast to polymyalgia rheumatica and rheumatoid arthritis, treatment with low-dose glucocorticoids usually produces a prompt and enduring remission after several months. Follow-up evaluations are necessary not only to assure this diagnosis is posterior, but also to observe for the possible occurrence of associated neoplasms.

Cardiac cachexia: hic et nunc: "hic et nunc" - here and now.

PubMed

Loncar, Goran; Springer, Jochen; Anker, Markus; Doehner, Wolfram; Lainscak, Mitja

2015-12-15

Cardiac cachexia (CC) is the clinical entity at the end of chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. Better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick-up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF.

Cardiac cachexia: hic et nunc

PubMed Central

Loncar, Goran; Springer, Jochen; Anker, Markus; Doehner, Wolfram

2016-01-01

Abstract Cardiac cachexia (CC) is the clinical entity at the end of the chronic natural course of heart failure (HF). Despite the efforts, even the most recent definition of cardiac cachexia has been challenged, more precisely, the addition of new criteria on top of obligatory weight loss. The pathophysiology of CC is complex and multifactorial. A better understanding of pathophysiological pathways in body wasting will contribute to establish potentially novel treatment strategies. The complex biochemical network related with CC and HF pathophysiology underlines that a single biomarker cannot reflect all of the features of the disease. Biomarkers that could pick up the changes in body composition before they convey into clinical manifestations of CC would be of great importance. The development of preventive and therapeutic strategies against cachexia, sarcopenia, and wasting disorders is perceived as an urgent need by healthcare professionals. The treatment of body wasting remains an unresolved challenge to this day. As CC is a multifactorial disorder, it is unlikely that any single agent will be completely effective in treating this condition. Among all investigated therapeutic strategies, aerobic exercise training in HF patients is the most proved to counteract skeletal muscle wasting and is recommended by treatment guidelines for HF. PMID:27386168

Translating Guidelines Into Practice: Interpreting the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk.

PubMed

Waite, Laura H; Phan, Yvonne L; Spinler, Sarah A

2017-10-01

In 2016, the American College of Cardiology released a decision pathway, based on expert consensus, to guide use of non-statin agents in the management of atherosclerotic cardiovascular disease risk. The purpose of this article is to assist practitioners, health systems and managed care entities with interpreting this consensus statement in order to simplify implementation of the recommendations into patient care. Major themes from the consensus statement are briefly summarized and explained. Drug therapy recommendations are condensed into a single algorithm, while tables correlate each recommended regimen with the appropriate patient population from both a patient-level and systems-level perspective. Finally, a patient case with evidence-based decision support is explored. These tools allow practitioners to make appropriate patient-specific decisions about the use of non-statin pharmacotherapy and enable health systems and managed care entities to more readily identify guideline-appropriate use of these agents upon review of patient profiles or prescribing patterns. This article provides resources for healthcare providers that facilitate uptake of these recommendations into clinical practice.

Preclinical drug development.

PubMed

Brodniewicz, Teresa; Grynkiewicz, Grzegorz

2010-01-01

Life sciences provide reasonably sound prognosis for a number and nature of therapeutic targets on which drug design could be based, and search for new chemical entities--future new drugs, is now more than ever based on scientific principles. Nevertheless, current very long and incredibly costly drug discovery and development process is very inefficient, with attrition rate spanning from many thousands of new chemical structures, through a handful of validated drug leads, to single successful new drug launches, achieved in average after 13 years, with compounded cost estimates from hundreds of thousands to over one billion US dollars. Since radical pharmaceutical innovation is critically needed, number of new research projects concerning this area is steeply rising outside of big pharma industry--both in academic environment and in small private companies. Their prospective success will critically depend on project management, which requires combined knowledge of scientific, technical and legal matters, comprising regulations concerning admission of new drug candidates to be subjects of clinical studies. This paper attempts to explain basic rules and requirements of drug development within preclinical study period, in case of new chemical entities of natural or synthetic origin, which belong to low molecular weight category.

Overlapping Morphologic and Immunohistochemical Features of Hashimoto Thyroiditis and IgG4-Related Thyroid Disease.

PubMed

Raess, Philipp W; Habashi, Arlette; El Rassi, Edward; Milas, Mira; Sauer, David A; Troxell, Megan L

2015-05-01

Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity.

Is the common cold a clinical entity or a cultural concept?

PubMed

Eccles, R

2013-03-01

Common cold is the most common infectious disease of mankind and the term is widely used in the clinical literature as though it were a defined clinical syndrome. Clinical studies on this syndrome often use elaborate symptom scoring systems to diagnose a common cold. The symptom scores are based on a study conducted over 50 years ago to retrospectively diagnose experimental cold and this method cannot be applied to diagnosis of common cold in the community. Diagnosis of the common cold by virology is not feasible because of the number of viruses and the variability in the disease states caused by the viruses. Because of the familiarity of subjects with common cold and the variability in symptomatology it seems a more reasonable approach to use self-diagnosis of common cold for clinical research studies and accept that the common cold is a cultural concept and not a clinical entity.

Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain.

PubMed

Taber, Louise; Lynch, Shau Yu; He, Ellie; Ripa, Steven R

2016-01-01

To evaluate long-term use of Hysingla(®) ER (HYD), a single-entity, extended-release, once-daily hydrocodone bitartrate tablet with abuse-deterrent properties in patients with moderate-to-severe chronic noncancer and nonneuropathic pain. This open-label study consisted of a dose-titration period (up to 45 days), a 52-week maintenance period and a 24-week extension period. Opioid-naïve or opioid-experienced patients with controlled or uncontrolled chronic pain conditions were treated with HYD 20-120 mg daily. Supplemental nonopioid and short-acting opioid analgesics were permitted. This paper presents the results of 106 patients who continued HYD treatment for up to 76 weeks. Primary safety measures included the incidence of adverse events, as well as audiologic, clinical laboratory and electrocardiogram measurements. Effectiveness was measured by the change between baseline and the overall 76-week treatment period in "average pain over the last 24 h" (0 = no pain, 10 = pain as bad as you can imagine), Brief Pain Inventory-Short Form survey, Medical Outcomes Study 36-Item Short Form Health Survey, Medical Outcomes Study Sleep Scale-Revised and concomitant nonstudy opioid analgesic use. Among 410 patients who completed the maintenance period, 106 continued into the extension. Of these, 83 (78%) completed the entire 76-week treatment period. Treatment-emergent adverse events were typical of those observed with μ-opioid agonists. No study drug abuse or diversion was reported. Clinically important analgesia and functional improvement were achieved during the dose-titration period and were maintained in most patients throughout 76 weeks without the need for continued HYD dose increases or changes in concomitant nonstudy opioid analgesics. The mean pain score was 6.1 at baseline, 3.8 at the end of the dose titration period and 3.8 through 76 weeks. HYD was generally well tolerated. No unexpected safety concerns emerged. Pain control was sustained throughout 76 weeks of treatment.

48 CFR 252.211-7003 - Item identification and valuation.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., used to retrieve data encoded on machine-readable media. Concatenated unique item identifier means— (1... Defense Logistics Information System (DLIS) Commercial and Government Entity (CAGE) Code). Issuing agency... identifier. Item means a single hardware article or a single unit formed by a grouping of subassemblies...

Melorheostosis: a rare entity: a case report.

PubMed

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease.

Melorheostosis: a rare entity: a case report

PubMed Central

Kherfani, Abdelhakim; Mahjoub, Hachem

2014-01-01

Melorheostosis is a rare entity belonging to the group of sclerotic bone dysplasias. Described for the first time in 1922 by Leri, it remains imperfectly known as clinical presentations are highly variable, and the etiological diagnosis is not fully elucidated. We report a case of polyostoticmelorheostosis for which radiological investigations were complete, in order to study this disease. PMID:25489356

Thoracoscopic treatment of congenital esophageal stenosis in combination with H-type tracheoesophageal fistula.

PubMed

van Poll, Daan; van der Zee, David C

2012-08-01

Congenital esophageal stenosis combined with H-type tracheoesophageal fistula is a rare clinical entity that is often not diagnosed until months or sometimes many years after birth. We present a case of a boy who presented both these entities and was treated by thoracoscopy. Copyright © 2012 Elsevier Inc. All rights reserved.

[The clinical view through the Archives: the clinical notes of 2009].

PubMed

Samolski, Daniel; Martín Robles, Irene; Castillo Villegas, Diego

2010-12-01

The Clinical Notes published in 2009 serve as a resource to reflect on clinical aspects relevant to different clinical entities. Through this review an attempt is likewise made to bring the reader closer to the clinical reality of our environment. Copyright © 2010 SEPAR. Published by Elsevier Espana. All rights reserved.

Naming unique entities in the semantic variant of primary progressive aphasia and Alzheimer's disease: Towards a better understanding of the semantic impairment.

PubMed

Montembeault, M; Brambati, S M; Joubert, S; Boukadi, M; Chapleau, M; Laforce, R Jr; Wilson, M A; Macoir, J; Rouleau, I

2017-01-27

While the semantic variant of primary progressive aphasia (svPPA) is characterized by a predominant semantic memory impairment, episodic memory impairments are the clinical hallmark of Alzheimer's disease (AD). However, AD patients also present with semantic deficits, which are more severe for semantically unique entities (e.g. a famous person) than for common concepts (e.g. a beaver). Previous studies in these patient populations have largely focused on famous-person naming. Therefore, we aimed to evaluate if these impairments also extend to other semantically unique entities such as famous places and famous logos. In this study, 13 AD patients, 9 svPPA patients, and 12 cognitively unimpaired elderly subjects (CTRL) were tested with a picture-naming test of non-unique entities (Boston Naming Test) and three experimental tests of semantically unique entities assessing naming of famous persons, places, and logos. Both clinical groups were overall more impaired at naming semantically unique entities than non-unique entities. Naming impairments in AD and svPPA extended to the other types of semantically unique entities, since a CTRL>AD>svPPA pattern was found on the performance of all naming tests. Naming famous places and famous persons appeared to be most impaired in svPPA, and both specific and general semantic knowledge for these entities were affected in these patients. Although AD patients were most significantly impaired on famous-person naming, only their specific semantic knowledge was impaired, while general knowledge was preserved. Post-hoc neuroimaging analyses also showed that famous-person naming impairments in AD correlated with atrophy in the temporo-parietal junction, a region functionally associated with lexical access. In line with previous studies, svPPA patients' impairment in both naming and semantic knowledge suggest a more profound semantic impairment, while naming impairments in AD may arise to a greater extent from impaired lexical access, even though semantic impairment for specific knowledge is also present. These results highlight the critical importance of developing and using a variety of semantically-unique-entity naming tests in neuropsychological assessments of patients with neurodegenerative diseases, which may unveil different patterns of lexical-semantic deficits. Copyright © 2016 Elsevier Ltd. All rights reserved.

[CLINICAL ENTITIES AND CHARACTERISTICS OF PAIN IN PATIENTS WITH RHEUMATIC DISEASES].

PubMed

Prus, Višnja; Kardum, Željka

Musculoskeletal pain is the most common symptom present in almost all rheumatic diseases. Rheumatic diseases include more than 150 clinical entities. There is no uniform classification of rheumatic diseases. In general, we distinguish inflammatory rheumatic diseases, non-inflammatory degenerative articular diseases, systemic connective tissue diseases, metabolic disorders with articular manifestations, and regional and extended pain syndromes. According to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant sensation associated with tissue damage or reported simultaneously with such damage. Pain has a physical, mental, and social component. In rheumatic diseases the pain is mostly chronic and may severely impair the patient’s general condition. The defining criteria involve a period of more than 3 or 6 months, and according to some definitions more than 6 weeks. In most cases the pain is nociceptive rather than neuropathic. Musculoskeletal pain, especially chronic pain, is a global public health problem because of its prevalence, as well as the frequently associated muslculoskeletal function impairment and development of chronic pain syndrome, which can be considered as a separate clinical entity and requires a biopsychosocial treatment approach.

Nucleic Acid-Based Nanoconstructs

Cancer.gov

Focuses on the design, synthesis, characterization, and development of spherical nucleic acid constructs as effective nanotherapeutic, single-entity agents for the treatment of glioblastoma multiforme and prostate cancers.

[Angiolymphoid hyperplasia with eosinophilia with bilateral involvement of the lacrimal glands].

PubMed

Baráková, Drahomíra; Sâch, Josef; Kuchynka, Pavel; Rêdinová, Magdalena; Kocur, Ivo

2002-05-01

Angiolymphoid hyperplasia with eosinophilia (ALHE) and Kimura's disease are two rarely occurring disorders very similar to each other; however, they are individual nosological entities. For a long time they were considered as a single disease due to the frequency of similar characteristics. The majority of authors have recently considered these diseases as two individual entities with some reciprocal specifications, both clinical as well as morphological. We report on the case of a 76-year old male white European who had suffered for more than six years from subcutaneous tumour formations in different parts of the body. Eyelid oedema on the right side with palpable resistance under the upper temporal edge of the orbit initially occurred five years after the first symptoms of the disease. A similar finding occurred on the left side after eight months. The tumours on both sides were surgically removed and sent for histological analysis. A unilateral recurrence of the finding appeared after one year, followed by surgical intervention and histological examination. Tumour infiltrate in the first two orbita excisions was topically related to lacrimal gland structures; these structures were not found in the third excision. The case was histologically diagnosed as ALHE despite some similar characteristics with Kimura's disease. The diagnosis of ALHE was histologically supported, especially by the absence of lymphatic follicle formations and fibrotisation in the infiltrate, and the identification of the appearance of epitheloid up to histiocytoid of proliferating endothelium, which forms small lumens. The diagnosis of ALHE was additionally supported by the fact that the incidence of Kimura's disease in white Europeans is very rare. According to our findings, both entities overlap one another, even in some characteristics considered to be distinguishing. The question arises, therefore, whether the strict separation of these nosological entities can indeed be determined with one hundred percent accuracy.

Clinical multiplexed exome sequencing distinguishes adult oligodendroglial neoplasms from astrocytic and mixed lineage gliomas.

PubMed

Cryan, Jane B; Haidar, Sam; Ramkissoon, Lori A; Bi, Wenya Linda; Knoff, David S; Schultz, Nikolaus; Abedalthagafi, Malak; Brown, Loreal; Wen, Patrick Y; Reardon, David A; Dunn, Ian F; Folkerth, Rebecca D; Santagata, Sandro; Lindeman, Neal I; Ligon, Azra H; Beroukhim, Rameen; Hornick, Jason L; Alexander, Brian M; Ligon, Keith L; Ramkissoon, Shakti H

2014-09-30

Classifying adult gliomas remains largely a histologic diagnosis based on morphology; however astrocytic, oligodendroglial and mixed lineage tumors can display overlapping histologic features. We used multiplexed exome sequencing (OncoPanel) on 108 primary or recurrent adult gliomas, comprising 65 oligodendrogliomas, 28 astrocytomas and 15 mixed oligoastrocytomas to identify lesions that could enhance lineage classification. Mutations in TP53 (20/28, 71%) and ATRX (15/28, 54%) were enriched in astrocytic tumors compared to oligodendroglial tumors of which 4/65 (6%) had mutations in TP53 and 2/65 (3%) had ATRX mutations. We found that oligoastrocytomas harbored mutations in TP53 (80%, 12/15) and ATRX (60%, 9/15) at frequencies similar to pure astrocytic tumors, suggesting that oligoastrocytomas and astrocytomas may represent a single genetic or biological entity. p53 protein expression correlated with mutation status and showed significant increases in astrocytomas and oligoastrocytomas compared to oligodendrogliomas, a finding that also may facilitate accurate classification. Furthermore our OncoPanel analysis revealed that 15% of IDH1/2 mutant gliomas would not be detected by traditional IDH1 (p.R132H) antibody testing, supporting the use of genomic technologies in providing clinically relevant data. In all, our results demonstrate that multiplexed exome sequencing can support evaluation and classification of adult low-grade gliomas with a single clinical test.

Distance-near disparity esotropia: can we shrink the gap?

PubMed

Burke, J P

2015-02-01

Distance-near disparity esotropias are a group of heterogenous usually acquired strabismus disorders, where the angle of misalignment at near exceeds that at distance by 10 prism diopters or more, where the accurate correction of refractive errors and ambylopia are important early objectives. These aetiologically diverse entities respond non-uniformally to strabismus surgery and bifocals. The management challenge is one of 'shrinking' the disparity so that the affected individuals can develop and comfortably maintain binocular single vision and/or optimal alignment. Surgical procedures have continued to evolve but none of the current operative procedures are superior for all patients. Subclassifying this strabismus and highlighting publication data from more homogenous clinical series may assist with the optimisation of future management and treatment outcomes.

Idiopathic thoracic transdural intravertebral spinal cord herniation

PubMed Central

Turel, Mazda K; Wewel, Joshua T; Kerolus, Mena G; O'Toole, John E

2017-01-01

Idiopathic spinal cord herniation is a rare and often missed cause of thoracic myelopathy. The clinical presentation and radiological appearance is inconsistent and commonly confused with a dorsal arachnoid cyst and often is a misdiagnosed entity. While ventral spinal cord herniation through a dural defect has been previously described, intravertebral herniation is a distinct entity and extremely rare. We present the case of a 70-year old man with idiopathic thoracic transdural intravertebral spinal cord herniation and discuss the clinico-radiological presentation, pathophysiology and operative management along with a review the literature of this unusual entity. PMID:29021685

Orthostatic hypotension as an unusual clinical manifestation of pheochromocytoma: a case report.

PubMed

Bortnik, Miriam; Occhetta, Eraldo; Marino, Paolo

2008-08-01

Pheochromocytoma is a rare endocrine tumor which can have a highly variable presentation related to increased catecholamine secretion. We report the case of a 74-year-old man in whom recurrent episodes of syncope due to orthostatic hypotension were the only clinical manifestations of this challenging entity. Diagnosis of pheochromocytoma was achieved by biochemical test samples and computed tomography scans. Surgical excision of the tumor resulted in clinical improvement with normalization of catecholamine concentrations and no more episodes of orthostatic hypotension during a follow-up of 24 months. Although rare, pheochromocytoma may frequently cause disorders of orthostatic tolerance; because of its meaningful implications, screening for this entity should be considered in case of recurrent syncopal episodes due to new-onset orthostatic hypotension.

Linitis plastica of the bypassed stomach 7 years after Roux-en-Y gastric bypass: a case report.

PubMed

Haenen, Filip Wn; Gys, Ben; Moreels, Tom; Michielsen, Maartje; Gys, Tobie; Lafullarde, Thierry

2017-12-01

Laparoscopic Roux-en-Y gastric bypass (RYGB) is currently the preferred surgical procedure to treat morbid obesity. It has proven its effects on excess weight loss and its positive effect on comorbidities. One of the main issues, however, is the post-operative evaluation of the bypassed gastric remnant. In literature, cancer of the excluded stomach after RYGB is rare. We describe the case of a 52-year-old woman with gastric linitis plastica in the bypassed stomach after Roux-en-Y gastric bypass, diagnosed by means of laparoscopy and Single-Balloon enteroscopy, and it is clinical importance. Linitis plastica of the excluded stomach after RYGB is a very rare entity. This case report shows the importance of long-term post-operative follow-up, and the importance of single-balloon enteroscopy for visualization of the bypassed stomach remnant, when other investigations remain without results. This case report is only the second report of a linitis plastica in the bypassed stomach after Roux-en-Y gastric bypass.

Accuracy control in Monte Carlo radiative calculations

NASA Technical Reports Server (NTRS)

Almazan, P. Planas

1993-01-01

The general accuracy law that rules the Monte Carlo, ray-tracing algorithms used commonly for the calculation of the radiative entities in the thermal analysis of spacecraft are presented. These entities involve transfer of radiative energy either from a single source to a target (e.g., the configuration factors). or from several sources to a target (e.g., the absorbed heat fluxes). In fact, the former is just a particular case of the latter. The accuracy model is later applied to the calculation of some specific radiative entities. Furthermore, some issues related to the implementation of such a model in a software tool are discussed. Although only the relative error is considered through the discussion, similar results can be derived for the absolute error.

Spectrum of MRI findings in clinical athletic pubalgia.

PubMed

Zajick, Donald C; Zoga, Adam C; Omar, Imran M; Meyers, William C

2008-03-01

Athletic pubalgia is a frequently encountered syndrome for clinicians who treat active patients participating in a wide variety of athletic endeavors worldwide. Pathologies associated with this clinical scenario span anatomically from the pubic symphysis to the hip and include a myriad of poorly understood and incompletely described musculoskeletal entities, many of which are centered about the pubic symphysis and its tendinous attachments. In this article, we discuss the relevant anatomy and pathophysiology for the most frequently encountered of these disorders, using magnetic resonance (MR) images as a guide. We describe an MR imaging protocol tailored to clinical athletic pubalgia. We then review reproducible MRI patterns of pathology about the pubic symphysis, the rectus abdominis/adductor aponeurosis and the inguinal ring, as well as a group of clinically confounding entities remote from the symphysis but visible by MRI.

Organizing to Implement Technology in the NASA Science Organization

NASA Technical Reports Server (NTRS)

Bauer, Robert; Pasciuto, Michael

2005-01-01

As part of a NASA reorganization to support the new Vision for Space Exploration, a number of space and Earth science activities were combined into a single organization. This merger provided an opportunity to review and revise technology development within the new entity. While this process has yet to be finalized, an overview . of some of the options and considerations is provided. Examples from one portion of the new entity, the Earth-Sun System Technology program, are used as illustrations.

Clinical translation of handheld optical coherence tomography: practical considerations and recent advancements

NASA Astrophysics Data System (ADS)

Monroy, Guillermo L.; Won, Jungeun; Spillman, Darold R.; Dsouza, Roshan; Boppart, Stephen A.

2017-12-01

Since the inception of optical coherence tomography (OCT), advancements in imaging system design and handheld probes have allowed for numerous advancements in disease diagnostics and characterization of the structural and optical properties of tissue. OCT system developers continue to reduce form factor and cost, while improving imaging performance (speed, resolution, etc.) and flexibility for applicability in a broad range of fields, and nearly every clinical specialty. An extensive array of components to construct customized systems has also become available, with a range of commercial entities that produce high-quality products, from single components to full systems, for clinical and research use. Many advancements in the development of these miniaturized and portable systems can be linked back to a specific challenge in academic research, or a clinical need in medicine or surgery. Handheld OCT systems are discussed and explored for various applications. Handheld systems are discussed in terms of their relative level of portability and form factor, with mention of the supporting technologies and surrounding ecosystem that bolstered their development. Additional insight from our efforts to implement systems in several clinical environments is provided. The trend toward well-designed, efficient, and compact handheld systems paves the way for more widespread adoption of OCT into point-of-care or point-of-procedure applications in both clinical and commercial settings.

Cutaneous Manifestations of Non-Celiac Gluten Sensitivity: Clinical Histological and Immunopathological Features.

PubMed

Bonciolini, Veronica; Bianchi, Beatrice; Del Bianco, Elena; Verdelli, Alice; Caproni, Marzia

2015-09-15

The dermatological manifestations associated with intestinal diseases are becoming more frequent, especially now when new clinical entities, such as Non-Celiac Gluten Sensitivity (NCGS), are identified. The existence of this new entity is still debated. However, many patients with diagnosed NCGS that present intestinal manifestations have skin lesions that need appropriate characterization. We involved 17 patients affected by NCGS with non-specific cutaneous manifestations who got much better after a gluten free diet. For a histopathological and immunopathological evaluation, two skin samples from each patient and their clinical data were collected. The median age of the 17 enrolled patients affected by NCGS was 36 years and 76% of them were females. On the extensor surfaces of upper and lower limbs in particular, they all presented very itchy dermatological manifestations morphologically similar to eczema, psoriasis or dermatitis herpetiformis. This similarity was also confirmed histologically, but the immunopathological analysis showed the prevalence of deposits of C3 along the dermo-epidermal junction with a microgranular/granular pattern (82%). The exact characterization of new clinical entities such as Cutaneous Gluten Sensitivity and NCGS is an important objective both for diagnostic and therapeutic purposes, since these are patients who actually benefit from a GFD (Gluten Free Diet) and who do not adopt it only for fashion.

The C-reactive protein.

PubMed

Clyne, B; Olshaker, J S

1999-01-01

C-reactive protein (CRP) was identified in 1930 and was subsequently considered to be an "acute phase protein," an early indicator of infectious or inflammatory conditions. Since its discovery, CRP has been studied as a screening device for inflammation, a marker for disease activity, and as a diagnostic adjunct. Improved methods of quantifying CRP have led to increased application to clinical medicine. In the emergency department (ED), CRP must be interpreted in the clinical context; no single value can be used to rule in or rule out a specific diagnosis. We conclude that CRP has limited utility in the ED. It may be a useful adjunct to serial examinations in equivocal presentations of appendicitis in those centers without ready access to computed tomography (CT) scan. It may be elevated with complications or treatment failures in patients with pneumonia, pancreatitis, pelvic inflammatory disease (PID), and urinary tract infections. In patients with meningitis, neonatal sepsis, and occult bacteremia, CRP is usually elevated. However, CRP has no role in diagnosing these clinical entities, and a normal CRP level should never delay antibiotic coverage.

A novel NOTCH2 mutation identified in a Korean family with Hajdu-Cheney syndrome showing phenotypic diversity.

PubMed

Han, Mi Seon; Ko, Jung Min; Cho, Tae-Joon; Park, Woong-Yang; Cheong, Hae Il

2015-01-01

Hajdu-Cheney syndrome (HCS) and serpentine fibula-polycystic kidney syndrome (SFPKS) share many similarities, including craniofacial abnormalities, bony deformities, and renal involvement. Because mutations in exon 34 of NOTCH2 have been identified recently in both HCS and SFPKS patients, it has been suggested that these two syndromes be classed as the same disorder. A 3-year-old boy presented with polycystic kidneys and club feet detected during the fetal period; however, acroosteolysis and curved fibulae were not observed. His mother showed osteoporosis and had a history of compression fractures in the spine without renal anomalies. Although the same novel mutation in NOTCH2 was found in both the mother and her son, these patients displayed different clinical manifestations. In this report, we present a familial case of HCS in a boy and his mother that was suspected on physical examination and radiological findings. We speculate that HCS and SFPKS are a single disease entity with a wide spectrum of clinical manifestations associated with truncating mutations in exon 34 of NOTCH2. © 2015 by the Association of Clinical Scientists, Inc.

31 CFR 363.171 - How do I redeem a converted savings bond?

Code of Federal Regulations, 2014 CFR

2014-07-01

... converted savings bond? (a) Before final maturity—(1) Savings bond of any series registered in the single... bond of any series registered either in the single owner, owner with beneficiary, or entity form of registration any time prior to final maturity after the minimum holding period through your TreasuryDirect...

31 CFR 363.171 - How do I redeem a converted savings bond?

Code of Federal Regulations, 2011 CFR

2011-07-01

... converted savings bond? (a) Before final maturity—(1) Savings bond of any series registered in the single... bond of any series registered either in the single owner, owner with beneficiary, or entity form of registration any time prior to final maturity after the minimum holding period through your TreasuryDirect...

31 CFR 363.171 - How do I redeem a converted savings bond?

Code of Federal Regulations, 2010 CFR

2010-07-01

... converted savings bond? (a) Before final maturity—(1) Savings bond of any series registered in the single... bond of any series registered either in the single owner, owner with beneficiary, or entity form of registration any time prior to final maturity after the minimum holding period through your TreasuryDirect...

31 CFR 363.171 - How do I redeem a converted savings bond?

Code of Federal Regulations, 2013 CFR

2013-07-01

... converted savings bond? (a) Before final maturity—(1) Savings bond of any series registered in the single... bond of any series registered either in the single owner, owner with beneficiary, or entity form of registration any time prior to final maturity after the minimum holding period through your TreasuryDirect...

31 CFR 363.171 - How do I redeem a converted savings bond?

Code of Federal Regulations, 2012 CFR

2012-07-01

... converted savings bond? (a) Before final maturity—(1) Savings bond of any series registered in the single... bond of any series registered either in the single owner, owner with beneficiary, or entity form of registration any time prior to final maturity after the minimum holding period through your TreasuryDirect...

75 FR 78676 - De Facto Criteria for Establishing a Separate Rate in Antidumping Proceedings Involving Non...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-16

...In antidumping proceedings involving non-market economy (``NME'') countries,\\1\\ the Department of Commerce (``the Department'') has a rebuttable presumption that the export activities of all companies within the country are subject to government control and, thus, should be assessed a single antidumping duty rate (i.e., the NME- Entity rate). It is the Department's policy to assign to all exporters of merchandise subject to investigation in an NME country this single rate unless an exporter can demonstrate that it is sufficiently independent so as to be entitled to a ``separate rate'' (i.e., a dumping margin separate from the margin assigned to the NME-Entity). Exporters can demonstrate this independence through the absence of both de jure and de facto governmental control over their export activities. ---------------------------------------------------------------------------

Post hoc analyses: after the facts.

PubMed

Srinivas, Titte R; Ho, Bing; Kang, Joseph; Kaplan, Bruce

2015-01-01

Prospective clinical trials are constructed with high levels of internal validity. Sample size and power considerations usually address primary endpoints. Primary endpoints have traditionally included events that are becoming increasingly less common and thus have led to growing use of composite endpoints and noninferiority trial designs in transplantation. This approach may mask real clinical benefit in one or the other domain with regard to either clinically relevant secondary endpoints or other unexpected findings. In addition, endpoints solely chosen based on power considerations are prone to misjudgment of actual treatment effect size as well as consistency of that effect. In the instances where treatment effects may have been underestimated, valuable information may be lost if buried within a composite endpoint. In all these cases, analyses and post hoc analyses of data become relevant in informing practitioners about clinical benefits or safety signals that may not be captured by the primary endpoint. On the other hand, there are many pitfalls in using post hoc determined endpoints. This short review is meant to allow readers to appreciate post hoc analysis not as an entity with a single approach, but rather as an analysis with unique limitations and strengths that often raise new questions to be addressed in further inquiries.

Liver Cirrhosis: Evaluation, Nutritional Status, and Prognosis

PubMed Central

Nishikawa, Hiroki; Osaki, Yukio

2015-01-01

The liver is the major organ for the metabolism of three major nutrients: protein, fat, and carbohydrate. Chronic hepatitis C virus infection is the major cause of chronic liver disease. Liver cirrhosis (LC) results from different mechanisms of liver injury that lead to necroinflammation and fibrosis. LC has been seen to be not a single disease entity but one that can be graded into distinct clinical stages related to clinical outcome. Several noninvasive methods have been developed for assessing liver fibrosis and these methods have been used for predicting prognosis in patients with LC. On the other hand, subjects with LC often have protein-energy malnutrition (PEM) and poor physical activity. These conditions often result in sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictive factors for poorer survival in patients with LC. Based on these backgrounds, several methods for evaluating nutritional status in patients with chronic liver disease have been developed and they have been preferably used in the clinical field practice. In this review, we will summarize the current knowledge in the field of LC from the viewpoints of diagnostic method, nutritional status, and clinical outcomes. PMID:26494949

Top-Level Categories of Constitutively Organized Material Entities - Suggestions for a Formal Top-Level Ontology

PubMed Central

Vogt, Lars; Grobe, Peter; Quast, Björn; Bartolomaeus, Thomas

2011-01-01

Background Application oriented ontologies are important for reliably communicating and managing data in databases. Unfortunately, they often differ in the definitions they use and thus do not live up to their potential. This problem can be reduced when using a standardized and ontologically consistent template for the top-level categories from a top-level formal foundational ontology. This would support ontological consistency within application oriented ontologies and compatibility between them. The Basic Formal Ontology (BFO) is such a foundational ontology for the biomedical domain that has been developed following the single inheritance policy. It provides the top-level template within the Open Biological and Biomedical Ontologies Foundry. If it wants to live up to its expected role, its three top-level categories of material entity (i.e., ‘object’, ‘fiat object part’, ‘object aggregate’) must be exhaustive, i.e. every concrete material entity must instantiate exactly one of them. Methodology/Principal Findings By systematically evaluating all possible basic configurations of material building blocks we show that BFO's top-level categories of material entity are not exhaustive. We provide examples from biology and everyday life that demonstrate the necessity for two additional categories: ‘fiat object part aggregate’ and ‘object with fiat object part aggregate’. By distinguishing topological coherence, topological adherence, and metric proximity we furthermore provide a differentiation of clusters and groups as two distinct subcategories for each of the three categories of material entity aggregates, resulting in six additional subcategories of material entity. Conclusions/Significance We suggest extending BFO to incorporate two additional categories of material entity as well as two subcategories for each of the three categories of material entity aggregates. With these additions, BFO would exhaustively cover all top-level types of material entity that application oriented ontologies may use as templates. Our result, however, depends on the premise that all material entities are organized according to a constitutive granularity. PMID:21533043

Nosological status and definition of schizophrenia: Some considerations for DSM-V and ICD-11.

PubMed

Tandon, Rajiv; Maj, Mario

2008-12-01

Although dementia praecox or schizophrenia has been considered a unique disease entity for the past century, its definitions and boundaries have varied over this period. In this article, we examine the changing conceptualization of schizophrenia over the past 100 years and make some recommendations with regards to its definition in DSM-V and ICD-11. We summarize clinical features of schizophrenia in terms of symptomatology, course, and outcome. We examine factors that lead to changing definitions of a disorder such as schizophrenia, with specific reference to the evolution of its definition from DSM-1 (American Psychiatric Association, Washington, DC, 1952) to the current DSM-IV-TR. Efforts to elucidate the etiology and pathophysiology of schizophrenia have been hampered by its imprecise definition and continuing transformations in its conceptualization. The definition of schizophrenia, at any given time, has been influenced by available diagnostic tools and treatments, other clinical considerations, extant knowledge and scientific paradigms. It is now clear that schizophrenia does not represent a single disease with a unitary etiology or pathogenetic process. Despite limitations in the concept, however, alternative approaches thus far have been unsuccessful in better defining the syndrome of schizophrenia or its component entities. Whereas changing definitions of schizophrenia might impede research into its nature and development of more effective treatments, only a better understanding of schizophrenia can lead to its more precise definition. We consider the implications of our observations for DSM-V and ICD-11 definitions of schizophrenia and summarize some emerging preliminary recommendations. Copyright © 2008 Elsevier B.V. All rights reserved.

Coreference analysis in clinical notes: a multi-pass sieve with alternate anaphora resolution modules.

PubMed

Jonnalagadda, Siddhartha Reddy; Li, Dingcheng; Sohn, Sunghwan; Wu, Stephen Tze-Inn; Wagholikar, Kavishwar; Torii, Manabu; Liu, Hongfang

2012-01-01

This paper describes the coreference resolution system submitted by Mayo Clinic for the 2011 i2b2/VA/Cincinnati shared task Track 1C. The goal of the task was to construct a system that links the markables corresponding to the same entity. The task organizers provided progress notes and discharge summaries that were annotated with the markables of treatment, problem, test, person, and pronoun. We used a multi-pass sieve algorithm that applies deterministic rules in the order of preciseness and simultaneously gathers information about the entities in the documents. Our system, MedCoref, also uses a state-of-the-art machine learning framework as an alternative to the final, rule-based pronoun resolution sieve. The best system that uses a multi-pass sieve has an overall score of 0.836 (average of B(3), MUC, Blanc, and CEAF F score) for the training set and 0.843 for the test set. A supervised machine learning system that typically uses a single function to find coreferents cannot accommodate irregularities encountered in data especially given the insufficient number of examples. On the other hand, a completely deterministic system could lead to a decrease in recall (sensitivity) when the rules are not exhaustive. The sieve-based framework allows one to combine reliable machine learning components with rules designed by experts. Using relatively simple rules, part-of-speech information, and semantic type properties, an effective coreference resolution system could be designed. The source code of the system described is available at https://sourceforge.net/projects/ohnlp/files/MedCoref.

Cutaneous metastasis of transitional cell bladder carcinoma: a rare presentation and literature review.

PubMed

Salemis, Nikolaos S; Gakis, Christos; Zografidis, Andreas; Gourgiotis, Stavros

2011-01-01

Cutaneous metastasis from transitional cell bladder carcinoma is a rare clinical entity associated with poor prognosis. We present a case of cutaneous metastasis arising from a transitional cell bladder carcinoma in a male patient who had undergone a radical cystectomy and bilateral ureterostomy 17 months previously. The cutaneous metastasis became evident 3 months before the manifestations of generalized recurrent disease. An awareness of this rare clinical entity and high index of suspicion is needed to rule out metastatic spread in patients with a previous history of transitional cell bladder carcinoma presenting with cutaneous nodules. Definitive diagnosis requires a histological confirmation, but prognosis is generally poor.

Unconsummated marriages: a separate and different clinical entity.

PubMed

Gindin, Leon Roberto; Resnicoff, Diana

2002-01-01

We bring our experience in the treatment of unconsummated marriages (UM). We postulate that it is an independent clinical entity. Since 1991, 199 couples with UM have sought treatment in our center in Buenos Aires. A new approach to this problem is based on an intensive treatment session that lasts a whole day and a pledge to pay only if therapy succeeds. The outcome was a success (97%) with coitus consummation. We make a long-term follow up. The advantages are the brevity of the treatment and lack of desertions. We postulate that UM cannot be approached with an individual perspective or with the usual psychotherapy techniques.

Biological Gene Delivery Vehicles: Beyond Viral Vectors

PubMed Central

Seow, Yiqi; Wood, Matthew J

2009-01-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications. PMID:19277019

Biological gene delivery vehicles: beyond viral vectors.

PubMed

Seow, Yiqi; Wood, Matthew J

2009-05-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.

Semiquantitative bacterial observations with group B streptococcal vulvovaginitis.

PubMed Central

Monif, G R

1999-01-01

OBJECTIVE: Group B streptococcal (GBS) vulvovaginitis is a poorly-delineated clinical entity. The purpose of this study is to report semiquantitative data from four cases of GBS vulvovaginitis and to comment on their significance in terms of the in vitro inhibitory capabilities of GBS. METHODOLOGY: Four patients whose clinical presentations were consistent with GBS vulvovaginitis, from whom GBS was isolated and for whom semi-quantitative as well as qualitative microbiologic data existed, were identified. RESULTS: To produce vulvovaginitis, GBS must be at a high multiplicity (10(8) CFU/g of vaginal fluid). Single coisolates were identified in three of the four cases (two cases of Escherichia coli and one case of Staphylococcus aureus). Group B streptococcus does not inhibit either of these bacteria in vitro. CONCLUSION: When the growth requirements for the demonstration of in vitro inhibition for GBS or lack thereof are met in vivo, the in vivo observations are consistent with those projected from the in vitro data. PMID:10524667

Spontaneous Rectus Sheath Hematoma: an Overview of 4-Year Single Center Experience.

PubMed

Aktürk, Okan Murat; Kayılıoğlu, Selami Ilgaz; Aydoğan, İhsan; Dinç, Tolga; Yildiz, Baris; Cete, Mükerrem; Erdoğan, Ahmet; Coşkun, Faruk

2015-12-01

Rectus sheath hematoma is a clinical entity characterized by the presence of blood within rectus abdominis muscle sheath. The aim of this study was to analyze clinical characteristics, diagnostic approach, treatment strategy, and outcomes of patients with rectus sheath hematoma. Patients diagnosed and treated for spontaneous rectus sheath hematoma between March 2010 and March 2014 were included in the study. A total of 10 patients were diagnosed as spontaneous rectus sheath hematoma. The mean age was 66.5 ± 16.9 years, and the mean hospital stay was 4.4 ± 1.8 days. There was no mortality. Six patients were using anticoagulant or antiplatelet agents. Eight patients recovered after conservative treatment. Two patients underwent surgery. Spontaneous rectus sheath hematoma is associated with anticoagulant therapy. Cases with abdominal pain and a non-pulsatile abdominal mass particularly in elderly women should be kept in mind. Treatment is mostly based on supportive care to preserve hemodynamic stability.

Annular lichenoid dermatitis of youth ... and beyond: a series of 6 cases.

PubMed

Cesinaro, Anna Maria; Sighinolfi, Pamela; Greco, Antonietta; Garagnani, Lorella; Conti, Andrea; Fantini, Fabrizio

2009-05-01

Annular lichenoid dermatitis of youth (ALDY) is a clinico-pathologic entity described in children and young patients, clinically reminiscent of morphea, annular erythema, vitiligo or mycosis fungoides. We report on six patients presenting single or multiple lesions, distributed particularly on the flanks and abdomen, with clinical and histologic features consistent with ALDY. Two patients were young girls and four were adults males. Three patients received topical therapy and four showed complete resolution of the lesions after a 24-65 months follow-up. Analogously to the cases reported so far, immunohistochemistry showed a T cell infiltrate with a predominance of CD8+ lymphocytes, while T cell receptor rearrangement was absent in all cases. It seems appropriate to include annular lichenoid dermatitis of youth among the dermatoses with a lichenoid pattern. For the first time, we found that it can affect also adult patients, therefore we propose to rename the disease annular lichenoid dermatitis. The differential diagnosis with mycosis fungoides, especially in adult patients, is particularly crucial for their proper management and treatment.

Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers

PubMed Central

DeKosky, Steven T.; Blennow, Kaj; Ikonomovic, Milos D.; Gandy, Sam

2014-01-01

Over the past decade, public awareness of the long-term pathological consequences of traumatic brain injury (TBI) has increased. Such awareness has been stimulated mainly by reports of progressive neurological dysfunction in athletes exposed to repetitive concussions in high-impact sports such as boxing and American football, and by the rising number of TBIs in war veterans who are now more likely to survive explosive blasts owing to improved treatment. Moreover, the entity of chronic traumatic encephalopathy (CTE)—which is marked by prominent neuropsychiatric features including dementia, parkinsonism, depression, agitation, psychosis, and aggression—has become increasingly recognized as a potential late outcome of repetitive TBI. Annually, about 1% of the population in developed countries experiences a clinically relevant TBI. The goal of this Review is to provide an overview of the latest understanding of CTE pathophysiology, and to delineate the key issues that are challenging clinical and research communities, such as accurate quantification of the risk of CTE, and development of reliable biomarkers for single-incident TBI and CTE. PMID:23558985

Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers.

PubMed

DeKosky, Steven T; Blennow, Kaj; Ikonomovic, Milos D; Gandy, Sam

2013-04-01

Over the past decade, public awareness of the long-term pathological consequences of traumatic brain injury (TBI) has increased. Such awareness has been stimulated mainly by reports of progressive neurological dysfunction in athletes exposed to repetitive concussions in high-impact sports such as boxing and American football, and by the rising number of TBIs in war veterans who are now more likely to survive explosive blasts owing to improved treatment. Moreover, the entity of chronic traumatic encephalopathy (CTE)--which is marked by prominent neuropsychiatric features including dementia, parkinsonism, depression, agitation, psychosis, and aggression--has become increasingly recognized as a potential late outcome of repetitive TBI. Annually, about 1% of the population in developed countries experiences a clinically relevant TBI. The goal of this Review is to provide an overview of the latest understanding of CTE pathophysiology, and to delineate the key issues that are challenging clinical and research communities, such as accurate quantification of the risk of CTE, and development of reliable biomarkers for single-incident TBI and CTE.

Economic impact of converting an interventional pain medicine physician office-based practice into a provider-based ambulatory pain practice.

PubMed

Grider, Jay S; Findley, Kelley A; Higdon, Courtney; Curtright, Jonathan; Clark, Don P

2014-01-01

One consequence of the shifting economic health care landscape is the growing trend of physician employment and practice acquisition by hospitals. These acquired practices are often converted into hospital- or provider-based clinics. This designation brings the increased services of the hospital, the accreditation of the hospital, and a new billing structure verses the private clinic (the combination of the facility and professional fee billing). One potential concern with moving to a provider-based designation is that this new structure might make the practice less competitive in a marketplace that may still be dominated by private physician office-based practices. The aim of the current study was to evaluate the impact of the provider-based/hospital fee structure on clinical volume. Determine the effect of transition to a hospital- or provider-based practice setting (with concomitant cost implications) on patient volume in the current practice milieu.   Community hospital-based academic interventional pain medicine practice. Economic analysis of effect of change in price structure on clinical volumes. The current study evaluates the effect of a change in designation with price implications on the demand for clinical services that accompany the transition to a hospital-based practice setting from a physician office setting in an academic community hospital. Clinical volumes of both procedures and clinic volumes increased in a mature practice setting following transition to a provider-based designation and the accompanying facility and professional fee structure. Following transition to a provider-based designation clinic visits were increased 24% while procedural volume demand did not change. Single practice entity and single geographic location in southeastern United States. The conversion to a hospital- or provider-based setting does not negatively impact clinical volume and referrals to community-based pain medicine practice. These results imply that factors other than price are a driver of patient choice.  

Dynamic neural networking as a basis for plasticity in the control of heart rate.

PubMed

Kember, G; Armour, J A; Zamir, M

2013-01-21

A model is proposed in which the relationship between individual neurons within a neural network is dynamically changing to the effect of providing a measure of "plasticity" in the control of heart rate. The neural network on which the model is based consists of three populations of neurons residing in the central nervous system, the intrathoracic extracardiac nervous system, and the intrinsic cardiac nervous system. This hierarchy of neural centers is used to challenge the classical view that the control of heart rate, a key clinical index, resides entirely in central neuronal command (spinal cord, medulla oblongata, and higher centers). Our results indicate that dynamic networking allows for the possibility of an interplay among the three populations of neurons to the effect of altering the order of control of heart rate among them. This interplay among the three levels of control allows for different neural pathways for the control of heart rate to emerge under different blood flow demands or disease conditions and, as such, it has significant clinical implications because current understanding and treatment of heart rate anomalies are based largely on a single level of control and on neurons acting in unison as a single entity rather than individually within a (plastically) interconnected network. Copyright © 2012 Elsevier Ltd. All rights reserved.

Clinical Documents: Attribute-Values Entity Representation, Context, Page Layout And Communication

PubMed Central

Lovis, Christian; Lamb, Alexander; Baud, Robert; Rassinoux, Anne-Marie; Fabry, Paul; Geissbühler, Antoine

2003-01-01

This paper presents how acquisition, storage and communication of clinical documents are implemented at the University Hospitals of Geneva. Careful attention has been given to user-interfaces, in order to support complex layouts, spell checking, templates management with automatic prefilling in order to facilitate acquisition. A dual architecture has been developed for storage using an attributes-values entity unified database and a consolidated, patient-centered, layout-respectful files-based storage, providing both representation power and sinsert (peed of accesses. This architecture allows great flexibility to store a continuum of data types from simple type values up to complex clinical reports. Finally, communication is entirely based on HTTP-XML internally and a HL-7 CDA interface V2 is currently studied for external communication. Some of the problem encountered, mostly concerning the typology of documents and the ontology of clinical attributes are evoked. PMID:14728202

Early descriptions of acromegaly and gigantism and their historical evolution as clinical entities.

PubMed

Mammis, Antonios; Eloy, Jean Anderson; Liu, James K

2010-10-01

Giants have been a subject of fascination throughout history. Whereas descriptions of giants have existed in the lay literature for millennia, the first attempt at a medical description was published by Johannes Wier in 1567. However, it was Pierre Marie, in 1886, who established the term "acromegaly" for the first time and established a distinct clinical diagnosis with clear clinical descriptions in 2 patients with the characteristic presentation. Multiple autopsy findings revealed a consistent correlation between acromegaly and pituitary enlargement. In 1909, Harvey Cushing postulated a “hormone of growth" as the underlying pathophysiological trigger involved in pituitary hypersecretion in patients with acromegaly. This theory was supported by his observations of clinical remission in patients with acromegaly in whom he had performed hypophysectomy. In this paper, the authors present some of the early accounts of acromegaly and gigantism, and describe its historical evolution as a medical and surgical entity.

[Significance of group A streptococcal infections in human pathology].

PubMed

Cvjetković, Dejan; Jovanović, Jovana; Hrnjaković-Cvjetković, Ivana; Aleksić-Dordević, Mirjana; Stefan-Mikić, Sandra

2008-01-01

Group A streptococci is the causative agent in 80 percents of human streptococcal infections. The only member of this group is Streptococcus pyogenes. CLINICALFEATURES OF GAS INFECTIONS: The various clinical entities and related complications caused by pyogenic streptococci are reviewed in the article. Pharyngitis, scarlet fever, skin and soft tissue infections (pyoderma, cellulitis, perianal dermatitis, necrotising fasciitis) and streptococcal toxic shock syndrome are described. The way of setting the diagnosis including epidemiological data, clinical features and the course of illness, laboratory findings and supportive diagnostic methods are represented in the article. The most important clinical entities which should be discussed in differential diagnosis of diseases caused by pyogenic streptococci are listed. The major principles of etiologic treatment through widely accepted strategies related to first choice antibiotics and alternatives are reviewed.

Federal Funding Accountability and Transparency Act

EPA Pesticide Factsheets

Public Law 109-282, the Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), requires disclosure of all entities and organizations receiving Federal funds through a single publicly accessible website.

Intraosseous calcium migration in calcifying tendinitis: a rare cause of single sclerotic injury in the humeral head (2010: 2b).

PubMed

Martin, S; Rapariz, J M

2010-05-01

Intratendinous deposits of hydroxyapatite crystals are very common, particularly in the rotator cuff. In rare cases, the calcium located in the thickness of the supraspinatus tendon can suffer intraosseous migration into the greater tuberosity. We present a case of this rare entity: a 28-year-old patient who attended with pain and functional weakness in the left shoulder. The plain radiograph showed a sclerotic lesion in the greater tuberosity of the humeral head with a radiolucent halo. The MRI showed a lytic lesion containing the calcium inside and associated with an extensive pattern of oedema of the accompanying bone marrow. A plain radiograph taken 6 months before showed a calcifying tendinitis in the thickness of the supraspinatus tendon. A large number of entities can present as single sclerotic lesions of the humeral head. The diagnostic key lies in the existence of the calcifying tendinitis in the earlier study. The treatment of this disease consists of surgical removal of the calcium. The recognition of this entity is important to avoid unnecessary complementary tests and aggressive surgery, given that the surgical treatment is curative and leads to disappearance of the symptoms.

Segmental volvulus in the neonate: A particular clinical entity.

PubMed

Khen-Dunlop, Naziha; Beaudoin, Sylvie; Marion, Blandine; Rousseau, Véronique; Giuseppi, Agnes; Nicloux, Muriel; Grevent, David; Salomon, Laurent J; Aigrain, Yves; Lapillonne, Alexandre; Sarnacki, Sabine

2017-03-01

Complete intestinal volvulus is mainly related to congenital anomalies of the so-called intestinal malrotation, whereas segmental volvulus appears as a distinct entity, mostly observed during the perinatal period. Because these two situations are still lumped together, the aim of this study was to describe the particular condition of neonatal segmental volvulus. We analyzed the circumstances of diagnosis and management of 17 consecutives neonates operated for segmental volvulus more than a 10-year period in a single institution. During the same period, 19 cases of neonatal complete midgut volvulus were operated. Prenatal US exam anomalies were observed in 16/17 (94%) of segmental volvulus, significantly more frequently than in complete volvulus (p=0.003). Intestinal malposition was described peroperatively in all cases of complete volvulus, but also in 4/17 segmental volvulus (23%). Intestinal resection was performed in 88% of segmental volvulus when only one extensive intestinal necrosis was observed in complete volvulus. Parenteral nutrition was required in all patients with segmental volvulus with a median duration of 50days (range 5-251). Segmental volvulus occurs mainly prenatally and leads to fetal ultrasound anomalies. This situation, despite a limited length of intestinal loss, is associated to significant postnatal morbidity. Treatment study. Level IV. Copyright © 2016 Elsevier Inc. All rights reserved.

Tremor entities and their classification: an update.

PubMed

Gövert, Felix; Deuschl, Günther

2015-08-01

This review focuses on important new findings in the field of tremor and illustrates the consequences for the current definition and classification of tremor. Since 1998 when the consensus criteria for tremor were proposed, new variants of tremors and new diagnostic methods were discovered that have changed particularly the concepts of essential tremor and dystonic tremor. Accumulating evidence exists that essential tremor is not a single entity rather different conditions that share the common symptom action tremor without other major abnormalities. Tremor is a common feature in patients with adult-onset focal dystonia and may involve several different body parts and forms of tremor. Recent advances, in particular, in the field of genetics, suggest that dystonic tremor may even be present without overt dystonia. Monosymptomatic asymmetric rest and postural tremor has been further delineated, and apart from tremor-dominant Parkinson's disease, there are several rare conditions including rest and action tremor with normal dopamine transporter imaging (scans without evidence of dopaminergic deficit) and essential tremor with tremor at rest. Increasing knowledge in the last decades changed the view on tremors and highlights several caveats in the current tremor classification. Given the ambiguous assignment between tremor phenomenology and tremor etiology, a more cautious definition of tremors on the basis of clinical assessment data is needed.

Accelerated long-term forgetting and autobiographical memory disorders in temporal lobe epilepsy: One entity or two?

PubMed

Lemesle, B; Planton, M; Pagès, B; Pariente, J

Temporal lobe epilepsy (TLE) is a type of epilepsy that often has a negative impact on patients' memory. Despite the importance of patients' complaints in this regard, the difficulties described by these patients are often not easy to demonstrate through a standard neuropsychological assessment. Accelerated long-term forgetting and autobiographical memory disorders are the two main memory impairments reported in the literature in patients with TLE. However, the methods used by different authors to evaluate long-term memory and autobiographical memory are heterogeneous. This heterogeneity can lead to differences in the observed results as well as how they are interpreted. Yet, despite the methodological differences, objectification of such memory deficits appears to be both specific and robust within this patient population. Analysis of the literature shows that accelerated long-term forgetting and autobiographical memory disorders share the same clinical characteristics. This leads to the assumption that they are, in fact, only one entity and that their evaluation may be done through a single procedure. Our proposal is to place this evaluation within the context of memory consolidation disorders. With such a perspective, evaluation of accelerated forgetting in autobiographical memory should consist of identifying a disorder in the formation and/or recovery of new memory traces. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Leiomyosarcoma: One disease or distinct biologic entities based on site of origin?

PubMed

Worhunsky, David J; Gupta, Mihir; Gholami, Sepideh; Tran, Thuy B; Ganjoo, Kristen N; van de Rijn, Matt; Visser, Brendan C; Norton, Jeffrey A; Poultsides, George A

2015-06-01

Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin. Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses. From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P < 0.001), but not site of origin, size, grade, or margin status, were independently associated with worse DSS. A significant number of recurrences and disease-related deaths were noted beyond 5 years. Although larger and higher grade, retroperitoneal and uterine LMS share similar survival and recurrence patterns with their trunk and extremity counterparts. LMS of various anatomic sites may not represent distinct disease processes based on clinical outcomes. The presence of metastatic disease remains the most important prognostic factor for LMS. © 2015 Wiley Periodicals, Inc.

77 FR 11778 - Reform of Federal Policies Relating to Grants and Cooperative Agreements; Cost Principles and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-28

... contracts that that are subject to ``full coverage'' under the Cost Accounting Standards (CAS) as defined at... full Single Audit. These Audits would be strengthened per the ideas in reforms 2-5 (below) to give... the full Single Audit for entities expending more than $3 million would ensure that agencies still...

CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease.

PubMed

Anders, Hans-Joachim; Huber, Tobias B; Isermann, Berend; Schiffer, Mario

2018-06-01

The increasing global prevalence of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has prompted research efforts to tackle the growing epidemic of diabetic kidney disease (DKD; also known as diabetic nephropathy). The limited success of much of this research might in part be due to the fact that not all patients diagnosed with DKD have renal dysfunction as a consequence of their diabetes mellitus. Patients who present with CKD and diabetes mellitus (type 1 or type 2) can have true DKD (wherein CKD is a direct consequence of their diabetes status), nondiabetic kidney disease (NDKD) coincident with diabetes mellitus, or a combination of both DKD and NDKD. Preclinical studies using models that more accurately mimic these three entities might improve the ability of animal models to predict clinical trial outcomes. Moreover, improved insights into the pathomechanisms that are shared by these entities - including sodium-glucose cotransporter 2 (SGLT2) and renin-angiotensin system-driven glomerular hyperfiltration and tubular hyper-reabsorption - as well as those that are unique to individual entities might lead to the identification of new treatment targets. Acknowledging that the clinical entity of CKD plus diabetes mellitus encompasses NDKD as well as DKD could help solve some of the urgent unmet medical needs of patients affected by these conditions.

Biomarker-driven phenotyping in Parkinson disease: a translational missing link in disease-modifying clinical trials

PubMed Central

Espay, Alberto J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Fernandez, Hubert H; Simon, David K.; Leverenz, James B.; Merola, Aristide; Chen-Plotkin, Alice; Brundin, Patrik; Kauffman, Marcelo A.; Erro, Roberto; Kieburtz, Karl; Woo, Daniel; Macklin, Eric A.; Standaert, David G.; Lang, Anthony E.

2016-01-01

Past clinical trials of putative neuroprotective therapies have targeted Parkinson disease (PD) as a single pathogenic disease entity. From an Oslerian clinico-pathologic perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: a single-mechanism therapy can affect most of those sharing the classic pathologic hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers) rather than clinical definitions are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller but well-defined subsets of PD amenable to successful neuroprotection. PMID:28233927

Balancing the Equation: Public Radio Comes of Age.

ERIC Educational Resources Information Center

Avery, Robert K.; Pepper, Robert

1979-01-01

The national development of public radio as a noncommercial medium is traced through the history of its national organizations, ending with the formation of its single programing and representational entity. (Author)

Accrued Cost Savings of a Free Clinic Using Quality-Adjusted Life Years Saved and Return on Investment.

PubMed

Sanders, Jim; Lacey, Marcus; Guse, Clare E

2017-01-01

Savings garnered through the provision of preventive services is a form of profit for health systems. Free clinics have been using this logic to demonstrate their cost-savings. The Community-Based Chronic Disease Management (CCDM) clinic treats hypertension using nurse-led teams, clinical protocols, and community-based settings. We calculated CCDM's cost-effectiveness from 2007 to 2013 using 2 metrics: Quality-adjusted life years (QALYs) saved and return on investment (ROI). QALYs were calculated using the Clinical Preventive Burden (CPB) score for hypertension care. ROI was calculated by tallying the savings from prevented heart attacks, strokes, and emergency department visits against the total operating costs. Using conservative assumptions for cost estimates, hypertension care resulted in a value of QALYs saved of $711,000 to $2,133,000 and an ROI ratio range of 0.35 to 1.20. Our study shows that when using conservative assumptions to calculate cost-savings, our free clinic did not save money. Cost-savings did occur, but the amount was modest, was less than that of cost-inputs, and was not likely captured by any single health entity. Although free clinics remain a vital health care access point for many Americans, it has yet to be demonstrated that they generate a net savings. © Copyright 2017 by the American Board of Family Medicine.

Discovery of new anticancer agents from higher plants

PubMed Central

Pan, Li; Chai, Hee-Byung; Kinghorn, A. Douglas

2012-01-01

1. ABSTRACT Small organic molecules derived from higher plants have been one of the mainstays of cancer chemotherapy for approximately the past half a century. In the present review, selected single chemical entity natural products of plant origin and their semi-synthetic derivatives currently in clinical trials are featured as examples of new cancer chemotherapeutic drug candidates. Several more recently isolated compounds obtained from plants showing promising in vivo biological activity are also discussed in terms of their potential as anticancer agents, with many of these obtained from species that grow in tropical regions. Since extracts of only a relatively small proportion of the ca. 300,000 higher plants on earth have been screened biologically to date, bioactive compounds from plants should play an important role in future anticancer drug discovery efforts. PMID:22202049

Protein-Based Therapeutic Killing for Cancer Therapies.

PubMed

Serna, Naroa; Sánchez-García, Laura; Unzueta, Ugutz; Díaz, Raquel; Vázquez, Esther; Mangues, Ramón; Villaverde, Antonio

2018-03-01

The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Digital biology and chemistry.

PubMed

Witters, Daan; Sun, Bing; Begolo, Stefano; Rodriguez-Manzano, Jesus; Robles, Whitney; Ismagilov, Rustem F

2014-09-07

This account examines developments in "digital" biology and chemistry within the context of microfluidics, from a personal perspective. Using microfluidics as a frame of reference, we identify two areas of research within digital biology and chemistry that are of special interest: (i) the study of systems that switch between discrete states in response to changes in chemical concentration of signals, and (ii) the study of single biological entities such as molecules or cells. In particular, microfluidics accelerates analysis of switching systems (i.e., those that exhibit a sharp change in output over a narrow range of input) by enabling monitoring of multiple reactions in parallel over a range of concentrations of signals. Conversely, such switching systems can be used to create new kinds of microfluidic detection systems that provide "analog-to-digital" signal conversion and logic. Microfluidic compartmentalization technologies for studying and isolating single entities can be used to reconstruct and understand cellular processes, study interactions between single biological entities, and examine the intrinsic heterogeneity of populations of molecules, cells, or organisms. Furthermore, compartmentalization of single cells or molecules in "digital" microfluidic experiments can induce switching in a range of reaction systems to enable sensitive detection of cells or biomolecules, such as with digital ELISA or digital PCR. This "digitizing" offers advantages in terms of robustness, assay design, and simplicity because quantitative information can be obtained with qualitative measurements. While digital formats have been shown to improve the robustness of existing chemistries, we anticipate that in the future they will enable new chemistries to be used for quantitative measurements, and that digital biology and chemistry will continue to provide further opportunities for measuring biomolecules, understanding natural systems more deeply, and advancing molecular and cellular analysis. Microfluidics will impact digital biology and chemistry and will also benefit from them if it becomes massively distributed.

Cluster-based single-sink wireless sensor networks and passive optical network converged network incorporating sideband modulation schemes

NASA Astrophysics Data System (ADS)

Kumar, Love; Sharma, Vishal; Singh, Amarpal

2018-02-01

Wireless sensor networks have tremendous applications, such as civil, military, and environmental monitoring. In most of the applications, sensor data are required to be propagated over the internet/core networks, which result in backhaul setback. Subsequently, there is a necessity to backhaul the sensed information of such networks together with prolonging of the transmission link. Passive optical network (PON) is next-generation access technology emerging as a potential candidate for convergence of the sensed data to the core system. Earlier, the work with single-optical line terminal-PON was demonstrated and investigated merely analytically. This work is an attempt to demonstrate a practical model of a bidirectional single-sink wireless sensor network-PON converged network in which the collected data from cluster heads are transmitted over PON networks. Further, modeled converged structure has been investigated under the influence of double, single, and tandem sideband modulation schemes incorporating a corresponding phase-delay to the sensor data entities that have been overlooked in the past. The outcome illustrates the successful fusion of the sensor data entities over PON with acceptable bit error rate and signal to noise ratio serving as a potential development in the sphere of such converged networks. It has also been revealed that the data entities treated with tandem side band modulation scheme help in improving the performance of the converged structure. Additionally, analysis for uplink transmission reported with queue theory in terms of time cycle, average time delay, data packet generation, and bandwidth utilization. An analytical analysis of proposed converged network shows that average time delay for data packet transmission is less as compared with time cycle delay.

Exercise Related Leg Pain (ERLP): a Review of The Literature

PubMed Central

2007-01-01

Exercise related leg pain (ERLP) is a regional pain syndrome described as pain between the knee and ankle which occurs with exercise. Indiscriminant use of terminology such as “shin splints” has resulted in ongoing confusion regarding the pathoanatomic entities associated with this pain syndrome. Each of the pathoanatomic entities – medial tibial stress syndrome, chronic exertional compartment syndrome, tibial and fibular stress fractures, tendinopathy, nerve entrapment, and vascular pathology – which manifest as ERLP are each described in terms of relevant anatomy, epidemiology, clinical presentation, associated pathomechanics, and intervention strategies. Evidence regarding risk factors for ERLP general and specific pathoanatomic entities are presented in the context of models of sports injury prevention. PMID:21522213

A critical appraisal of the mild axonal peripheral neuropathy of late neurologic Lyme disease

PubMed Central

Wormser, Gary P.; Strle, Franc; Shapiro, Eugene D.; Dattwyler, Raymond J.; Auwaerter, Paul G.

2018-01-01

In older studies, a chronic distal symmetric sensory neuropathy was reported as a relatively common manifestation of late Lyme disease in the United States. However, the original papers describing this entity had notable inconsistencies and certain inexplicable findings, such as reports that this condition developed in patients despite prior antibiotic treatment known to be highly effective for other manifestations of Lyme disease. More recent literature suggests that this entity is seen rarely, if at all. A chronic distal symmetric sensory neuropathy as a manifestation of late Lyme disease in North America should be regarded as controversial and in need of rigorous validation studies before acceptance as a documented clinical entity. PMID:27914746

An unusual case of primary spontaneous tension pneumothorax in a jamaican female.

PubMed

Johnson, M; French, S; Cornwall, D

2014-06-01

Spontaneous pneumothorax is a well-recognized entity with a classical presentation of acute onset chest pain and shortness of breath. It may be complicated by the development of a tension pneumothorax or a haemopneumothorax. We report an interesting case of a spontaneous tension haemopneumothorax which presented atypically and was diagnosed on computed tomography (CT) scan of the chest. The clinical and pathophysiological characteristics and treatment of this unusual entity is discussed.

Single-cell intracellular nano-pH probes.

PubMed

Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

2015-01-01

Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution.

Unilateral RS3PE in a Patient of Seronegative Rheumatoid Arthritis.

PubMed

Varshney, Ankur Nandan; Kumar, Nilesh; Tiwari, Ashutosh; Anand, Ravi; Prasad, Sashi Ranjan; Anand, Arvind; Mishra, Abhinandan; Singh, N K

2013-01-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare but well-reported clinical entity. It is classically described as symmetrical involvement of both upper extremities. Asymmetrical involvement had also been reported, but unilateral presentation is very rare. We hereby report a case of unilateral RS3PE in a patient of seronegative rheumatoid arthritis which was initially misdiagnosed as cellulitis and was given high dose antibiotics without any significant improvement. Later a rheumatologic consultation leads to a prompt diagnosis, and treatment with steroids leads to dramatic reversal of symptoms. This case demonstrates the rare presentation of this rare clinical entity and highlights the necessity of awareness regarding unilateral disease to clinicians.

A Challenging Case of Primary Breast Hodgkin's Lymphoma

PubMed Central

ZARNESCU, Narcis Octavian; ILIESIU, Andreea; PROCOP, Alexandru; TAMPA, Mircea; MATEI, Clara; SAJIN, Maria; COSTACHE, Mariana; DUMITRU, Adrian; LAZAROIU, Anca Mihaela

2015-01-01

Primary breast lymphoma (PBL) is a rare entity accounting for less than 1% of all breast malignancies. Diagnostic criteria for primary Hodgkin's lymphoma of the breast are: the presence of sufficient tissue for diagnosis, close interaction between mammary tissue and lymphomatous infiltrate and no evidence or prior diagnosis of widespread lymphoma. Our case illustrates an unusual presentation of Hodgkin's lymphoma of the breast: clinically as inflammatory breast cancer and core biopsy as granulomatous mastitis, the final diagnosis requiring surgical biopsy. Current information regarding this entity is scant, mainly build upon its rarity. In this paper we assess the clinical presentation, the step-by-step diagnosis, the treatment and the importance of immunohistochemistry in this uncommon condition. PMID:26225149

A Challenging Case of Primary Breast Hodgkin's Lymphoma.

PubMed

Zarnescu, Narcis Octavian; Iliesiu, Andreea; Procop, Alexandru; Tampa, Mircea; Matei, Clara; Sajin, Maria; Costache, Mariana; Dumitru, Adrian; Lazaroiu, Anca Mihaela

2015-03-01

Primary breast lymphoma (PBL) is a rare entity accounting for less than 1% of all breast malignancies. Diagnostic criteria for primary Hodgkin's lymphoma of the breast are: the presence of sufficient tissue for diagnosis, close interaction between mammary tissue and lymphomatous infiltrate and no evidence or prior diagnosis of widespread lymphoma. Our case illustrates an unusual presentation of Hodgkin's lymphoma of the breast: clinically as inflammatory breast cancer and core biopsy as granulomatous mastitis, the final diagnosis requiring surgical biopsy. Current information regarding this entity is scant, mainly build upon its rarity. In this paper we assess the clinical presentation, the step-by-step diagnosis, the treatment and the importance of immunohistochemistry in this uncommon condition.

Leiomyoma of the anal canal: report of two cases.

PubMed

Witz, M; Bernheim, J; Griffel, B; Dinbar, A

1986-10-01

Leiomyoma of the rectum and anal canal is an unusual clinical entity. Generally, it does not produce any clinical signs and in most cases it is discovered incidentally in the course of routine rectal examination. The clinical presentation, diagnosis, and surgical treatment are described in two presented cases of anal canal leiomyoma.

Vestibular Migraine: Clinical Challenges and Opportunities for Multidisciplinarity

PubMed Central

Luís, Leonel; Gonçalves, Freire; Pavão Martins, Isabel

2016-01-01

Migraine and vertigo are two very prevalent conditions in general population. The coexistence of both in the same subject is a significant clinical challenge, since it is not always possible to understand whether they are causally related or associated by chance, requiring different diagnostic and therapeutic approaches. In this review we analyze and summarize the actual knowledge about vestibular migraine (VM), focusing on the new concepts proposed by the International Classification of Headache Disorders 3-beta and by the Bárány Society and also addressing the former concepts, which are still present in clinical practice. We conclude that clinical studies using a multidisciplinary approach are crucial in this field, since different specialists observe the same pathology with different eyes. Clinical presentation of VM is variable in what concerns vestibular symptoms temporal relation with migraine headache, as well as in their accompanying manifestations. Biomarkers, either genomics or functional, and molecular imaging techniques will be helpful to clarify many aspects of the complexity of this entity, helping to define to what extent can VM be considered a separate and independent clinical entity. PMID:28082766

An intra-abdominal abscess or "rind" as a consequence of peritoneal dialysis-associated pseudomonas peritonitis.

PubMed

Culpepper, R Michael; Gore, Sarah; Rutecki, Gregory W

2013-01-01

Abdominal CT imaging has defined characteristics of two pathological entities specific to peritoneal dialysis patients. Both are associated with serious peritoneal complications. One is comprised of ascites accompanied by septation and loculated fluid pockets as a complication of bacterial peritonitis. The other is the syndrome of encapsulating peritoneal sclerosis. We present the evolution of a single, thick-walled fluid collection as a consequence of relapsing Pseudomonas aeruginosa peritonitis. The entity had distinctive features differing from either of the two previously described entities, and to our knowledge, has not been described previously. Our patient's radiological evolution resembled the formation of a pleural or peritoneal "rind." Peritonitis, as a result of Pseudomonas aeruginosa , may lead to "rind" formation as described with empyemas and is distinct from previously described intra-abdominal pathologies in peritoneal dialysis patients.

Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue: new entities and new variants of old entities recorded during the last 25 years. Part XII: appendix.

PubMed

Bisceglia, M; Spagnolo, D; Galliani, C; Fisher, C; Suster, S; Kazakov, D V; Cooper, K; Michal, M

2006-08-01

In an eleven part series published in Pathologica, we have presented various tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue (ST), which emerged as new entities or as variants of established entities during the last quarter of a century. Detailed clinicomorphological and differential diagnostic features of approximately sixty entities were chosen on the basis of their clinical significance and morphologic distinctiveness. The series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor, high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g., chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma), epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma group), extranodal dendritic or histiocytic proliferative processes (follicular dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform xanthomatous tumor), and tumors with myoepithelial differentiation. The section devoted to selected pseudotumoral entities considered representatives of the hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma, rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors of digits) and infections (bacillary angiomatosis), and normal organs (glomus coccygeum). To conclude the descriptive phase, supplementary material has now been collected and appended in an attempt to provide a quick digest of essential knowledge both for comparison and differential diagnosis. The data have been tailored to synthesize diverse sources, integrating clinical elements and references to articles that previously appeared in Part I ("Introduction"), Part II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At the very least we hope this final part ("Appendix") will provide the reader with a useful tabular organization of ST lesions and a reference resource.

Motivation and Organizational Principles for Anatomical Knowledge Representation

PubMed Central

Rosse, Cornelius; Mejino, José L.; Modayur, Bharath R.; Jakobovits, Rex; Hinshaw, Kevin P.; Brinkley, James F.

1998-01-01

Abstract Objective: Conceptualization of the physical objects and spaces that constitute the human body at the macroscopic level of organization, specified as a machine-parseable ontology that, in its human-readable form, is comprehensible to both expert and novice users of anatomical information. Design: Conceived as an anatomical enhancement of the UMLS Semantic Network and Metathesaurus, the anatomical ontology was formulated by specifying defining attributes and differentia for classes and subclasses of physical anatomical entities based on their partitive and spatial relationships. The validity of the classification was assessed by instantiating the ontology for the thorax. Several transitive relationships were used for symbolically modeling aspects of the physical organization of the thorax. Results: By declaring Organ as the macroscopic organizational unit of the body, and defining the entities that constitute organs and higher level entities constituted by organs, all anatomical entities could be assigned to one of three top level classes (Anatomical structure, Anatomical spatial entity and Body substance). The ontology accommodates both the systemic and regional (topographical) views of anatomy, as well as diverse clinical naming conventions of anatomical entities. Conclusions: The ontology formulated for the thorax is extendible to microscopic and cellular levels, as well as to other body parts, in that its classes subsume essentially all anatomical entities that constitute the body. Explicit definitions of these entities and their relationships provide the first requirement for standards in anatomical concept representation. Conceived from an anatomical viewpoint, the ontology can be generalized and mapped to other biomedical domains and problem solving tasks that require anatomical knowledge. PMID:9452983

Transforming to a computerized system for nursing care: organizational success within Magnet idealism.

PubMed

Lindgren, Carolyn L; Elie, Leslie G; Vidal, Elizabeth C; Vasserman, Alex

2010-01-01

In reaching the goal for standardized, quality care, a not-for-profit healthcare system consisting of seven institutional entities is transforming nursing practice guidelines, patient care workflow, and patient documents into electronic, online, real-time modalities for use across departments and all healthcare delivery entities of the system. Organizational structure and a strategic plan were developed for the 2-year Clinical Transformation Project. The Siemens Patient Care Document System was adopted and adapted to the hospitals' documentation and information needs. Two fast-track sessions of more than 100 nurses and representatives from other health disciplines were held to standardize assessments, histories, care protocols, and interdisciplinary plans of care for the top 10 diagnostic regulatory groups. Education needs of the users were addressed. After the first year, a productive, functional system is evidenced. For example, the bar-coded Medication Administration Check System is in full use on the clinical units of one of the hospitals, and the other institutional entities are at substantial stages of implementation of Patient Care Documentation System. The project requires significant allocation of personnel and financial resources for a highly functional informatics system that will transform clinical care. The project exemplifies four of the Magnet ideals and serves as a model for others who may be deciding about launching a similar endeavor.

Spatial layout affects speed discrimination

NASA Technical Reports Server (NTRS)

Verghese, P.; Stone, L. S.

1997-01-01

We address a surprising result in a previous study of speed discrimination with multiple moving gratings: discrimination thresholds decreased when the number of stimuli was increased, but remained unchanged when the area of a single stimulus was increased [Verghese & Stone (1995). Vision Research, 35, 2811-2823]. In this study, we manipulated the spatial- and phase relationship between multiple grating patches to determine their effect on speed discrimination thresholds. In a fusion experiment, we merged multiple stimulus patches, in stages, into a single patch. Thresholds increased as the patches were brought closer and their phase relationship was adjusted to be consistent with a single patch. Thresholds increased further still as these patches were fused into a single patch. In a fission experiment, we divided a single large patch into multiple patches by superimposing a cross with luminance equal to that of the background. Thresholds decreased as the large patch was divided into quadrants and decreased further as the quadrants were maximally separated. However, when the cross luminance was darker than the background, it was perceived as an occluder and thresholds, on average, were unchanged from that for the single large patch. A control experiment shows that the observed trend in discrimination thresholds is not due to the differences in perceived speed of the stimuli. These results suggest that the parsing of the visual image into entities affects the combination of speed information across space, and that each discrete entity effectively provides a single independent estimate of speed.

PROGRESS IN ACUTE MYELOID LEUKEMIA

PubMed Central

Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.

2014-01-01

Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

Primitive myxoid mesenchymal tumor of infancy in a preterm infant.

PubMed

Lam, Joseph; Lara-Corrales, Irene; Cammisuli, Salvatore; Somers, Gino R; Pope, Elena

2010-01-01

Primitive myxoid mesenchymal tumor of infancy is a recently recognized entity that has been added to the differential diagnosis of myxoid tumors of the soft tissue. Few cases have been reported of this entity in the literature, but none presenting in a preterm infant. We present the case and clinical course of a preterm boy with a primitive myxoid mesenchymal tumor of infancy that occurred following excision of a congenital juvenile xanthogranuloma. © 2010 Wiley Periodicals, Inc.

A database of natural products and chemical entities from marine habitat

PubMed Central

Babu, Padavala Ajay; Puppala, Suma Sree; Aswini, Satyavarapu Lakshmi; Vani, Metta Ramya; Kumar, Chinta Narasimha; Prasanna, Tallapragada

2008-01-01

Marine compound database consists of marine natural products and chemical entities, collected from various literature sources, which are known to possess bioactivity against human diseases. The database is constructed using html code. The 12 categories of 182 compounds are provided with the source, compound name, 2-dimensional structure, bioactivity and clinical trial information. The database is freely available online and can be accessed at http://www.progenebio.in/mcdb/index.htm PMID:19238254

Perceived visual speed constrained by image segmentation

NASA Technical Reports Server (NTRS)

Verghese, P.; Stone, L. S.

1996-01-01

Little is known about how or where the visual system parses the visual scene into objects or surfaces. However, it is generally assumed that the segmentation and grouping of pieces of the image into discrete entities is due to 'later' processing stages, after the 'early' processing of the visual image by local mechanisms selective for attributes such as colour, orientation, depth, and motion. Speed perception is also thought to be mediated by early mechanisms tuned for speed. Here we show that manipulating the way in which an image is parsed changes the way in which local speed information is processed. Manipulations that cause multiple stimuli to appear as parts of a single patch degrade speed discrimination, whereas manipulations that perceptually divide a single large stimulus into parts improve discrimination. These results indicate that processes as early as speed perception may be constrained by the parsing of the visual image into discrete entities.

Adverse event management of oral mucositis in patients with breast cancer.

PubMed

Seiler, Sabine; Kosse, Jens; Loibl, Sibylle; Jackisch, Christian

2014-04-01

Oral mucositis (OM) is a clinically important and frequent adverse event (AE) associated with cancer treatment with conventional chemotherapy as well as new targeted agents. Incidence and severity of OM vary from treatment to treatment and from patient to patient. The pathogenesis of chemotherapy-induced OM can be divided into 5 phases. OM induced by targeted therapies differs among other things in appearance, course, concomitant AEs and toxicity, and thus could be perceived as an entity distinct from chemotherapy-induced OM with an innate pathogenic mechanism. OM has a severe impact on a patient's quality of life (QoL) by causing complications such as pain and discomfort. Even more important are associated restrictions in nutrition and hydration. Thus, the efficacy of cancer therapy might be impaired due to the necessity of dose delays and dose reductions. Numerous preventive and therapeutic approaches have been evaluated, but currently no single agent has changed the standard of care in preventing and treating OM. Thus, the current management has evolved from clinical experience rather than clinical evidence. This article will review the AE 'OM' induced by breast cancer treatment with chemotherapy and targeted agents in order to provide practical guidance for management and prevention.

Perception of Animacy from the Motion of a Single Sound Object.

PubMed

Nielsen, Rasmus Høll; Vuust, Peter; Wallentin, Mikkel

2015-02-01

Research in the visual modality has shown that the presence of certain dynamics in the motion of an object has a strong effect on whether or not the entity is perceived as animate. Cues for animacy are, among others, self-propelled motion and direction changes that are seemingly not caused by entities external to, or in direct contact with, the moving object. The present study aimed to extend this research into the auditory domain by determining if similar dynamics could influence the perceived animacy of a sound source. In two experiments, participants were presented with single, synthetically generated 'mosquito' sounds moving along trajectories in space, and asked to rate how certain they were that each sound-emitting entity was alive. At a random point on a linear motion trajectory, the sound source would deviate from its initial path and speed. Results confirm findings from the visual domain that a change in the velocity of motion is positively correlated with perceived animacy, and changes in direction were found to influence animacy judgment as well. This suggests that an ability to facilitate and sustain self-movement is perceived as a living quality not only in the visual domain, but in the auditory domain as well. © 2015 SAGE Publications.

Coreference analysis in clinical notes: a multi-pass sieve with alternate anaphora resolution modules

PubMed Central

Li, Dingcheng; Sohn, Sunghwan; Wu, Stephen Tze-Inn; Wagholikar, Kavishwar; Torii, Manabu; Liu, Hongfang

2012-01-01

Objective This paper describes the coreference resolution system submitted by Mayo Clinic for the 2011 i2b2/VA/Cincinnati shared task Track 1C. The goal of the task was to construct a system that links the markables corresponding to the same entity. Materials and methods The task organizers provided progress notes and discharge summaries that were annotated with the markables of treatment, problem, test, person, and pronoun. We used a multi-pass sieve algorithm that applies deterministic rules in the order of preciseness and simultaneously gathers information about the entities in the documents. Our system, MedCoref, also uses a state-of-the-art machine learning framework as an alternative to the final, rule-based pronoun resolution sieve. Results The best system that uses a multi-pass sieve has an overall score of 0.836 (average of B3, MUC, Blanc, and CEAF F score) for the training set and 0.843 for the test set. Discussion A supervised machine learning system that typically uses a single function to find coreferents cannot accommodate irregularities encountered in data especially given the insufficient number of examples. On the other hand, a completely deterministic system could lead to a decrease in recall (sensitivity) when the rules are not exhaustive. The sieve-based framework allows one to combine reliable machine learning components with rules designed by experts. Conclusion Using relatively simple rules, part-of-speech information, and semantic type properties, an effective coreference resolution system could be designed. The source code of the system described is available at https://sourceforge.net/projects/ohnlp/files/MedCoref. PMID:22707745

Direct injury to right coronary artery in patients undergoing tricuspid annuloplasty.

PubMed

Díez-Villanueva, Pablo; Gutiérrez-Ibañes, Enrique; Cuerpo-Caballero, Gregorio P; Sanz-Ruiz, Ricardo; Abeytua, Manuel; Soriano, Javier; Sarnago, Fernando; Elízaga, Jaime; González-Pinto, Angel; Fernández-Avilés, Francisco

2014-04-01

Direct injury to the right coronary artery as a result of reparative operation on the tricuspid valve is a rare, probably underdiagnosed, but serious complication, which often involves dramatic clinical consequences. So far, only five cases have been described in the literature. We describe our single-center experience of this complication, and review and analyze relevant clinical and anatomic considerations related to this entity. Cases previously reported in the literature were also reviewed. We describe four cases of direct injury to the right coronary artery in patients undergoing tricuspid annuloplasty (DeVega annuloplasty, 3; ring annuloplasty, 1) in our institution since 2005. All patients had right ventricular dilatation and severely dilated tricuspid annulus. Right coronary artery occlusion always occurred between the right marginal artery and the crux of the heart. Patients presented with hemodynamic or electrical instability. Coronary flow could be restored in 2 patients (percutaneously 1; surgically 1), both of whom finally survived, while it was not technically possible in the other 2 (1 died). Occlusion of the right coronary artery in patients undergoing tricuspid annuloplasty is a rare complication that may occur if great annulus dilatation is present, thus altering both normal annular geometry and the relationship between the right coronary artery and the tricuspid annulus, particularly when DeVega annuloplasty is performed. Such an entity should be considered in the immediate postoperative period in an unstable patient, especially when complementary tests support this diagnosis. Prompt recognition and treatment can positively affect the patient's outcome, most often by means of an emergency revascularization strategy. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Sternal wound infection after cardiac surgery: incidence and risk factors according to clinical presentation.

PubMed

Lemaignen, A; Birgand, G; Ghodhbane, W; Alkhoder, S; Lolom, I; Belorgey, S; Lescure, F-X; Armand-Lefevre, L; Raffoul, R; Dilly, M-P; Nataf, P; Lucet, J C

2015-07-01

The incidence of surgical site infection (SSI) after cardiac surgery depends on the definition used. A distinction is generally made between mediastinitis, as defined by the US Centers for Disease Control and Prevention (CDC), and superficial SSI. Our objective was to decipher these entities in terms of presentation and risk factors. We performed a 7-year single centre analysis of prospective surveillance of patients with cardiac surgery via median sternotomy. SSI was defined as the need for reoperation due to infection. Among 7170 patients, 292 (4.1%) developed SSI, including 145 CDC-defined mediastinitis (CDC-positive SSI, 2.0%) and 147 superficial SSI without associated bloodstream infection (CDC-negative SSI, 2.1%). Median time to reoperation for CDC-negative SSI was 18 days (interquartile range, 14-26) and 16 (interquartile range, 11-24) for CDC-positive SSI (p 0.02). Microorganisms associated with CDC-negative SSI were mainly skin commensals (62/147, 41%) or originated in the digestive tract (62/147, 42%); only six were due to Staphylococcus aureus (4%), while CDC-positive SSI were mostly due to S. aureus (52/145, 36%) and germs from the digestive tract (52/145, 36%). Risk factors for SSI were older age, obesity, chronic obstructive bronchopneumonia, diabetes mellitus, critical preoperative state, postoperative vasopressive support, transfusion or prolonged ventilation and coronary artery bypass grafting, especially if using both internal thoracic arteries in female patients. The number of internal thoracic arteries used and factors affecting wound healing were primarily associated with CDC-negative SSI, whereas comorbidities and perioperative complications were mainly associated with CDC-positive SSI. These 2 entities differed in time to revision surgery, bacteriology and risk factors, suggesting a differing pathophysiology. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders

PubMed Central

de Pedro-Cuesta, Jesús; Martínez-Martín, Pablo; Rábano, Alberto; Alcalde-Cabero, Enrique; José García López, Fernando; Almazán-Isla, Javier; Ruiz-Tovar, María; Medrano, Maria-José; Avellanal, Fuencisla; Calero, Olga; Calero, Miguel

2016-01-01

Background: Sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (NDDs), there was a need to identify specific “drivers”, i.e., risk factors with impact on specific deposits, such as amyloid-β, tau, or α-synuclein, acting across entities. Objectives and Methods: Redefining drivers as “neither protein/gene- nor entity-specific features identifiable in the clinical and general epidemiology of conformational NDDs (CNDDs) as potential footprints of templating/spread/transfer mechanisms”, we conducted an analysis of the epidemiology of ten CNDDs, searching for patterns. Results: We identified seven potential drivers, each of which was shared by at least two CNDDs: 1) an age-at-exposure-related susceptibility to Creutzfeldt-Jakob disease (CJD) and several late-life CNDDs; 2) a relationship between age at onset, survival, and incidence; 3) shared genetic risk factors for CJD and late-life CNNDs; 4) partly shared personal (diagnostic, educational, behavioral, and social risk factors) predating clinical onset of late-life CNDDs; 5) two environmental risk factors, namely, surgery for sporadic CJD and amyotrophic lateral sclerosis, and Bordetella pertussis infection for Parkinson’s disease; 6) reticulo-endothelial system stressors or general drivers (andropause or premenopausal estrogen deficiency, APOEɛ4, and vascular risk factors) for late-life CNDDs such as dementia/Alzheimer’s disease, type-2 diabetes mellitus, and some sporadic cardiac and vascular degenerative diseases; and 7) a high, invariant incidence ratio of sporadic to genetic forms of mid- and late-life CNDDs, and type-2 diabetes mellitus. Conclusion: There might be a systematic epidemiologic pattern induced by specific proteins (PrP, TDP-43, SOD1, α-synuclein, amyloid-β, tau, Langerhans islet peptide, and transthyretin) or established combinations of these. PMID:26923014

On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

PubMed

Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

2015-08-01

The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Strategic planning in healthcare: the experience of the University of Wisconsin Hospital and Clinics.

PubMed

Sollenberger, Donna K

2006-01-01

In 1999, after 25 years of stable leadership from a single CEO, the University of Wisconsin Hospital and Clinics (UWHC) Authority Board named a new CEO. The 471-bed academic medical center had recently experienced significant change and challenges. In 1996, it had emerged as a public authority, a statutory designation by the state of Wisconsin that moved the hospital and clinics from the University of Wisconsin and the state of Wisconsin, and created it as a quasi-public entity with its own board. In 1999, when the new CEO was named, the hospital was experiencing a loss of revenue and market share, operating deficits, a 22 percent nurse vacancy rate, and patient satisfaction scores below the 40th percentile. The first task assigned to the new CEO by the board was the development of a new strategic plan that would reverse these trends and position UWHC as a premier academic hospital. The CEO began a strategic planning process that involved leaders, physicians, and staff from throughout the hospital and clinics, its affiliated medical school, and the physician practice plan. This article describes the collaborative, integrative, and communicative strategic planning process UWHC used; details the organization of the process; describes the results achieved by UWHC; and lists the lessons learned along the way.

Benign hepatocellular nodules of healthy liver: focal nodular hyperplasia and hepatocellular adenoma

PubMed Central

Roncalli, Massimo; Sciarra, Amedeo; Tommaso, Luca Di

2016-01-01

Owing to the progress of imaging techniques, benign hepatocellular nodules are increasingly discovered in the clinical practice. This group of lesions mostly arises in the context of a putatively normal healthy liver and includes either pseudotumoral and tumoral nodules. Focal nodular hyperplasia and hepatocellular adenoma are prototypical examples of these two categories of nodules. In this review we aim to report the main pathological criteria of differential diagnosis between focal nodular hyperplasia and hepatocellular adenoma, which mainly rests upon morphological and phenotypical features. We also emphasize that for a correct diagnosis the clinical context such as sex, age, assumption of oral contraceptives, associated metabolic or vascular disturbances is of paramount importance. While focal nodular hyperplasia is a single entity epidemiologically more frequent than adenoma, the latter is representative of a more heterogeneous group which has been recently and extensively characterized from a clinical, morphological, phenotypical and molecular profile. The use of the liver biopsy in addition to imaging and the clinical context are important diagnostic tools of these lesions. In this review we will survey their systematic pathobiology and propose a diagnostic algorithm helpful to increase the diagnostic accuracy of not dedicated liver pathologists. The differential diagnosis between so-called typical and atypical adenoma and well differentiated hepatocellular carcinoma will also be discussed. PMID:27189732

The evolving definition of essential tremor: What are we dealing with?

PubMed

Louis, Elan D

2018-01-01

Although essential tremor (ET) is commonly encountered in clinical practice, historically, there has been considerable disagreement as how to best define it, and now with a growing sense of its clinical complexity, how to best encapsulate it. Here, I draw attention to five issues of current uncertainty. A PubMed search conducted on June 19, 2017 crossed "essential tremor" with 9 second search terms (e.g., definition, diagnosis). There are several major issues of clinical and diagnostic uncertainty. Underlying each issue is a larger question about the nature of the underlying pathophysiology of ET. Does age of onset of ET matter? How much dystonia is acceptable in ET? How much in the way of "cerebellar signs" are acceptable? Are non-motor features due to the underlying disease or merely secondary to the clinical features? Is ET a single disease entity or something else? We are learning more about ET and, as a by-product of these efforts, are struggling with its definition. Further understanding the nature of the underlying disease pathogenesis as well as the role the cerebellum and cerebellar relays play in this process will likely provide important clues to enable us to bring order to areas of uncertainty. Copyright © 2017 Elsevier Ltd. All rights reserved.

H syndrome: the first 79 patients.

PubMed

Molho-Pessach, Vered; Ramot, Yuval; Camille, Frances; Doviner, Victoria; Babay, Sofia; Luis, Siekavizza Juan; Broshtilova, Valentina; Zlotogorski, Abraham

2014-01-01

H syndrome is an autosomal recessive genodermatosis with multisystem involvement caused by mutations in SLC29A3. We sought to investigate the clinical and molecular findings in 79 patients with this disorder. A total of 79 patients were included, of which 13 are newly reported cases. Because of the phenotypic similarity and molecular overlap with H syndrome, we included 18 patients with allelic disorders. For 31 patients described by others, data were gathered from the medical literature. The most common clinical features (>45% of patients) were hyperpigmentation, phalangeal flexion contractures, hearing loss, and short stature. Insulin-dependent diabetes mellitus and lymphadenopathy mimicking Rosai-Dorfman disease were each found in approximately 20%. Additional systemic features were described in less than 15% of cases. Marked interfamilial and intrafamilial clinical variability exists. Twenty mutations have been identified in SLC29A3, with no genotype-phenotype correlation. In the 31 patients described by others, data were collected from the medical literature. H syndrome is a multisystemic disease with clinical variability. Consequently, all SLC29A3-related diseases should be considered a single entity. Recognition of the pleomorphic nature of H syndrome is important for diagnosis of additional patients. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

The Independent Technical Analysis Process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duberstein, Corey A.; Ham, Kenneth D.; Dauble, Dennis D.

2007-04-13

The Bonneville Power Administration (BPA) contracted with the Pacific Northwest National Laboratory (PNNL) to provide technical analytical support for system-wide fish passage information (BPA Project No. 2006-010-00). The goal of this project was to produce rigorous technical analysis products using independent analysts and anonymous peer reviewers. In the past, regional parties have interacted with a single entity, the Fish Passage Center to access the data, analyses, and coordination related to fish passage. This project provided an independent technical source for non-routine fish passage analyses while allowing routine support functions to be performed by other well-qualified entities.

[What is dementia? 2. A fuzzy construct].

PubMed

Derouesné, Christian

2003-03-01

Since the publication of the third edition of the classification of mental disorders by the American Psychiatric Association, APA (DSM-III) in 1980, a large international consensus has been reached to define dementia as a multiple cognitive deficit centered by memory disturbances, interfering with the daily life activities and related to organic brain lesions. The DSM-III defined a diagnostic strategy in two steps. First to make the diagnosis of dementia according to the clinical criteria and then to specify its etiology. The more recent editions of the APA classification did not significantly modify these recommendations. The use of the DSM criteria has allowed important advances in epidemiological, clinical and therapeutic research. However, several criticisms should be addressed to the clinical diagnostic criteria as well as to the current concept of dementia. First, from a theoretical point of view, dementia is not a disease, not even a disorder. It only corresponds to a conventional collection of symptoms. Actually, clinical symptoms of dementia basically depend of the localization of brain lesions. Therefore, there could not be one single dementia syndrome. Similarly, the basis of the search for one "antidementia drug" should be questioned. From a clinical point of view, the DSM-IV criteria present some inaccuracies regarding the description of deficits in memory and executive functions as well as in the assessment of the interference of the cognitive decline with the activities of daily living. The definition of dementia as a purely cognitive deficit results in neglecting its psychological and relational manifestations which play a large part in the detection of dementia and its acceptance by the family. A major criticism concerns the definition of dementia as a sincle clinical entity with memory deficits as the core symptom. This definition is well adapted to Alzheimer's disease but results in delayed diagnosis or misclassification of dementias such as frontotemporal dementia or dementia with Lewy bodies in which memory deficits are minor or late. Presently, diagnostic strategy should be directed towards specific entities such as Alzheimer's disease which can be diagnosed accurately in mildly impaired individuals. It is proposed that the term dementia should only be used to specify a degree of severity of the disease, corresponding to the restriction of the patient's autonomy.

Compulsive buying: an overlooked entity.

PubMed

Basu, Bishnupriya; Basu, Saikat; Basu, Jharna

2011-08-01

Compulsive buying is an under-recognised entity among Indian psychiatrists. A Medline search, hand searching of journals and direct communications with lead investigators in compulsive buying have generated numerous studies. Overseas data indicate a community prevalence between 1% and 8% . The phenomenon can be an independent entity or appears as a comorbidity with another axis I or axis II disorder. A degree of suspicion on part of clinician regarding its possible presence is the key to its detection. A few rating instruments are available to quantify the morbidity and screening for compulsive buying. Management involves pharmacotherapy with SSRIs, psychotherapy, self-help groups and self-help books. Epidemiological and clinical studies on compulsive buying should be undertaken by Indian psychiatrists to provide better services for people suffering from compulsive buying.

Scalp Metastasis as the First Sign of Small-Cell Lung Cancer: Management and Literature Review

PubMed Central

Salemis, Nikolaos S.; Veloudis, Georgios; Spiliopoulos, Kyriakos; Nakos, Georgios; Vrizidis, Nikolaos; Gourgiotis, Stavros

2014-01-01

Cutaneous metastasis from primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 10% among various series. However, the presence of cutaneous metastasis as the first sign of a clinically silent visceral cancer is exceedingly rare. We describe here a case of an asymptomatic male patient who presented with a solitary scalp metastasis as the initial manifestation of an underlying small-cell lung cancer. Diagnostic evaluation revealed advanced disease. We conclude that the possibility of metastatic skin disease should always be considered in the differential diagnosis in patients with a history of smoking or lung cancer presenting with cutaneous nodules. Physicians should be aware of this rare clinical entity, and appropriate investigation should be arranged for early diagnosis and initiation of the appropriate treatment. The prognosis for most patients remains poor. PMID:25058760

Scalp metastasis as the first sign of small-cell lung cancer: management and literature review.

PubMed

Salemis, Nikolaos S; Veloudis, Georgios; Spiliopoulos, Kyriakos; Nakos, Georgios; Vrizidis, Nikolaos; Gourgiotis, Stavros

2014-01-01

Cutaneous metastasis from primary visceral malignancy is a relatively uncommon clinical entity, with a reported incidence ranging from 0.22% to 10% among various series. However, the presence of cutaneous metastasis as the first sign of a clinically silent visceral cancer is exceedingly rare. We describe here a case of an asymptomatic male patient who presented with a solitary scalp metastasis as the initial manifestation of an underlying small-cell lung cancer. Diagnostic evaluation revealed advanced disease. We conclude that the possibility of metastatic skin disease should always be considered in the differential diagnosis in patients with a history of smoking or lung cancer presenting with cutaneous nodules. Physicians should be aware of this rare clinical entity, and appropriate investigation should be arranged for early diagnosis and initiation of the appropriate treatment. The prognosis for most patients remains poor.

Advanced Pharmacotherapy Evidenced by Pathogenesis of Autism Spectrum Disorder

PubMed Central

Lee, Yeon Jung; Oh, Soo Hyun; Park, Chanmin; Hong, Minha; Lee, Ah Rah; Yoo, Hee Jeong; Shin, Chan Young; Cheon, Keun-Ah

2014-01-01

In clinical practice, pharmacological treatment is mostly focused on behavioral symptoms in everyday life. Nevertheless, persistent effort continues to develop medication for causal treatment. Recent changes in diagnostic criteria from Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) to DSM-5 would affect not only diagnosing approaches, but also therapeutic approaches. Because previous pervasive developmental disorders have been integrated into a single entity, the autism spectrum disorder (ASD), we have to prepare for what medications are valuable for the ASD. In this article, we reviewed the following etiological treatment: acetylcholine and glutamate related medicine; amino acid medicine such as secretin, endogenous opioid, and oxytocin; complementary and alternative medicine such as chelating agents, vitamins, and omega-3; promising drugs related to the scope of pharmacogenetics currently under study. PMID:24851117

Drug development costs when financial risk is measured using the Fama-French three-factor model.

PubMed

Vernon, John A; Golec, Joseph H; Dimasi, Joseph A

2010-08-01

In a widely cited article, DiMasi, Hansen, and Grabowski (2003) estimate the average pre-tax cost of bringing a new molecular entity to market. Their base case estimate, excluding post-marketing studies, was $802 million (in $US 2000). Strikingly, almost half of this cost (or $399 million) is the cost of capital (COC) used to fund clinical development expenses to the point of FDA marketing approval. The authors used an 11% real COC computed using the capital asset pricing model (CAPM). But the CAPM is a single factor risk model, and multi-factor risk models are the current state of the art in finance. Using the Fama-French three factor model we find that the cost of drug development to be higher than the earlier estimate. Copyright (c) 2009 John Wiley & Sons, Ltd.

The DSM diagnostic criteria for vaginismus.

PubMed

Binik, Yitzchak M

2010-04-01

Vaginal spasm has been considered the defining diagnostic characteristic of vaginismus for approximately 150 years. This remarkable consensus, based primarily on expert clinical opinion, is preserved in the DSM-IV-TR. The available empirical research, however, does not support this definition nor does it support the validity of the DSM-IV-TR distinction between vaginismus and dyspareunia. The small body of research concerning other possible ways or methods of diagnosing vaginismus is critically reviewed. Based on this review, it is proposed that the diagnoses of vaginismus and dyspareunia be collapsed into a single diagnostic entity called "genito-pelvic pain/penetration disorder." This diagnostic category is defined according to the following five dimensions: percentage success of vaginal penetration; pain with vaginal penetration; fear of vaginal penetration or of genito-pelvic pain during vaginal penetration; pelvic floor muscle dysfunction; medical co-morbidity.

POLG1 mutations and stroke like episodes: a distinct clinical entity rather than an atypical MELAS syndrome.

PubMed

Cheldi, Antonella; Ronchi, Dario; Bordoni, Andreina; Bordo, Bianca; Lanfranconi, Silvia; Bellotti, Maria Grazia; Corti, Stefania; Lucchini, Valeria; Sciacco, Monica; Moggio, Maurizio; Baron, Pierluigi; Comi, Giacomo Pietro; Colombo, Antonio; Bersano, Anna

2013-01-15

POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations.

[Cyclothymic obsessive-compulsive disorder. Clinical characteristics of a neglected and under-recognized entity].

PubMed

Hantouche, E G; Demonfaucon, C; Angst, J; Perugi, G; Allilaire, J F; Akiskal, H S

2002-04-13

Clinical research is largely focused on depressive comorbidity in obsessional compulsive disorder (OCD). However some recent publications have suggested that bipolar comorbidity occurs in authentic OCD and its presence has a differential impact on the clinical picture and course of OCD. Recent data from the collaborative survey conducted with AFTOC (French Association of patients suffering from OCD) have revealed a high rate of bipolar comorbidity in OCD: 30% for hypomania and 50% for cyclothymia. The present paper presents further comparative analyses between OCD with (n = 302) versus without cyclothymia (n = 272). The sub-group "Cyclothymic OCD" is characterized by a different clinical picture (higher frequency of aggressive, impulsive, religious and sexual obsessions, and compulsions of control, hoarding, repetition), episodic course, higher rate of major depressive episodes (with more intensity and recurrence) associated with higher rates of suicide attempts and psychiatric admissions, and less favorable response to anti-OCD treatments. These data suggested that cyclothymic OCD could represent a specific distinct variant form of OCD. More vigilance is needed toward this entity which is largely under-recognized in clinical practice.

Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.

PubMed

Bando, Hironori; Iguchi, Genzo; Yamamoto, Masaaki; Hidaka-Takeno, Ryoko; Takahashi, Yutaka

2015-03-01

Various hypothalamic-pituitary diseases cause hypopituitarism. Inflammation related to autoimmunity also causes hypopituitarism. Hypophysitis is a representative disease caused by autoimmunity. Generally, anterior pituitary hormones are non-specifically impaired in this condition, but specific hormone defects have been reported in some cases. Anti-PIT-1 (pituitary-specific transcription factor 1) antibody syndrome is a novel clinical entity that presents an acquired combined pituitary hormone deficiency characterized by a specific defect in growth hormone, prolactin, and thyroid-stimulating hormone. Circulating anti-PIT-1 antibody along with various autoantibodies are detected with multiple endocrine organopathy, meeting the definition of autoimmune polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that specifically react with PIT-1 protein play an important role in the development of this syndrome.

Unilateral RS3PE in a Patient of Seronegative Rheumatoid Arthritis

PubMed Central

Varshney, Ankur Nandan; Kumar, Nilesh; Tiwari, Ashutosh; Anand, Ravi; Prasad, Sashi Ranjan; Anand, Arvind; Mishra, Abhinandan; Singh, N. K.

2013-01-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare but well-reported clinical entity. It is classically described as symmetrical involvement of both upper extremities. Asymmetrical involvement had also been reported, but unilateral presentation is very rare. We hereby report a case of unilateral RS3PE in a patient of seronegative rheumatoid arthritis which was initially misdiagnosed as cellulitis and was given high dose antibiotics without any significant improvement. Later a rheumatologic consultation leads to a prompt diagnosis, and treatment with steroids leads to dramatic reversal of symptoms. This case demonstrates the rare presentation of this rare clinical entity and highlights the necessity of awareness regarding unilateral disease to clinicians. PMID:23662237

Electrons, Photons, and Force: Quantitative Single-Molecule Measurements from Physics to Biology

PubMed Central

2011-01-01

Single-molecule measurement techniques have illuminated unprecedented details of chemical behavior, including observations of the motion of a single molecule on a surface, and even the vibration of a single bond within a molecule. Such measurements are critical to our understanding of entities ranging from single atoms to the most complex protein assemblies. We provide an overview of the strikingly diverse classes of measurements that can be used to quantify single-molecule properties, including those of single macromolecules and single molecular assemblies, and discuss the quantitative insights they provide. Examples are drawn from across the single-molecule literature, ranging from ultrahigh vacuum scanning tunneling microscopy studies of adsorbate diffusion on surfaces to fluorescence studies of protein conformational changes in solution. PMID:21338175

Partial uniparental isodisomy of chromosome 16 unmasks a deleterious biallelic mutation in IFT140 that causes Mainzer-Saldino syndrome.

PubMed

Helm, Benjamin M; Willer, Jason R; Sadeghpour, Azita; Golzio, Christelle; Crouch, Eric; Vergano, Samantha Schrier; Katsanis, Nicholas; Davis, Erica E

2017-07-19

The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite the advances in gene discovery, this group of entities continues to pose a diagnostic challenge, in part due to significant genetic and phenotypic heterogeneity and variability. We consulted a pediatric case from asymptomatic, non-consanguineous parents who presented as a suspected ciliopathy due to a constellation of retinal, renal, and skeletal findings. Although clinical panel sequencing of genes implicated in nephrotic syndromes yielded no likely causal mutation, an oligo-SNP microarray identified a ~20-Mb region of homozygosity, with no altered gene dosage, on chromosome 16p13. Intersection of the proband's phenotypes with known disease genes within the homozygous region yielded a single candidate, IFT140, encoding a retrograde intraflagellar transport protein implicated previously in several ciliopathies, including the phenotypically overlapping Mainzer-Saldino syndrome (MZSDS). Sanger sequencing yielded a maternally inherited homozygous c.634G>A; p.Gly212Arg mutation altering the exon 6 splice donor site. Functional studies in cells from the proband showed that the locus produced two transcripts: a majority message containing a mis-splicing event that caused a premature termination codon and a minority message homozygous for the p.Gly212Arg allele. Zebrafish in vivo complementation studies of the latter transcript demonstrated a loss of function effect. Finally, we conducted post-hoc trio-based whole exome sequencing studies to (a) test the possibility of other causal loci in the proband and (b) explain the Mendelian error of segregation for the IFT140 mutation. We show that the proband harbors a chromosome 16 maternal heterodisomy, with segmental isodisomy at 16p13, likely due to a meiosis I error in the maternal gamete. Using clinical phenotyping combined with research-based genetic and functional studies, we have characterized a recurrent IFT140 mutation in the proband; together, these data are consistent with MZSDS. Additionally, we report a rare instance of a uniparental isodisomy unmasking a deleterious mutation to cause a ciliary disorder.

Resolving Rivalries and Realigning Goals: Challenges of Clinical and Research Multiteam Systems.

PubMed

Gerber, David E; Reimer, Torsten; Williams, Erin L; Gill, Mary; Loudat Priddy, Laurin; Bergestuen, Deidi; Schiller, Joan H; Kirkpatrick, Haskell; Craddock Lee, Simon J

2016-11-01

This article describes the care processes for a 64-year-old man with newly diagnosed advanced non-small-cell lung cancer who was enrolled in a first-line clinical trial of a new immunotherapy regimen. The case highlights the concept of multiteam systems in cancer clinical research and clinical care. Because clinical research represents a highly dynamic entity-with studies frequently opening, closing, and undergoing modifications-concerted efforts of multiple teams are needed to respond to these changes while continuing to provide consistent, high-level care and timely, accurate clinical data. The case illustrates typical challenges of multiteam care processes. Compared with clinical tasks that are routinely performed by single teams, multiple-team care greatly increases the demands for communication, collaboration, cohesion, and coordination among team members. As the case illustrates, the described research team and clinical team are separated, resulting in suboptimal function. Individual team members interact predominantly with members of their own team. A considerable number of team members lack regular interaction with anyone outside their team. Accompanying this separation, the teams enact rivalries that impede collaboration. The teams have misaligned goals and competing priorities that create competition. Collective identity and cohesion across the two teams are low. Research team and clinical team members have limited knowledge of the roles and work of individuals outside their team. Recommendations to increase trust and collaboration are provided. Clinical providers and researchers may incorporate these themes into development and evaluation of multiteam systems, multidisciplinary teams, and cross-functional teams within their own institutions.

Assignment of a gene for autosomal recessive retinitis pigmentosa (RP12) to chromosome 1q31-q32.1 in an inbred and genetically heterogeneous disease population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Soest, S.; Ingeborgh Van Den Born, L.; Bergen, A.A.B.

1994-08-01

Linkage analysis was carried out in a large family segregating for autosomal recessive retinitis pigmentosa (arRP), originating from a genetically isolated population in The Netherlands. Within the family, clinical heterogeneity was observed, with a major section of the family segregating arRP with characteristic para-arteriolar preservation of the retinal pigment epithelium (PPRPE). In the remainder of the arRP patients no PPRPE was found. Initially, all branches of the family were analyzed jointly, and linkage was found between the marker F13B, located at 1q31-q32.1, and RP12 ({Zeta}{sub max} = 4.99 at 8% recombination). Analysis of linkage heterogeneity between five branches of themore » family yielded significant evidence for nonallelic genetic heterogeneity within this family, coinciding with the observed clinical differences. Multipoint analysis, carried out in the branches that showed linkage, favored the locus order 1cen-D1S158-(F13B, RP12)-D1S53-1qter ({Zeta}{sub max} = 9.17). The finding of a single founder allele associated with the disease phenotype supports this localization. This study reveals that even in a large family, apparently segregating for a single disease entity, genetic heterogeneity can be detected and resolved successfully. 35 refs., 5 figs.« less

Towards Clinical Applications of Anti-endotoxin Antibodies; A Re-appraisal of the Disconnect

PubMed Central

Hurley, James C.

2013-01-01

Endotoxin is a potent mediator of a broad range of patho-physiological effects in humans. It is present in all Gram negative (GN) bacteria. It would be expected that anti-endotoxin therapies, whether antibody based or not, would have an important adjuvant therapeutic role along with antibiotics and other supportive therapies for GN infections. Indeed there is an extensive literature relating to both pre-clinical and clinical studies of anti-endotoxin antibodies. However, the extent of disconnect between the generally successful pre-clinical studies versus the failures of the numerous large clinical trials of antibody based and other anti-endotoxin therapies is under-appreciated and unexplained. Seeking a reconciliation of this disconnect is not an abstract academic question as clinical trials of interventions to reduce levels of endotoxemia levels are ongoing. The aim of this review is to examine new insights into the complex relationship between endotoxemia and sepsis in an attempt to bridge this disconnect. Several new factors to consider in this reappraisal include the frequency and types of GN bacteremia and the underlying mortality risk in the various study populations. For a range of reasons, endotoxemia can no longer be considered as a single entity. There are old clinical trials which warrant a re-appraisal in light of these recent advances in the understanding of the structure-function relationship of endotoxin. Fundamentally however, the disconnect not only remains, it has enlarged. PMID:24351718

Machine learning to parse breast pathology reports in Chinese.

PubMed

Tang, Rong; Ouyang, Lizhi; Li, Clara; He, Yue; Griffin, Molly; Taghian, Alphonse; Smith, Barbara; Yala, Adam; Barzilay, Regina; Hughes, Kevin

2018-06-01

Large structured databases of pathology findings are valuable in deriving new clinical insights. However, they are labor intensive to create and generally require manual annotation. There has been some work in the bioinformatics community to support automating this work via machine learning in English. Our contribution is to provide an automated approach to construct such structured databases in Chinese, and to set the stage for extraction from other languages. We collected 2104 de-identified Chinese benign and malignant breast pathology reports from Hunan Cancer Hospital. Physicians with native Chinese proficiency reviewed the reports and annotated a variety of binary and numerical pathologic entities. After excluding 78 cases with a bilateral lesion in the same report, 1216 cases were used as a training set for the algorithm, which was then refined by 405 development cases. The Natural language processing algorithm was tested by using the remaining 405 cases to evaluate the machine learning outcome. The model was used to extract 13 binary entities and 8 numerical entities. When compared to physicians with native Chinese proficiency, the model showed a per-entity accuracy from 91 to 100% for all common diagnoses on the test set. The overall accuracy of binary entities was 98% and of numerical entities was 95%. In a per-report evaluation for binary entities with more than 100 training cases, 85% of all the testing reports were completely correct and 11% had an error in 1 out of 22 entities. We have demonstrated that Chinese breast pathology reports can be automatically parsed into structured data using standard machine learning approaches. The results of our study demonstrate that techniques effective in parsing English reports can be scaled to other languages.

Towards an Obesity-Cancer Knowledge Base: Biomedical Entity Identification and Relation Detection

PubMed Central

Lossio-Ventura, Juan Antonio; Hogan, William; Modave, François; Hicks, Amanda; Hanna, Josh; Guo, Yi; He, Zhe; Bian, Jiang

2017-01-01

Obesity is associated with increased risks of various types of cancer, as well as a wide range of other chronic diseases. On the other hand, access to health information activates patient participation, and improve their health outcomes. However, existing online information on obesity and its relationship to cancer is heterogeneous ranging from pre-clinical models and case studies to mere hypothesis-based scientific arguments. A formal knowledge representation (i.e., a semantic knowledge base) would help better organizing and delivering quality health information related to obesity and cancer that consumers need. Nevertheless, current ontologies describing obesity, cancer and related entities are not designed to guide automatic knowledge base construction from heterogeneous information sources. Thus, in this paper, we present methods for named-entity recognition (NER) to extract biomedical entities from scholarly articles and for detecting if two biomedical entities are related, with the long term goal of building a obesity-cancer knowledge base. We leverage both linguistic and statistical approaches in the NER task, which supersedes the state-of-the-art results. Further, based on statistical features extracted from the sentences, our method for relation detection obtains an accuracy of 99.3% and a f-measure of 0.993. PMID:28503356

Globulomaxillary cysts--do they really exist?

PubMed

Dammer, U; Driemel, O; Mohren, W; Giedl, C; Reichert, T E

2014-01-01

The so-called "globulomaxillary cyst", described as a fissural cyst, caused by entrapped epithelium between the nasal and maxillary process, is no longer considered for its own entity. Nevertheless, cystic lesions, which correspond to the previous image of globulomaxillary cysts, do still occur in daily practice. This raises the question to which entities pathological processes in this particular region actually belong to. In a retrospective study, 17 cases (12 men and 5 women, 12-59 years old) of primarily diagnosed globulomaxillary cysts are analysed according to clinical, radiological and histological aspects, catamnestic processed and assigned to a new entity. The results are compared with the international literature and draws conclusions on the diagnostic and therapeutic procedure. Seven lateral periodontal cysts, four radicular cysts, two keratocystic odontogenic tumours, one adenomatoid odontogenic tumour, one periapical granuloma, one residual cyst and one undefined jaw cyst were determined. According to the results of our study and the data from the international literature, the entity globulomaxillary cyst is no longer justified.

The mass-action law based algorithms for quantitative econo-green bio-research.

PubMed

Chou, Ting-Chao

2011-05-01

The relationship between dose and effect is not random, but rather governed by the unified theory based on the median-effect equation (MEE) of the mass-action law. Rearrangement of MEE yields the mathematical form of the Michaelis-Menten, Hill, Henderson-Hasselbalch and Scatchard equations of biochemistry and biophysics, and the median-effect plot allows linearization of all dose-effect curves regardless of potency and shape. The "median" is the universal common-link and reference-point for the 1st-order to higher-order dynamics, and from single-entities to multiple-entities and thus, it allows the all for one and one for all unity theory to "integrate" simple and complex systems. Its applications include the construction of a dose-effect curve with a theoretical minimum of only two data points if they are accurately determined; quantification of synergism or antagonism at all dose and effect levels; the low-dose risk assessment for carcinogens, toxic substances or radiation; and the determination of competitiveness and exclusivity for receptor binding. Since the MEE algorithm allows the reduced requirement of the number of data points for small size experimentation, and yields quantitative bioinformatics, it points to the deterministic, efficient, low-cost biomedical research and drug discovery, and ethical planning for clinical trials. It is concluded that the contemporary biomedical sciences would greatly benefit from the mass-action law based "Green Revolution".

Occupational vocal cord dysfunction due to exposure to wood dust and xerographic toner.

PubMed

Muñoz, Xavier; Roger, Alex; De la Rosa, David; Morell, Ferran; Cruz, Maria J

2007-04-01

Vocal cord dysfunction is a poorly understood entity that is often misdiagnosed as asthma. Both irritant and non-irritant vocal cord dysfunction have been described. This report presents two cases of irritant vocal cord dysfunction secondary to specific environmental exposure, the first to iroko and western red cedar wood (a carpenter) and the second to xerographic printing toner (a secretary). Several tests were performed, including chest radiographs, measurements of total serum immunoglobulin E, skin prick tests with common pneumoallergens (as well as iroko and western red cedar in the first case), pulmonary function studies, methacholine challenge testing, specific inhalation challenge performed with suspected agents in a single-blinded fashion, and peak expiratory flow testing and fiberoptic rhinolaryngoscopy (in case 1). During the specific inhalation challenge, the patients showed dysphonia, chest tightness, inspiratory stridor, and flattening of the inspiratory limb of the maximum flow-volume loop in spirometry, with no significant decreases in the level of forced expiratory volume in 1 second; fiberoptic rhinolaryngoscopy confirmed the diagnosis of vocal cord dysfunction in case 1. It is important to know that agents that can cause occupational asthma can also cause vocal cord dysfunction. The mechanisms by which these agents produce vocal cord dysfunction are unknown. The differences in the clinical presentation of the patients described relative to the reported cases suggest that more than one pathophysiological mechanism may be implicated in the genesis of this entity.

Intestinal Behçet's Disease: A True Inflammatory Bowel Disease or Merely an Intestinal Complication of Systemic Vasculitis?

PubMed Central

Kim, Duk Hwan

2016-01-01

Behçet's disease (BD) is a multi-systemic inflammatory disorder of an unknown etiology and shows a chronic recurrent clinical course. When the disease involves the alimentary tract, it is called intestinal BD because of its clinical importance. Intestinal BD is more frequently reported in East Asian countries than in Western or Middle Eastern countries. While any part of the gastrointestinal tract can be involved, the most common location of intestinal BD is the ileocecal area. A few, large, deep ulcerations with discrete border are characteristic endoscopic findings of intestinal BD. Currently, there is no single gold standard test or pathognomonic finding of intestinal BD. However, recently developed novel diagnostic criteria and a disease activity index have helped in assessing intestinal BD. As intestinal BD shares a lot of characteristics with inflammatory bowel disease, including genetic background, clinical manifestations, and therapeutic strategies, distinguishing between the two diseases in clinical practice is quite difficult. However, biologic agents such as anti-tumor necrosis factor α antibody shows a considerable efficacy similar to inflammatory bowel disease cases. It is important to distinguish and treat those two disease entities separately from the standpoint of precise medicine. Clinicians should require comprehensive knowledge regarding the similarities and differences between intestinal BD and inflammatory bowel disease for making an accurate clinical decision. PMID:26632379

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland.

PubMed

Seethala, Raja R; Stenman, Göran

2017-03-01

The salivary gland section in the 4th edition of the World Health Organization classification of head and neck tumors features the description and inclusion of several entities, the most significant of which is represented by (mammary analogue) secretory carcinoma. This entity was extracted mainly from acinic cell carcinoma based on recapitulation of breast secretory carcinoma and a shared ETV6-NTRK3 gene fusion. Also new is the subsection of "Other epithelial lesions," for which key entities include sclerosing polycystic adenosis and intercalated duct hyperplasia. Many entities have been compressed into their broader categories given clinical and morphologic similarities, or transitioned to a different grouping as was the case with low-grade cribriform cystadenocarcinoma reclassified as intraductal carcinoma (with the applied qualifier of low-grade). Specific grade has been removed from the names of the salivary gland entities such as polymorphous adenocarcinoma, providing pathologists flexibility in assigning grade and allowing for recognition of a broader spectrum within an entity. Cribriform adenocarcinoma of (minor) salivary gland origin continues to be divisive in terms of whether it should be recognized as a distinct category. This chapter also features new key concepts such as high-grade transformation. The new paradigm of translocations and gene fusions being common in salivary gland tumors is featured heavily in this chapter.

42 CFR 55a.102 - Who is eligible to apply for a Black Lung clinics grant?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Who is eligible to apply for a Black Lung clinics... SERVICES GRANTS PROGRAM GRANTS FOR BLACK LUNG CLINICS General Provisions § 55a.102 Who is eligible to apply for a Black Lung clinics grant? Any State or public or private entity may apply for a grant under this...

42 CFR 55a.102 - Who is eligible to apply for a Black Lung clinics grant?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Who is eligible to apply for a Black Lung clinics... SERVICES GRANTS PROGRAM GRANTS FOR BLACK LUNG CLINICS General Provisions § 55a.102 Who is eligible to apply for a Black Lung clinics grant? Any State or public or private entity may apply for a grant under this...

[Pain disorders in traumatized individuals - neurophysiology and clinical presentation].

PubMed

Egloff, N; Hirschi, A; von Känel, R

2012-01-18

This overview portrays the salient physiological mechanisms being involved in the clinical manifestation of chronic pain in traumatized patients. A «hypermnesia-hyperarousal-model» is purported to support the neurophysiologic plausibility of the trauma-pain-relationship. We discuss seven characteristic clinical pain entities which alone or in combination can be found in patients with a previous psychological trauma.

Mutation in PLK4, encoding a master regulator of centriole formation, defines a novel locus for primordial dwarfism.

PubMed

Shaheen, Ranad; Al Tala, Saeed; Almoisheer, Agaadir; Alkuraya, Fowzan S

2014-12-01

Primordial dwarfism (PD) is a heterogeneous clinical entity characterised by severe prenatal and postnatal growth deficiency. Despite the recent wave of disease gene discovery, the causal mutations in many PD patients remain unknown. To describe a PD family that maps to a novel locus. Clinical, imaging and laboratory phenotyping of a new family with PD followed by autozygosity mapping, linkage analysis and candidate gene sequencing. We describe a multiplex consanguineous Saudi family in which two full siblings and one half-sibling presented with classical features of Seckel syndrome in addition to optic nerve hypoplasia. We were able to map the phenotype to a single novel locus on 4q25-q28.2, in which we identified a five base-pair deletion in PLK4, which encodes a master regulator of centriole duplication. Our discovery further confirms the role of genes involved in centriole biology in the pathogenesis of PD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Practical experience with the maintenance and auditing of a large medical ontology.

PubMed

Baorto, David; Li, Li; Cimino, James J

2009-06-01

The Medical Entities Dictionary (MED) has served as a unified terminology at New York Presbyterian Hospital and Columbia University for more than 20 years. It was initially created to allow the clinical data from the disparate information systems (e.g., radiology, pharmacy, and multiple laboratories, etc.) to be uniquely codified for storage in a single data repository, and functions as a real time terminology server for clinical applications and decision support tools. Being conceived as a knowledge base, the MED incorporates relationships among local terms, between local terms and external standards, and additional knowledge about terms in a semantic network structure. Over the past two decades, we have sought to develop methods to maintain, audit and improve the content of the MED, such that it remains true to its original design goals. This has resulted in a complex, multi-faceted process, with both manual and automated components. In this paper, we describe this process, with examples of its effectiveness. We believe that our process provides lessons for others who seek to maintain complex, concept-oriented controlled terminologies.

Practical Experience with the Maintenance and Auditing of a Large Medical Ontology

PubMed Central

Baorto, David; Li, Li; Cimino, James J.

2012-01-01

The Medical Entities Dictionary (MED) has served as a unified terminology at New York Presbyterian Hospital and Columbia University for more than 20 years. It was initially created to allow the clinical data from the disparate information systems (e.g., radiology, pharmacy, and multiple laboratories, etc) to be uniquely codified for storage in a single data repository, and functions as a real time terminology server for clinical applications and decision support tools. Being conceived as a knowledge base, the MED incorporates relationships among local terms, between local terms and external standards, and additional knowledge about terms in a semantic network structure. Over the past two decades, we have sought to develop methods to maintain, audit and improve the content of the MED, such that it remains true to its original design goals. This has resulted in a complex, multi-faceted process, with both manual and automated components. In this paper, we describe this process, with examples of its effectiveness. We believe that our process provides lessons for others who seek to maintain complex, concept-oriented controlled terminologies. PMID:19285569

[Clinical examination of the hip joint in adults].

PubMed

Grifka, J; Keshmiri, A; Maderbacher, G; Craiovan, B

2014-12-01

Complaints in the region of the hips and pelvis are often difficult to classify. This is due to the fact that pain projection and overlapping can occur; therefore, the complete region of the lumbar spine, pelvis and hips must be considered as a single entity in which alterations can result in radiation throughout the whole region. There are many different anatomical structures within the pelvic region so that the function of various muscle components can be impaired and cause pathological alterations to positional relationships of bony structures or even alterations to other soft tissues, such as ligaments, tendons and labra. In terms of differential diagnostics the groin must be seen as the weak point of the peritoneum and vascular system and taken into consideration. Therefore, a detailed and targeted medical history, functional testing and specific examinations and tests are necessary to narrow down the pathology in question and reach a definitive diagnosis. Orthopedic surgeons must know which conspicuous features can lead to which problems and which anatomical structures are likely to be affected by irritation. The results of the clinical examination are the basis for targeted imaging diagnostics and subsequent therapy.

[Clinical examination of the hip joint in adults].

PubMed

Grifka, J; Keshmiri, A; Maderbacher, G; Craiovan, B

2015-07-01

Complaints in the region of the hips and pelvis are often difficult to classify. This is due to the fact that pain projection and overlapping can occur; therefore, the complete region of the lumbar spine, pelvis and hips must be considered as a single entity in which alterations can result in radiation throughout the whole region. There are many different anatomical structures within the pelvic region so that the function of various muscle components can be impaired and cause pathological alterations to positional relationships of bony structures or even alterations to other soft tissues, such as ligaments, tendons and labra. In terms of differential diagnostics the groin must be seen as the weak point of the peritoneum and vascular system and taken into consideration. Therefore, a detailed and targeted medical history, functional testing and specific examinations and tests are necessary to narrow down the pathology in question and reach a definitive diagnosis. Orthopedic surgeons must know which conspicuous features can lead to which problems and which anatomical structures are likely to be affected by irritation. The results of the clinical examination are the basis for targeted imaging diagnostics and subsequent therapy.

Avascular Necrosis of the Capitate

PubMed Central

Bekele, Wosen; Escobedo, Eva; Allen, Robert

2011-01-01

Avascular necrosis of the capitate is a rare entity. The most common reported etiology is trauma. We report a case of avascular necrosis of the capitate in a patient with chronic wrist pain that began after a single episode of remote trauma. PMID:22470799

7 CFR 4280.101 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE LOANS AND GRANTS Renewable Energy Systems and Energy Efficiency... agricultural producers and rural small businesses for the purpose of purchasing and installing renewable energy systems and energy efficiency improvements in rural areas. Financial assistance to any single entity may...

Single-tier city logistics model for single product

NASA Astrophysics Data System (ADS)

Saragih, N. I.; Nur Bahagia, S.; Suprayogi; Syabri, I.

2017-11-01

This research develops single-tier city logistics model which consists of suppliers, UCCs, and retailers. The problem that will be answered in this research is how to determine the location of UCCs, to allocate retailers to opened UCCs, to assign suppliers to opened UCCs, to control inventory in the three entities involved, and to determine the route of the vehicles from opened UCCs to retailers. This model has never been developed before. All the decisions will be simultaneously optimized. Characteristic of the demand is probabilistic following a normal distribution, and the number of product is single.

Reverberation index: a novel metric by which to quantify the impact of a scientific entity on a given field.

PubMed

Kathleen Bandt, S; Dacey, Ralph G

2017-09-01

The authors propose a novel bibilometric index, the reverberation index (r-index), as a comparative assessment tool for use in determining differential reverberation between scientific fields for a given scientific entity. Conversely, this may allow comparison of 2 similar scientific entities within a single scientific field. This index is calculated using a relatively simple 3-step process. Briefly, Thompson Reuters' Web of Science is used to produce a citation report for a unique search parameter (this may be an author, journal article, or topical key word). From this citation report, a list of citing journals is retrieved from which a weighted ratio of citation patterns across journals can be calculated. This r-index is then used to compare the reverberation of the original search parameter across different fields of study or wherever a comparison is required. The advantage of this novel tool is its ability to transcend a specific component of the scientific process. This affords application to a diverse range of entities, including an author, a journal article, or a topical key word, for effective comparison of that entity's reverberation within a scientific arena. The authors introduce the context for and applications of the r-index, emphasizing neurosurgical topics and journals for illustration purposes. It should be kept in mind, however, that the r-index is readily applicable across all fields of study.

Whiteheadian Actual Entitities and String Theory

NASA Astrophysics Data System (ADS)

Bracken, Joseph A.

2012-06-01

In the philosophy of Alfred North Whitehead, the ultimate units of reality are actual entities, momentary self-constituting subjects of experience which are too small to be sensibly perceived. Their combination into "societies" with a "common element of form" produces the organisms and inanimate things of ordinary sense experience. According to the proponents of string theory, tiny vibrating strings are the ultimate constituents of physical reality which in harmonious combination yield perceptible entities at the macroscopic level of physical reality. Given that the number of Whiteheadian actual entities and of individual strings within string theory are beyond reckoning at any given moment, could they be two ways to describe the same non-verifiable foundational reality? For example, if one could establish that the "superject" or objective pattern of self- constitution of an actual entity vibrates at a specific frequency, its affinity with the individual strings of string theory would be striking. Likewise, if one were to claim that the size and complexity of Whiteheadian 'societies" require different space-time parameters for the dynamic interrelationship of constituent actual entities, would that at least partially account for the assumption of 10 or even 26 instead of just 3 dimensions within string theory? The overall conclusion of this article is that, if a suitably revised understanding of Whiteheadian metaphysics were seen as compatible with the philosophical implications of string theory, their combination into a single world view would strengthen the plausibility of both schemes taken separately. Key words: actual entities, subject/superjects, vibrating strings, structured fields of activity, multi-dimensional physical reality.

Single-cell intracellular nano-pH probes†

PubMed Central

Özel, Rıfat Emrah; Lohith, Akshar; Mak, Wai Han; Pourmand, Nader

2016-01-01

Within a large clonal population, such as cancerous tumor entities, cells are not identical, and the differences between intracellular pH levels of individual cells may be important indicators of heterogeneity that could be relevant in clinical practice, especially in personalized medicine. Therefore, the detection of the intracellular pH at the single-cell level is of great importance to identify and study outlier cells. However, quantitative and real-time measurements of the intracellular pH of individual cells within a cell population is challenging with existing technologies, and there is a need to engineer new methodologies. In this paper, we discuss the use of nanopipette technology to overcome the limitations of intracellular pH measurements at the single-cell level. We have developed a nano-pH probe through physisorption of chitosan onto hydroxylated quartz nanopipettes with extremely small pore sizes (~100 nm). The dynamic pH range of the nano-pH probe was from 2.6 to 10.7 with a sensitivity of 0.09 units. We have performed single-cell intracellular pH measurements using non-cancerous and cancerous cell lines, including human fibroblasts, HeLa, MDA-MB-231 and MCF-7, with the pH nanoprobe. We have further demonstrated the real-time continuous single-cell pH measurement capability of the sensor, showing the cellular pH response to pharmaceutical manipulations. These findings suggest that the chitosan-functionalized nanopore is a powerful nano-tool for pH sensing at the single-cell level with high temporal and spatial resolution. PMID:27708772

Mining heart disease risk factors in clinical text with named entity recognition and distributional semantic models.

PubMed

Urbain, Jay

2015-12-01

We present the design, and analyze the performance of a multi-stage natural language processing system employing named entity recognition, Bayesian statistics, and rule logic to identify and characterize heart disease risk factor events in diabetic patients over time. The system was originally developed for the 2014 i2b2 Challenges in Natural Language in Clinical Data. The system's strengths included a high level of accuracy for identifying named entities associated with heart disease risk factor events. The system's primary weakness was due to inaccuracies when characterizing the attributes of some events. For example, determining the relative time of an event with respect to the record date, whether an event is attributable to the patient's history or the patient's family history, and differentiating between current and prior smoking status. We believe these inaccuracies were due in large part to the lack of an effective approach for integrating context into our event detection model. To address these inaccuracies, we explore the addition of a distributional semantic model for characterizing contextual evidence of heart disease risk factor events. Using this semantic model, we raise our initial 2014 i2b2 Challenges in Natural Language of Clinical data F1 score of 0.838 to 0.890 and increased precision by 10.3% without use of any lexicons that might bias our results. Copyright © 2015 Elsevier Inc. All rights reserved.

Mondor's disease of the breast. A retrospective review.

PubMed

Salemis, Nikolaos S; Merkouris, Stamatios; Kimpouri, Konstantina

2011-01-01

Mondor's disease is a rare benign clinical entity characterized by thrombophlebitis of the superficial veins of the anterolateral thoraco-abdominal wall. Although several predisposing factors have been reported, the exact pathogenesis remains unclear. We retrospectively reviewed the medical records of all patients older than 14 years who were diagnosed with Mondor's disease of the breast at the Breast Cancer Surgery Unit of Army General Hospital over a 3-year period. Five cases of Mondor's disease were identified among 5717 breast examinations performed during the study period. In 4 patients the disease was considered to be idiopathic. Ultrasonography established the diagnosis in all patients but mammography was inconclusive in two cases due to the presence of dense breast tissue. Four patients received symptomatic treatment. All patients had complete clinical resolution within 2-8 weeks of presentation, and they are well without any evidence of recurrence for 3 to 32 months later. No cases were associated with breast cancer. Mondor's disease of the breast is a rare benign self-limiting clinical entity. Ultrasonography is the diagnostic modality of choice but mammography may be inconclusive in the presence of dense breast tissue. Awareness of this rare entity is mandatory to prevent an unnecessary biopsy whereas the patients should be reassured of the benign nature of this disorder. Thorough evaluation is however necessary to rule out an underlying breast cancer or another systemic disease.

Determining similarity of scientific entities in annotation datasets

PubMed Central

Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

2015-01-01

Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug–drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called ‘AnnSim’ that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1–1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/ PMID:25725057

Determining similarity of scientific entities in annotation datasets.

PubMed

Palma, Guillermo; Vidal, Maria-Esther; Haag, Eric; Raschid, Louiqa; Thor, Andreas

2015-01-01

Linked Open Data initiatives have made available a diversity of scientific collections where scientists have annotated entities in the datasets with controlled vocabulary terms from ontologies. Annotations encode scientific knowledge, which is captured in annotation datasets. Determining relatedness between annotated entities becomes a building block for pattern mining, e.g. identifying drug-drug relationships may depend on the similarity of the targets that interact with each drug. A diversity of similarity measures has been proposed in the literature to compute relatedness between a pair of entities. Each measure exploits some knowledge including the name, function, relationships with other entities, taxonomic neighborhood and semantic knowledge. We propose a novel general-purpose annotation similarity measure called 'AnnSim' that measures the relatedness between two entities based on the similarity of their annotations. We model AnnSim as a 1-1 maximum weight bipartite match and exploit properties of existing solvers to provide an efficient solution. We empirically study the performance of AnnSim on real-world datasets of drugs and disease associations from clinical trials and relationships between drugs and (genomic) targets. Using baselines that include a variety of measures, we identify where AnnSim can provide a deeper understanding of the semantics underlying the relatedness of a pair of entities or where it could lead to predicting new links or identifying potential novel patterns. Although AnnSim does not exploit knowledge or properties of a particular domain, its performance compares well with a variety of state-of-the-art domain-specific measures. Database URL: http://www.yeastgenome.org/ © The Author(s) 2015. Published by Oxford University Press.

Non compaction cardiomyopathy: Review of a controversial entity.

PubMed

Lorca, Rebeca; Rozado, José; Martín, María

2018-05-11

Non-compaction cardiomyopathy is a heterogeneous and complex entity concerning which there are still many doubts to be resolved. While the American Heart Association includes it among genetic cardiomyopathies, the European Society of Cardiology treats it as an unclassified cardiomyopathy. It may present in a sporadic or familial form, isolated or associated with other heart diseases, affecting only the left ventricle or both and can sometimes appear as a mixed phenotype in patients with other cardiomyopathies. Different forms of clinical presentation are also associated with its different morphological manifestations, and even non-compaction of the left ventricle may be triggered by other physiological or pathological processes. The purpose of this review is an update of this entity and its controversies. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

New daily persistent headache: An evolving entity.

PubMed

Uniyal, Ravi; Paliwal, Vimal Kumar; Anand, Sucharita; Ambesh, Paurush

2018-01-01

New daily persistent headache (NDPH) is characterized by an abrupt onset of headache that becomes a daily entity, is unremitting and continuous from the onset, and lasts for more than 3 months. Dr Walter Vanast first described NDPH in the year 1986. Originally, it was proposed as a chronic daily headache but it was placed under "other primary headaches" in the International Classification of Headache Disorder Second Edition (ICHD 2nd edition). However, with evolving literature and better understanding of its clinical characteristics, it was classified as a "chronic daily headache" in the ICHD 3 rd edition beta. There are still many knowledge-gaps regarding the underlying cause, pathophysiology, natural history and treatment of NDPH. This review tries to revisit the entity and discusses the current status of understanding regarding NDPH.

Clinical and Demographic Characteristics Related to Onset

PubMed Central

Norris, Scott A; Jinnah, H A; Espay, Alberto J.; Klein, Christine; Brüggemann, Norbert; Barbano, Richard L.; Malaty, Irene; Rodriguez, Ramon L.; Vidailhet, Marie; Roze, Emmanuel; Reich, Stephen G.; Berman, Brian D.; LeDoux, Mark S.; Richardson, Sarah Pirio; Agarwal, Pinky; Mari, Zoltan; Ondo, William; Shih, Ludy C; Fox, Susan; Berardelli, Alfredo; Testa, Claudia M; Chang, Florence CF; Troung, Daniel; Nahab, Fatta; Xie, Tao; Hallett, Mark; Rosen, Ami R; Wright, Laura J; Perlmutter, JS

2016-01-01

Background Clinical characteristics of isolated, idiopathic cervical dystonia such as onset site and spread to and from additional body regions have been addressed in single-site studies with limited data and incomplete or variable dissociation of focal and segmental subtypes. Objectives To characterize clinical characteristics and demographics of isolated, idiopathic cervical dystonia in the largest standardized, multicenter cohort. Methods The Dystonia Coalition, through a consortium of 37 recruiting sites in North America, Europe and Australia recruited 1477 participants with focal (60.7%) or segmental (39.3%) cervical dystonia on examination. Clinical and demographic characteristics were evaluated in terms of the body region of dystonia onset and spread. Results Site of dystonia onset was: a) focal neck only (78.5%), b) focal onset elsewhere with later segmental spread to neck (13.3%), and c) segmental onset with initial neck involvement (8.2%).Frequency of spread from focal cervical to segmental dystonia (22.8%) was consistent with prior reports, but frequency of segmental onset with initial neck involvement was substantially higher than 3% previously reported. Cervical dystonia with focal neck onset, more than other subtypes, is associated with spread and tremor of any type. Sensory tricks were less frequent in cervical dystonia with segmental components, and segmental cervical onset occurred at an older age. Conclusions Subgroups had modest but significant differences in the clinical characteristics that may represent different clinical entities or pathophysiologic subtypes. These findings are critical for design and implementation of studies to describe, treat, or modify disease progression in idiopathic isolated cervical dystonia. PMID:27753188

Primary rhabdomyosarcoma of the pineal gland.

PubMed

Lau, Steven K M; Cykowski, Matthew D; Desai, Shiv; Cao, Ying; Fuller, Gregory N; Bruner, Janet; Okazaki, Ian

2015-05-01

To report a case of primary rhabdomyosarcoma (RMS) of the pineal gland in an adult, as well as review the literature on this rare entity. The case is compared with previous reports of similar entities, with emphasis on this patient's characteristics and clinical presentation, investigations, and management. Diagnosis of primary RMS of the pineal gland was based on the presence of strap cells and multinucleated myotube-like structures, as well as tumor cell expression of skeletal muscle markers consistent with myogenic differentiation. Multimodality treatment was initiated based on pediatric protocols. Unfortunately, the disease progressed on treatment, and the patient survived only 5 months from diagnosis. Pineal RMS is a rare disease with poor prognosis. Optimal management is unknown but likely to involve aggressive multimodality therapy. Copyright© by the American Society for Clinical Pathology.

The benefits of looking across many cancer genomes

Cancer.gov

Cancer is not a single entity, but rather, it is more than one hundred complex and distinct diseases, with most cancer types demanding a unique treatment strategy. TCGA researchers have developed a formal project for a cross tumor analysis, called Pan-Can

Prevention of data duplication for high throughput sequencing repositories

PubMed Central

Gabdank, Idan; Chan, Esther T; Davidson, Jean M; Hilton, Jason A; Davis, Carrie A; Baymuradov, Ulugbek K; Narayanan, Aditi; Onate, Kathrina C; Graham, Keenan; Miyasato, Stuart R; Dreszer, Timothy R; Strattan, J Seth; Jolanki, Otto; Tanaka, Forrest Y; Hitz, Benjamin C

2018-01-01

Abstract Prevention of unintended duplication is one of the ongoing challenges many databases have to address. Working with high-throughput sequencing data, the complexity of that challenge increases with the complexity of the definition of a duplicate. In a computational data model, a data object represents a real entity like a reagent or a biosample. This representation is similar to how a card represents a book in a paper library catalog. Duplicated data objects not only waste storage, they can mislead users into assuming the model represents more than the single entity. Even if it is clear that two objects represent a single entity, data duplication opens the door to potential inconsistencies between the objects since the content of the duplicated objects can be updated independently, allowing divergence of the metadata associated with the objects. Analogously to a situation in which a catalog in a paper library would contain by mistake two cards for a single copy of a book. If these cards are listing simultaneously two different individuals as current book borrowers, it would be difficult to determine which borrower (out of the two listed) actually has the book. Unfortunately, in a large database with multiple submitters, unintended duplication is to be expected. In this article, we present three principal guidelines the Encyclopedia of DNA Elements (ENCODE) Portal follows in order to prevent unintended duplication of both actual files and data objects: definition of identifiable data objects (I), object uniqueness validation (II) and de-duplication mechanism (III). In addition to explaining our modus operandi, we elaborate on the methods used for identification of sequencing data files. Comparison of the approach taken by the ENCODE Portal vs other widely used biological data repositories is provided. Database URL: https://www.encodeproject.org/ PMID:29688363

Complex posttraumatic stress disorder: The need to consolidate a distinct clinical syndrome or to reevaluate features of psychiatric disorders following interpersonal trauma?

PubMed

Giourou, Evangelia; Skokou, Maria; Andrew, Stuart P; Alexopoulou, Konstantina; Gourzis, Philippos; Jelastopulu, Eleni

2018-03-22

Complex posttraumatic stress disorder (Complex PTSD) has been recently proposed as a distinct clinical entity in the WHO International Classification of Diseases, 11 th version, due to be published, two decades after its first initiation. It is described as an enhanced version of the current definition of PTSD, with clinical features of PTSD plus three additional clusters of symptoms namely emotional dysregulation, negative self-cognitions and interpersonal hardship, thus resembling the clinical features commonly encountered in borderline personality disorder (BPD). Complex PTSD is related to complex trauma which is defined by its threatening and entrapping context, generally interpersonal in nature. In this manuscript, we review the current findings related to traumatic events predisposing the above-mentioned disorders as well as the biological correlates surrounding them, along with their clinical features. Furthermore, we suggest that besides the present distinct clinical diagnoses (PTSD; Complex PTSD; BPD), there is a cluster of these comorbid disorders, that follow a continuum of trauma and biological severity on a spectrum of common or similar clinical features and should be treated as such. More studies are needed to confirm or reject this hypothesis, particularly in clinical terms and how they correlate to clinical entities' biological background, endorsing a shift from the phenomenologically only classification of psychiatric disorders towards a more biologically validated classification.

“Partial duplication of lower lip and hemimandible” A rare case

PubMed Central

Nayak, Bibhuti Bhusan; Mohanty, Nilamani

2012-01-01

Duplication of mandible and lower lip is a very rare congenital entity. We report an extremely uncommon case of Congenital Duplication of Lower lip and Mandible in a 3 year old girl, who was treated surgically in a single stage for correction of both lip and mandible. This was a commissure preserving single staged procedure. The Surgical procedure, the problems related to this anomaly and the embryology are discussed. PMID:23450337

45 CFR 60.12 - Reporting adverse actions taken against clinical privileges.

Code of Federal Regulations, 2014 CFR

2014-10-01

... privileges of a physician or dentist for a period longer than 30 days, (ii) Acceptance of the surrender of clinical privileges or any restriction of such privileges by a physician or dentist: (A) While the physician or dentist is under investigation by the health care entity relating to possible incompetence or...

45 CFR 60.12 - Reporting adverse actions taken against clinical privileges.

Code of Federal Regulations, 2013 CFR

2013-10-01

... privileges of a physician or dentist for a period longer than 30 days, (ii) Acceptance of the surrender of clinical privileges or any restriction of such privileges by a physician or dentist: (A) While the physician or dentist is under investigation by the health care entity relating to possible incompetence or...

Swyer Syndrome With Gonadoblastoma: A Clinicoradiological Approach.

PubMed

Agarwal, Arjit; Agarwal, Shubhra

2017-01-01

Primary amenorrhea is a common diagnostic challenge in the gynecology department, wherein there are numerous causes that need to be approached in a systematic manner. However, when a case with a pelvic lump or a solid pelvic mass presents to a gynecologist or a radiologist, the approach becomes difficult to justify amenorrhea and pelvic mass as a single entity. We present the case of a 36-year-old female with the complaints of primary amenorrhea with a pelvic mass. The case was approached keeping in view the diagnostic possibilities and applying the role of clinical, radiological, and laboratory analyses. The final diagnosis of Swyer syndrome with gonadoblastoma was made, and she was further subjected to operative resection and hormonal therapy. This study stresses on the approach to a case, wherein the diagnosis was based only on the clinician's acumen and the radiologist's expertise, providing a way to simplify the protocol in the evaluation of such types of cases.

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

PubMed

Howard, Rebecca; Rattray, Magnus; Prosperi, Mattia; Custovic, Adnan

2015-07-01

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as 'asthma endotypes'. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies.

Herpes zoster - typical and atypical presentations.

PubMed

Dayan, Roy Rafael; Peleg, Roni

2017-08-01

Varicella- zoster virus infection is an intriguing medical entity that involves many medical specialties including infectious diseases, immunology, dermatology, and neurology. It can affect patients from early childhood to old age. Its treatment requires expertise in pain management and psychological support. While varicella is caused by acute viremia, herpes zoster occurs after the dormant viral infection, involving the cranial nerve or sensory root ganglia, is re-activated and spreads orthodromically from the ganglion, via the sensory nerve root, to the innervated target tissue (skin, cornea, auditory canal, etc.). Typically, a single dermatome is involved, although two or three adjacent dermatomes may be affected. The lesions usually do not cross the midline. Herpes zoster can also present with unique or atypical clinical manifestations, such as glioma, zoster sine herpete and bilateral herpes zoster, which can be a challenging diagnosis even for experienced physicians. We discuss the epidemiology, pathophysiology, diagnosis and management of Herpes Zoster, typical and atypical presentations.

The whole-genome landscape of medulloblastoma subtypes

PubMed Central

Northcott, Paul A.; Buchhalter, Ivo; Morrissy, A. Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Groebner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H.; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M.; Erkek, Serap; Jones, David T.W.; Worst, Barbara C.; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D.; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D.; Wolf, Stephan; Robinson, Giles W.; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M.G.; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L.; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M.; Mora, Jaume; McLendon, Roger E.; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J.M.; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O.; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A.; Pfister, Stefan M.; Taylor, Michael D.; Lichter, Peter

2018-01-01

Summary Current therapies for medulloblastoma (MB), a highly malignant childhood brain tumor, impose debilitating effects on the developing child, warranting deployment of molecularly targeted treatments with reduced toxicities. Prior studies failed to disclose the full spectrum of driver genes and molecular processes operative in MB subgroups. Herein, we detail the somatic landscape across 491 sequenced MBs and molecular heterogeneity amongst 1,256 epigenetically analyzed cases, identifying subgroup-specific driver alterations including previously unappreciated actionable targets. Driver mutations explained the majority of Group 3 and Group 4 patients, remarkably enhancing previous knowledge. Novel molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions targeting KBTBD4 and ‘enhancer hijacking’ driving PRDM6 activation. Thus, application of integrative genomics to an unprecedented cohort of clinical samples derived from a single childhood cancer entity disclosed a series of new cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for treating MB patients. PMID:28726821

Coexistence of amelanotic melanoma and liposarcoma.

PubMed

Jeong, Taek Jo; Lee, Eun Ju; Haw, Sik; Shin, Min Kyung; Haw, Choong Rim

2009-11-01

An amelanotic malignant melanoma is characterized by little or no pigment. It is frequently misdiagnosed because it is a rare entity in general, and because of its unusual clinical features. Liposarcoma is one of the most common adult soft tissue sarcomas. We encountered a case of amelanotic melanoma with a concurrent liposarcoma. A 68-year-old man presented with a single, 1.5x1.5 cm round erythematous, eroded nodule on the left heel. A biopsy specimen showed atypical, pleomorphic tumor cells with little melanin pigment. The tumor cells were positive for S-100, HMB-45 and negative for cytokeratins. These findings were consistent with amelanotic melanoma. On positron emission tomography/computed tomography (PET/CT), a hypermetabolic lesion was found in the left buttock. This lesion was excised and diagnosed as a well-differentiated liposarcoma. An association between sarcomas and other primary malignancies has been reported. However, an association between melanoma and liposarcoma is rare.

Clonal outbreak of Trichophyton tonsurans tinea capitis gladiatorum among wrestlers in Adana, Turkey.

PubMed

Ilkit, Macit; Ali Saracli, Mehmet; Kurdak, Hatice; Turac-Bicer, Aygul; Yuksel, Tuba; Karakas, Mehmet; Schuenemann, Eric; Abdel-Rahman, Susan M

2010-05-01

Tinea capitis gladiatorum and tinea corporis gladiatorum caused by the anthropophilic dermatophyte Trichophyton tonsurans are well-known clinical entities in individuals involved in combat sports, e.g., wrestlers and judo practitioners. We present an outbreak of Trichophyton tonsurans tinea capitis gladiatorum among wrestlers at a boarding school in Adana, Turkey. Fourteen of the 29 wrestlers examined (48.3%) harbored the pathogen, including eight asymptomatic scalp carriers, five with tinea capitis superficialis, and one asymptomatic trunk carrier. Dermatophytes were isolated from samples of the neck (1), nape (1), trunk (3) and inguinal area (2) in four of the five tinea capitis cases. A total of five inanimate objects, i.e., two wrestling mats, two pillowcases, and one sheet were also found to be positive for T. tonsurans. Mixed-marker strain typing examining 24 sequence variations in 12 gene loci confirmed that the outbreak was caused by a single strain of T. tonsurans.

Longitudinal associations between post-traumatic distress and depressive symptoms following a traumatic event: a test of three models.

PubMed

Schindel-Allon, I; Aderka, I M; Shahar, G; Stein, M; Gilboa-Schechtman, E

2010-10-01

Symptoms of post-traumatic stress disorder (PTSD) and depression are highly co-morbid following a traumatic event. Nevertheless, decisive evidence regarding the direction of the relationship between these clinical entities is missing. The aim of the present study was to examine the nature of this relationship by comparing a synchronous change model (PTSD and depression are time synchronous, possibly stemming from a third common factor) with a demoralization model (i.e. PTSD symptoms causing depression) and a depressogenic model (i.e. depressive symptoms causing PTSD symptoms). Israeli adult victims of single-event traumas (n=156) were assessed on measures of PTSD and depression at 2, 4 and 12 weeks post-event. A cross-lagged structural equation modeling (SEM) analysis provided results consistent with the synchronous change model and the depressogenic model. Depressive symptoms may play an important role in the development of post-traumatic symptoms.

Is undifferentiated spondyloarthritis a discrete entity? A debate.

PubMed

Deodhar, Atul; Miossec, Pierre; Baraliakos, Xenofon

2018-01-01

The concept of undifferentiated spondyloarthritis has been introduced recently to describe a clinical setting where the classical features of spondyloarthritis (SpA) are not fully present. Whether this is a discrete entity was the basis of a debate during the 4th International Congress on Controversies in Rheumatology & Autoimmunity held in Bologna, Italy 9-11 March 2017. The pro and con aspects of the debate are presented. The implications of the debate are important ranging from diagnostic aspects to consequences for the society and the payers. Copyright © 2017 Elsevier B.V. All rights reserved.

Gastric Volvulus: A Rare Entity Case Report and Literature Review

PubMed Central

Akhtar, Aisha; Sheikh, Abdul Ahad E; Sheikh, Abu Baker; Perisetti, Abhilash

2018-01-01

Gastric volvulus is a rare entity defined as an abnormal rotation of the stomach around itself. It is a diagnosis of exclusion; the clinical index of suspicion is always low and is mostly diagnosed on imaging or on the surgery table. When it occurs, it is an emergency due to the risk of strangulation and consequent gangrene of the stomach. Mesentero-axial (MA) gastric volvuli constitute one-third of all cases. Here, we are present an interesting case of acute MA gastric volvulus diagnosed with imaging and treated subsequently. PMID:29755908

Lenticular fibroxanthomatous nodule.

PubMed

Lee, Seok J; Ling, Jun X; Aaberg, Thomas M; Grossniklaus, Hans E

2003-02-01

To describe two patients with unique lenticular nodular proliferations. Observational case reports. The clinical histories and pathologic findings of two patients with lenticular nodular proliferations were reviewed. One patient with persistent hyperplastic primary vitreous and another patient with trauma developed lenticular nodular proliferations. The nodules were vascularized collections of foamy histiocytes, multinucleated cells, lens capsule, and lens epithelium that had undergone fibrous metaplasia. The lesions were classified as lenticular fibroxanthomatous nodules. A lenticular fibroxanthomatous nodule is a unique clinicopathologic entity that should be differentiated from Soemmerring ring, Elschnig pearl, and other simulating entities such as juvenile xanthogranuloma.

Current approach in the diagnosis and management of posterior uveitis

PubMed Central

Sudharshan, S; Ganesh, Sudha K; Biswas, Jyotrimay

2010-01-01

Posterior uveitic entities are varied entities that are infective or non-infective in etiology. They can affect the adjacent structures such as the retina, vitreous, optic nerve head and retinal blood vessels. Thorough clinical evaluation gives a clue to the diagnosis while ancillary investigations and laboratory tests assist in confirming the diagnosis. Newer evolving techniques in the investigations and management have increased the diagnostic yield. In case of diagnostic dilemma, intraocular fluid evaluation for polymerase chain testing for the genome and antibody testing against the causative agent provide greater diagnostic ability. PMID:20029144

The A to Z of healthcare data breaches.

PubMed

Kobus, Theodore J

2012-01-01

There currently exists a myriad of privacy laws that impact a healthcare entity, including more than 47 notification laws that require notification when a data breach occurs, as well as the breach notification requirements of the Health Information Technology for Economic and Clinical Health Act. Given the plethora of issues a healthcare entity faces, there are certain principles that can be built into an organization's philosophy that will comply with the law and help protect it from reputational harm. © 2012 American Society for Healthcare Risk Management of the American Hospital Association.

Modeling Clinical Information Needs in the Context of a Specific Patient

PubMed Central

Price, Susan L.

2000-01-01

Investigators have tried various approaches to link clinical information directly to information sources that may contain answers to clinical questions. Developing a model of clinical information needs that may arise in the context of viewing information about a specific patient is a preliminary step to finding an efficient, useful solution to the information retrieval problem. This poster illustrates a method of modeling clinical information needs in the context of a specific patient that that is adapted from entity-relationship models used in database design.

Alliance through Change

ERIC Educational Resources Information Center

Sebalj, Darlene; Hudson, Susan; Ryan, Jan; Wight-Boycott, Juliet

2007-01-01

Following a landmark organisational change event within the University of Western Sydney, when the university ceased operating as a federation of four distinct, inter-related elements and merged to become a single entity, four foundation College Managers made a strategic decision to form an alliance. This alliance significantly enhanced the…

POLG1 mutations and stroke like episodes: a distinct clinical entity rather than an atypical MELAS syndrome

PubMed Central

2013-01-01

Background POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. Case presentation We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. Conclusion The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations. PMID:23324391

The molecular biology of soft-tissue sarcomas and current trends in therapy.

PubMed

Quesada, Jorge; Amato, Robert

2012-01-01

Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.

The conundrum of juvenile psoriatic arthritis.

PubMed

Ravelli, Angelo; Consolaro, Alessandro; Schiappapietra, Benedetta; Martini, Alberto

2015-01-01

Juvenile psoriatic arthritis (JPsA) has provided paediatric rheumatologists with a controversial topic for many years. The principal area of contention centres on the discordance between its treatment as a single diagnostic category in current classification schemes and the demonstration of its heterogeneous nature. A further point of debate is the distinctiveness of JPsA as an entity. Owing to these uncertainties, the concept of JPsA has evolved over the years and there have been several changes in its definition and diagnostic criteria. Recently, strong evidence has been provided that the spectrum of JPsA include at least two distinct subgroups, one that has the same characteristics as early-onset ANA-positive JIA, and another that is part of the spectrum of spondyloarthropathies and resembles the forms of psoriatic arthritis in adults that belong to the same disease family. These findings call for a revision of the classification of childhood arthritis, that refutes the assumptions that children with JPsA constitute a single homogeneous population and that JPsA should be considered an individual disease entity.

A statistical approach to combining multisource information in one-class classifiers

DOE PAGES

Simonson, Katherine M.; Derek West, R.; Hansen, Ross L.; ...

2017-06-08

A new method is introduced in this paper for combining information from multiple sources to support one-class classification. The contributing sources may represent measurements taken by different sensors of the same physical entity, repeated measurements by a single sensor, or numerous features computed from a single measured image or signal. The approach utilizes the theory of statistical hypothesis testing, and applies Fisher's technique for combining p-values, modified to handle nonindependent sources. Classifier outputs take the form of fused p-values, which may be used to gauge the consistency of unknown entities with one or more class hypotheses. The approach enables rigorousmore » assessment of classification uncertainties, and allows for traceability of classifier decisions back to the constituent sources, both of which are important for high-consequence decision support. Application of the technique is illustrated in two challenge problems, one for skin segmentation and the other for terrain labeling. Finally, the method is seen to be particularly effective for relatively small training samples.« less

A statistical approach to combining multisource information in one-class classifiers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simonson, Katherine M.; Derek West, R.; Hansen, Ross L.

A new method is introduced in this paper for combining information from multiple sources to support one-class classification. The contributing sources may represent measurements taken by different sensors of the same physical entity, repeated measurements by a single sensor, or numerous features computed from a single measured image or signal. The approach utilizes the theory of statistical hypothesis testing, and applies Fisher's technique for combining p-values, modified to handle nonindependent sources. Classifier outputs take the form of fused p-values, which may be used to gauge the consistency of unknown entities with one or more class hypotheses. The approach enables rigorousmore » assessment of classification uncertainties, and allows for traceability of classifier decisions back to the constituent sources, both of which are important for high-consequence decision support. Application of the technique is illustrated in two challenge problems, one for skin segmentation and the other for terrain labeling. Finally, the method is seen to be particularly effective for relatively small training samples.« less

Bridging cobalt-calixarene subunits into a Co8 entity or a chain with 4,4‧-bipyridyl

NASA Astrophysics Data System (ADS)

Liu, Wei; Liu, Mei; Du, Shangchao; Li, Yafeng; Liao, Wuping

2014-02-01

Two novel calixarene-based compounds, {[Co4Cl(TC4A)(HCOO)3]2(4,4‧-bpy)2} (CIAC-206) and {[Co3(H2O)(SC4A-SO2)(HCOO)2]2(4,4‧-bpy)}n (CIAC-207) (H4TC4A = p-tert-butylthiacalix[4]arene, SC4A-SO2 = p-tert-butylsulfonylcalix[4]arene, 4,4‧-bpy = 4,4‧-bipyridyl) were synthesized under solvothermal conditions, and characterized by single crystal X-ray diffraction analysis, TG-DSC analysis, elemental analysis and IR spectroscopy. These two structures are featured with isolated Z-shaped Co8 entities containing two Co4-TC4A subunits bridged by two parallel 4,4‧-bpy (CIAC-206) and some zigzag chains with [Co3-SC4A-SO2]2 dimers bridged by single 4,4‧-bpy (CIAC-207), respectively. In order to evaluate their properties, the N2 sorption behavior and magnetic property were examined.

Multimodal molecular analysis of astroblastoma enables reclassification of most cases into more specific molecular entities.

PubMed

Wood, Matthew D; Tihan, Tarik; Perry, Arie; Chacko, Geeta; Turner, Clinton; Pu, Cunfeng; Payne, Christopher; Yu, Alexander; Bannykh, Serguei I; Solomon, David A

2018-03-01

Astroblastoma is a rare and controversial glioma with variable clinical behavior. The diagnosis currently rests on histologic findings of a circumscribed glioma with astroblastomatous pseudorosettes and vascular hyalinization. Immunohistochemical studies have suggested different oncogenic drivers, such as BRAF p.V600E, but very few cases have been studied using genome-wide methodologies. Recent genomic profiling identified a subset of CNS embryonal tumors with astroblastoma-like morphology that harbored MN1 gene fusions, termed "CNS high-grade neuroepithelial tumors with MN1 alteration" (CNS-HGNET-MN1). To further characterize the genetic alterations that drive astroblastomas, we performed targeted next-generation sequencing (NGS) of 500 cancer-associated genes in a series of eight cases. We correlated these findings with break-apart fluorescence in situ hybridization (FISH) analysis of the MN1 locus and genome-wide DNA methylation profiling. Four cases showed MN1 alteration by FISH, including two pediatric cases that lacked other pathogenic alterations, and two adult cases that harbored other cancer-associated gene mutations or copy number alterations (eg, CDKN2A/B homozygous deletion, TP53, ATM and TERT promoter mutations). Three of these cases grouped with the CNS-HGNET-MN1 entity by methylation profiling. Two of four MN1 intact cases by FISH showed genetic features of either anaplastic pleomorphic xanthoastrocytoma (BRAF p.V600E mutation, CDKN2A/B homozygous deletion and TERT promoter mutation) or IDH-wildtype glioblastoma (trisomy 7, monosomy 10, CDK4 amplification and TP53, NRAS and TERT promoter mutations) and these cases had an aggressive clinical course. Two clinically indolent cases remained unclassifiable despite multimodal molecular analysis. We conclude that astroblastoma histology is not specific for any entity including CNS-HGNET-MN1, and that additional genetic characterization should be considered for astroblastomas, as a number of these tumors likely contain a methylation profile or genetic alterations that suggest classification as other tumor entities. Our heterogeneous molecular findings help to explain the clinical unpredictability of astroblastoma. © 2017 International Society of Neuropathology.

Assessing the Representation of Occupation Information in Free-Text Clinical Documents Across Multiple Sources

PubMed Central

Lindemann, Elizabeth A.; Chen, Elizabeth S.; Rajamani, Sripriya; Manohar, Nivedha; Wang, Yan; Melton, Genevieve B.

2017-01-01

There has been increasing recognition of the key role of social determinants like occupation on health. Given the relatively poor understanding of occupation information in electronic health records (EHRs), we sought to characterize occupation information within free-text clinical document sources. From six distinct clinical sources, 868 total occupation-related sentences were identified for the study corpus. Building off approaches from previous studies, refined annotation guidelines were created using the National Institute for Occupational Safety and Health Occupational Data for Health data model with elements added to increase granularity. Our corpus generated 2,005 total annotations representing 39 of 41 entity types from the enhanced data model. Highest frequency entities were: Occupation Description (17.7%); Employment Status – Not Specified (12.5%); Employer Name (11.0%); Subject (9.8%); Industry Description (6.2%). Our findings support the value for standardizing entry of EHR occupation information to improve data quality for improved patient care and secondary uses of this information. PMID:29295142

Motor palsies of cranial nerves (excluding VII) after vaccination: reports to the US Vaccine Adverse Event Reporting System.

PubMed

Woo, Emily Jane; Winiecki, Scott K; Ou, Alan C

2014-01-01

We reviewed cranial nerve palsies, other than VII, that have been reported to the US Vaccine Adverse Event Reporting System (VAERS). We examined patterns for differences in vaccine types, seriousness, age, and clinical characteristics. We identified 68 reports of cranial nerve palsies, most commonly involving the oculomotor (III), trochlear (IV), and abducens (VI) nerves. Isolated cranial nerve palsies, as well as palsies occurring as part of a broader clinical entity, were reported. Forty reports (59%) were classified as serious, suggesting that a cranial nerve palsy may sometimes be the harbinger of a broader and more ominous clinical entity, such as a stroke or encephalomyelitis. There was no conspicuous clustering of live vs. inactivated vaccines. The patient age range spanned the spectrum from infants to the elderly. Independent data may help to clarify whether, when, and to what extent the rates of cranial nerve palsies following particular vaccines may exceed background levels.

Clinically distinct presentations of copper deficiency myeloneuropathy and cytopenias in a patient using excessive zinc-containing denture adhesive.

PubMed

Cathcart, Sahara J; Sofronescu, Alina G

2017-08-01

While copper deficiency has long been known to cause cytopenias, copper deficiency myeloneuropathy is a more recently described entity. Here, we present the case of two clinically distinct presentations of acquired copper deficiency syndromes secondary to excessive use of zinc-containing denture adhesive over five years: myeloneuropathy and severe macrocytic anemia and neutropenia. Extensive laboratory testing and histologic evaluation of the liver and bone marrow, were necessary to rule out other disease processes and establish the diagnosis of copper deficiency. The initial presentation consisted of a myelopathy involving the posterior columns. Serum and urine copper were significantly decreased, and serum zinc was elevated. On second presentation (five years later), multiple hematological abnormalities were detected. Serum copper was again decreased, while serum zinc was elevated. Zinc overload is a preventable cause of copper deficiency syndromes. This rare entity presented herein highlights the importance of patient, as well as provider, education. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

A Dimensional Bus model for integrating clinical and research data.

PubMed

Wade, Ted D; Hum, Richard C; Murphy, James R

2011-12-01

Many clinical research data integration platforms rely on the Entity-Attribute-Value model because of its flexibility, even though it presents problems in query formulation and execution time. The authors sought more balance in these traits. Borrowing concepts from Entity-Attribute-Value and from enterprise data warehousing, the authors designed an alternative called the Dimensional Bus model and used it to integrate electronic medical record, sponsored study, and biorepository data. Each type of observational collection has its own table, and the structure of these tables varies to suit the source data. The observational tables are linked to the Bus, which holds provenance information and links to various classificatory dimensions that amplify the meaning of the data or facilitate its query and exposure management. The authors implemented a Bus-based clinical research data repository with a query system that flexibly manages data access and confidentiality, facilitates catalog search, and readily formulates and compiles complex queries. The design provides a workable way to manage and query mixed schemas in a data warehouse.

Post-Traumatic Osteoarthritis of the Ankle: A Distinct Clinical Entity Requiring New Research Approaches

PubMed Central

Delco, Michelle L.; Kennedy, John G.; Bonassar, Lawrence J.; Fortier, Lisa A.

2017-01-01

The diagnosis of ankle osteoarthritis (OA) is increasing as a result of advancements in non-invasive imaging modalities such as magnetic resonance imaging, improved arthroscopic surgical technology and heightened awareness among clinicians. Unlike OA of the knee, primary or age-related ankle OA is rare, with the majority of ankle OA classified as post-traumatic (PTOA). Ankle trauma, more specifically ankle sprain, is the single most common athletic injury, and no effective therapies are available to prevent or slow progression of PTOA. Despite the high incidence of ankle trauma and OA, ankle-related OA research is sparse, with the majority of clinical and basic studies pertaining to the knee joint. Fundamental differences exist between joints including their structure and molecular composition, response to trauma, susceptibility to OA, clinical manifestations of disease, and response to treatment. Considerable evidence suggests that research findings from knee should not be extrapolated to the ankle, however few ankle-specific preclinical models of PTOA are currently available. The objective of this article is to review the current state of ankle OA investigation, highlighting important differences between the ankle and knee that may limit the extent to which research findings from knee models are applicable to the ankle joint. Considerations for the development of new ankle-specific, clinically relevant animal models are discussed. PMID:27764893

Hypophosphatemia-induced Cardiomyopathy.

PubMed

Ariyoshi, Nobuhiro; Nogi, Masayuki; Ando, Akika; Watanabe, Hideaki; Umekawa, Sari

2016-09-01

Relatively few studies have been conducted to evaluate the effect of hypophosphatemia on cardiac function. The goal of this review was to determine whether there is an association between hypophosphatemia and cardiac function and to increase awareness of hypophosphatemia-induced cardiomyopathy as a new clinical entity and a reversible cause of heart failure. We searched MEDLINE and PubMed from 1971 until March 2015 for primary studies, which reported the relationship between hypophosphatemia and cardiac function. A total of 837 articles were initially obtained. Of these articles, 826 publications were excluded according to the inclusion and exclusion criteria. In all, 11 articles were included in this review. These articles included 7 case series or case reports, 1 case-control study, 1 pretest versus posttest in a single group and 2 animal studies. In conclusion, the mechanisms of hypophosphatemia in cardiomyopathy have been reported to be a depletion of adenosine triphosphate in myocardial cells and decreased 2,3-diphosphoglycerate in erythrocytes. After correction of hypophosphatemia, left ventricular performance seems to improve in patients with severe hypophosphatemia, but not in those with mild-to-moderate hypophosphatemia. However, analyses of the relationship between cardiac function and hypophosphatemia using clinical end points have not been conducted. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Hypertension and Atrial Fibrillation: An Intimate Association of Epidemiology, Pathophysiology, and Outcomes.

PubMed

Dzeshka, Mikhail S; Shahid, Farhan; Shantsila, Alena; Lip, Gregory Y H

2017-08-01

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia found in clinical practice. AF rarely exists as a single entity but rather as part of a diverse clinical spectrum of cardiovascular diseases, related to structural and electrical remodeling within the left atrium, leading to AF onset, perpetuation, and progression. Due to the high overall prevalence within the AF population arterial hypertension plays a significant role in the pathogenesis of AF and its complications. Fibroblast proliferation, apoptosis of cardiomyocytes, gap junction remodeling, accumulation of collagen both in atrial and ventricular myocardium all accompany ageing-related structural remodeling with impact on electrical activity. The presence of hypertension also stimulates oxidative stress, systemic inflammation, rennin-angiotensin-aldosterone and sympathetic activation, which further drives the remodeling process in AF. Importantly, both hypertension and AF independently increase the risk of cardiovascular and cerebrovascular events, e.g., stroke and myocardial infarction. Given that both AF and hypertension often present with limited on patient wellbeing, treatment may be delayed resulting in development of complications as the first clinical manifestation of the disease. Antithrombotic prevention in AF combined with strict blood pressure control is of primary importance, since stroke risk and bleeding risk are both greater with underlying hypertension. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Commercializing biomedical research through securitization techniques.

PubMed

Fernandez, Jose-Maria; Stein, Roger M; Lo, Andrew W

2012-10-01

Biomedical innovation has become riskier, more expensive and more difficult to finance with traditional sources such as private and public equity. Here we propose a financial structure in which a large number of biomedical programs at various stages of development are funded by a single entity to substantially reduce the portfolio's risk. The portfolio entity can finance its activities by issuing debt, a critical advantage because a much larger pool of capital is available for investment in debt versus equity. By employing financial engineering techniques such as securitization, it can raise even greater amounts of more-patient capital. In a simulation using historical data for new molecular entities in oncology from 1990 to 2011, we find that megafunds of $5–15 billion may yield average investment returns of 8.9–11.4% for equity holders and 5–8% for 'research-backed obligation' holders, which are lower than typical venture-capital hurdle rates but attractive to pension funds, insurance companies and other large institutional investors.

Symbolic emblems of the Levantine Aurignacians as a regional entity identifier (Hayonim Cave, Lower Galilee, Israel).

PubMed

Tejero, José-Miguel; Belfer-Cohen, Anna; Bar-Yosef, Ofer; Gutkin, Vitaly; Rabinovich, Rivka

2018-05-15

The Levantine Aurignacian is a unique phenomenon in the local Upper Paleolithic sequence, showing greater similarity to the West European classic Aurignacian than to the local Levantine archaeological entities preceding and following it. Herewith we highlight another unique characteristic of this entity, namely, the presence of symbolic objects in the form of notched bones (mostly gazelle scapulae) from the Aurignacian levels of Hayonim Cave, Lower Galilee, Israel. Through both macroscopic and microscopic analyses of the items, we suggest that they are not mere cut marks but rather are intentional (decorative?) human-made markings. The significance of this evidence for symbolic behavior is discussed in its chrono-cultural and geographical contexts. Notched bones are among the oldest symbolic expressions of anatomically modern humans. However, unlike other Paleolithic sites where such findings were reported in single numbers, the number of these items recovered at Hayonim Cave is sufficient to assume they possibly served as an emblem of the Levantine Aurignacian.

Current Evaluation of the Millennium Phytomedicine— Ginseng (II): Collected Chemical Entities, Modern Pharmacology, and Clinical Applications Emanated from Traditional Chinese Medicine

PubMed Central

Jia, Lee; Zhao, Yuqing; Liang, Xing-Jie

2009-01-01

This review, a sequel to part 1 in the series, collects about 107 chemical entities separated from the roots, leaves and flower buds of Panax ginseng, quinquefolius and notoginseng, and categorizes these entities into about 18 groups based on their structural similarity. The bioactivities of these chemical entities are described. The ‘Yin and Yang’ theory and the fundamentals of the ‘five elements’ applied to the traditional Chinese medicine (TCM) are concisely introduced to help readers understand how ginseng balances the dynamic equilibrium of human physiological processes from the TCM perspectives. This paper concerns the observation and experimental investigation of biological activities of ginseng used in the TCM of past and present cultures. The current biological findings of ginseng and its medical applications are narrated and critically discussed, including 1) its antihyperglycemic effect that may benefit type II diabetics; in vitro and in vivo studies demonstrated protection of ginseng on beta-cells and obese diabetic mouse models. The related clinical trial results are stated. 2) its aphrodisiac effect and cardiovascular effect that partially attribute to ginseng’s bioactivity on nitric oxide (NO); 3) its cognitive effect and neuropharmacological effect that are intensively tested in various rat models using purified ginsenosides and show a hope to treat Parkinson’s disease (PD); 4) its uses as an adjuvant or immunotherapeutic agent to enhance immune activity, appetite and life quality of cancer patients during their chemotherapy and radiation. Although the apoptotic effect of ginsenosides, especially Rh2, Rg3 and Compound K, on various tumor cells has been shown via different pathways, their clinical effectiveness remains to be tested. This paper also updates the antioxidant, anti-inflammatory, anti-apoptotic and immune-stimulatory activities of ginseng, its ingredients and commercial products, as well as common side effects of ginseng mainly due to its overdose, and its pharmacokinetics. PMID:19689273

Current evaluation of the millennium phytomedicine- ginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine.

PubMed

Jia, Lee; Zhao, Yuqing; Liang, Xing-Jie

2009-01-01

This review, a sequel to part 1 in the series, collects about 107 chemical entities separated from the roots, leaves and flower buds of Panax ginseng, quinquefolius and notoginseng, and categorizes these entities into about 18 groups based on their structural similarity. The bioactivities of these chemical entities are described. The 'Yin and Yang' theory and the fundamentals of the 'five elements' applied to the traditional Chinese medicine (TCM) are concisely introduced to help readers understand how ginseng balances the dynamic equilibrium of human physiological processes from the TCM perspectives. This paper concerns the observation and experimental investigation of biological activities of ginseng used in the TCM of past and present cultures. The current biological findings of ginseng and its medical applications are narrated and critically discussed, including 1) its antihyperglycemic effect that may benefit type II diabetics; in vitro and in vivo studies demonstrated protection of ginseng on beta-cells and obese diabetic mouse models. The related clinical trial results are stated. 2) its aphrodisiac effect and cardiovascular effect that partially attribute to ginseng's bioactivity on nitric oxide (NO); 3) its cognitive effect and neuropharmacological effect that are intensively tested in various rat models using purified ginsenosides and show a hope to treat Parkinson's disease (PD); 4) its uses as an adjuvant or immunotherapeutic agent to enhance immune activity, appetite and life quality of cancer patients during their chemotherapy and radiation. Although the apoptotic effect of ginsenosides, especially Rh2, Rg3 and Compound K, on various tumor cells has been shown via different pathways, their clinical effectiveness remains to be tested. This paper also updates the antioxidant, anti-inflammatory, anti-apoptotic and immune-stimulatory activities of ginseng, its ingredients and commercial products, as well as common side effects of ginseng mainly due to its overdose, and its pharmacokinetics.

ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

PubMed Central

Hayreh, Sohan Singh

2011-01-01

The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual acuity improvement during the first 7 days differs significantly (p<0.001) among the 4 types of CRAO; among them, in eyes with initial visual acuity of counting finger or worse, visual acuity improved, remained stable or deteriorated in nonarteritic CRAO in 22%, 66% and 12% respectively; in nonarteritic CRAO with cilioretinal artery sparing in 67%, 33% and none respectively; and in transient nonarteritic CRAO in 82%, 18% and none respectively. Arteritic CRAO shows no change. Recent studies have shown that administration of local intra-arterial thrombolytic agent not only has no beneficial effect but also can be harmful. Prevalent multiple misconceptions on CRAO are discussed. Branch retinal artery occlusion Pathogeneses, clinical features and management of various types of BRAO are discussed at length. The natural history of visual acuity outcome shows a final visual acuity of 20/40 or better in 89% of permanent BRAO cases, 100% of transient BRAO and 100% of nonarteritic CLRAO alone. Cotton wools spots These are common, non-specific acute focal retinal ischemic lesions, seen in many retinopathies. Their pathogenesis and clinical features are discussed in detail. Amaurosis fugax Its pathogenesis, clinical features and management are described. PMID:21620994

Balancing exploration and exploitation in transferring research into practice: a comparison of five knowledge translation entity archetypes

PubMed Central

2013-01-01

Background Translating knowledge from research into clinical practice has emerged as a practice of increasing importance. This has led to the creation of new organizational entities designed to bridge knowledge between research and practice. Within the UK, the Collaborations for Leadership in Applied Health Research and Care (CLAHRC) have been introduced to ensure that emphasis is placed in ensuring research is more effectively translated and implemented in clinical practice. Knowledge translation (KT) can be accomplished in various ways and is affected by the structures, activities, and coordination practices of organizations. We draw on concepts in the innovation literature—namely exploration, exploitation, and ambidexterity—to examine these structures and activities as well as the ensuing tensions between research and implementation. Methods Using a qualitative research approach, the study was based on 106 semi-structured, in-depth interviews with the directors, theme leads and managers, key professionals involved in research and implementation in nine CLAHRCs. Data was also collected from intensive focus group workshops. Results In this article we develop five archetypes for organizing KT. The results show how the various CLAHRC entities work through partnerships to create explorative research and deliver exploitative implementation. The different archetypes highlight a range of structures that can achieve ambidextrous balance as they organize activity and coordinate practice on a continuum of exploration and exploitation. Conclusion This work suggests that KT entities aim to reach their goals through a balance between exploration and exploitation in the support of generating new research and ensuring knowledge implementation. We highlight different organizational archetypes that support various ways to maintain ambidexterity, where both exploration and exploitation are supported in an attempt to narrow the knowledge gaps. The KT entity archetypes offer insights on strategies in structuring collaboration to facilitate an effective balance of exploration and exploitation learning in the KT process. PMID:24007259

Balancing exploration and exploitation in transferring research into practice: a comparison of five knowledge translation entity archetypes.

PubMed

Oborn, Eivor; Barrett, Michael; Prince, Karl; Racko, Girts

2013-09-05

Translating knowledge from research into clinical practice has emerged as a practice of increasing importance. This has led to the creation of new organizational entities designed to bridge knowledge between research and practice. Within the UK, the Collaborations for Leadership in Applied Health Research and Care (CLAHRC) have been introduced to ensure that emphasis is placed in ensuring research is more effectively translated and implemented in clinical practice. Knowledge translation (KT) can be accomplished in various ways and is affected by the structures, activities, and coordination practices of organizations. We draw on concepts in the innovation literature--namely exploration, exploitation, and ambidexterity--to examine these structures and activities as well as the ensuing tensions between research and implementation. Using a qualitative research approach, the study was based on 106 semi-structured, in-depth interviews with the directors, theme leads and managers, key professionals involved in research and implementation in nine CLAHRCs. Data was also collected from intensive focus group workshops. In this article we develop five archetypes for organizing KT. The results show how the various CLAHRC entities work through partnerships to create explorative research and deliver exploitative implementation. The different archetypes highlight a range of structures that can achieve ambidextrous balance as they organize activity and coordinate practice on a continuum of exploration and exploitation. This work suggests that KT entities aim to reach their goals through a balance between exploration and exploitation in the support of generating new research and ensuring knowledge implementation. We highlight different organizational archetypes that support various ways to maintain ambidexterity, where both exploration and exploitation are supported in an attempt to narrow the knowledge gaps. The KT entity archetypes offer insights on strategies in structuring collaboration to facilitate an effective balance of exploration and exploitation learning in the KT process.

75 FR 11993 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... before April 12, 2010 to be assured of consideration. Community Development Financial Institutions (CDFI... related to Community Development Entity (CDE)/New Markets Tax Credit material events, as well as Community Development Financial Institutions (CDFI) material events in a single form. The form will provide a more...

38 CFR 61.66 - Financial management.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Financial management. 61... § 61.66 Financial management. (a) All recipients must comply with applicable requirements of the Single...) All entities receiving assistance under this part must use a financial management system that follows...

38 CFR 61.66 - Financial management.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Financial management. 61... § 61.66 Financial management. (a) All recipients must comply with applicable requirements of the Single...) All entities receiving assistance under this part must use a financial management system that follows...

Issues to be Considered in the Evaluation of Technical Proposals from the Ada (Trademark) Language Perspective.

DTIC Science & Technology

1985-06-10

flowcharts - hierarchical charts - data flow diagrams - finite state diagrams - control flow diagrams - decision tables/trees - entity-relationship...and beginners ; for example, is prompting via menus provided for beginners and single keystroke capability provided for experienced users? 2-13 - input

13 CFR 121.103 - How does SBA determine affiliation?

Code of Federal Regulations, 2013 CFR

2013-01-01

... be found where an individual, concern, or entity exercises control indirectly through a third party..., and may find affiliation even though no single factor is sufficient to constitute affiliation. (6) In.... In addition, affiliation will not be found based upon the performance of common administrative...

13 CFR 121.103 - How does SBA determine affiliation?

Code of Federal Regulations, 2012 CFR

2012-01-01

... directors or shareholders. (4) Affiliation may be found where an individual, concern, or entity exercises... the totality of the circumstances, and may find affiliation even though no single factor is sufficient... common ownership or common management. In addition, affiliation will not be found based upon the...

13 CFR 121.103 - How does SBA determine affiliation?

Code of Federal Regulations, 2014 CFR

2014-01-01

... directors or shareholders. (4) Affiliation may be found where an individual, concern, or entity exercises... the totality of the circumstances, and may find affiliation even though no single factor is sufficient.... In addition, affiliation will not be found based upon the performance of common administrative...

24 CFR 58.32 - Project aggregation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Project aggregation. 58.32 Section... Environmental Review Process: Documentation, Range of Activities, Project Aggregation and Classification § 58.32 Project aggregation. (a) A responsible entity must group together and evaluate as a single project all...

75 FR 12422 - Notice of Funds Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-15

.... Affiliate means any company or entity that Controls, is Controlled by, or is under common Control with another company; 3. Affordable Housing means rental or for-sale single-family or multi-family housing that..., health care, childcare, educational, cultural, and/or social services) operate which, In Conjunction With...

24 CFR 58.32 - Project aggregation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Project aggregation. 58.32 Section... Environmental Review Process: Documentation, Range of Activities, Project Aggregation and Classification § 58.32 Project aggregation. (a) A responsible entity must group together and evaluate as a single project all...

24 CFR 58.32 - Project aggregation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false Project aggregation. 58.32 Section... Environmental Review Process: Documentation, Range of Activities, Project Aggregation and Classification § 58.32 Project aggregation. (a) A responsible entity must group together and evaluate as a single project all...

24 CFR 58.32 - Project aggregation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Project aggregation. 58.32 Section... Environmental Review Process: Documentation, Range of Activities, Project Aggregation and Classification § 58.32 Project aggregation. (a) A responsible entity must group together and evaluate as a single project all...

Overgrowth syndromes with vascular anomalies.

PubMed

Blei, Francine

2015-04-01

Overgrowth syndromes with vascular anomalies encompass entities with a vascular anomaly as the predominant feature vs those syndromes with predominant somatic overgrowth and a vascular anomaly as a more minor component. The focus of this article is to categorize these syndromes phenotypically, including updated clinical criteria, radiologic features, evaluation, management issues, pathophysiology, and genetic information. A literature review was conducted in PubMed using key words "overgrowth syndromes and vascular anomalies" as well as specific literature reviews for each entity and supportive genetic information (e.g., somatic mosaicism). Additional searches in OMIM and Gene Reviews were conducted for each syndrome. Disease entities were categorized by predominant clinical features, known genetic information, and putative affected signaling pathway. Overgrowth syndromes with vascular anomalies are a heterogeneous group of disorders, often with variable clinical expression, due to germline or somatic mutations. Overgrowth can be focal (e.g., macrocephaly) or generalized, often asymmetrically (and/or mosaically) distributed. All germ layers may be affected, and the abnormalities may be progressive. Patients with overgrowth syndromes may be at an increased risk for malignancies. Practitioners should be attentive to patients having syndromes with overgrowth and vascular defects. These patients require proactive evaluation, referral to appropriate specialists, and in some cases, early monitoring for potential malignancies. Progress in identifying vascular anomaly-related overgrowth syndromes and their genetic etiology has been robust in the past decade and is contributing to genetically based prenatal diagnosis and new therapies targeting the putative causative genetic mutations. Copyright © 2015 Mosby, Inc. All rights reserved.

Pharmacodynamic Activity of Dapivirine and Maraviroc Single Entity and Combination Topical Gels for HIV-1 Prevention.

PubMed

Dezzutti, Charlene S; Yandura, Sarah; Wang, Lin; Moncla, Bernard; Teeple, Elizabeth A; Devlin, Brid; Nuttall, Jeremy; Brown, Elizabeth R; Rohan, Lisa C

2015-11-01

Dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor, and maraviroc (MVC), a CCR5 antagonist, were formulated into aqueous gels designed to prevent mucosal HIV transmission. 0.05% DPV, 0.1% MVC, 0.05% DPV/0.1% MVC and placebo gels were evaluated for pH, viscosity, osmolality, and in vitro release. In vitro assays and mucosal tissues were used to evaluate anti-HIV activity. Viability (Lactobacilli only) and epithelial integrity in cell lines and mucosal tissues defined safety. The gels were acidic and viscous. DPV gel had an osmolality of 893 mOsm/kg while the other gels had an osmolality of <100 mOsm/kg. MVC release was similar from the single and combination gels (~5 μg/cm(2)/min(1/2)), while DPV release was 10-fold less from the single as compared to the combination gel (0.4331 μg/cm(2)/min(1/2)). Titrations of the gels showed 10-fold more drug was needed to protect ectocervical than colonic tissue. The combination gel showed ~10- and 100-fold improved activity as compared to DPV and MVC gel, respectively. All gels were safe. The DPV/MVC gel showed a benefit blocking HIV infection of mucosal tissue compared to the single entity gels. Combination products with drugs affecting unique steps in the viral replication cycle would be advantageous for HIV prevention.

The PAVE (peeling-assisted volume-enhancing) lift: A retrospective 6-year clinical analysis of a combined approach for facial rejuvenation.

PubMed

Kaye, Kai Oliver; Schaller, Hans-Eberhard; Jaminet, Patrick; Gonser, Phillipp

2016-08-01

The peeling-assisted volume-enhancing (PAVE) lift is a single-stage approach that combines superficial musculoaponeurotic system (SMAS) plication techniques with fat grafting and different peeling agents. To evaluate the safety of this approach, we analyzed the records of 159 patients who underwent surgery between 2008 and 2014. The percentage of complications observed was not higher than values reported in the literature for each treatment entity: surgical facelift: n=3 haematomas (1.89 %), n=2; temporary apraxia of the mandibular branch (1.26%); fat transfer: minor asymmetry in n = 5 cases (3.14%); peeling: temporary hyperpigmentation in trichloroacetic acid (n = 5; 3.8%) and phenol peels (n = 4; 3.1%), permanent hypopigmentation (n = 6; 5.6%), formation of skin miliae persisting longer than 2 to 3 months (n = 5; 4.6%) and prolonged erythema (n = 3; 0.28%) in phenol peels. The single-stage use of chemical peels, autologous fat transfer, and surgical rhytidectomy was safe. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

What is misophonia and how can we treat it?

PubMed

Cavanna, Andrea E

2014-04-01

Selective sound sensitivity syndrome or misophonia is a chronic condition characterized by unpleasant emotional experiences and autonomic arousal in response to specific sounds. Over the last few years there have been a few reports detailing the clinical features associated with this condition. These focused reports raise interesting questions about the nosological status of this potentially disabling clinical entity.

Interactive publications: creation and usage

NASA Astrophysics Data System (ADS)

Thoma, George R.; Ford, Glenn; Chung, Michael; Vasudevan, Kirankumar; Antani, Sameer

2006-02-01

As envisioned here, an "interactive publication" has similarities to multimedia documents that have been in existence for a decade or more, but possesses specific differentiating characteristics. In common usage, the latter refers to online entities that, in addition to text, consist of files of images and video clips residing separately in databases, rarely providing immediate context to the document text. While an interactive publication has many media objects as does the "traditional" multimedia document, it is a self-contained document, either as a single file with media files embedded within it, or as a "folder" containing tightly linked media files. The main characteristic that differentiates an interactive publication from a traditional multimedia document is that the reader would be able to reuse the media content for analysis and presentation, and to check the underlying data and possibly derive alternative conclusions leading, for example, to more in-depth peer reviews. We have created prototype publications containing paginated text and several media types encountered in the biomedical literature: 3D animations of anatomic structures; graphs, charts and tabular data; cell development images (video sequences); and clinical images such as CT, MRI and ultrasound in the DICOM format. This paper presents developments to date including: a tool to convert static tables or graphs into interactive entities, authoring procedures followed to create prototypes, and advantages and drawbacks of each of these platforms. It also outlines future work including meeting the challenge of network distribution for these large files.

Melanotic MiT family translocation neoplasms: Expanding the clinical and molecular spectrum of this unique entity of tumors.

PubMed

Saleeb, Rola M; Srigley, John R; Sweet, Joan; Doucet, Cedric; Royal, Virginie; Chen, Ying-Bei; Brimo, Fadi; Evans, Andrew

2017-11-01

MiT family translocation tumors are a group of neoplasms characterized by translocations involving MiT family transcription factors. The translocation renal cell carcinomas, TFE3 (Xp11.2) and TFEB (t6;11) are known members of this family. Melanotic Xp11 translocation renal cancer is a more recently described entity. To date only 14 cases have been described. It is characterized by a distinct set of features including a nested epithelioid morphology, melanin pigmentation, labeling for markers of melanocytic differentiation, lack of labeling for markers of renal tubular differentiation, predominance in a younger age population and association with aggressive clinical behavior. There are noted similarities between that entity and TFE3 associated PEComas. There are no cases reported of equivalent melanotic TFEB translocation renal cancer. We report 2 rare cases of melanotic translocation renal neoplasms. The first is a melanotic TFE3 translocation renal cancer with an indolent clinical course, occurring in a patient more than 3-decades older than the usual average age in which such tumors have been described. The other case is, to our knowledge, the first reported melanotic TFEB translocation cancer of the kidney. Both cases exhibit the same H&E morphology as previously reported in melanotic translocation renal cancers and label accordingly with HMB45 and Melan-A. While the TFE3 melanotic tumor lacked any evidence of renal tubular differentiation, the TFEB melanotic cancer exhibited some staining for renal tubular markers. Based on the unique features noted above, these two cases expand the clinical and molecular spectrum of the melanotic translocation renal cancers. Copyright © 2017 Elsevier GmbH. All rights reserved.

Breast lesions of uncertain malignant nature and limited metastatic potential: Proposals to improve their recognition and clinical management

PubMed Central

Rakha, Emad A.; Badve, Sunil; Eusebi, Vincenzo; Reis-Filho, Jorge S.; Fox, Stephen B.; Dabbs, David J.; Decker, Thomas; Hodi, Zsolt; Ichihara, Shu; Lee, Andrew HS.; Palacios, José; Richardson, Andrea L.; Vincent-Salomon, Anne; Schmitt, Fernando C.; Tan, Puay-Hoon; Tse, Gary M.; Ellis, Ian O.

2016-01-01

Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are traditionally classified into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey-zone between benign and malignant as their behaviour cannot be predicted reliably. Defined pathological categorisation of such lesions is challenging and for some entities is recognised to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over-treatment or under-treatment. The rarity of these lesions makes acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification, behaviour and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions remain of uncertain malignant nature such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of 1) breast lesions of uncertain malignant nature and 2) breast lesions of limited metastatic potential, are proposed with details of which histological entities could be included in each category, and their management implications are discussed. PMID:26348644

A review of sub acute subdural hematoma (SASDH) with our institutional experience and its management by double barrel technique (DbT): A novel technique.

PubMed

Tripathy, Soubhagya R; Swarnakar, Pankaj K; Mishra, Sanjib; Mishra, Sudhanshu S; Dhir, Manmath K; Behera, Sanjay K; Nath, Pratap C; Jena, Somnath P; Mohanta, Itibrata; Das, Deepak; Satapathy, Mani C; Rout, Sitansu K; Behera, Bikash R; Parida, Deepak K; Rath, Tanushree S

2016-01-01

Subacute subdural hematoma (SASDH) is an entity which is yet to capture the popular imagination among the neurosurgeons. Its management is often equated clinically to that of the chronic subdural hematoma (CSDH). However, their neurological deterioration is usually rapid, which seems to align them with acute subdural hematoma (ASDH). We proceed for their epidemiological evaluation. The advantages of a novel "double barrel technique (DbT)" over the conventional burrhole drainage are also presented. This retrospective study was conducted on all the patients having clinical and radiological evidence of SASDH, admitted to a tertiary care referral institute, during the period August 2013 to December 2015. Postoperatively, patients were followed-up for 3-24 months. 46.87% of the patients belonged to the 35-54 year age group with a male predominance (3.6:1); 68.7% had a history of alcohol abuse, whereas aspirin users were 25%. 87.5% cases were unilateral, 18.75% were hemispheric, and 46.87% were present on the left side. Altered consciousness (100%) followed by headache (37.5%) were the most common presenting clinical features. SASDH is an uncommon neurosurgical entity (0.89% of traumatic brain injury cases in our study) and mimics both CSDH as well as ASDH. The true incidence of SASDH may have been underestimated due to its clinical imitation with CSDH. This study in a South Asian nation also provides the epidemiological data of this rare neurosurgical entity. Outcome of surgery is good; our retrospective study confirms that "DbT" is an adequate and safe treatment. However, a better designed, randomized control trial will be needed to reinforce our findings.

Clinical and electrophysiological characteristics of patients with paroxysmal intra-His block with narrow QRS complexes.

PubMed

Ragupathi, Loheetha; Johnson, Drew; Greenspon, Arnold; Frisch, Daniel; Ho, Reginald T; Pavri, Behzad B

2018-04-18

Atrioventricular (AV) block is usually due to infranodal disease and associated with a wide QRS complex; such patients often progress to complete AV block and pacemaker dependency. Uncommonly, infranodal AV block can occur within the His bundle with a narrow QRS complex. The aims of this study were to define clinical/echocardiographic characteristics of patients with AV block within the His bundle and report progression to pacemaker dependency. We retrospectively identified patients with narrow QRS complexes and documented intra-His delay or block at electrophysiology study (group A) or with electrocardiogram-documented Mobitz II AV block/paroxysmal AV block (group B). Clinical, electrophysiological, and echocardiographic variables at presentation and pacemaker parameters at the last follow-up visit were evaluated. Twenty-seven patients (19 women) were identified (mean age 64 ± 13 years; range, 38-85 years). Four patients who had <1 month of follow-up were excluded. There were 12 patients in group A and 11 in group B; 21 of 23 presented with syncope/presyncope. All patients received pacemakers: 8 single chamber and 15 dual chamber. After a median follow-up of 6.4 years, the median percentage of ventricular pacing was 1% (interquartile range 0%-4.66%). One patient developed true pacemaker dependency. Aortic and/or mitral annular calcification was present in 13 of 22 patients with available echocardiograms. Patients who present with syncope and narrow QRS complexes with intra-His delay or Mobitz II paroxysmal AV block with narrow QRS complexes rarely progress to pacemaker dependency and require infrequent pacing. This entity is more common in women, with a higher prevalence of aortic and/or mitral annular calcification. If confirmed by additional studies, single-chamber pacemaker may be sufficient. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Spatio-Temporal Data Model for Integrating Evolving Nation-Level Datasets

NASA Astrophysics Data System (ADS)

Sorokine, A.; Stewart, R. N.

2017-10-01

Ability to easily combine the data from diverse sources in a single analytical workflow is one of the greatest promises of the Big Data technologies. However, such integration is often challenging as datasets originate from different vendors, governments, and research communities that results in multiple incompatibilities including data representations, formats, and semantics. Semantics differences are hardest to handle: different communities often use different attribute definitions and associate the records with different sets of evolving geographic entities. Analysis of global socioeconomic variables across multiple datasets over prolonged time is often complicated by the difference in how boundaries and histories of countries or other geographic entities are represented. Here we propose an event-based data model for depicting and tracking histories of evolving geographic units (countries, provinces, etc.) and their representations in disparate data. The model addresses the semantic challenge of preserving identity of geographic entities over time by defining criteria for the entity existence, a set of events that may affect its existence, and rules for mapping between different representations (datasets). Proposed model is used for maintaining an evolving compound database of global socioeconomic and environmental data harvested from multiple sources. Practical implementation of our model is demonstrated using PostgreSQL object-relational database with the use of temporal, geospatial, and NoSQL database extensions.

Building Scalable Knowledge Graphs for Earth Science

NASA Astrophysics Data System (ADS)

Ramachandran, R.; Maskey, M.; Gatlin, P. N.; Zhang, J.; Duan, X.; Bugbee, K.; Christopher, S. A.; Miller, J. J.

2017-12-01

Estimates indicate that the world's information will grow by 800% in the next five years. In any given field, a single researcher or a team of researchers cannot keep up with this rate of knowledge expansion without the help of cognitive systems. Cognitive computing, defined as the use of information technology to augment human cognition, can help tackle large systemic problems. Knowledge graphs, one of the foundational components of cognitive systems, link key entities in a specific domain with other entities via relationships. Researchers could mine these graphs to make probabilistic recommendations and to infer new knowledge. At this point, however, there is a dearth of tools to generate scalable Knowledge graphs using existing corpus of scientific literature for Earth science research. Our project is currently developing an end-to-end automated methodology for incrementally constructing Knowledge graphs for Earth Science. Semantic Entity Recognition (SER) is one of the key steps in this methodology. SER for Earth Science uses external resources (including metadata catalogs and controlled vocabulary) as references to guide entity extraction and recognition (i.e., labeling) from unstructured text, in order to build a large training set to seed the subsequent auto-learning component in our algorithm. Results from several SER experiments will be presented as well as lessons learned.

Improving the Accuracy of Attribute Extraction using the Relatedness between Attribute Values

NASA Astrophysics Data System (ADS)

Bollegala, Danushka; Tani, Naoki; Ishizuka, Mitsuru

Extracting attribute-values related to entities from web texts is an important step in numerous web related tasks such as information retrieval, information extraction, and entity disambiguation (namesake disambiguation). For example, for a search query that contains a personal name, we can not only return documents that contain that personal name, but if we have attribute-values such as the organization for which that person works, we can also suggest documents that contain information related to that organization, thereby improving the user's search experience. Despite numerous potential applications of attribute extraction, it remains a challenging task due to the inherent noise in web data -- often a single web page contains multiple entities and attributes. We propose a graph-based approach to select the correct attribute-values from a set of candidate attribute-values extracted for a particular entity. First, we build an undirected weighted graph in which, attribute-values are represented by nodes, and the edge that connects two nodes in the graph represents the degree of relatedness between the corresponding attribute-values. Next, we find the maximum spanning tree of this graph that connects exactly one attribute-value for each attribute-type. The proposed method outperforms previously proposed attribute extraction methods on a dataset that contains 5000 web pages.

Convergent evolution of gene networks by single-gene duplications in higher eukaryotes.

PubMed

Amoutzias, Gregory D; Robertson, David L; Oliver, Stephen G; Bornberg-Bauer, Erich

2004-03-01

By combining phylogenetic, proteomic and structural information, we have elucidated the evolutionary driving forces for the gene-regulatory interaction networks of basic helix-loop-helix transcription factors. We infer that recurrent events of single-gene duplication and domain rearrangement repeatedly gave rise to distinct networks with almost identical hub-based topologies, and multiple activators and repressors. We thus provide the first empirical evidence for scale-free protein networks emerging through single-gene duplications, the dominant importance of molecular modularity in the bottom-up construction of complex biological entities, and the convergent evolution of networks.

Simultaneous bilateral distal biceps tendon ruptures repaired using an endobutton technique: a case report.

PubMed

Dacambra, Mark P; Walker, Richard Ea; Hildebrand, Kevin A

2013-08-23

The simultaneous rupture of both distal biceps tendons is a rare clinical entity that is difficult to treat and can have poor outcomes. A variety of treatment and rehabilitation options exist and have been reported for single sided and staged bilateral repairs, but none have described an approach for acute bilateral ruptures. Repairing distal biceps tendon ruptures using a single anterior incision and a cortical suspensory button technique has become increasingly popular in recent years. We present a report of our surgical approach using an endobutton technique and rehabilitation algorithm for this unusual injury pattern. A 43-year-old Caucasian man presented with acute onset bilateral elbow pain while lifting a large sheet of drywall off the ground. He initially felt a 'pop' on the right and almost immediately felt another on the left after having to quickly shift the weight. He was unable to continue working and sought medical attention. His pain was predominantly in his bilateral antecubital fossae and he had significant swelling and ecchymoses. His clinical examination demonstrated no palpable tendon, a retracted biceps muscle belly, and clear supination weakness. Magnetic resonance imaging was performed and showed bilateral distal biceps tendon ruptures with retraction on both sides. After discussion with our patient, we decided that both sides would be repaired using a single anterior incision with endobutton fixation, first his right followed by his left six weeks later. Overall, our patient did very well and had returned to full manual work by our last follow-up at 30 months. Although he was never able to return to competitive recreational hockey and was left with mild lateral antebrachial cutaneous nerve dysesthesias on his right, he felt he was at 85% of his premorbid level of function. We describe what we believe to be, to the best of our knowledge, the first case of simultaneous bilateral distal biceps tendon ruptures successfully treated with a single-incision endobutton technique, which represents a valid option in managing this difficult problem.

An ontologically founded architecture for information systems in clinical and epidemiological research.

PubMed

Uciteli, Alexandr; Groß, Silvia; Kireyev, Sergej; Herre, Heinrich

2011-08-09

This paper presents an ontologically founded basic architecture for information systems, which are intended to capture, represent, and maintain metadata for various domains of clinical and epidemiological research. Clinical trials exhibit an important basis for clinical research, and the accurate specification of metadata and their documentation and application in clinical and epidemiological study projects represents a significant expense in the project preparation and has a relevant impact on the value and quality of these studies.An ontological foundation of an information system provides a semantic framework for the precise specification of those entities which are presented in this system. This semantic framework should be grounded, according to our approach, on a suitable top-level ontology. Such an ontological foundation leads to a deeper understanding of the entities of the domain under consideration, and provides a common unifying semantic basis, which supports the integration of data and the interoperability between different information systems.The intended information systems will be applied to the field of clinical and epidemiological research and will provide, depending on the application context, a variety of functionalities. In the present paper, we focus on a basic architecture which might be common to all such information systems. The research, set forth in this paper, is included in a broader framework of clinical research and continues the work of the IMISE on these topics.

Multiple Intelligences: Current Trends in Assessment

ERIC Educational Resources Information Center

Harman, Marsha J.; Kordinak, S. Thomas; Bruce, A. Jerry

2009-01-01

With his theory of multiple intelligences, Howard Gardner challenged the presumption that intelligence is a single innate entity. He maintained that multiple intelligences exist and are related to specific brain areas and symbol systems. Each of the intelligences has its merits and limits, but by using a multiple intelligences approach, more…

Genomic sequences of two novel Levivirus single-stranded RNA coliphages (family Leviviridae): Evidence for recombination in environmental strains

EPA Science Inventory

Bacteriophages are likely the most abundant entities in the aquatic environment, yet knowledge of their ecology is limited. During a fecal source-tracking study, two genetically novel Leviviridae strains were discovered. Although the novel strains were isolated from coastal wat...

17 CFR 150.1 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... POSITIONS § 150.1 Definitions. As used in this part— (a) Spot month means the futures contract next to...) Single month means each separate futures trading month, other than the spot month future. (c) All-months means the sum of all futures trading months including the spot month future. (d) Eligible entity means...

10 CFR 603.1015 - Execution.

Code of Federal Regulations, 2010 CFR

2010-01-01

... properly authorize one participant to sign on behalf of the other participants and are binding on all... entering into an agreement signed by a single member on behalf of a consortium that is not a legal entity... agreement individually or to allow them to designate one member to sign on all members' behalf. Reporting...

10 CFR 603.1015 - Execution.

Code of Federal Regulations, 2011 CFR

2011-01-01

... properly authorize one participant to sign on behalf of the other participants and are binding on all... entering into an agreement signed by a single member on behalf of a consortium that is not a legal entity... agreement individually or to allow them to designate one member to sign on all members' behalf. Reporting...

7 CFR 3550.73 - Manufactured homes.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE DIRECT SINGLE FAMILY HOUSING LOANS AND GRANTS Section 502 Origination § 3550.73 Manufactured homes... 502 loans on manufactured homes are subject to the same conditions as all other section 502 loans. (a... loans will be made on a manufactured home sold by any entity that is not an approved dealer-contractor...

18 CFR 33.3 - Additional information requirements for applications involving horizontal competitive impacts.

Code of Federal Regulations, 2011 CFR

2011-04-01

... result of the proposed transaction, a single corporate entity obtains ownership or control over the... applicant may provide other analyses for defining relevant markets (e.g. the Hypothetical Monopolist Test with or without the assumption of price discrimination) in addition to the delivered price test under...

18 CFR 33.3 - Additional information requirements for applications involving horizontal competitive impacts.

Code of Federal Regulations, 2013 CFR

2013-04-01

... result of the proposed transaction, a single corporate entity obtains ownership or control over the... applicant may provide other analyses for defining relevant markets (e.g. the Hypothetical Monopolist Test with or without the assumption of price discrimination) in addition to the delivered price test under...

18 CFR 33.3 - Additional information requirements for applications involving horizontal competitive impacts.

Code of Federal Regulations, 2012 CFR

2012-04-01

... result of the proposed transaction, a single corporate entity obtains ownership or control over the... applicant may provide other analyses for defining relevant markets (e.g. the Hypothetical Monopolist Test with or without the assumption of price discrimination) in addition to the delivered price test under...

18 CFR 33.3 - Additional information requirements for applications involving horizontal competitive impacts.

Code of Federal Regulations, 2014 CFR

2014-04-01

... result of the proposed transaction, a single corporate entity obtains ownership or control over the... applicant may provide other analyses for defining relevant markets (e.g. the Hypothetical Monopolist Test with or without the assumption of price discrimination) in addition to the delivered price test under...

18 CFR 33.3 - Additional information requirements for applications involving horizontal competitive impacts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... result of the proposed transaction, a single corporate entity obtains ownership or control over the... applicant may provide other analyses for defining relevant markets (e.g. the Hypothetical Monopolist Test with or without the assumption of price discrimination) in addition to the delivered price test under...

Character and Citizenship Education: Conversations between Personal and Societal Values

ERIC Educational Resources Information Center

Sim, Jasmine B.-Y.; Low, Ee Ling

2012-01-01

The theme of this special issue is "Character and Citizenship Education: Conversations between Personal and Societal Values." Character education and citizenship education, taken separately or as a single entity are currently riding high on the political and educational policy agendas of several governments (Arthur, 2003; Berkowitz & Bier, 2007;…

Business as Usual: Amazon.com and the Academic Library

ERIC Educational Resources Information Center

Van Ullen, Mary K.; Germain, Carol Anne

2002-01-01

In 1999, Steve Coffman proposed that libraries form a single interlibrary loan based entity patterned after Amazon.com. This study examined the suitability of Amazon.com's Web interface and record enhancements for academic libraries. Amazon.com could not deliver circulating monographs in the University at Albany Libraries' collection quickly…

The Semantics of Plurals: A Defense of Singularism

ERIC Educational Resources Information Center

Florio, Salvatore

2010-01-01

In this dissertation, I defend "semantic singularism", which is the view that syntactically plural terms, such as "they" or "Russell and Whitehead", are semantically singular. A semantically singular term is a term that denotes a single entity. Semantic singularism is to be distinguished from "syntactic singularism", according to which…

Perceptual Ratings of Subgroups of Ataxic Dysarthria

ERIC Educational Resources Information Center

Spencer, Kristie A.; France, Ashley A.

2016-01-01

Background: The speech characteristics of ataxic dysarthria are known to be quite diverse. The varied presentation of this dysarthria challenges researchers and clinicians alike, and brings into question whether it is a single entity. While the possibility of subtypes of ataxic dysarthria has been suggested, the nature of these putative groups…

Roma as the Others

ERIC Educational Resources Information Center

Doubek, David; Levínská, Marketa; Bittnerová, Dana

2015-01-01

While it is common to speak about "Roma culture" as a single entity, the questions posed by Roma culture are more complex. We are speaking about the general issues pertaining to various manifestations of this culture in the context of the Czech Republic. It must be stressed that under "Roma," we understand a family resemblance…

14 CFR 1214.102 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Space Shuttle Flights of Payloads for Non-U.S. Government, Reimbursable Customers § 1214.102 Definitions. (a) Customer. Any non-U.S. government person or entity who, by virtue of a contract or other... in § 1214.115 for 1 day of single-shift, on-orbit mission operations. (d) Jettison. To physically...

14 CFR 1214.102 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Space Shuttle Flights of Payloads for Non-U.S. Government, Reimbursable Customers § 1214.102 Definitions. (a) Customer. Any non-U.S. government person or entity who, by virtue of a contract or other... in § 1214.115 for 1 day of single-shift, on-orbit mission operations. (d) Jettison. To physically...

14 CFR 1214.102 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Space Shuttle Flights of Payloads for Non-U.S. Government, Reimbursable Customers § 1214.102 Definitions. (a) Customer. Any non-U.S. government person or entity who, by virtue of a contract or other... in § 1214.115 for 1 day of single-shift, on-orbit mission operations. (d) Jettison. To physically...

14 CFR 1214.102 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Space Shuttle Flights of Payloads for Non-U.S. Government, Reimbursable Customers § 1214.102 Definitions. (a) Customer. Any non-U.S. government person or entity who, by virtue of a contract or other... in § 1214.115 for 1 day of single-shift, on-orbit mission operations. (d) Jettison. To physically...

Private Placement Debt Financing for Public Entities

ERIC Educational Resources Information Center

Holman, Lance S.

2010-01-01

Private placement financing is a debt or capital lease obligation arranged between a municipality or a 501(c) (3) not-for-profit organization and a single sophisticated institutional investor. The investor can be a bank, insurance company, finance company, hedge fund, or high-net worth individual. Private placement financing is similar to…

Genetics Home Reference: L1 syndrome

MedlinePlus

... X-linked hydrocephalus: evidence for closely related clinical entities of unknown molecular bases. Acta Neuropathol. 2013 Sep; ... F. Three cases with L1 syndrome and two novel mutations in the L1CAM gene. Eur J Pediatr. ...

Which is guilty in self-induced penile fractures: marital status, culture or geographic region? A case series and literature review.

PubMed

Al Ansari, A; Talib, R A; Shamsodini, A; Hayati, A; Canguven, O; Al Naimi, A

2013-01-01

Penile fracture is a well-recognized and relatively uncommon clinical entity. It was previously reported that the incidence of penile fracture varies according to various geographic regions. In order to determine whether marital status or culture other than geographic region is involved in the etiology of penile fracture in our country, the charts of 122 men diagnosed with penile fracture were retrospectively reviewed. Detailed history including cause, symptoms, country of origin and a single-question self-report of erectile dysfunction was used for all cases. Diagnosis of our cases was mainly based on history and physical examination and ultrasonography. Immediate or delayed surgical repair of penile fracture included a degloving circumferential, and an additional direct incision, if the site of the tear could not be reached via degloving, was performed. The patients were evaluated after 1 week and 1, 3, and 6 months follow-up by penile examination, recording complications, and with a single-question self-report questionnaire after 3 and 6 months. The most common cause of penile fracture was manual bending of the erected penis in 66 out of 122 (54.1%) of our study patients. In our study, we believe that the prime causes of bending the penis are single status and culture, which are influencing factors irrespective of the geographic distribution.

Isolation, Analysis and Antimicrobial Activity of the Acidic Fractions of Mastic, Kurdica, Mutica and Cabolica Gums from Genus Pistacia

PubMed Central

Sharifi, Mohammad Sharif; Hazell, Stuart Loyd

2012-01-01

The chemical entities of Mastic, Kurdica, Mutica and Cabolica gums from genus Pistacia have been isolated and characterised by GC-Mass Spectrometry, High Performance Liquid Chromatography and Column Chromatography. These chemical entities were screened for anti-microbial activities against nine strains of Helicobacter pylori and some other Gram-negative and Gram-positive bacteria. The most bioactive components were structurally analysed. These components mimic steroid compounds, in particular, the known antibiotic Fusidic acid. Some of these chemical entities have produced promising data that could lead to the development of a novel class of antimicrobial agents that may have application in the treatment of infectious disease. Kill kinetics have been also performed, and the produced data were evaluated by Generalized Multiplicative Analysis Of Variance (GEMANOVA) for the bactericidal and bacteriostatic activities which can be clinically significant. The isolated components were all bactericidal. PMID:22980113

Cryptogenic stroke. A non-diagnosis.

PubMed

Gutiérrez-Zúñiga, Raquel; Fuentes, Blanca; Díez-Tejedor, Exuperio

2018-04-30

The term cryptogenic stroke refers to a stroke for which there is no specific attributable cause after a comprehensive evaluation. However, there are differences between the diagnostic criteria of etiological classifications used in clinical practice. An improvement in diagnostic tools such advances in monitoring for atrial fibrillation, advances in vascular imaging and evidence regarding the implication of patent foramen oval on the risk of stroke specially in young patients are reducing the proportion of stroke patients without etiological diagnosis. We carried out a critical review of the current concept of cryptogenic stroke, as a non-diagnosis, avoiding the simplification of it and reviewing the different entities that could fall under this diagnosis and reviewing the different entities that could fall under this diagnosis; and therefore avoid the same treatment for differents entities with uncertains results. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Primary disorders of the lymphatic vessels--a unified concept.

PubMed

Levine, C

1989-03-01

Congenital defects of lymphatics constitute a spectrum of disorders that may manifest with a variety of clinical presentations including lymphedema, chylous effusions, lymphangiomatous malformations with cystic masses and localized gigantism, and intestinal lymphangiectasia with malabsorption. These entities constitute a relatively rare group of disorders, the origin of which remains somewhat controversial, but in some it appears to be due to early lymphatic obstruction. Five cases are described, which demonstrate the anatomical pathology of these entities. A classification and description of the defects is also presented. An attempt is made to present a unified theory of origin for this seemingly diverse group of diseases. While these entities may be challenging from a diagnostic and therapeutic standpoint, a wide variety of imaging modalities, which includes lymphography, computed tomography scanning, and ultrasound, may be used to diagnose the extent and internal structural characteristics of the abnormalities.

Moore-Federman syndrome and acromicric dysplasia: are they the same entity?

PubMed Central

Winter, R M; Patton, M A; Challener, J; Mueller, R F; Baraitser, M

1989-01-01

Four unrelated patients are reported with short stature, stiffness of the joints, short fingers, inability to make a fist, and thickened skin on the forearms. Investigations have failed to show a lysosomal storage disorder and radiographs show non-specific changes with a delayed carpal bone age. The clinical features in the four children are very similar to the recently described acromicric dysplasia. There are also similarities to Moore-Federman syndrome which has only been described in one family. The case is made that acromicric dysplasia and Moore-Federman syndrome are the same entity. Images PMID:2732993

Politics and Graduate Medical Education in Internal Medicine: A Dynamic Landscape.

PubMed

Wardrop, Richard M; Berkowitz, Lee R

2017-02-01

The promotion of change and growth within medical education is oftentimes the result of a complex mix of societal, cultural and economic forces. Graduate medical education in internal medicine is not immune to these forces. Several entities and organizations can be identified as having a major influence on internal medicine training and graduate medical education as a whole. We have reviewed how this is effectively accomplished through these entities and organizations. The result is a constantly changing and dynamic landscape for internal medicine training. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Breast cancer - one term, many entities?

PubMed

Bertos, Nicholas R; Park, Morag

2011-10-01

Breast cancer, rather than constituting a monolithic entity, comprises heterogeneous tumors with different clinical characteristics, disease courses, and responses to specific treatments. Tumor-intrinsic features, including classical histological and immunopathological classifications as well as more recently described molecular subtypes, separate breast tumors into multiple groups. Tumor-extrinsic features, including microenvironmental configuration, also have prognostic significance and further expand the list of tumor-defining variables. A better understanding of the features underlying heterogeneity, as well as of the mechanisms and consequences of their interactions, is essential to improve targeting of existing therapies and to develop novel agents addressing specific combinations of features.

Product-related research: how research can contribute to successful life-cycle management.

PubMed

Sandner, Peter; Ziegelbauer, Karl

2008-05-01

Declining productivity with decreasing new molecular entity output combined with increased R&D spending is one of the key challenges for the entire pharmaceutical industry. In order to offset decreasing new molecular entity output, life-cycle management activities for established drugs become more and more important to maintain or even expand clinical indication and market opportunities. Life-cycle management covers a whole range of activities from strategic pricing to a next generation product launch. In this communication, we review how research organizations can contribute to successful life-cycle management strategies using phosphodiesterase 5 inhibitors as an example.

Surfer's myelopathy: case report and review.

PubMed

Karabegovic, Amna; Strachan-Jackman, Shirley; Carr, David

2011-09-01

Nontraumatic spinal cord injury from surfing is a new entity first described in 2004 and likely of ischemic etiology. We report the case of a 25-year-old man who presented to the emergency department with a 2-week history of lower extremity weakness after surfing in Indonesia. The patient reported developing low back pain, lower extremity weakness, sensory changes, and urinary retention shortly after his first surfing lesson. The patient was subsequently diagnosed with surfer's myelopathy. The purpose of this report is to review the clinical presentation, etiology, risk factors, and management of this increasingly described entity.

A new autosomal dominant syndrome of distinctive face showing ptosis and prominent eyes associated with cleft palate, ear anomalies, and learning disability.

PubMed

Tyshchenko, N; Neuhann, T M; Gerlach, E; Hahn, G; Heisch, K; Rump, A; Schrock, E; Tinschert, S; Hackmann, K

2011-09-01

We report on three patients from two families with apparently a novel clinical entity. The main features of which include unusual craniofacial dysmorphism with ptosis, prominent eyes, flat midface, Cupid's bow configuration of the upper lip, low-set, posteriorly rotated small ears, as well as conductive hearing loss, cleft palate, heart defect, and mild developmental delay. We suggest that this entity is an autosomal dominant disorder given the occurrence in a mother and daughter as well as in an unrelated boy. Copyright © 2011 Wiley-Liss, Inc.

The Mobile Team of Parasitology-Mycology, a medical entity for educational purposes to serve sick patients.

PubMed

Desoubeaux, G; Simon, E G; Perrotin, D; Chandenier, J

2014-06-01

The Mobile Team of Parasitology-Mycology is a movable entity of the Parasitology-Mycology laboratory of Tours University Hospital, France. In contrast to the usual prerogatives of biomedical laboratories, the Mobile Team of Parasitology-Mycology is requested to intervene directly at bedside in various clinical departments, or even outside the hospital facility. Although its actions are of course primarily devoted to specialized diagnostic and therapeutic purposes, the Mobile Team also plays an important educational role in the medical training of undergraduate or graduate students. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

A clinical analysis of two indolent lymphoma entities: mantle cell lymphoma and marginal zone lymphoma (including the mucosa-associated lymphoid tissue and monocytoid B-cell subcategories): a Southwest Oncology Group study.

PubMed

Fisher, R I; Dahlberg, S; Nathwani, B N; Banks, P M; Miller, T P; Grogan, T M

1995-02-15

The objectives of this study were (1) to determine the clinical presentation and natural history associated with two newly recognized pathologic entities termed mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL), including the mucosa-associated lymphoid tissue (MALT) and monocytoid B-cell subcategories, and (2) to determine whether these entities differ clinically from the other relatively indolent non-Hodgkin's lymphomas with which they have been previously classified. We reviewed the conventional pathology and clinical course of 376 patients who had no prior therapy; had stage III/IV disease; were classified as Working Formulation categories A, B, C, D, or E; and received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) on Southwest Oncology Group (SWOG) studies no. 7204, 7426, or 7713. All slides were reviewed by the three pathologists who reached a consensus diagnosis. Age, sex, performance status, bone marrow and/or gastrointestinal involvement, failure-free survival, and overall survival were compared among all the categories. We found that (1) MCL and MZL each represent approximately 10% of stage III or IV patients previously classified as Working Formulation categories A through E and treated with CHOP on SWOG clinical trials; (2) the failure-free survival and overall survival of patients with MZL is the same as that of patients with Working Formulation categories A through E, but the failure-free survival and overall survival of the monocytoid B-cell patients were higher than that of the MALT lymphoma patients (P = .009 and .007, respectively); and (3) the failure-free survival and overall survival of patients with MCL is significantly worse than that of patients with Working Formulation categories A through E (P = .0002 and .0001, respectively). In conclusion, patients with advanced stage MALT lymphomas may have a more aggressive course than previously recognized. Patients with MCL do not have an indolent lymphoma and are candidates for innovative therapy.

Tuberculous pseudotumor of the liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhekne, R.D.; Moore, W.H.; Long, S.E.

1987-10-01

Tuberculosis of the liver in association with generalized miliary tuberculosis is not an uncommon clinical entity. A solitary tuberculous liver abscess, however, is rare. Two such cases, in which there was no clinical evidence of extrahepatic tuberculosis, are reported. The similarities between this condition and other causes of hepatic lesions are discussed, with particular emphasis placed on the imaging patterns of various diagnostic imaging procedures.

Granulomatous lobular mastitis.

PubMed

Miliauskas, J R; Pieterse, A S; Williams, R S

1995-02-01

Two cases of benign lobular granulomatous mastitis, both clinically felt to be carcinoma, are reported. One patient was cured by local excision of the mass while the other was cured by oral prednisolone, demonstrating the variable ways to treat this entity. The clinical and histological features were similar to those noted in previous reports. Immunological studies revealed predominantly stromal T lymphocytes and only duct intra-epithelial T lymphocytes.

Age-related monoclonal gammapathies: clinical lessons from the aging C57BL mouse.

PubMed

Radl, J

1990-07-01

In this article the long-held notion that benign monoclonal gammapathy (BMG) is a premalignant stage in the development of multiple myeloma (MM) is attacked. Jiri Radl argues that clinical and experimental observations indicate that they are separate entities which may be distinguished in the laboratory and which should be managed in radically different ways.

A retrospective clinico-pathological study comparing lichen planus pigmentosus with ashy dermatosis.

PubMed

Cheng, Hui Mei; Chuah, Sai Yee; Gan, Emily Yiping; Jhingan, Anjali; Thng, Steven Tien Guan

2018-04-10

Controversy persists as to whether lichen planus pigmentosus and ashy dermatosis are separate clinical entities. This study was conducted to examine the clinicopathological features and treatment outcome of the two conditions. A retrospective medical chart review of all patients who were diagnosed with lichen planus pigmentosus or ashy dermatosis was conducted. The information collected included the participants' age at onset, site of onset, duration of disease, presence of precipitating factors, distribution of disease, pigmentation and presence of symptoms. In patients from whom a biopsy was taken the histopathological reports were included. Altogether 26 patients with ashy dermatosis and 29 with lichen planus pigmentosus were included in the study. Compared with ashy dermatosis, lichen planus pigmentosus had a more localised distribution with a preponderance for facial involvement, compared with the truncal preponderance in ashy dermatosis. Ashy dermatosis tended to have a more stable clinical course than lichen planus pigmentosus, which was more likely to wax and wane. The utility of histopathology in differentiating between the two conditions is low. Ashy dermatosis and lichen planus pigmentosus, as defined in this study, appear to be two separate clinical entities with distinguishable clinical features and natural histories. © 2018 The Australasian College of Dermatologists.

[Tumoral calcinoses in a chronic hemodialysis patient: The role of SPECT/CT hybrid imaging].

PubMed

Matrane, Aboubakr; Hiroual, Soufiane; Bsiss, Mohamed Aziz; Doubli, Safa Bennani

2018-05-01

Tumoral calcinosis is a rare benign disease, defined by the presence of calcified deposits in periarticular tissues. It can be hereditary or secondary at chronic renal failure at the stage of dialysis. This work illustrates the contribution of single-photon emission computed tomography (SPECT/CT) in the diagnosis and management of tumoral calcinoses in a chronic hemodialysis patient, based on a clinical case. A 62-year-old patient, chronic hemodialysis since 24 years, presented a mechanical pain shoulders, knees and hips with limitation of joint mobility. The clinical exam found a mass of soft tissue in the buttocks. The radiological exam showed the presence of periarticular calcifications with no bone involvement. The SPECT/CT revealed a multifocal tumoral calcinosis affecting shoulders, elbows, wrists, hips and knees, associated with alveolar and abdominal calcinosis. Tumoral calcinosis is a distinct clinicopathological entity characterised by periarticular soft tissue calcium deposits. The SPECT/CT is important in the diagnosis, the assessment of extension and monitoring of tumoral calcinosis after treatment. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

[The affective pathology in patients with adolescent bulimia nervosa].

PubMed

Grachev, V V

To investigate affective pathology in patients with adolescent bulimia nervosa (BN) and to analyze comorbid mutual influences of these clinical entities. A sample consisted of 52 young female patients, aged from 13.9 to 17.4 years, who simultaneously meet ICD-10 criteria of F50.2 - typical BN and F30-F39 - mood disorders. The Eating Attitudes Test (EAT-26) and the Beck Depression Inventory were used for psychometric assessment. Duration of follow-up ranged from 1 to 7 years. The common forms of affective disorders comorbid with adolescent BN were dysthymia and bipolar affective disorder (BAD) type II. Less often BN manifested in association with psychogenic endoform depressions. And the less typical was comorbidity of BN with endogenous recurrent unipolar depression. The normalization of mood and transition depression to hypomania contributed to the remission of eating disorders. Worst clinical and social outcome was detected in patients with long-term persistent hypothymia caused by dysthymia or protracted depressive episodes of recurrent depressive disorder. A more favorable outcome was seen in patients with alternation of depression and hypomania in the structure of the BAD type II and the best outcome in patients with single episode of psychogenic endoform depression.

Pathologic Outcomes following Urethral Diverticulectomy in Women

PubMed Central

Laudano, Melissa A.; Jamzadeh, Asha E.; Lee, Richard K.; Robinson, Brian D.; Tyagi, Renuka; Kaplan, Steven A.; Te, Alexis E.

2014-01-01

Purpose. Although most urethral diverticula in women are benign, there is a subset of patients who develop malignant changes. Limited studies report the pathologic findings associated with this relatively rare entity. We describe the clinicopathologic findings of women who underwent urethral diverticulectomy. Methods. A consecutive series of 29 women who underwent surgical resection of a urethral diverticulum were identified between 1992 and 2013. Clinical and radiographic data was collected by retrospective review of patient medical records. All pathological slides were rereviewed by a single urologic pathologist. Results. Of the 14 women with clinical data, 9 (64%) presented with urgency, 7 (50%) with urinary frequency, 3 (21%) with urinary incontinence, and 3 (21%) with dysuria. Mean diverticular size was 2.3 (±1.4) cm. Although one patient (3%) had invasive adenocarcinoma on final pathology, the remaining 28 cases (97%) demonstrated benign features. The most common findings were inflammation (55%) and nephrogenic adenoma (21%). Conclusions. Although most urethral diverticula in women are benign, there is a subset of patients who develop malignancy in association with the diverticulum. In this series, 97% of cases had a benign histology. These findings are important when counseling patients regarding treatment options. PMID:24860605

Pathologic Outcomes following Urethral Diverticulectomy in Women.

PubMed

Laudano, Melissa A; Jamzadeh, Asha E; Dunphy, Claire; Lee, Richard K; Robinson, Brian D; Tyagi, Renuka; Kaplan, Steven A; Te, Alexis E; Chughtai, Bilal

2014-01-01

Purpose. Although most urethral diverticula in women are benign, there is a subset of patients who develop malignant changes. Limited studies report the pathologic findings associated with this relatively rare entity. We describe the clinicopathologic findings of women who underwent urethral diverticulectomy. Methods. A consecutive series of 29 women who underwent surgical resection of a urethral diverticulum were identified between 1992 and 2013. Clinical and radiographic data was collected by retrospective review of patient medical records. All pathological slides were rereviewed by a single urologic pathologist. Results. Of the 14 women with clinical data, 9 (64%) presented with urgency, 7 (50%) with urinary frequency, 3 (21%) with urinary incontinence, and 3 (21%) with dysuria. Mean diverticular size was 2.3 (±1.4) cm. Although one patient (3%) had invasive adenocarcinoma on final pathology, the remaining 28 cases (97%) demonstrated benign features. The most common findings were inflammation (55%) and nephrogenic adenoma (21%). Conclusions. Although most urethral diverticula in women are benign, there is a subset of patients who develop malignancy in association with the diverticulum. In this series, 97% of cases had a benign histology. These findings are important when counseling patients regarding treatment options.

[Acute lymphoblastic leukemia: a genomic perspective].

PubMed

Jiménez-Morales, Silvia; Hidalgo-Miranda, Alfredo; Ramírez-Bello, Julián

In parallel to the human genome sequencing project, several technological platforms have been developed that let us gain insight into the genome structure of human entities, as well as evaluate their usefulness in the clinical approach of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, genomic tools promise to be useful to detect patients at high risk of relapse, either at diagnosis or during treatment (minimal residual disease), and they also increase the possibility to identify cases at risk of adverse reactions to chemotherapy. Therefore, the physician could offer patient-tailored therapeutic schemes. A clear example of the useful genomic tools is the identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl transferase (TPMT) gene, where the presence of two null alleles (homozygous or compound heterozygous) indicates the need to reduce the dose of mercaptopurine by up to 90% to avoid toxic effects which could lead to the death of the patient. In this review, we provide an overview of the genomic perspective of ALL, describing some strategies that contribute to the identification of biomarkers with potential clinical application. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Progress in the development of animal models of acute kidney injury and its impact on drug discovery.

PubMed

Sanz, Ana B; Sanchez-Niño, María Dolores; Martín-Cleary, Catalina; Ortiz, Alberto; Ramos, Adrián M

2013-07-01

Acute kidney injury (AKI) is a clinical syndrome characterized by the acute loss of kidney function. AKI is increasingly frequent and is associated with impaired survival and chronic kidney disease progression. Experimental AKI models have contributed to a better understanding of pathophysiological mechanisms but they have not yet resulted in routine clinical application of novel therapeutic approaches. The authors present the advances in experimental AKI models over the last decade. Furthermore, the authors review their current and expected impact on novel drug discovery. New AKI models have been developed in rodents and non-rodents. Non-rodents allow the evaluation of specific aspects of AKI in both bigger animals and simpler organisms such as drosophila and zebrafish. New rodent models have recently reproduced described clinical entities, such as aristolochic and warfarin nephropathies, and have also provided better models for old entities such as thrombotic microangiopathy-induced AKI. Several therapies identified in animal models are now undergoing clinical trials in human AKI, including p53 RNAi and bone-marrow derived mesenchymal stem cells. It is conceivable that further refinement of animal models in combination with ongoing trials and novel trials based on already identified potential targets will eventually yield effective therapies for clinical AKI.

3M syndrome: a report of four cases in two families.

PubMed

Güven, Ayla; Cebeci, Ayşe Nurcan

2011-01-01

3M syndrome is a rare entity characterized by severe growth retardation, dysmorphic features and skeletal changes as its major components. It is differentiated from other types of dwarfism by its clinical features and by the typical slender long bones and foreshortened vertebral bodies that can be visualized radiographically. 3M syndrome has an autosomal recessive mode of inheritance. An early diagnosis is important for genetic counseling. In this report, we present four children (3 males, 1 female) from two families who were aged between 4(11/12) and 10(11/12) years and had clinical findings of 3M syndrome. One of these patients had received growth hormone (GH) treatment which was discontinued due to an inadequate height gain. Physicians should be aware of this entity in the differential diagnosis of children with severe short stature and mild skeletal changes.

Metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract. Management and literature review.

PubMed

Salemis, Nikolaos S; Seretis, Charalambos; Seretis, Fotios; Christofyllakis, Charalambos; Karalis, Georgios

2014-01-01

Multifocal soft tissue sarcoma is a rare clinical entity occurring in 1% of patients with extremity soft tissue sarcoma and in 4.5% of patients with liposarcoma. Multifocal disease may arise either synchronously or metachronously and has been associated with poor prognosis. Herein, we have described a rare case of metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract that developed 14 months after the resection of a myxoid buttock liposarcoma. Diagnostic evaluation and management of the patient are discussed along with a review of the relevant literature. We conclude that multifocal myxoid liposarcoma is a rare clinical entity that usually represents metastatic disease with poor prognosis. A thorough imaging and careful physical examination are essential in the preoperative evaluation and postoperative follow-up of patients with myxoid extremity liposarcomas, as these tumors are known to have a tendency to spread toward extrapulmonary sites, frequently without pulmonary metastases.

Metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract. Management and literature review

PubMed Central

Salemis, Nikolaos S.; Seretis, Charalambos; Seretis, Fotios; Christofyllakis, Charalambos; Karalis, Georgios

2014-01-01

Multifocal soft tissue sarcoma is a rare clinical entity occurring in 1% of patients with extremity soft tissue sarcoma and in 4.5% of patients with liposarcoma. Multifocal disease may arise either synchronously or metachronously and has been associated with poor prognosis. Herein, we have described a rare case of metachronous multifocal myxoid liposarcoma involving the gastrointestinal tract that developed 14 months after the resection of a myxoid buttock liposarcoma. Diagnostic evaluation and management of the patient are discussed along with a review of the relevant literature. We conclude that multifocal myxoid liposarcoma is a rare clinical entity that usually represents metastatic disease with poor prognosis. A thorough imaging and careful physical examination are essential in the preoperative evaluation and postoperative follow-up of patients with myxoid extremity liposarcomas, as these tumors are known to have a tendency to spread toward extrapulmonary sites, frequently without pulmonary metastases. PMID:24678225

Palisaded Neutrophilic and Granulomatous Dermatitis/Interstitial Granulomatous Dermatitis Overlap: A Striking Clinical and Histologic Presentation With "Burning Rope Sign" and Subsequent Mirror-Image Contralateral Recurrence.

PubMed

Kern, Malan; Shiver, Mallory B; Addis, Kristen M; Gardner, Jerad M

2017-09-01

Palisaded neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis are uncommon granulomatous dermatoses that often arise in association with rheumatoid arthritis. These 2 entities have overlapping features and may exist on a spectrum. We report an intriguing case of a 53-year-old man with advanced rheumatoid arthritis who presented with a large indurated painful truncal plaque with a palpable cord in addition to a papulonodular eruption on his dorsal hands. Furthermore, our patient had a recurrence in a near-identical mirror-image pattern on the contralateral trunk. The constellation of clinical and histopathological findings in our patient further suggests that palisaded neutrophilic and granulomatous dermatitis and interstitial granulomatous dermatitis exist as overlapping disease entities on a continuum. In addition, we propose that recurrence of skin findings may be indicative of the severity of the underlying systemic disease process.

Nontraumatic head and neck injuries: a clinical approach. Part 2.

PubMed

Brea Álvarez, B; Esteban García, L; Tuñón Gómez, M; Cepeda Ibarra, Y

Nontraumatic emergencies of the head and neck represent a challenge in the field of neuroradiology for two reasons. As explained in the first part of this update, these entities affect an area where the thorax joins the cranial cavity and can thus compromise both structures; second, they are uncommon, so they are not well known. Maintaining the same approach as in the first part, focusing on the clinical presentations in the emergency department rather than on the anatomic regions affected, we will study the entities that present with two patterns: those that present with a combination of cervical numbness, dysphagia, and dyspnea and those that present with acute sensory deficits. In the latter group, we will specifically focus on visual deficits, because this is the most common symptom that calls for urgent imaging studies. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

[Pneumomediastinum, giant subcutaneous emphysema and pneumoperitoneum revealed by jaw pain. Uncommon physiopathology of pneumomediastinum].

PubMed

Le Loch, J-B; Freymond, N; Khettab, F; Pacheco, Y; Devouassoux, G

2008-02-01

Spontaneous pneumomediastinum is a rare entity, predominantly described in young man. The association of acute dyspnea, chest pains and subcutaneous emphysema is usually reported. We report the observation of a pneumomediastinum, fortuitously discovered in front of an isolated giant subcutaneous emphysema in a 59 year old man. The recent clinical history was only marked by the presence of intense and acute dental pains. Associated with a pneumoperitoneum, a retro-pneumoperitoneum, this clinical presentation is uncommon and differs from previous published case reports. Despite a complete evaluation of classical risk factors, its origin remains uncertain. However, the presence of huge dental injuries led to consider such local origin, facilitating air diffusion. This case report allows to reconsider spontaneous pneumomediastinum entity and to propose additional physiopathological mechanisms. This original description underlines the interest to systematically perform dental examination in the presence of unexplained pneumomediastinum.

Clinical features of hidradenitis suppurativa and Crohn disease: what do these two entities have in common?

PubMed

Vilarrasa Rull, E; González Lama, Y

2016-09-01

Hidradenitis suppurativa (HS) and Crohn disease (CD) are chronic, recurrent inflammatory diseases. They share certain clinical characteristics and flares are common in both. Both entities are usually diagnosed between the second and third decades of life and share risk factors such as smoking and overweight. In CD, as in HS, acute untreated episodes of inflammation can lead to sequels such as abscesses, fistulas and stenosis. Consequently, early management is of the utmost importance. Some patients have both diseases. The estimated prevalence of SH in CD patients is 12.4%-17.9%, while the prevalence of CD in HS patients is around 3%. The presence of HS in patients with inflammatory bowel disease (IBD) is associated with an earlier onset of IBD and with more frequent need for anti-TNF-alpha therapy and surgical resection. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.

3M Syndrome: A Report of Four Cases in Two Families

PubMed Central

Cebeci, Ayşe Nurcan

2011-01-01

3M syndrome is a rare entity characterized by severe growth retardation, dysmorphic features and skeletal changes as its major components. It is differentiated from other types of dwarfism by its clinical features and by the typical slender long bones and foreshortened vertebral bodies that can be visualized radiographically. 3M syndrome has an autosomal recessive mode of inheritance. An early diagnosis is important for genetic counseling. In this report, we present four children (3 males, 1 female) from two families who were aged between 411/12 and 1011/12 years and had clinical findings of 3M syndrome. One of these patients had received growth hormone (GH) treatment which was discontinued due to an inadequate height gain. Physicians should be aware of this entity in the differential diagnosis of children with severe short stature and mild skeletal changes. Conflict of interest:None declared. PMID:21911330

Clinical benchmarking for the office practitioner enabled by the online health record

PubMed Central

Ricciardi, TN; Masarie, FE; Landholt, T; Middleton, B

2000-01-01

Payer organizations, regulatory entities, and delivery networks are placing increasing pressure on physicians to report aggregate information about their patients and practice of medicine. Historically, clinicians have been ill-equipped to respond to these pressures when their practices have relied upon payer records for clinical information management. Key Industry Drivers: Physicians need specific information from their practices for the purposes of contract management, preventive care, office productivity, and utilization reviews. Value Statement: Clinical data captured at the point of care can support reporting requirements, and supplement or replace laboriously-collected data derived from billing and other administrative systems. Information from the Online Health Record can empower the individual physician to assess what is going on in their practice of medicine, as opposed to being "profiled" by an external entity. We created a secure web-based system that provides access to a clinical data mart, to allow online benchmarking for the individual or office practitioner. Providers used a web-enabled documentation system to document the clinical facts of the encounter. A nightly set of routines extracts data from the online chart into the clinical data mart built in a relational database. The system uses a clinical vocabulary server to map provider-entered strings to normalized clinical concepts. The system loads chart data into a dimensional data model, to simplify data representation and ensure fast query performance. Providers can access their own profiles from a secure web browser. PMID:11080030

Immunotactoid Glomerulopathy and Cryoglobulinemic Nephropathy: Two Entities with Many Similarities. A Unified Conceptual Approach.

PubMed

Herrera, Guillermo A; Ojemakinde, Kunle O; Turbat-Herrera, Elba A; Gu, Xin; Zeng, Xu; Iskandar, Samy S

2015-01-01

Immunotactoid glomerulopathy is a rare disorder that has been characterized at the ultrastructural level. Due to its rarity, there are few comprehensive studies relating to this disorder. Electron microscopy essentially characterizes this disease. The glomerular electron dense deposits which are typical of this condition consist of aggregates of highly organized microtubular structures of various diameters, but generally measuring 30-50 nm in width with a propensity to dispose themselves in parallel bundles intersecting in different planes. This study compares a large series of patients with cryoglobulinemic nephropathy with a series of patients with immunotactoid glomerulopathy to address whether there may be similarities that warrant considering these two entities part of a spectrum. This study reviews the clinicopathologic features of both entities and emphasizes ultrastructural findings that characterize them. Significant immunomorphologic overlap was found when these two disorders were compared in this study. There were also striking similarities in clinical presentation/behavior, laboratory findings and prognosis. Proteomic analysis has also demonstrated similar spectra for both entities. We postulate that immunotactoid glomerulopathy and cryoglobulinemic nephropathy are part of the spectrum of renal manifestations in patients with circulating cryoglobulins and renal disease.

[The clinical characteristics of pulmonary benign metastasizing leiomyoma].

PubMed

Wang, H P; Shi, J H; Zhang, L

2017-07-01

Objective: Pulmonary benign metastasizing leiomyoma (PBML) is a rare entity that leiomyoma of uterus metastasized to the lung. The clinical characteristics of this rare disease were analyzed in this article. Methods: The detailed clinical records of 7 patients diagnosed as PBML at Peking Union Medical College Hospital between January 2001 and June 2015 were reviewed. Results: All patients were women with median age of 44 years (range 28-62). Symptoms included dyspnea (2/7), chest pain (1/7), cyanosis (1/7), cough (1/7) and bloody sputum (1/7), while 4/7 cases were asymptomatic. Six patients had the past-history of leiomyoma of uterus 20 months to 14 years ago among whom 5 patients received hysterectomy. Chest CT showed bilateral, random-distributed multiple round solid nodules, or diffuse-distributed miliary nodules, or single solid nodule, even some small cavities. Extra-pulmonary metastasis was found in left superclavicular lymph node (1 case) and right heart (1 case). Histological tissues were obtained by video-assisted thoracic surgery lung biopsy (4/7), mass resection on tricuspid valve (1/7), transbronchil lung biopsy (1/7), and CT-guided percutaneous lung biopsy (1/7). Pathology showed an interlacing pattern by spindle cells having elongated nuclei without cellular atypia. Ki-67 index was less than 1%. Molecules such as smooth muscle antibody, estrogen receptor (ER) and progestrone receptor (PR) were positive in immunohistochemistry staining. Neither letrozole nor zoladex was effective. Two patients responded to bilateral adnexectomy, presenting as shrunk nodules. No relapsed disease was seen in one patient with single nodule after resection. There was only one patient with disease-related mortality, whose chest CT showed milliary nodules. Conclusion: Although CT findings of PBML are similar to malignancies, the clinical outcome is good. Despite the positive expression of ER and PR, the effectiveness of hormone related treatment is limited. And periodical follow up is suggested even to those uneventful patients.

Small bowel perforation secondary to metastatic non-small cell lung cancer. A rare entity with a dismal prognosis.

PubMed

Salemis, Nikolaos S; Nikou, Efstathios; Liatsos, Christos; Gakis, Christos; Karagkiouzis, Grigorios; Gourgiotis, Stavros

2012-09-01

The incidence of gastrointestinal metastases from lung cancer is higher than previously thought as they have been reported in 2-14% of the cases in autopsy studies. However, clinically significant metastases are rare. Small bowel perforation secondary to metastatic non-small cell lung cancer is a very rare clinical entity. The aim of this study is to describe a case of ileal perforation in a patient with intestinal metastases of a non-small cell lung cancer, along with a review of the literature. A 57-year-old male with a history of non-small cell lung cancer was referred to our emergency department with signs and symptoms of acute surgical abdomen. A computed tomography scan demonstrated dilated small bowel loops, liver deposits, and signs of perforation of an intra-abdominal hollow viscus. Emergency exploratory laparotomy revealed diffuse purulent peritonitis and a perforated ileal tumor. A segmental small bowel resection and primary anastomosis were performed. Histological and immunohistochemical findings were consistent with a metastatic non-small cell lung carcinoma. Additional evaluation revealed widespread metastatic disease. Unfortunately, despite adjuvant treatment, the patient died of progressive disease 2 months after surgery. Small bowel perforation due to metastatic non-small cell lung cancer is a very rare clinical entity. The possibility of small bowel metastases should be kept in mind in patients with lung cancer presenting with an acute abdomen. Intestinal perforation occurs in advanced stages and is usually a sign of widespread disease. Aggressive surgery can provide effective palliation and may improve short-term survival. The prognosis is however dismal.

Clinical and Neuroradiological Spectrum of Metronidazole Induced Encephalopathy: Our Experience and the Review of Literature

PubMed Central

Panwar, Ajay; Pandit, Alak; Das, Susanta Kumar; Joshi, Bhushan

2016-01-01

Metronidazole is an antimicrobial agent mainly used in the treatment of several protozoal and anaerobic infections, additionally, is often used in hepatic encephalopathy and Crohn disease. Apart from peripheral neuropathy, metronidazole can also cause symptoms of central nervous system dysfunction like ataxic gait, dysarthria, seizures, and encephalopathy which may result from both short term and chronic use of this drug and is collectively termed as “metronidazole induced encephalopathy”(MIE). Neuroimaging forms the backbone in clinching the diagnosis of this uncommon entity, especially in cases where there is high index of suspicion of intoxication. Although typical sites of involvement include cerebellum, brain stem and corpus callosum, however, lesions of other sites have also been reported. Once diagnosed, resolution of findings on Magnetic Resonance Imaging (MRI) of the Brain along with clinical improvement remains the mainstay of monitoring. Here we review the key clinical features and MRI findings of MIE as reported in medical literature. We also analyze implication of use of this drug in special situations like hepatic encephalopathy and brain abscess and discuss our experience regarding this entity. PMID:27504340

Oral dyskinesia: a clinical overview.

PubMed

Blanchet, Pierre J; Rompré, Pierre H; Lavigne, Gilles J; Lamarche, Claude

2005-01-01

Dentists may be the first health care professionals to recognize unusual and abnormal oral movements collectively termed oral dyskinesias. The aims of this clinical overview are to raise the dental community's awareness about this important and complex topic and describe the clinical features and management of the main entities. A MEDLINE search of the different entities reported in the English and French literature was conducted. The main findings of a field study on oral dyskinesia were also reviewed. Involuntary movement disorders are often drug related. In other cases, excessive oral movements may occur at any age in relation to various neuropsychiatric conditions. Orofacial dystonia apparently triggered by dental procedures has also been reported. Edentulousness has been associated with oral stereotypes. In a survey of 352 edentulous elderly individuals attending daycare centers, only 7% displayed visible oral sterotypes, and ill-fitting dentures were suggested as a possible triggering factor for the majority. A multidisciplinary evaluation is desirable in the care of individuals with oral dyskinesia and in the selection of those who may benefit from a prosthodontic approach. A good knowledge of potentially offending drugs may allow avoidance of unnecessary procedures.

Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults.

PubMed

DeLario, Melissa R; Sheehan, Andrea M; Ataya, Ramona; Bertuch, Alison A; Vega, Carlos; Webb, C Renee; Lopez-Terrada, Dolores; Venkateswaran, Lakshmi

2012-05-01

Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients. Copyright © 2012 Wiley Periodicals, Inc.

26 CFR 51.4T - Information provided by the agencies (temporary).

Code of Federal Regulations, 2013 CFR

2013-04-01

... sales price (ASP) for each Healthcare Common Procedure Coding System (HCPCS) code for the sales year...IdentifiableDataFiles/03_PartBNationalSummaryDataFile.asp to obtain the number of allowed billing units per... respective NDCs) manufactured by a single entity, CMS will multiply the annual weighted ASP by the total...

26 CFR 51.4T - Information provided by the agencies (temporary).

Code of Federal Regulations, 2014 CFR

2014-04-01

... sales price (ASP) for each Healthcare Common Procedure Coding System (HCPCS) code for the sales year...IdentifiableDataFiles/03_PartBNationalSummaryDataFile.asp to obtain the number of allowed billing units per... respective NDCs) manufactured by a single entity, CMS will multiply the annual weighted ASP by the total...

26 CFR 51.4T - Information provided by the agencies (temporary).

Code of Federal Regulations, 2012 CFR

2012-04-01

... sales price (ASP) for each Healthcare Common Procedure Coding System (HCPCS) code for the sales year...IdentifiableDataFiles/03_PartBNationalSummaryDataFile.asp to obtain the number of allowed billing units per... respective NDCs) manufactured by a single entity, CMS will multiply the annual weighted ASP by the total...

21 CFR 4.1 - What is the scope of this subpart?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false What is the scope of this subpart? 4.1 Section 4.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL REGULATION... operating system at facilities that manufacture co-packaged or single-entity combination products. ...

Close Air Support Allocation for Extended Counterinsurgency: Is Our Doctrine Lacking

DTIC Science & Technology

2010-04-01

timely and accurate deconfliction of those aircraft. They act as the primary command and control for all aircraft in the theater and are extremely...only merge the real time CAS control fuctions into a single entity. It is not to eliminate the capacity of the ASOC to participate in land

77 FR 26686 - Transmission Planning Reliability Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-07

... Normal (No Contingency) Conditions (Category A), TPL-002-1b--System Performance Following Loss of a... Reliability Standard should not allow an entity to plan for the loss of non-consequential firm load in the... approval of its proposal to revise and clarify footnote `b' ``in regard to load loss following a single...

78 FR 31890 - Antidisruptive Practices Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-28

... trade when the settlement price is determined under the rules of that registered entity.\\14\\ \\13\\ Id...) does not require a pattern of activity, even a single instance of trading activity can be disruptive of... post hoc analysis which labels a trade or a series of trades ``disruptive.' ''). \\61\\ See, e.g., CME at...

Reemerging Sudan Ebola Virus Disease in Uganda, 2011

PubMed Central

Shoemaker, Trevor; Balinandi, Stephen; Campbell, Shelley; Wamala, Joseph Francis; McMullan, Laura K.; Downing, Robert; Lutwama, Julius; Mbidde, Edward; Ströher, Ute; Rollin, Pierre E.; Nichol, Stuart T.

2012-01-01

Two large outbreaks of Ebola hemorrhagic fever occurred in Uganda in 2000 and 2007. In May 2011, we identified a single case of Sudan Ebola virus disease in Luwero District. The establishment of a permanent in-country laboratory and cooperation between international public health entities facilitated rapid outbreak response and control activities. PMID:22931687

Different Neurodevelopmental Symptoms Have a Common Genetic Etiology

ERIC Educational Resources Information Center

Pettersson, Erik; Anckarsäter, Henrik; Gillberg, Christopher; Lichtenstein, Paul

2013-01-01

Background: Although neurodevelopmental disorders are demarcated as discrete entities in the Diagnostic Statistical Manual of mental disorders, empirical evidence indicates that there is a high degree of overlap among them. The first aim of this investigation was to explore if a single general factor could account for the large degree of observed…

Evidence-Based Practice for Teachers of Children with Autism: A Dynamic Approach

ERIC Educational Resources Information Center

Lubas, Margaret; Mitchell, Jennifer; De Leo, Gianluca

2016-01-01

Evidence-based practice related to autism research is a controversial topic. Governmental entities and national agencies are defining evidence-based practice as a specific set of interventions that educators should implement; however, large-scale efforts to generalize autism research, which are often single-subject case designs, may be a setback…

14 CFR Sec. 2-3 - Distribution of revenues and expenses within entities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... CERTIFICATED AIR CARRIERS General Accounting Provisions Sec. 2-3 Distribution of revenues and expenses within.... (c) Expense items contributing to more than one function shall be charged to the general overhead functions to which applicable except that where only incidental contribution is made to more than a single...

Pitfalls in Aggregating Performance Measures in Higher Education

ERIC Educational Resources Information Center

Williams, Ross; de Rassenfosse, Gaétan

2016-01-01

National and international rankings of universities are now an accepted part of the higher education landscape. Rankings aggregate different performance measures into a single scale and therefore depend on the methods and weights used to aggregate. The most common method is to scale each variable relative to the highest performing entity prior to…

14 CFR § 1214.102 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Provisions Regarding Space Shuttle Flights of Payloads for Non-U.S. Government, Reimbursable Customers § 1214.102 Definitions. (a) Customer. Any non-U.S. government person or entity who, by virtue of a contract... services listed in § 1214.115 for 1 day of single-shift, on-orbit mission operations. (d) Jettison. To...

41 CFR 101-6.2109 - How does the Administrator receive and respond to comments?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS GENERAL 6... transmits a State process recommendation for a program selected under § 101-6.2106. (b)(1) The single point... and entities where there is no State process recommendation. (2) If a State process recommendation is...

2D-3D MIGRATION AND CONFORMATIONAL MULTIPLICATION OF CHEMICALS IN LARGE CHEMICAL INVENTORIES

EPA Science Inventory

Chemical interactions are three-dimensional (3D) in nature and require modeling chemicals as 3D entities. In turn, using 3D models of chemicals leads to the realization that a single 2D structure can have hundreds of different conformations, and the electronic properties of these...

37 CFR 1.710 - Patents subject to extension of the patent term.

Code of Federal Regulations, 2013 CFR

2013-07-01

... product as defined in paragraph (b) of this section, either alone or in combination with other ingredients... active ingredient of a new human drug, antibiotic drug, or human biological product (as those terms are... or ester of the active ingredient, as a single entity or in combination with another active...

37 CFR 1.710 - Patents subject to extension of the patent term.

Code of Federal Regulations, 2014 CFR

2014-07-01

... product as defined in paragraph (b) of this section, either alone or in combination with other ingredients... active ingredient of a new human drug, antibiotic drug, or human biological product (as those terms are... or ester of the active ingredient, as a single entity or in combination with another active...

37 CFR 1.710 - Patents subject to extension of the patent term.

Code of Federal Regulations, 2011 CFR

2011-07-01

... product as defined in paragraph (b) of this section, either alone or in combination with other ingredients... active ingredient of a new human drug, antibiotic drug, or human biological product (as those terms are... or ester of the active ingredient, as a single entity or in combination with another active...

37 CFR 1.710 - Patents subject to extension of the patent term.

Code of Federal Regulations, 2010 CFR

2010-07-01

... product as defined in paragraph (b) of this section, either alone or in combination with other ingredients... active ingredient of a new human drug, antibiotic drug, or human biological product (as those terms are... or ester of the active ingredient, as a single entity or in combination with another active...

37 CFR 1.710 - Patents subject to extension of the patent term.

Code of Federal Regulations, 2012 CFR

2012-07-01

... product as defined in paragraph (b) of this section, either alone or in combination with other ingredients... active ingredient of a new human drug, antibiotic drug, or human biological product (as those terms are... or ester of the active ingredient, as a single entity or in combination with another active...

Auto immune hemolytic anemia in a child precipitated by chicken pox.

PubMed

Billoo, Samina Shamim; Jamalvi, Syed Waseem

2008-05-01

Auto Immune Hemolytic Anemia (AIHA) is a rare entity in children. We report a case of an adolescent girl with AIHA, which was precipitated by chicken pox. Clinical course over 3 years, till remission is described.

Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome.

PubMed

Pillai, Sekhar C; Hacohen, Yael; Tantsis, Esther; Prelog, Kristina; Merheb, Vera; Kesson, Alison; Barnes, Elizabeth; Gill, Deepak; Webster, Richard; Menezes, Manoj; Ardern-Holmes, Simone; Gupta, Sachin; Procopis, Peter; Troedson, Christopher; Antony, Jayne; Ouvrier, Robert A; Polfrit, Yann; Davies, Nicholas W S; Waters, Patrick; Lang, Bethan; Lim, Ming J; Brilot, Fabienne; Vincent, Angela; Dale, Russell C

2015-04-01

Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immune-mediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome. By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis). An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission. We have defined clinical and radiologic phenotypes of infectious and immune-mediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority. Copyright © 2015 by the American Academy of Pediatrics.

Pharmacodynamic activity of Dapivirine and Maraviroc single entity and combination topical gels for HIV-1 prevention

PubMed Central

Dezzutti, Charlene S.; Yandura, Sarah; Wang, Lin; Moncla, Bernard; Teeple, Elizabeth A.; Devlin, Brid; Nuttall, Jeremy; Brown, Elizabeth R.; Rohan, Lisa C.

2015-01-01

Purpose Dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor, and maraviroc (MVC), a CCR5 antagonist, were formulated into aqueous gels designed to prevent mucosal HIV transmission. Methods 0.05% DPV, 0.1% MVC, 0.05% DPV/0.1% MVC and placebo gels were evaluated for pH, viscosity, osmolality, and in vitro release. In vitro assays and mucosal tissues were used to evaluate anti-HIV activity. Viability (Lactobacilli only) and epithelial integrity in cell lines and mucosal tissues defined safety. Results The gels were acidic and viscous. DPV gel had an osmolality of 893 mOsm/kg while the other gels had an osmolality of <100 mOsm/kg. MVC release was similar from the single and combination gels (~5 μg/cm2/min1/2), while DPV release was 10-fold less from the single as compared to the combination gel (0.4331 μg/cm2/min1/2). Titrations of the gels showed 10-fold more drug was needed to protect ectocervical than colonic tissue. The combination gel showed ~10- and 100-fold improved activity as compared to DPV and MVC gel, respectively. All gels were safe. Conclusions The DPV/MVC gel showed a benefit blocking HIV infection of mucosal tissue compared to the single entity gels. Combination products with drugs affecting unique steps in the viral replication cycle would be advantageous for HIV prevention. PMID:26078001

A systems biology approach to the global analysis of transcription factors in colorectal cancer.

PubMed

Pradhan, Meeta P; Prasad, Nagendra K A; Palakal, Mathew J

2012-08-01

Biological entities do not perform in isolation, and often, it is the nature and degree of interactions among numerous biological entities which ultimately determines any final outcome. Hence, experimental data on any single biological entity can be of limited value when considered only in isolation. To address this, we propose that augmenting individual entity data with the literature will not only better define the entity's own significance but also uncover relationships with novel biological entities.To test this notion, we developed a comprehensive text mining and computational methodology that focused on discovering new targets of one class of molecular entities, transcription factors (TF), within one particular disease, colorectal cancer (CRC). We used 39 molecular entities known to be associated with CRC along with six colorectal cancer terms as the bait list, or list of search terms, for mining the biomedical literature to identify CRC-specific genes and proteins. Using the literature-mined data, we constructed a global TF interaction network for CRC. We then developed a multi-level, multi-parametric methodology to identify TFs to CRC. The small bait list, when augmented with literature-mined data, identified a large number of biological entities associated with CRC. The relative importance of these TF and their associated modules was identified using functional and topological features. Additional validation of these highly-ranked TF using the literature strengthened our findings. Some of the novel TF that we identified were: SLUG, RUNX1, IRF1, HIF1A, ATF-2, ABL1, ELK-1 and GATA-1. Some of these TFs are associated with functional modules in known pathways of CRC, including the Beta-catenin/development, immune response, transcription, and DNA damage pathways. Our methodology of using text mining data and a multi-level, multi-parameter scoring technique was able to identify both known and novel TF that have roles in CRC. Starting with just one TF (SMAD3) in the bait list, the literature mining process identified an additional 116 CRC-associated TFs. Our network-based analysis showed that these TFs all belonged to any of 13 major functional groups that are known to play important roles in CRC. Among these identified TFs, we obtained a novel six-node module consisting of ATF2-P53-JNK1-ELK1-EPHB2-HIF1A, from which the novel JNK1-ELK1 association could potentially be a significant marker for CRC.

Emerald: an object-based language for distributed programming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutchinson, N.C.

1987-01-01

Distributed systems have become more common, however constructing distributed applications remains a very difficult task. Numerous operating systems and programming languages have been proposed that attempt to simplify the programming of distributed applications. Here a programing language called Emerald is presented that simplifies distributed programming by extending the concepts of object-based languages to the distributed environment. Emerald supports a single model of computation: the object. Emerald objects include private entities such as integers and Booleans, as well as shared, distributed entities such as compilers, directories, and entire file systems. Emerald objects may move between machines in the system, but objectmore » invocation is location independent. The uniform semantic model used for describing all Emerald objects makes the construction of distributed applications in Emerald much simpler than in systems where the differences in implementation between local and remote entities are visible in the language semantics. Emerald incorporates a type system that deals only with the specification of objects - ignoring differences in implementation. Thus, two different implementations of the same abstraction may be freely mixed.« less

Complying with the Health Insurance Portability and Accountability Act. Privacy standards.

PubMed

Shuren, A W; Livsey, K

2001-11-01

The Privacy Rule: Limits the use and disclosure of PHI to purposes of treatment, payment, or routine health care operations. Requires covered entities to provide advance notice to the public of its policy governing disclosure of PHI. Requires entities covered by the Standard to secure general client consent to use and to disclose PHI for treatment, payment, or routine health care operations and to obtain specific client authorization to use or to disclose PHI for all other purposes unless the disclosure is specifically permitted without consent or authorization (e.g., a covered entity may disclose PHI to a health care oversight agency such as the Office of the Inspector General without first obtaining client authorization). In certain situations, a covered entity need only obtain client agreement to disclose PHI which may be oral or inferred from the circumstances surrounding the disclosure. For example, a covered entity could disclose PHI to a relative caring for the individual who is the subject of the health information. Expects covered entities to take measures to protect PHI from both inadvertent and deliberate misuse and disclosure. Requires, except in certain circumstances, the amount of PHI disclosed on any occasion to be limited to the minimum necessary to achieve the purpose of the disclosure. Gives individuals more control of their health information by permitting them to review and amend health information pertaining to themselves and to demand an accounting of persons to whom their health information has been disclosed. Establishes terms under which a covered entity may disclose PHI to a business associate. Permits states to maintain state laws that are more stringent than the Privacy Rule. The statute provides for significant civil and criminal penalties for failure to comply with the Standards. Violations are punishable by fines as much as $250,000 and 10 years imprisonment. The HHS, Office of Civil Rights is charged with enforcing the Standards. The HHS is expected to issue a single Enforcement Rule applicable to all three of the HIPAA Administrative Simplification Standards. Many worksite records will not be protected under the HIPAA Privacy Rule because employers are not covered entities and few occupational health professionals meet the criteria of being considered a covered entity. Nevertheless, occupational health professionals need to be knowledgeable about the application of HIPAA in the occupational health care setting. Furthermore, given that the Rule does not preempt state privacy laws that are more stringent than the Standards, occupational health professionals should monitor legislative activity related to privacy in the states in which they practice. To date, Oregon, Texas, and New Jersey have broadened HIPAA's definitions to create more covered entities and services.

Pregnancy-related mortality in California: causes, characteristics, and improvement opportunities.

PubMed

Main, Elliott K; McCain, Christy L; Morton, Christine H; Holtby, Susan; Lawton, Elizabeth S

2015-04-01

To compare specific maternal and clinical characteristics and contributing factors among the five leading causes of pregnancy-related mortality to develop focused clinical and public health prevention programs. California pregnancy-related deaths from 2002-2005 were identified with enhanced surveillance using linked birth and death certificates. A multidisciplinary committee reviewed medical records, autopsy reports, and coroner reports to determine cause of death, clinical and demographic characteristics, chance to alter outcome, contributing factors (at health care provider, facility, and patient levels), and quality improvement opportunities. The five leading causes of death were compared with each other and with the overall California birth population. Among the 207 pregnancy-related deaths, the five leading causes were cardiovascular disease, preeclampsia or eclampsia, hemorrhage, venous thromboembolism, and amniotic fluid embolism. Among the leading causes of death, we identified differing patterns for race, maternal age, body mass index, timing of death, and method of delivery. Overall, there was a good-to-strong chance to alter the outcome in 41% of deaths, with the highest rates of preventability among hemorrhage (70%) and preeclampsia (60%) deaths. Health care provider, facility, and patient contributing factors also varied by cause of death. Pregnancy-related mortality should not be considered a single clinical entity. Reducing mortality requires in-depth examination of individual causes of death. The five leading causes exhibit different characteristics, degrees of preventability, and contributing factors, with the greatest improvement opportunities identified for hemorrhage and preeclampsia. These findings provide additional support for hospital, state, and national maternal safety programs.

The fourth branchial complex anomaly: a rare clinical entity.

PubMed

Patel, Alpen B; Hinni, Michael L

2011-01-01

Fourth branchial pouch anomalies are rare congenital disorders of the neck and are a consequence of abnormal development of the branchial apparatus during embryogenesis. Failure to appropriately recognize these anomalies may result in misdiagnosis, insufficient treatment, and continued recurrence. Here, we present an unique presentation of two cases, describe their diagnosis, clinical course, and management, and review the literature regarding these interesting anomalies.

The Fourth Branchial Complex Anomaly: A Rare Clinical Entity

PubMed Central

Patel, Alpen B.; Hinni, Michael L.

2011-01-01

Fourth branchial pouch anomalies are rare congenital disorders of the neck and are a consequence of abnormal development of the branchial apparatus during embryogenesis. Failure to appropriately recognize these anomalies may result in misdiagnosis, insufficient treatment, and continued recurrence. Here, we present an unique presentation of two cases, describe their diagnosis, clinical course, and management, and review the literature regarding these interesting anomalies. PMID:22937376

EPIRUS-NET: A Wireless Health Telematics Network in Greece

DTIC Science & Technology

2001-10-25

has also to be made. The system is represented of three basic layers: the database layer, the middleware and the Hospital Daily Progress Anamnesis ... Anamnesis . The Encounter entry is uniquely identified by the incremental ID, IID, attribute. Each encounter entry is associated with a clinical...the main entities of the system (Hospital, Patient, Anamnesis , Encounter, Clinical Examination, Daily Progress, Examination, Release Ticket), along

Chronic daily headache: correlation between the 2004 and the 1988 International Headache Society diagnostic criteria.

PubMed

Bigal, Marcelo E; Tepper, Stewart J; Sheftell, Fred D; Rapoport, Alan M; Lipton, Richard B

2004-01-01

In a previous study, we compared the 1988 International Headache Society (IHS) criteria and the Silberstein-Lipton criteria (S-L) in a subspeciality clinic sample of 638 patients with chronic daily headache (CDH) assessed both clinically and with headache diaries. Both systems allowed for the classification of most patients with CDH. The 1988 IHS classification required multiple diagnoses and was more complex to apply. The aim of this study was to revisit the same database, now comparing the prior classification systems with the new 2004 IHS classification. In contrast with the 1st edition, the 2nd edition includes criteria for chronic migraine (CM), new daily persistent headache (NDPH), and hemicrania continua (HC). We reviewed the clinical records and the headache diaries of 638 patients seen between 1980 and 2001 at a headache center. All patients had primary CDH according to the S-L criteria. Using the S-L criteria as a reference, of the 158 patients with transformed migraine (TM) without medication overuse, just 9 (5.6%) met 2004 IHS criteria for CM. Most of the subjects were classified using combinations of migraine and CTTH diagnoses, much like the 1988 IHS classification. Similarly, using the new IHS system, just 41/399 (10.2%) subjects with TM with medication overuse were classified as probable CM with probable medication overuse. Most patients with NDPH without overuse were easily classified using the 2004 criteria (95.8%). Regarding NDPH with medication overuse, the diagnostic groups were much like results for the 1st edition. All patients with chronic tension-type headache (CTTH) and hemicrania continua (HC) according to the S-L system were easily classified using the 2004 IHS criteria. We conclude that the 2004 IHS criteria facilitate the classification of NDPH without medication overuse and HC. For subjects with TM according to the S-L system, the new IHS criteria are complex to use and require multiple diagnoses. Very few patients with TM in the S-L system could be classified with a single diagnosis in the 2004 IHS classification. In fact, CM was so rare that it would be virtually impossible to conduct clinical trials of this entity using the 2004 IHS criteria. Clinical trials of this entity should therefore be conducted using the S-L criteria. Finally, we propose that in the 3rd edition of the IHS classification, the diagnosis of NDPH be revised so as not to exclude migraine features.

Participation of racial/ethnic groups in clinical trials and race-related labeling: a review of new molecular entities approved 1995-1999.

PubMed Central

Evelyn, B.; Toigo, T.; Banks, D.; Pohl, D.; Gray, K.; Robins, B.; Ernat, J.

2001-01-01

Few recent data are available from formal evaluations of approved new drug applications to address perceptions that racial and ethnic groups are under-represented in clinical trials of new drugs. This study reviews racial and ethnic group participation in clinical trials and race-related labeling for new molecular entities approved during a five-year period by the Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER). This was a retrospective review of FDA medical officers' reviews of clinical trial protocols and product labeling for 185 new molecular entities (NME's) approved by CDER between January 1,1995, and December 31, 1999. Enrollment data were obtained from the reviews and tabulated according to race/ethnicity. The approved product labeling was searched for statements related to product testing in various racial/ethnic groups. All data were compiled and analyzed using Microsoft Access. This study quantifies the participation of racial/ethnic groups in clinical trials by year and therapeutic category. Additionally, the study categorizes labeling based on the types of effects described as related to race/ethnicity. Racial and ethnic groups appear to participate in clinical trials to varying degrees. African Americans participated in trials to the greatest extent; however, their participation steadily declined from 12% in 1995 to 6% in 1999. Among trials known to be conducted only in the U.S., African-American participation is comparable to their representation in the U.S. population. In all cases, participants designated as Hispanic appear to be far below their representation in the population. Some differences in participation for all racial and ethnic groups are seen when comparisons from year-to-year or among drug classes are made. Labeling for 45% (84/185) of the products contained some statement about race, although in only 8% (15/185) were differences related to race described. Fifty percent (50%) of the effects were pharmacokinetic, 39% were efficacy, and 11% were safety. One product label recommended a change in dosage based on racial differences. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 PMID:11798060

Building a comprehensive syntactic and semantic corpus of Chinese clinical texts.

PubMed

He, Bin; Dong, Bin; Guan, Yi; Yang, Jinfeng; Jiang, Zhipeng; Yu, Qiubin; Cheng, Jianyi; Qu, Chunyan

2017-05-01

To build a comprehensive corpus covering syntactic and semantic annotations of Chinese clinical texts with corresponding annotation guidelines and methods as well as to develop tools trained on the annotated corpus, which supplies baselines for research on Chinese texts in the clinical domain. An iterative annotation method was proposed to train annotators and to develop annotation guidelines. Then, by using annotation quality assurance measures, a comprehensive corpus was built, containing annotations of part-of-speech (POS) tags, syntactic tags, entities, assertions, and relations. Inter-annotator agreement (IAA) was calculated to evaluate the annotation quality and a Chinese clinical text processing and information extraction system (CCTPIES) was developed based on our annotated corpus. The syntactic corpus consists of 138 Chinese clinical documents with 47,426 tokens and 2612 full parsing trees, while the semantic corpus includes 992 documents that annotated 39,511 entities with their assertions and 7693 relations. IAA evaluation shows that this comprehensive corpus is of good quality, and the system modules are effective. The annotated corpus makes a considerable contribution to natural language processing (NLP) research into Chinese texts in the clinical domain. However, this corpus has a number of limitations. Some additional types of clinical text should be introduced to improve corpus coverage and active learning methods should be utilized to promote annotation efficiency. In this study, several annotation guidelines and an annotation method for Chinese clinical texts were proposed, and a comprehensive corpus with its NLP modules were constructed, providing a foundation for further study of applying NLP techniques to Chinese texts in the clinical domain. Copyright © 2017. Published by Elsevier Inc.

Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus

PubMed Central

Chong, Vui Heng

2013-01-01

Heterotopic gastric mucosa of the proximal esophagus (HGMPE), also referred to as “inlet patch” or “cervical inlet patch”, is a salmon colored patch that is usually located just distal to the upper esophageal sphincter. HGMPE is uncommon with endoscopic studies reporting a prevalence ranging from less than one percent to 18%. Most HGMPE are asymptomatic and are detected incidentally during endoscopy for evaluations of other gastrointestinal complaints. Most consider HGMPE as clinically irrelevant entity. The clinical significance of HGMPE is mainly acid related or neoplastic transformation. The reported prevalence of laryngopharyngeal reflux symptoms varies from less than 20% to as high as 73.1%. However, most of these symptoms are mild. Clinically significant acid related complications such as bleeding, ulcerations, structure and fistulization have been reported. Although rare, dysplastic changes and malignancies in association with HGMPE have also been reported. Associations with Barrett’s esophagus have also been reported but the findings so far have been conflicting. There are still many areas that are unknown or not well understood and these include the natural history of HGMPE, risk factors for complications, role of Helicobacter pylori infection and factors associated with malignant transformations. Follow-up may need to be considered for patients with complications of HGMPE and surveillance if biopsies show intestinal metaplasia or dysplastic changes. Despite the overall low incidence of clinically relevant manifestations reported in the literature, HGMPE is a clinically significant entity but further researches are required to better understand its clinical significance. PMID:23372354

TaggerOne: joint named entity recognition and normalization with semi-Markov Models

PubMed Central

Leaman, Robert; Lu, Zhiyong

2016-01-01

Motivation: Text mining is increasingly used to manage the accelerating pace of the biomedical literature. Many text mining applications depend on accurate named entity recognition (NER) and normalization (grounding). While high performing machine learning methods trainable for many entity types exist for NER, normalization methods are usually specialized to a single entity type. NER and normalization systems are also typically used in a serial pipeline, causing cascading errors and limiting the ability of the NER system to directly exploit the lexical information provided by the normalization. Methods: We propose the first machine learning model for joint NER and normalization during both training and prediction. The model is trainable for arbitrary entity types and consists of a semi-Markov structured linear classifier, with a rich feature approach for NER and supervised semantic indexing for normalization. We also introduce TaggerOne, a Java implementation of our model as a general toolkit for joint NER and normalization. TaggerOne is not specific to any entity type, requiring only annotated training data and a corresponding lexicon, and has been optimized for high throughput. Results: We validated TaggerOne with multiple gold-standard corpora containing both mention- and concept-level annotations. Benchmarking results show that TaggerOne achieves high performance on diseases (NCBI Disease corpus, NER f-score: 0.829, normalization f-score: 0.807) and chemicals (BioCreative 5 CDR corpus, NER f-score: 0.914, normalization f-score 0.895). These results compare favorably to the previous state of the art, notwithstanding the greater flexibility of the model. We conclude that jointly modeling NER and normalization greatly improves performance. Availability and Implementation: The TaggerOne source code and an online demonstration are available at: http://www.ncbi.nlm.nih.gov/bionlp/taggerone Contact: zhiyong.lu@nih.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27283952

TaggerOne: joint named entity recognition and normalization with semi-Markov Models.

PubMed

Leaman, Robert; Lu, Zhiyong

2016-09-15

Text mining is increasingly used to manage the accelerating pace of the biomedical literature. Many text mining applications depend on accurate named entity recognition (NER) and normalization (grounding). While high performing machine learning methods trainable for many entity types exist for NER, normalization methods are usually specialized to a single entity type. NER and normalization systems are also typically used in a serial pipeline, causing cascading errors and limiting the ability of the NER system to directly exploit the lexical information provided by the normalization. We propose the first machine learning model for joint NER and normalization during both training and prediction. The model is trainable for arbitrary entity types and consists of a semi-Markov structured linear classifier, with a rich feature approach for NER and supervised semantic indexing for normalization. We also introduce TaggerOne, a Java implementation of our model as a general toolkit for joint NER and normalization. TaggerOne is not specific to any entity type, requiring only annotated training data and a corresponding lexicon, and has been optimized for high throughput. We validated TaggerOne with multiple gold-standard corpora containing both mention- and concept-level annotations. Benchmarking results show that TaggerOne achieves high performance on diseases (NCBI Disease corpus, NER f-score: 0.829, normalization f-score: 0.807) and chemicals (BioCreative 5 CDR corpus, NER f-score: 0.914, normalization f-score 0.895). These results compare favorably to the previous state of the art, notwithstanding the greater flexibility of the model. We conclude that jointly modeling NER and normalization greatly improves performance. The TaggerOne source code and an online demonstration are available at: http://www.ncbi.nlm.nih.gov/bionlp/taggerone zhiyong.lu@nih.gov Supplementary data are available at Bioinformatics online. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.

Biomedical named entity extraction: some issues of corpus compatibilities.

PubMed

Ekbal, Asif; Saha, Sriparna; Sikdar, Utpal Kumar

2013-01-01

Named Entity (NE) extraction is one of the most fundamental and important tasks in biomedical information extraction. It involves identification of certain entities from text and their classification into some predefined categories. In the biomedical community, there is yet no general consensus regarding named entity (NE) annotation; thus, it is very difficult to compare the existing systems due to corpus incompatibilities. Due to this problem we can not also exploit the advantages of using different corpora together. In our present work we address the issues of corpus compatibilities, and use a single objective optimization (SOO) based classifier ensemble technique that uses the search capability of genetic algorithm (GA) for NE extraction in biomedicine. We hypothesize that the reliability of predictions of each classifier differs among the various output classes. We use Conditional Random Field (CRF) and Support Vector Machine (SVM) frameworks to build a number of models depending upon the various representations of the set of features and/or feature templates. It is to be noted that we tried to extract the features without using any deep domain knowledge and/or resources. In order to assess the challenges of corpus compatibilities, we experiment with the different benchmark datasets and their various combinations. Comparison results with the existing approaches prove the efficacy of the used technique. GA based ensemble achieves around 2% performance improvements over the individual classifiers. Degradation in performance on the integrated corpus clearly shows the difficulties of the task. In summary, our used ensemble based approach attains the state-of-the-art performance levels for entity extraction in three different kinds of biomedical datasets. The possible reasons behind the better performance in our used approach are the (i). use of variety and rich features as described in Subsection "Features for named entity extraction"; (ii) use of GA based classifier ensemble technique to combine the outputs of multiple classifiers.

Web-TCGA: an online platform for integrated analysis of molecular cancer data sets.

PubMed

Deng, Mario; Brägelmann, Johannes; Schultze, Joachim L; Perner, Sven

2016-02-06

The Cancer Genome Atlas (TCGA) is a pool of molecular data sets publicly accessible and freely available to cancer researchers anywhere around the world. However, wide spread use is limited since an advanced knowledge of statistics and statistical software is required. In order to improve accessibility we created Web-TCGA, a web based, freely accessible online tool, which can also be run in a private instance, for integrated analysis of molecular cancer data sets provided by TCGA. In contrast to already available tools, Web-TCGA utilizes different methods for analysis and visualization of TCGA data, allowing users to generate global molecular profiles across different cancer entities simultaneously. In addition to global molecular profiles, Web-TCGA offers highly detailed gene and tumor entity centric analysis by providing interactive tables and views. As a supplement to other already available tools, such as cBioPortal (Sci Signal 6:pl1, 2013, Cancer Discov 2:401-4, 2012), Web-TCGA is offering an analysis service, which does not require any installation or configuration, for molecular data sets available at the TCGA. Individual processing requests (queries) are generated by the user for mutation, methylation, expression and copy number variation (CNV) analyses. The user can focus analyses on results from single genes and cancer entities or perform a global analysis (multiple cancer entities and genes simultaneously).

Comparative symptomatology of burnout and depression.

PubMed

Bianchi, Renzo; Boffy, Claire; Hingray, Coraline; Truchot, Didier; Laurent, Eric

2013-06-01

The link between burnout and depression remains unclear. In this study, we compared depressive symptoms in 46 burned-out workers, 46 outpatients experiencing a major depressive episode, and 453 burnout-free workers to test the distinctiveness of burnout as a clinical entity. Participants with burnout and major depressive episode reported similar, severe levels of overall depressive symptoms. The between-syndrome overlap was further verified for eight of the nine major depressive episode diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.). Our findings do not support the view hypothesizing that burnout and depression are separate entities and question the nosological added value of the burnout construct.

[Nonspecific interstitial pneumonitis: a clinicopathologic entity, histologic pattern or unclassified group of heterogeneous interstitial pneumonitis?].

PubMed

Morais, António; Moura, M Conceição Souto; Cruz, M Rosa; Gomes, Isabel

2004-01-01

Nonspecific interstitial pneumonitis (NSIP) initially described by Katzenstein and Fiorelli in 1994, seems to be a distinct clinicopathologic entity among idiopathic interstitial pneumonitis (IIP). Besides different histologic features from other IIP, NSIP is characterized by a better long-term outcome, associated with a better steroids responsiveness than idiopathic pulmonar fibrosis (IPF), where usually were included. Thus, differentiating NSIP from other IIP, namely IPF is very significant, since it has important therapeutic and prognostic implications. NSIP encloses different pathologies, namely those with inflammatory predominance (cellular subtype) or fibrous predominance (fibrosing subtype). NSIP is reviewed and discussed by the authors, after two clinical cases description.

MRI findings in acute hyperammonemic encephalopathy resulting from decompensated chronic liver disease.

PubMed

Sureka, Jyoti; Jakkani, Ravi Kanth; Panwar, Sanuj

2012-06-01

Hyperammonemic encephalopathy is a type of metabolic encephalopathy with diversified etiology. Hyperammonemia is the end result of several metabolic disorders such as congenital deficiencies of urea cycle enzymes, hepatic encephalopathy, Reye's syndrome and other toxic encephalopathies. Non-specific clinical presentation poses a great challenge in early diagnosis of this entity. Irrespective of the underlying etiology, hyperammonemia causes a distinctive pattern of brain parenchymal injury. The cingulate gyrus and insular cortex are more vulnerable to this type of toxic insult. Characteristic magnetic resonance imaging findings in combination with laboratory parameters can help to differentiate this entity from other metabolic encephalopathy and thus aiding in early diagnosis and treatment.

Politics, culture, and the legitimacy of disease: the case of Buerger's disease.

PubMed

Lockwood, Stephen J; Bresler, Scott C; Granter, Scott R

2016-09-01

Thromboangiitis obliterans (TAO) or Buerger's disease is a rare form of vasculitis with distinctive clinical and pathological features that carries significant morbidity, often leading to amputation, and is strongly associated with tobacco smoking. Despite its distinctive clinicopathological characteristics, the existence of TAO as an entity sui generis was challenged for many years as it languished in relative obscurity. Then, as societal attitudes towards smoking changed, TAO not only became accepted as a disease entity, it quite literally became a poster child to illustrate the ills of smoking. Herein, we examine the history of TAO to illustrate the power of societal attitudes and politics in shaping medicine.

Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

PubMed

Schee, Jie Ping; Viswanathan, Shanthi

2018-05-01

We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

Case Report: A giant but silent adrenal pheochromocytoma – a rare entity

PubMed Central

Munakomi, Sunil; Rajbanshi, Saroj; Adhikary, Prof Shailesh

2016-01-01

Herein we report a rare entity of a giant adrenal pheochromocytoma in a fifty-year-old male presenting with a vague abdominal pain. A computerised tomogram of the abdomen revealed a well-defined  left supraadrenal giant lesion with no evidence of invasion to surrounding structures.The patient underwent surgical excision without any untoward postoperative events. Histopathological study revealed a benign pheochromocytoma. This report highlights the importance of acknowledging the fact that sometimes a giant adrenal pheochromocytoma can present with paucity of clinical  signs and symptoms.Thorough investigations and a multidisciplinary team approach may lead  to a better outcome in these patients. PMID:27785358

Room-temperature ultrafast nonlinear spectroscopy of a single molecule

NASA Astrophysics Data System (ADS)

Liebel, Matz; Toninelli, Costanza; van Hulst, Niek F.

2018-01-01

Single-molecule spectroscopy aims to unveil often hidden but potentially very important contributions of single entities to a system's ensemble response. Albeit contributing tremendously to our ever growing understanding of molecular processes, the fundamental question of temporal evolution, or change, has thus far been inaccessible, thus painting a static picture of a dynamic world. Here, we finally resolve this dilemma by performing ultrafast time-resolved transient spectroscopy on a single molecule. By tracing the femtosecond evolution of excited electronic state spectra of single molecules over hundreds of nanometres of bandwidth at room temperature, we reveal their nonlinear ultrafast response in an effective three-pulse scheme with fluorescence detection. A first excitation pulse is followed by a phase-locked de-excitation pulse pair, providing spectral encoding with 25 fs temporal resolution. This experimental realization of true single-molecule transient spectroscopy demonstrates that two-dimensional electronic spectroscopy of single molecules is experimentally within reach.

Prophylaxis of migraine headaches with riboflavin: A systematic review.

PubMed

Thompson, D F; Saluja, H S

2017-08-01

Migraine headache is a relatively common, debilitating condition that costs our healthcare system over 78 billion dollars per year. Riboflavin has been advocated as a safe, effective prophylactic therapy for the prevention of migraines. The purpose of this study was to provide a systematic review of the current role of riboflavin in the prophylaxis of migraine headache. A MEDLINE literature search inclusive of the dates 1966-2016 was performed using the search terms: riboflavin and migraine disorders. Excerpta Medica was searched from 1980 to 2016 using the search terms: riboflavin and migraine. Additionally, Web of Science was searched using the terms riboflavin and migraine inclusive of 1945-2016. Bibliographies of all relevant papers were reviewed for additional citations. We utilized the PRISMA guidelines to select English language, human, clinical trials of riboflavin as a single entity or in combination, review articles, and supporting pharmacokinetic and pharmacogenomic data assessing the efficacy and mechanism of riboflavin therapy in the prophylactic treatment of migraine headache. A total of 11 clinical trials reveal a mixed effect of riboflavin in the prophylaxis of migraine headache. Five clinical trials show a consistent positive therapeutic effect in adults; four clinical trials show a mixed effect in paediatric and adolescent patients, and two clinical trials of combination therapy have not shown benefit. Adverse reactions with riboflavin have generally been mild. Riboflavin is well tolerated, inexpensive and has demonstrated efficacy in the reduction of adult patient's migraine headache frequency. Additional data are needed, however, to resolve questions involving pharmacokinetic issues and pharmacogenomic implications of therapy. © 2017 John Wiley & Sons Ltd.

Clinical and histopathologic study of benign lichenoid keratosis on the face.

PubMed

Kim, Han Su; Park, Eun Joo; Kwon, In Ho; Kim, Kwang Ho; Kim, Kwang Joong

2013-10-01

Benign lichenoid keratosis is a cutaneous entity that consists of a nonpruritic papule or slightly indurated plaque that is histologically characterized by a band-like inflammatory infiltrate with interface involvement. The purpose of this study was to investigate the clinical and histopathologic features of benign lichenoid keratosis localized on the face. Fourteen benign lichenoid keratosis patients diagnosed clinically and histopathologically in our clinic during the 10-year period from 2002 to 2012 were studied. Thirteen female and 1 male patients were included. The mean age at diagnosis was 46.5 years. The color of most of the lesions was brown (10 cases, 71%). The cheek was the most commonly involved area (10 cases, 71%). All of the lesions were single. There were 9 (64%) flat lesion cases and 5 (36%) raised lesion cases. Most patients denied having any symptoms; 3 had mild pruritus. The histopathological findings indicated that all the cases exhibited lichenoid inflammatory infiltrate obscuring the dermal-epidermal junction and vacuolar alteration of basal cell layer. The lesions showed focal parakeratosis (79%), melanophages (79%), hyperkeratosis (71%), and necrotic keratinocytes (71%). Solar elastosis (50%) and acanthosis (43%) were also seen frequently. Diagnosis of benign lichenoid keratosis should be made by a combination of clinical manifestations and histopathological findings. In particular, benign lichenoid keratosis should be considered if a middle-aged patient presents a solitary asymptomatic brown lesion on the face. We think benign lichenoid keratosis may be a specific disorder rather than the inflammatory stage of regressing solar lentigines, large cell acanthoma or reticulated seborrheic keratosis.

The epidemiology of molluscum contagiosum in children.

PubMed

Dohil, Magdalene A; Lin, Peggy; Lee, James; Lucky, Anne W; Paller, Amy S; Eichenfield, Lawrence F

2006-01-01

Molluscum contagiosum (MC) is a viral disorder of the skin and mucous membranes characterized by discrete single or multiple, flesh-colored papules. Although MC as a clinical entity is well defined and commonly observed, few data regarding its epidemiology in the pediatric population exist. Our purpose was to collect epidemiologic data on children with MC with regard to age, gender, ethnicity, degree of involvement, relation to pre-existing atopic dermatitis (AD), and immune status. A retrospective chart review was conducted. All subjects were seen at 3 tertiary pediatric dermatology referral centers with two of the sites based at a Children's Hospital. A total of 302 patient charts with the Current Procedural Terminology code diagnosis of MC seen over a 6- to 8-month period were reviewed. Approximately 80% of the patients were younger than 8 years old. The majority of patients (63%) had more than 15 lesions. All but one patient were otherwise healthy, as determined by history and clinical examination. Approximately 24% of the patients presented with a history of previous or active coexistent AD. However, children with AD were at risk for an increased number of lesions. These data provide valuable updated information on the demographics and clinical presentation of MC in pediatric patients in the United States. Limitations include that this was a retrospective study with a population limited to tertiary pediatric dermatology referral centers.

Gene therapy in liver diseases: state-of-the-art and future perspectives.

PubMed

Domvri, Kalliopi; Zarogoulidis, Paul; Porpodis, Konstantinos; Koffa, Maria; Lambropoulou, Maria; Kakolyris, Stylianos; Kolios, George; Zarogoulidis, Konstantinos; Chatzaki, Ekaterini

2012-12-01

Gene therapy is a fundamentally novel therapeutic approach that involves introducing genetic material into target cells in order to fight or prevent disease. A number of different strategies of gene therapy are tested at experimental and clinical levels, including: a) replacing a mutated gene that causes disease with a healthy copy of the gene, b) inactivating a mutated gene that its improper function causes pathogenesis, c) introducing a new gene coding a therapeutic compound to fight a disease, d) introducing to the target organ an enzyme converting an inactive pro-drug to its cytotoxic metabolite. In gene therapy, the transcriptional machinery of the patient is used to produce the active factor that exerts the intended therapeutic effect, ideally in a permanent, tissue-specific and manageable way. The liver is a major target for gene therapy, presenting inherited metabolic defects of single-gene etiology, but also severe multifactorial pathologies with limited therapeutic options such as hepatocellular carcinoma. The initial promising results from gene therapy strategies in liver diseases were followed by skepticism on the actual clinical value due to specificity, efficacy, toxicity and immune limitations, but are recently re-evaluated due to progress in vector technology and monitoring techniques. The significant amount of experimental data along with the available information from clinical trials are systematically reviewed here and presented per pathological entity. Finally, future perspectives of gene therapy protocols in hepatology are summarized.

Streptococcal necrotizing myositis: a case report and clinical review.

PubMed

Hourmozdi, Justin J; Hawley, Dean A; Hadi, Christiane M; Tahir, Bilal; Seupaul, Rawle A

2014-03-01

Streptococcal necrotizing myositis, also known as gangrenous myositis, is a very rare and severe soft tissue infection that predominately involves skeletal muscle and, eventually, superficial fascia and surrounding tissues. The presentation is often nonspecific until the rapidly progressing clinical course becomes apparent. A high morbidity and mortality rate has been reported in the small number of cases since 1900. Despite several attempts to better define the different entities causing necrotizing myositis, no single definitive causal relationship has been defined. A review of the literature is presented here to help clinicians distinguish those with necrotizing myositis from those with nonnecrotizing myositis when the clinician is at all confronted with the suspicion for such an infection. The case presented is that of a 48-year-old woman who had streptococcal necrotizing myositis. She died roughly 72 h after admission. After the patient's death, the clinical team sought consent for autopsy. Hospital staff made contact with family, and information was obtained from the family that the onset of the patient's symptoms was allegedly temporally related to her acquisition of a new tattoo on the right back, where the tattoo process allegedly included injection of cremated ashes of a pet dog. A high level of suspicion for necrotizing myositis must be maintained for a patient with unexplained severe muscle pain and soft tissue swelling accompanied by systemic inflammatory response syndrome. Copyright © 2014 Elsevier Inc. All rights reserved.

New Antiretroviral Therapies for Pediatric HIV Infection

PubMed Central

Morris, Jennifer L.; Kraus, Donna M.

2005-01-01

Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome affect millions of children worldwide. The development of antiretroviral therapy has significantly improved the morbidity and mortality of pediatric patients infected with HIV. Currently, 4 classes of antiretroviral agents exist: nucleoside / nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, and entry inhibitors. A total of 21 single-entity antiretroviral agents and 4 co-formulated antiretroviral products hold Food and Drug Administration (FDA) approval for treatment of HIV-1 infection. However, not all of these agents are indicated for use in patients less than 18 years of age. Since the year 2000, 7 new antiretroviral agents (atazanavir, emtricitabine, enfuvirtide, fosamprenavir, lopinavir/ritonavir, tenofovir, and tipranavir) have been approved by the FDA for use in adult patients as part of combination therapy for the treatment of HIV-1 infection. Although only 3 of these newer agents (emtricitabine, enfuvirtide, and lopinavir/ritonavir) are currently FDA approved for use in pediatric patients, pediatric clinical studies of the other 4 new agents are currently underway. The purpose of this article is to review these 7 new antiretroviral agents and describe their roles in the treatment of pediatric HIV infection. For each drug, the following information will be addressed: FDA-approved indication and age groups, clinical efficacy, pharmacokinetics, adverse drug reactions, clinically relevant drug interactions, pediatric and adult dosing, dosage forms, administration, and place in the treatment of pediatric HIV infection. PMID:23118639

Brief Report: Acrocallosal Syndrome and Autism

ERIC Educational Resources Information Center

Steiner, Carlos Eduardo; Guerreiro, Marilisa Mantovani; Marques-de-Faria, Antonia Paula

2004-01-01

The authors describe a boy presenting with acrocallosal syndrome and autism. Clinical features included craniofacial dysmorphisms, polydactyly, and mental retardation, besides behavioral symptoms compatible with autism. Neuroimaging revealed hypoplasia of the corpus callosum and cerebellar abnormalities. The role of this entity and other…

Risk Modeling of Interdependent Complex Systems of Systems: Theory and Practice.

PubMed

Haimes, Yacov Y

2018-01-01

The emergence of the complexity characterizing our systems of systems (SoS) requires a reevaluation of the way we model, assess, manage, communicate, and analyze the risk thereto. Current models for risk analysis of emergent complex SoS are insufficient because too often they rely on the same risk functions and models used for single systems. These models commonly fail to incorporate the complexity derived from the networks of interdependencies and interconnectedness (I-I) characterizing SoS. There is a need to reevaluate currently practiced risk analysis to respond to this reality by examining, and thus comprehending, what makes emergent SoS complex. The key to evaluating the risk to SoS lies in understanding the genesis of characterizing I-I of systems manifested through shared states and other essential entities within and among the systems that constitute SoS. The term "essential entities" includes shared decisions, resources, functions, policies, decisionmakers, stakeholders, organizational setups, and others. This undertaking can be accomplished by building on state-space theory, which is fundamental to systems engineering and process control. This article presents a theoretical and analytical framework for modeling the risk to SoS with two case studies performed with the MITRE Corporation and demonstrates the pivotal contributions made by shared states and other essential entities to modeling and analysis of the risk to complex SoS. A third case study highlights the multifarious representations of SoS, which require harmonizing the risk analysis process currently applied to single systems when applied to complex SoS. © 2017 Society for Risk Analysis.

Clinical and echocardiographic characteristics of papillary fibroelastomas: a retrospective and prospective study in 162 patients

NASA Technical Reports Server (NTRS)

Sun, J. P.; Asher, C. R.; Yang, X. S.; Cheng, G. G.; Scalia, G. M.; Massed, A. G.; Griffin, B. P.; Ratliff, N. B.; Stewart, W. J.; Thomas, J. D.

2001-01-01

BACKGROUND: Cardiac papillary fibroelastoma (CPF) is a primary cardiac neoplasm that is increasingly detected by echocardiography. The clinical manifestations of this entity are not well described. METHODS AND RESULTS: In a 16-year period, we identified patients with CPF from our pathology and echocardiography databases. A total of 162 patients had pathologically confirmed CPF. Echocardiography was performed in 141 patients with 158 CPFs, and 48 patients had CPFs that were not visible by echocardiography (<0.2 cm), leaving an echocardiographic subgroup of 93 patients with 110 CPFs. An additional 45 patients with a presumed diagnosis of CPF were identified. The mean age of the patients was 60+/-16 years of age, and 46.1% were male. Echocardiographically, the mean size of the CPFs was 9+/-4.6 mm; 82.7% occurred on valves (aortic more than mitral), 43.6% were mobile, and 91.4% were single. During a follow-up period of 11+/-22 months, 23 of 26 patients with a prospective diagnosis of CPF that was confirmed by pathological examination had symptoms that could be attributable to embolization. In the group of 45 patients with a presumed diagnosis of CPF, 3 patients had symptoms that were likely due to embolization (incidence, 6.6%) during a follow-up period of 552+/-706 days. CONCLUSIONS: CPFs are generally small and single, occur most often on valvular surfaces, and may be mobile, resulting in embolization. Because of the potential for embolic events, symptomatic patients, patients undergoing cardiac surgery for other lesions, and those with highly mobile and large CPFs should be considered for surgical excision.

Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines

PubMed Central

Kriegs, Malte; Gatzemeier, Fruzsina; Krüger, Katharina; Möckelmann, Nikolaus; Fritz, Gerhard; Petersen, Cordula; Knecht, Rainald; Rothkamm, Kai; Rieckmann, Thorsten

2016-01-01

Patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) show better survival rates than those with HPV-negative HNSCC. While an enhanced radiosensitivity of HPV-positive tumors is clearly evident from single modality treatment, cisplatin is never administered as monotherapy and therefore its contribution to the enhanced cure rates of HPV-positive HNSCC is not known. Both cisplatin and radiotherapy can cause severe irreversible side effects and therefore various clinical studies are currently testing deintensified regimes for patients with HPV-positive HNSCC. One strategy is to omit cisplatin-based chemotherapy or replace it by less toxic treatments but the risk assessment of these approaches remains difficult. In this study we have compared the cytotoxic effects of cisplatin in a panel of HPV-positive and -negative HNSCC cell lines alone and when combined with radiation. While cisplatin-treated HPV-positive strains showed a slightly stronger inhibition of proliferation, there was no difference regarding colony formation. Cellular responses to the drug, namely cell cycle distribution, apoptosis and γH2AX-induction did not differ between the two entities but assessment of cisplatin-DNA-adducts suggests differences regarding the mechanisms that determine cisplatin sensitivity. Combining cisplatin with radiation, we generally observed an additive but only in a minority of strains from both entities a clear synergistic effect on colony formation. In summary, HPV-positive and -negative HNSCC cells were equally sensitive to cisplatin. Therefore replacing cisplatin may be feasible but the substituting agent should be of similar efficacy in order not to jeopardize the high cure rates for HPV-positive HNSCC. PMID:27127883

The emergence of overweight as a disease entity: measuring up normality.

PubMed

Jutel, Annemarie

2006-11-01

As Charles Rosenberg [(2002). The tyranny of diagnosis. The Milbank Quarterly, 80, 237-260] has recently written, clinical diagnosis contributes to imposing structure on cultural reality in a manner which is not unproblematic. A social power resides in the process of naming diseases-one, which legitimises concerns, explains reality, naturalises deviance and imposes status. But clinical entities are not static, as both the concerns of society, and the technological ability of practitioners change (what Rosenberg refers to as the "iatrogenesis of nosology"), so too do the range of labels available for identifying disease. In this paper, I argue that being "overweight," once predominantly an adjectival descriptor of corpulence, a physical sign or a symptom, and even, in some cultures, a sign of wealth and status, is undergoing the transformation to disease entity. I suggest that evidence of this is present in both the frequency and the way in which the term is being used by the media, the medical establishment and the laity. I argue that this change stems from the convergence of two particular phenomena. The first is the belief in the neutrality of quantification, and the objectivity that measurement brings to qualitative description. The second is the importance attributed to normative appearance in health. I discuss some of the implications of this evolution and its impact on health practices, including the exploitation of this purported disease state for commercial benefit.

Functionalized poly(ethylene glycol) diacrylate microgels by microfluidics: In situ peptide encapsulation for in serum selective protein detection.

PubMed

Celetti, Giorgia; Natale, Concetta Di; Causa, Filippo; Battista, Edmondo; Netti, Paolo A

2016-09-01

Polymeric microparticles represent a robustly platform for the detection of clinically relevant analytes in biological samples; they can be functionalized encapsulating a multiple types of biologics entities, enhancing their applications as a new class of colloid materials. Microfluidic offers a versatile platform for the synthesis of monodisperse and engineered microparticles. In this work, we report microfluidic synthesis of novel polymeric microparticles endowed with specific peptide due to its superior specificity for target binding in complex media. A peptide sequence was efficiently encapsulated into the polymeric network and protein binding occurred with high affinity (KD 0.1-0.4μM). Fluidic dynamics simulation was performed to optimize the production conditions for monodisperse and stable functionalized microgels. The results demonstrate the easy and fast realization, in a single step, of functionalized monodisperse microgels using droplet-microfluidic technique, and how the inclusion of the peptide within polymeric network improve both the affinity and the specificity of protein capture. Copyright © 2016 Elsevier B.V. All rights reserved.

Large mass affecting retroperitoneal great vessels: a rare presentation of a cancer of unknown primary with diagnostic dilemma and challenged surgical intervention.

PubMed

Stakia, Paraskevi; Lagos, Panagiotis; Gourgiotis, Stavros; Tzilalis, Vasilios D; Aloizos, Stavros; Salemis, Nikolaos S

2009-01-01

Cancers of unknown primary site (CUPs) consist of a clinical entity which accounts for 3-5% of all solid tumor patients. They are metastatic solid tumors whose fundamental characteristic is the absence of identifiable site of the primary tumor. We report the case of a completely asymptomatic 34-year-old man with a palpated huge mass found incidentally in the left abdomen. All the investigations were normal. During the operation, a large mass was identified 2 cm below the left renal artery which was displacing and encompassing the great retroperitoneal vessels and the left ureter. A complete resection of the mass was performed while the histological examination revealed a solitary retroperitoneal lymph node categorized as metastatic adenocarcinoma of unknown primary site. It is essential to assess the high incidence of patients with cancer who present with CUP. Early surgical excision of the metastatic lesion followed by adjuvant combination chemotherapy should be considered for patients with only a single site of malignancy.

High-risk multiple myeloma: a multifaceted entity, multiple therapeutic challenges.

PubMed

Muchtar, Eli; Magen, Hila; Gertz, Morie A

2017-06-01

The term high-risk multiple myeloma is aimed to identify a heterogeneous group of patients who are more likely to progress and die early of their disease. Therefore, recognition of these patients is crucial. With the increase in the number of treatment options, the outcome for high-risk patients has probably improved, although the true extent of this improvement remains unknown, due to both the heterogeneous components of high-risk disease and its under-representation in clinical trials. In this article, we review the definitions of high-risk disease, emphasizing the fact that no single definition can represent the entire high-risk population. In the second part, we review the treatment options available for the management of high-risk myeloma as well as our general approach for high-risk disease. In light of the poor prognosis associated with high-risk myeloma, even in the current era, new approaches for the management of this subset of patients are needed.

Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer.

PubMed

Hart, Phil A; Bellin, Melena D; Andersen, Dana K; Bradley, David; Cruz-Monserrate, Zobeida; Forsmark, Christopher E; Goodarzi, Mark O; Habtezion, Aida; Korc, Murray; Kudva, Yogish C; Pandol, Stephen J; Yadav, Dhiraj; Chari, Suresh T

2016-11-01

Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps. Copyright © 2016 Elsevier Ltd. All rights reserved.

Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer

PubMed Central

Hart, Phil A; Bellin, Melena D; Andersen, Dana K; Bradley, David; Cruz-Monserrate, Zobeida; Forsmark, Christopher E; Goodarzi, Mark O; Habtezion, Aida; Korc, Murray; Kudva, Yogish C; Pandol, Stephen J; Yadav, Dhiraj; Chari, Suresh T

2017-01-01

Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps. PMID:28404095

Nanoparticles speckled by ready-to-conjugate lanthanide complexes for multimodal imaging

NASA Astrophysics Data System (ADS)

Biju, Vasudevanpillai; Hamada, Morihiko; Ono, Kenji; Sugino, Sakiko; Ohnishi, Takashi; Shibu, Edakkattuparambil Sidharth; Yamamura, Shohei; Sawada, Makoto; Nakanishi, Shunsuke; Shigeri, Yasushi; Wakida, Shin-Ichi

2015-09-01

Multimodal and multifunctional contrast agents receive enormous attention in the biomedical imaging field. Such contrast agents are routinely prepared by the incorporation of organic molecules and inorganic nanoparticles (NPs) into host materials such as gold NPs, silica NPs, polymer NPs, and liposomes. Despite their non-cytotoxic nature, the large size of these NPs limits the in vivo distribution and clearance and inflames complex pharmacokinetics, which hinder the regulatory approval for clinical applications. Herein, we report a unique method that combines magnetic resonance imaging (MRI) and fluorescence imaging modalities together in nanoscale entities by the simple, direct and stable conjugation of novel biotinylated coordination complexes of gadolinium(iii) to CdSe/ZnS quantum dots (QD) and terbium(iii) to super paramagnetic iron oxide NPs (SPION) but without any host material. Subsequently, we evaluate the potentials of such lanthanide-speckled fluorescent-magnetic NPs for bioimaging at single-molecule, cell and in vivo levels. The simple preparation and small size make such fluorescent-magnetic NPs promising contrast agents for biomedical imaging.

The whole-genome landscape of medulloblastoma subtypes.

PubMed

Northcott, Paul A; Buchhalter, Ivo; Morrissy, A Sorana; Hovestadt, Volker; Weischenfeldt, Joachim; Ehrenberger, Tobias; Gröbner, Susanne; Segura-Wang, Maia; Zichner, Thomas; Rudneva, Vasilisa A; Warnatz, Hans-Jörg; Sidiropoulos, Nikos; Phillips, Aaron H; Schumacher, Steven; Kleinheinz, Kortine; Waszak, Sebastian M; Erkek, Serap; Jones, David T W; Worst, Barbara C; Kool, Marcel; Zapatka, Marc; Jäger, Natalie; Chavez, Lukas; Hutter, Barbara; Bieg, Matthias; Paramasivam, Nagarajan; Heinold, Michael; Gu, Zuguang; Ishaque, Naveed; Jäger-Schmidt, Christina; Imbusch, Charles D; Jugold, Alke; Hübschmann, Daniel; Risch, Thomas; Amstislavskiy, Vyacheslav; Gonzalez, Francisco German Rodriguez; Weber, Ursula D; Wolf, Stephan; Robinson, Giles W; Zhou, Xin; Wu, Gang; Finkelstein, David; Liu, Yanling; Cavalli, Florence M G; Luu, Betty; Ramaswamy, Vijay; Wu, Xiaochong; Koster, Jan; Ryzhova, Marina; Cho, Yoon-Jae; Pomeroy, Scott L; Herold-Mende, Christel; Schuhmann, Martin; Ebinger, Martin; Liau, Linda M; Mora, Jaume; McLendon, Roger E; Jabado, Nada; Kumabe, Toshihiro; Chuah, Eric; Ma, Yussanne; Moore, Richard A; Mungall, Andrew J; Mungall, Karen L; Thiessen, Nina; Tse, Kane; Wong, Tina; Jones, Steven J M; Witt, Olaf; Milde, Till; Von Deimling, Andreas; Capper, David; Korshunov, Andrey; Yaspo, Marie-Laure; Kriwacki, Richard; Gajjar, Amar; Zhang, Jinghui; Beroukhim, Rameen; Fraenkel, Ernest; Korbel, Jan O; Brors, Benedikt; Schlesner, Matthias; Eils, Roland; Marra, Marco A; Pfister, Stefan M; Taylor, Michael D; Lichter, Peter

2017-07-19

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and 'enhancer hijacking' events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

Ways of Hoping: Navigating the Paradox of Hope and Despair in Chronic Pain.

PubMed

Eaves, Emery R; Nichter, Mark; Ritenbaugh, Cheryl

2016-03-01

In this paper, we explore hope in the context of living with chronic pain. Individuals with chronic pain from temporomandibular disorder(s) were interviewed four to five times over the course of their 18-month participation in a clinical trial investigating the effectiveness of Traditional Chinese Medicine. We sought to understand shifts in participants' descriptions of expectations and hopefulness, particularly with regard to the work involved in counterbalancing positive thinking with buffers against disappointment. We found hope to be a dynamic and multifaceted mindset as distinct from being a single entity to be measured. Drawing upon Polanyi's concept of tacit knowing, we explore how different ways of hoping emerge and index one another in participant narratives. We offer a working typology of hope and raise as an issue the manner in which the paradox of hope--hoping enough to carry on while keeping hopes in check to avoid the ever-present possibility of despair--complicates simplistic notions of the relationship between positive thinking and the placebo response.

Landmark lecture: Perloff lecture: Tribute to Professor Joseph Kayle Perloff and lessons learned from him: aortopathy in adults with CHD.

PubMed

Niwa, Koichiro

2017-12-01

Marfan syndrome, bicuspid aortic valve, and/or coarctation of the aorta are associated with medial abnormalities of the ascending aortic or para-coarctation aorta. Medial abnormalities in the ascending aorta are prevalent in other type of patients with a variety of CHDs such as single ventricle, persistent truncus arteriosus, transposition of the great arteries, hypoplastic left heart syndrome, and tetralogy of Fallot, encompassing a wide age range and may predispose to dilatation, aneurysm, and rapture necessitating aortic valve and root surgery. These CHDs exhibit ongoing dilatation of the aortic root and reduced aortic elasticity and increased aortic stiffness that may relate to intrinsic properties of the aortic root. These aortic dilatation and increased stiffness can induce aortic aneurysm, rapture of the aorta, and aortic regurgitation, but also provoke left ventricular hypertrophy, reduced coronary artery flow, and left ventricular failure. Therefore, a new clinical entity can be used to call this association of aortic pathophysiological abnormality, aortic dilation, and aorto-left ventricular interaction - "aortopathy".

Mycosis fungoides of the true vocal cord: a case report and review of the literature.

PubMed

Maleki, Zahra; Azmi, Farrukh

2010-09-01

Mycosis fungoides is the most common type of cutaneous malignant T cell lymphoma which primarily affects skin. However, extracutaneous manifestation may occur in advanced stages, mostly observed in postmortem studies. We present a case of mycosis fungoides that disseminated to the true vocal cord of a 48-year-old African American man who presented with hoarseness. Only two cases that have also demonstrated a rare involvement of the true vocal cord have been reported in the English literature. In both cases, mycosis fungoides infiltration of the true vocal cord was seen postmortem, along with visceral dissemination of mycosis fungoides. We herein describe a single extracutaneous manifestation of mycosis fungoides in the true vocal cord of a living patient with a 21-year diagnosis of mycosis fungoides. Vocal cord involvement by mycosis fungoides must be considered as one of the differential diagnoses in any mycosis fungoides patients who complain of persistent hoarseness. Awareness of this entity is clinically important due to the necessity of a different management.

The basics of cell therapy to treat cardiovascular disease: one cell does not fit all.

PubMed

Taylor, Doris A; Robertson, Matthew J

2009-09-01

Cardiovascular disease represents a continuum of disease entities whose medical treatments differ. Cell therapy is a 21st century approach to treating cardiovascular disease and is being applied worldwide. However, no concerted approach exists for defining the best cell population(s) to use, or the best treatment conditions. It is naïve to believe that a single treatment -even a stem cell- can be found to treat the entire spectrum of cardiovascular disease. We describe the continuum of ischemic heart disease, the potential uses of cells for treating this continuum, and the basic issues that must be considered when contemplating cardiovascular cell therapy. The clinical goal is cardiac and vascular regeneration. Whether cells can deliver this remains to be determined. The correct cell, the ideal therapeutic window, and the patient likewise are open to debate. This article is designed to provide insights into the early, middle, and later stages of cardiovascular disease and how cells might be used differently for treatment at each stage.

78 FR 24241 - John Hancock Exchange-Traded Fund Trust, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

...\\ and Investing Fund's Sub-Advisory Group,\\28\\ to control a Single-Tier Fund within the meaning of... trusts outside of the same group of investment companies as the series to acquire Shares; and (f) certain... an entity controlling, controlled by or under common control with the Adviser and (b) comply with the...

76 FR 76221 - Filings Required of Multiple Employer Welfare Arrangements and Certain Other Related Entities

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

... single employer if such trades or businesses are within the same control group. The term ``control group'' means a group of trades or businesses under common control, and the determination of whether a trade or... not group health plans (``non-plan MEWAs''), the proposal preserves the structure promulgated as part...

75 FR 53973 - Guidance for Industry; Small Entities Compliance Guide-Designation of New Animal Drugs for Minor...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-02

... Communications Staff (HFV-12), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Pl... other than cattle, horses, swine, chickens, turkeys, dogs, and cats) in the United States or to major.... Comments Submit written requests for single copies of the guidance to the Communications Staff (HFV-12...

41 CFR 101-42.403 - Sales methods and procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... persons on the general sales mailing list but shall be sent to only those persons and entities which have..., with respect to hazardous materials, shall: (1) Limit the materials in each lot for sale to a single... content. (c) For a bid to be considered for award, the bidder must sign the following certification: The...

41 CFR 101-42.403 - Sales methods and procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... persons on the general sales mailing list but shall be sent to only those persons and entities which have..., with respect to hazardous materials, shall: (1) Limit the materials in each lot for sale to a single... content. (c) For a bid to be considered for award, the bidder must sign the following certification: The...

24 CFR 92.504 - Participating jurisdiction responsibilities; written agreements; on-site inspection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... in written agreements. The contents of the agreement may vary depending upon the role the entity is asked to assume or the type of project undertaken. This section details basic requirements by role and... housing owner, sponsor or developer (other than single-family owner-occupant)—(i) Use of the HOME funds...

24 CFR 92.504 - Participating jurisdiction responsibilities; written agreements; on-site inspection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... in written agreements. The contents of the agreement may vary depending upon the role the entity is asked to assume or the type of project undertaken. This section details basic requirements by role and... housing owner, sponsor or developer (other than single-family owner-occupant)—(i) Use of the HOME funds...

12 CFR 250.407 - Interlocking relationship involving securities affiliate of brokerage firm.

Code of Federal Regulations, 2010 CFR

2010-01-01

... costs, and to the condition of the market for municipal and State bonds during the past year, a field in..., has become rather widespread in recent years. Accordingly, other cases may arise where a partner in... as a single entity or enterprise for purposes of section 32. (j) The remaining question was whether...

Hybrid Architectures and Their Impact on Intelligent Design

NASA Technical Reports Server (NTRS)

Kandel, Abe

1996-01-01

In this presentation we investigate a novel framework for the design of autonomous fuzzy intelligent systems. The system integrates the following modules into a single autonomous entity: (1) a fuzzy expert system; (2) artificial neural network; (3) genetic algorithm; and (4) case-base reasoning. We describe the integration of these units into one intelligent structure and discuss potential applications.

On Balance: Lessons in Effective Coordination from the Washington State Board for Community and Technical Colleges--An Organizational Perspective

ERIC Educational Resources Information Center

Kirlin, Mary; Shulock, Nancy

2012-01-01

The challenge of producing the systemic changes that are needed to boost educational attainment and economic competitiveness across the country falls heavily on entities that coordinate public postsecondary institutions. Coordination of postsecondary education, whether of a single system of institutions or across an entire state, requires…

76 FR 43981 - Circular Welded Austenitic Stainless Pressure Pipe From the People's Republic of China: Final...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

.... (``Jiuli TC'') and Huzhou Jiuli Welded Stainless Steel Pipe Co., Ltd. (``Jiuli SD Co.''), the collapsed... the Preliminary Results, the Department found that Jiuli TC and Jiuli SD Co. are affiliated pursuant... collapsing Jiuli TC and Jiuli SD Co. into a single entity. Accordingly, the Department based its margin...

Economic Adjustment/Conversion

DTIC Science & Technology

1985-07-01

55 11. State and Local Economic Development Process ...................... 61 PART IV: ECNOMIC AND SOCIAL SERVICE ASSISTANCE TO PERSONS 12. Special...defense production which occurs in plants essentially ded- icated to that purpose. Although a major weapon system is usually budgeted as a single entity...and cuait; of life are essential to attracting new firms and especially important to retaining existing businesses. Research indicates that

A spatial database of wildfires in the United States, 1992-2011

Treesearch

K. C. Short

2014-01-01

The statistical analysis of wildfire activity is a critical component of national wildfire planning, operations, and research in the United States (US). However, there are multiple federal, state, and local entities with wildfire protection and reporting responsibilities in the US, and no single, unified system of wildfire record keeping exists. To conduct even the...

A spatial database of wildfires in the United States, 1992-2011 [Discussions

Treesearch

K. C. Short

2013-01-01

The statistical analysis of wildfire activity is a critical component of national wildfire planning, operations, and research in the United States (US). However, there are multiple federal, state, and local entities with wildfire protection and reporting responsibilities in the US, and no single, unified system of wildfire record-keeping exists. To conduct even the...

47 CFR 80.103 - Digital selective calling (DSC) operating procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... DSC “Acknowledgment of distress calls” and “Distress relays.” (See subpart W of this part.) (d) Group calls to vessels under the common control of a single entity are authorized. A group call identity may... (ITU), Place des Nations, CH-1211 Geneva 20, Switzerland. [68 FR 46961, Aug. 7, 2003, as amended at 73...

47 CFR 80.103 - Digital selective calling (DSC) operating procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... DSC “Acknowledgment of distress calls” and “Distress relays.” (See subpart W of this part.) (d) Group calls to vessels under the common control of a single entity are authorized. A group call identity may... (ITU), Place des Nations, CH-1211 Geneva 20, Switzerland. [68 FR 46961, Aug. 7, 2003, as amended at 73...

D’Andrea’s disease (angiomegaly): a currently well-defined nosological entitys.

PubMed

Taurone, S; Spoletini, M; Di Matteo, F M; Mele, R; Tromba, L; Grippaudo, F R; Minni, A; Artico, M

2017-01-01

In 1997 D’Andrea et al. described a new nosological entity the characteristics of which consisted of lengthening, dilation and tortuosity of blood vessels, arteries or veins, less prominent, but also less circumscribed than an aneurysm. This condition does not necessarily imply specific aneurysm formation although aneurysms at multiple sites are a frequent observation. The term used by authors for angiomegaly of the venous system was venomegaly and the analogous condition of the arterial system was termed arteriomegaly. Although tortuosity and dilation of arteries and veins have been widely reported, suggesting a systemic disorder which affects the structural integrity of all vessels, most papers dealing with this intriguing condition did not describe any alterations in the components of vessel walls. In the present paper, the authors describe a well-defined condition, D’Andrea’s Disease (or DD, in this article), analyzing its salient morphological and clinical features and clarifying this pathological condition as a distinct and now well-defined nosological entity.

Liquid Posterior Fossa Epidural Hematoma in Pediatric Trauma: A Single-Center Case Series.

PubMed

Han, Kun; Li, Zhaojian; Yin, Hongwei; Yao, Weicheng; Lan, Xiaolei; Bo, Yongli

2018-06-14

 Liquid posterior fossa epidural hematoma (LPFEH) following head trauma is uncommon, and very few such cases have been described in the literature. Eight patients with this entity and their treatments are presented here.  We performed a single-institution retrospective analysis of all patients with diagnosed LPFEH over a 3-year period. Collected data included clinical history, laboratory results, treatment, and review of all imaging studies performed.  Eight pediatric cases were identified with imaging findings consistent with LPFEH; no adult case was identified. Enlargement of ventricles appeared on computed tomography (CT) in six cases, and secondary epilepsy onset occurred in three cases with severe dilated ventricles. Routine hematologic and coagulation tests failed to disclose anemia or abnormal coagulation in each case. Five patients underwent burr-hole drainage of the hematoma and recovered completely. Conservative therapy was adopted in three patients for small hematomas, and hematoma enlargement was not observed in the follow-up CT scans.  LPFEH is a rare subtype of traumatic epidural hematoma specifically recognized in the pediatric population. Minimally invasive burr-hole drainage is a feasible procedure for the patient with evident space-occupying effect. Coagulation dysfunction or low hemoglobin as a possible contributing factor and its role in formation of LPFEH was excluded. Georg Thieme Verlag KG Stuttgart · New York.

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

42 CFR 2a.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

...-RESEARCH SUBJECTS § 2a.2 Definitions. (a) Secretary means the Secretary of Health and Human Services and... subdivision or agency, business trust, partnership, association, or other legal entity. (c) Research means... includes, but is not limited to, behavioral science studies, surveys, evaluations, and clinical...

Efficient Execution Methods of Pivoting for Bulk Extraction of Entity-Attribute-Value-Modeled Data

PubMed Central

Luo, Gang; Frey, Lewis J.

2017-01-01

Entity-attribute-value (EAV) tables are widely used to store data in electronic medical records and clinical study data management systems. Before they can be used by various analytical (e.g., data mining and machine learning) programs, EAV-modeled data usually must be transformed into conventional relational table format through pivot operations. This time-consuming and resource-intensive process is often performed repeatedly on a regular basis, e.g., to provide a daily refresh of the content in a clinical data warehouse. Thus, it would be beneficial to make pivot operations as efficient as possible. In this paper, we present three techniques for improving the efficiency of pivot operations: 1) filtering out EAV tuples related to unneeded clinical parameters early on; 2) supporting pivoting across multiple EAV tables; and 3) conducting multi-query optimization. We demonstrate the effectiveness of our techniques through implementation. We show that our optimized execution method of pivoting using these techniques significantly outperforms the current basic execution method of pivoting. Our techniques can be used to build a data extraction tool to simplify the specification of and improve the efficiency of extracting data from the EAV tables in electronic medical records and clinical study data management systems. PMID:25608318

Contact dermatitis in saffron workers: clinical profile and identification of contact sensitizers in a saffron-cultivating area of Kashmir Valley of North India.

PubMed

Hassan, Iffat; Kamili, Afifa; Rasool, Farhan; Nehvi, Firdous; Rather, Parvaiz; Yasmin, Salwee; Pampori, Rafiq A; Jabeen, Yasmeen; Yaseen, Atiya; Bashir, Safia; Naaz, Saima

2015-01-01

Saffron, a bulbous perennial plant belonging to Iridaceae family, is the most expensive cultivated herb that is widely used for industrial and nonindustrial purposes. However, besides its attractive and valuable properties, contact dermatitis due to saffron is an uncommon reported entity. The aims of this study were to determine the clinical pattern patch-testing profile of contact dermatitis in saffron workers and to identify the most common allergens/sensitizers. One hundred ten saffron workers were patch-tested with 39 allergens, which included Indian standard series antigens, plant series antigens, and extracts from different parts of saffron flower. The allergens in Indian standard series accounted for 52.44% of positive reactions. Plant series and different parts of saffron accounted for 47.56% of the positive reactions. Among those patients with positive responses to the supplemental saffron allergens, 83.3% were of present or past relevance. The data observed in the present study confirm that the saffron dermatitis is a distinct clinical entity with characteristic clinical presentation and has a strong significance as an occupational allergen in those handling this plant. Patch testing with different parts of saffron flower has a role to play in finding out the etiological cause.

Segmental stiff skin syndrome (SSS): A distinct clinical entity.

PubMed

Myers, Kathryn L; Mir, Adnan; Schaffer, Julie V; Meehan, Shane A; Orlow, Seth J; Brinster, Nooshin K

2016-07-01

Stiff skin syndrome (SSS) is a noninflammatory, fibrosing condition of the skin, often affecting the limb girdles. We present 4 new patients with SSS with largely unilateral, segmental distribution. To date, reported cases of SSS have been grouped based on generally accepted clinical and histopathologic findings. The purpose of this study was to analyze differences in clinical and histopathologic findings between previously reported SSS cases. This is a retrospective review of 4 new cases and 48 previously published cases of SSS obtained from PubMed search. Of 52 total cases, 18 (35%) were segmentally distributed and 34 (65%) were widespread. The average age of onset was 4.1 years versus 1.6 years for segmental versus widespread SSS, respectively. Limitation in joint mobility affected 44% of patients with segmental SSS and 97% of patients with widespread SSS. Histopathologic findings were common between the 2 groups. This was a retrospective study of previously published cases limited by the completeness and accuracy of the reviewed cases. We propose a distinct clinical entity, segmental SSS, characterized by a segmental distribution, later age of onset, and less severe functional limitation. Both segmental SSS and widespread SSS share common diagnostic histopathologic features. Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.

Combination nucleoside/nucleotide reverse transcriptase inhibitors for treatment of HIV infection.

PubMed

Akanbi, Maxwell O; Scarsi, Kimberly K; Scarci, Kimberly; Taiwo, Babafemi; Murphy, Robert L

2012-01-01

The combination of two nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) and a third agent from another antiretroviral class is currently recommended for initial antiretroviral therapy. In general, N(t)RTIs remain relevant in subsequent regimens. There are currently six nucleoside reverse transcriptase inhibitors and one nucleotide reverse transcriptase inhibitor drug entities available, and several formulations that include two or more N(t)RTIs in a fixed-dose combination. These entities have heterogeneous pharmacological and clinical properties. Accordingly, toxicity, pill burden, dosing frequency, potential drug-drug interaction, preexisting antiretroviral drug resistance and comorbid conditions should be considered when constructing a regimen. This approach is critical in order to optimize virologic efficacy and clinical outcomes. This article reviews N(t)RTI combinations used in the treatment of HIV-infected adults. The pharmacological properties of each N(t)RTI, and the clinical trials that have influenced treatment guidelines are discussed. It is likely that N(t)RTIs will continue to dominate the global landscape of HIV treatment and prevention, despite emerging interest in N(t)RTI-free combination therapy. Clinical domains where only few alternatives to N(t)RTIs exist include treatment of HIV/HBV coinfection and HIV-2. There is a need for novel N(t)RTIs with enhanced safety and resistance profiles compared with current N(t)RTIs.

Safeguarding the future of independent, academic clinical cancer research in Europe for the benefit of patients.

PubMed

Negrouk, Anastassia; Lacombe, Denis; Cardoso, Fatima; Morin, Franck; Carrasco, Eva; Maurel, Joan; Maibach, Rudolf; Aranda, Enrique; Marais, Richard; Stahel, Rolf A

2017-01-01

Cancer is a complex disease that is constantly evolving. It is now the most common cause of death in Europe after cardiovascular diseases. There are inequalities among European countries, potentially unsustainable healthcare systems impacting quality of cancer care and increasing number of patients with cancer with rare conditions. Clinical and translational research are the backbone in establishing scientific advances as novel treatments and advancing progress to the benefit of patients. Commercially sponsored clinical trials are responsible for developing new medicines that can treat various disease areas, including cancer. It is important to note, however, that these clinical trials only assess the viability of compounds that are chosen by a commercial entity that funds the entire process. By their design and focus, these trials need to fulfil commercial interests and market expectations, which do not always coincide with patients' needs. As soon or even before novel treatments and compounds obtain formal market authorisation, academia will take these existing and new medicines to further conduct research in order to optimise their use, develop new combinations and with a strong focus on the patients and their needs. Established standard of care most commonly relies on clinical cancer research stemming from non-commercial entities, cooperative groups or academic clinical research. This article provides a consensus on the definition of academic research, illustrates its added value and suggests and calls to European Union institutions to support this type of research for the benefit of patients.

[Clinical manifestations of organizing pneumonia].

PubMed

Hunter, Martín; Ludueña, Ana; Telias, Irene; Aruj, Patricia; Rausch, Silvia; Suárez, Juan Pablo

Organizing pneumonia is a clinical entity asociated with nonspecific symptoms and radiological findings and abnormalities in pulmonary function tests. It is defined by the characteristic histopathological pattern: filling of alveoli and respiratory bronchioles by plugs of granulation tissue. It can be idiopathic (COP) or secondary to other causes (SOP). It is an unusual finding and the clinical and radiographic findings are nonspecific. For specific diagnosis an invasive procedure has to be done, but often empirical treatment is started when there's a clinical suspicion. We describe the clinical characteristics of 13 patients with histological diagnosis of organizing pneumonia. Data was obtained from their medical records. The median age was 76 years and the median time to diagnosis from the onset of symptoms was 31 days. In 10 cases the diagnosis was made by transbronchial biopsy. 8 patients required hospitalization, 4 of them received high doses of steroids and 3 required ventilatory support. One patient died from a cause attributable to this entity and 5 relapsed. Dyspnea, cough and fever were the most frequent symptoms. Most patients had more than one tomographic pattern being the most common ground glass opacities and alveolar consolidation. Nine patients were diagnosed with COP and 4 with SOP. The most frequent underlying cause of SOP was drug toxicity. The clinical characteristics of the reported cases are consistent with previously published series. As an interesting feature, there was a group of patients that needed high doses of steroids and ventilatory support.

Clinical and Radiological Profile of Acute Fibrinous and Organizing Pneumonia: A Retrospective Study.

PubMed

Dai, Jing-Hong; Li, Hui; Shen, Wei; Miao, Li-Yun; Xiao, Yong-Long; Huang, Mei; Cao, Meng-Shu; Wang, Yang; Zhu, Bin; Meng, Fan-Qing; Cai, Hou-Rong

2015-10-20

Acute fibrinous and organizing pneumonia (AFOP) is a unique pathological entity with intra-alveolar fibrin in the form of "fibrin balls" and organizing pneumonia. It was divided into rare idiopathic interstitial pneumonia according to the classification notified by American Thoracic Society/European Respiratory Society in 2013. As a rare pathological entity, it is still not well known and recognized by clinicians. We reviewed the clinical features of 20 patients with AFOP diagnosed in a teaching hospital. The medical records of 20 patients with biopsy-proven diagnosis of AFOP were retrospectively reviewed. The patients' symptoms, duration of the disease, comorbidities, clinical laboratory data, pulmonary function testing, radiographic studies, and the response to treatment were extracted and analyzed. Fever was the most common symptom and was manifested in 90% of AFOP patients. For clinical laboratory findings, systematic inflammatory indicators, including C-reactive protein and erythrocyte sedimentation rate, were significantly higher than normal in AFOP patients. In accordance with this increased indicators, injured liver functions were common in AFOP patients. Inversely, AFOP patients had worse clinical conditions including anemia and hypoalbuminemia. For pulmonary function testing, AFOP patients showed the pattern of restrictive mixed with obstructive ventilation dysfunction. For high-resolution computerized tomography (HRCT) findings, the most common pattern for AFOP patients was lobar consolidation which was very similar to pneumonia. However, unlike pneumonia, AFOP patients responded well to glucocorticoids. Patients with AFOP manifest as acute inflammatory-like clinical laboratory parameters and lobar consolidation on HRCT, but respond well to steroid.

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity

PubMed Central

Yang, Jason; Ciacci, Joseph D.

2017-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords “subacute sclerosing panencephalitis” and “brainstem” using the National Library of Medicine PubMed database (March 1981–September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment. PMID:29112137

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity.

PubMed

Upadhyayula, Pavan S; Yang, Jason; Yue, John K; Ciacci, Joseph D

2017-11-07

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords "subacute sclerosing panencephalitis" and "brainstem" using the National Library of Medicine PubMed database (March 1981-September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.