[Clinical laboratory tests supporting respiratory disease treatment--chairman's introductory remarks].

PubMed

Takai, Daiya

2014-12-01

The symposium consisted of four parts: history of lung function tests, nitric oxide for diagnosis and monitoring of bronchial asthma, radiological and functional changes of the lung in COPD, and combined pulmonary fibrosis and emphysema (CPFE) occasionally showing almost normal results in lung function tests. The history of lung function tests was presented by Dr. Naoko Tojo of the Tokyo Medical and Dental University. Nitric oxide tests in clinical use for diagnosis and monitoring of bronchial asthma were presented by Dr. Hiroyuki Nagase of Teikyo University. Radiological and functional changes of the lung in COPD were presented by Dr. Shigeo Muro of Kyoto University. Clinical features of combined pulmonary fibrosis and emphysema and their associated lung function were presented by Dr. Daiya Takai of the University of Tokyo. I hope that discussing the history of lung function tests until the present was useful for many medical technologists. (Review).

[Research activity in clinical biochemistry].

PubMed

Jørgensen, Henrik L; Larsen, Birger; Ingwersen, Peter; Rehfeld, Jens F

2008-09-01

Quantitative bibliometric measurements of research activity are frequently used, e.g. for evaluating applicants for academic positions. The purpose of this investigation is to assess research activity within the medical speciality of Clinical Biochemistry by comparing it with a matched control group from other medical specialities in Denmark. A list of all physicians registered in Denmark (23,127 persons) was drawn from the database "Laeger.dk". Of these, 5,202 were generalists (not included) while 11,691 were from other specialities. Of the 126 specialists from Clinical Biochemistry, 57 fulfilled the inclusion criteria. Each of these 57 was matched according to medical title with two randomly chosen specialists from other specialities, totaling 114. Using Medline and the Web of Science, the number of publications and the number of citations were then ascertained. 25% of the 11,691 specialists held a PhD degree or doctoral degree, DMSci, (Clinical Biochemistry: 61%). The 171 specialists included in the study had 9,823 papers in Medline and 10,140 papers in the Web of Science. The number of Medline papers per specialist was 71 for Clinical Biochemistry compared to 51 for the control group. The number of citations per specialist was 1,844 for Clinical Biochemistry compared to 816 for the control group. The top ten H-indices (of which 8 were in Clinical Biochemistry) ranged from 30 to 69. Both the number of papers and the number of citations were higher for Clinical Biochemistry than for the control group. The difference was most pronounced among professors.

[Antibacterial activity of panipenem against clinical isolates in 2000 and 2001].

PubMed

Abe, Tomomi; Fukuoka, Takashi; Sato, Yuki; Ito, Kazuyoshi; Sei, Masami

2002-12-01

As the post-marketing surveillance of panipenem/betamipron (Carbenin), MICs of panipenem (PAPM) against 1355 clinical isolates of 28 species from 15 medical institutions all over Japan from June 2000 to March 2001 were measured using the broth microdilution method approved by the Japanese Society of Chemotherapy and compared with those of parenteral carbapenem antibacterials, imipenem (IPM) and meropenem (MEPM), and parenteral cephem antibacterials, cefozopran, cefepime, and sulbactam/cefoperazone. The activity of PAPM was comparable to that of IPM against almost all species tested. Compared with MEPM, PAPM was more active against Gram-positive bacteria and Bacteroides spp., and less active against Gram-negative bacteria. Compared with the parenteral cephems, PAPM was more active against most of species tested and its MIC ranges were narrower than those of the cephems as were those of other carbapenems. In this surveillance study, the incidence of resistance in various species were as follows: 39.3% for methicillin-resistant Staphylococcus aureus, 47.3% for penicillin-intermediate Streptococcus pneumoniae (PISP), 15.1% for penicillin-resistant S. pneumoniae (PRSP), 0.9% for extended-spectrum beta-lactamase (ESBL) producing Escherichia coli, 3.4% for ESBL producing Klebsiella pneumoniae, 19.2% for beta-lactamase producing Haemophilus influenzae, 24.0% for beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae, and 1.0% for metallo-beta-lactamase producing Pseudomonas aeruginosa. Against these resistant strains, carbapenems including PAPM showed generally more potent activity than cephems. It was noted that PAPM showed the most potent activity against PISP and PRSP, which showed high incidence of 62.4% totally, among tested drugs. Metallo-beta-lactamase producing P. aeruginosa exhibited high resistance and BLNAR H. influenzae also exhibited low susceptibility against all tested drugs. But no remarkable change in the activity of PAPM against other species

Phenytoin: 80 years young, from epilepsy to breast cancer, a remarkable molecule with multiple modes of action.

PubMed

Keppel Hesselink, Jan M; Kopsky, David J

2017-08-01

In 1908 phenytoin (5,5-diphenylhydantoin) was first synthesized as a barbiturate derivative in Germany by professor Heinrich Biltz (1865-1943) and subsequently resynthesized by an American chemist of the pharmaceutical company Parke-Davis in 1923 in Detroit. Screening phenytoin did not reveal comparable sedative side effects as barbiturates and, thus, Parke-Davis discarded this compound as a useful drug. In 1936, phenytoin's anticonvulsive properties were identified via a new animal model for convulsive disorders, developed by Putnam and Merritt, who also evaluated its clinical value in a number of patients in the period 1937-1940. For many diseases, mechanism of action of phenytoin remains obscure. The voltage-gated sodium channel was and is generally regarded as the main target to explain phenytoin's activity as an anticonvulsant and an anti-arrhythmic drug. This target, however, does not explain many of the other clinical properties of phenytoin. We will explore a number of original articles on phenytoin published in its 80 years history and give extra attention to the various hypothesis and experiments done to elucidate its mechanisms of action. Phenytoin has been explored in over 100 different disorders; the last two promising indications tested in the clinic are breast cancer and optic neuritis. Most probably, there are multiple targets active for these various disorders, and the insight into which targets are relevant is still very incomplete. It is remarkable that many pharmacological studies tested one dose only, mostly 50 or 100 μM, doses which most probably are higher than the non-plasma bound phenytoin plasma levels obtained during treatment.

[Antibacterial activity of cefpodoxime against clinical isolates in 2000 and 2001].

PubMed

Abe, Tomomi; Fukuoka, Takashi; Sato, Yuki; Ito, Kazuyoshi; Sei, Masami

2002-12-01

As the post-marketing surveillance of cefpodoxime proxetil (Banan), MICs of cefpodoxime (CPDX, an active form of Banan) against 1090 clinical isolates of 22 species from 15 medical institutions all over Japan from June 2000 to March 2001 were measured using the broth microdilution method approved by the Japanese Society of Chemotherapy and compared with those of oral cephem antibacterials, cefaclor, cefdinir, cefditoren, and cefcapene. In this study, remarkable change in the activity of CPDX was observed in Streptococcus pneumoniae and Haemophilus influenzae compared with the susceptibility in the studies before Banan was launched. This cause is considered to be the increase in the incidence of the following resistant strains: penicillin-intermediate S. pneumoniae (47.3%), penicillin-resistant S. pneumoniae (PRSP, 15.1%), and beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae (24.0%), which were scarcely isolated in 1989 when Banan was launched. Other tested drugs also exhibited low activity against these resistant strains. However, CPDX showed comparatively good activity with MIC90 of 2 micrograms/mL against PRSP. Against methicillin-susceptible Staphylococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, and Moraxella catarrhalis, CPDX also showed comparatively good activity with MIC90 of < or = 4 micrograms/mL, which was almost equal to that in the studies before its marketing. Against quinolones-resistant Neisseria gonorrhoeae, CPDX showed excellent activity with MIC90 of 0.5 microgram/mL. Against members of the family Enterobacteriaceae except for Citrobacter freundii, Enterobacter spp., Proteus vulgaris, and Morganella morganii, CPDX showed good activity. However, in Escherichia coli, Klebsiella spp. Proteus spp., and Providencia spp., there are some high-resistant strains to all tested drugs including CPDX. Against Peptostreptococcus spp., MIC90 of CPDX was 8 micrograms/mL and its MIC range was widely distributed from 0.03 to 32

Gamma-Ray Attenuation Measurements as a Laboratory Experiment: Some Remarks

ERIC Educational Resources Information Center

Adamides, E.; Koutroubas, S. K.; Moshonas, N.; Yiasemides, K.

2011-01-01

In this article we make some significant remarks on the experimental study of the absorption of gamma radiation passing through matter. These remarks have to do with the seemingly unexpected trend of the measured intensity of radiation versus the thickness of the absorber, which puzzles students and its explanation eludes many laboratory…

Ted Sizer's Opening Remarks, Fall Forum 2000, Providence, Rhode Island

ERIC Educational Resources Information Center

Sizer, Theodore

2009-01-01

This article presents Ted Sizer's opening remarks during the Fall Forum in 2000 at Providence, Rhode Island. In his opening remarks, Sizer reviews what the Coalition of Essential Schools (CES) is, and what it is not. CES, he contends, is not a fixed school design but rather, a set of ideas, ideas and conditions and convictions, called principles,…

2011 Asia Pacific Few-Body Conference Summary Remarks

NASA Astrophysics Data System (ADS)

Gibson, B. F.

2013-03-01

These remarks represent the author's personal perspective regarding ideas presented at this fifth Asia Pacific Conference on Few-Body Problems in Physics. They are not intended as a comprehensive summary of what we witnessed during this week of stimulating presentations and intense discussions. However, these remarks do characterize some of the physics we heard and some of the key questions raised. The ideas presented will hopefully outlive the rapporteurs who brought their work and that of others to our attention here in the International Hall of the Sungkyunkwan University in Seoul, Republic of Korea. Finally, we bid adieu to our friend, colleague, and mentor, John A. Tjon.

Mars and the remarkable Viking results

NASA Technical Reports Server (NTRS)

Soffen, G. A.

1978-01-01

It is pointed out that the Viking missions to Mars are the most extraordinary and complex remote effort ever performed by man. Factors which made the Viking results so remarkable are related to the technological engineering accomplishment, the voluminous scientific data about the planet, and the public interest. Quite surprisingly it was found that the Viking 1 landing site was very similar to the California desert. Attention is given to details of spacecraft landing on the Martian surface, aspects of landing site selection, the design and the operation of Lander instruments, the nine different investigations performed by the Lander, the significance of the pictures obtained of Mars, the remarkable heterogeneity of the planet, the extent and variety of volcanism, the presence of water in the solid and gaseous form on the Martian surface, the presence of water in the liquid phase at some time in the past, the two natural Martian satellites, the composition of the Martian polar caps and their changes during the seasons, the composition of the atmosphere, and the biological results, which remain ambiguous.

[Industry-Academia Collaboration in the Clinical Laboratory Field: Chairmen's Introductory Remarks].

PubMed

Inaba, Tohru; Ikemoto, Toshiyuki

2016-01-01

Industry-academia collaboration has become essential in contemporary medicine. Therefore, many institutes including university corporations have promoted the establishment of an endowed chair and/or performed collaborative research. This symposium was held to overview the present status of industry-academia collaboration in the clinical laboratory field. As a representative of the industry, Mr. Taniguchi (Sysmex) presented the development process of M2BP Glycosylation Isomer, a new marker for liver fibrosis. Mr. Saitoh (Horiba) introduced the achievements of joint collaborative research with Kyoto Prefectural University of Medicine, especially the practical realization of an automated hematology analyzer capable of simultaneously measuring C-reactive protein. Mr. Setoyama (LSI Medience) presented on the characteristic collaboration between academia and commercial laboratories such as Tsukuba Medical Laboratory of Education and Research (TMER). On the other hand, as a representative of academia, Associate Prof. Imai (Kyoto Prefectural University of Medicine) summarized the necessity of clinical laboratories spread regenerative medicine. Finally, Prof. Koshiba (Hyogo College of Medicine) presented on the industry-academia collaboration in routine laboratory work in his institute.

12-NIF Dedication: Concluding remarks and video

ScienceCinema

Edward Moses

2017-12-09

The National Ignition Facility, the world's largest laser system, was dedicated at a ceremony on May 29, 2009 at Lawrence Livermore National Laboratory. These are the concluding remarks by NIF Director Edward Moses, and a brief video presentation.

The Emergence of Single Neurons in Clinical Neurology

PubMed Central

Cash, Sydney S.; Hochberg, Leigh R.

2015-01-01

Summary Single neuron actions and interactions are the sine qua non of brain function, and nearly all diseases and injuries of the central nervous system trace their clinical sequelae to neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is largely absent in clinical neuroscience. Advances in neurotechnology and computational capabilities, accompanied by shifts in theoretical frameworks, have led to renewed interest in the information represented by single neurons. Using direct interfaces with the nervous system, millisecond-scale information will soon be extracted from single neurons in clinical environments, supporting personalized treatment of neurologic and psychiatric disease. In this review we focus on single neuronal activity in restoring communication and motor control in patients suffering from devastating neurological injuries. We also explore the single neuron's role in epilepsy and movement disorders, surgical anesthesia, and in cognitive processes disrupted in neurodegenerative and neuropsychiatric disease. Finally, we speculate on how technological advances will revolutionize neurotherapeutics. PMID:25856488

The emergence of single neurons in clinical neurology.

PubMed

Cash, Sydney S; Hochberg, Leigh R

2015-04-08

Single neuron actions and interactions are the sine qua non of brain function, and nearly all diseases and injuries of the CNS trace their clinical sequelae to neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is largely absent in clinical neuroscience. Advances in neurotechnology and computational capabilities, accompanied by shifts in theoretical frameworks, have led to renewed interest in the information represented by single neurons. Using direct interfaces with the nervous system, millisecond-scale information will soon be extracted from single neurons in clinical environments, supporting personalized treatment of neurologic and psychiatric disease. In this Perspective, we focus on single-neuronal activity in restoring communication and motor control in patients suffering from devastating neurological injuries. We also explore the single neuron's role in epilepsy and movement disorders, surgical anesthesia, and in cognitive processes disrupted in neurodegenerative and neuropsychiatric disease. Finally, we speculate on how technological advances will revolutionize neurotherapeutics. Copyright © 2015 Elsevier Inc. All rights reserved.

Reporting recommendations for tumor marker prognostic studies (REMARK): explanation and elaboration

PubMed Central

2012-01-01

Background The Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) checklist consists of 20 items to report for published tumor marker prognostic studies. It was developed to address widespread deficiencies in the reporting of such studies. In this paper we expand on the REMARK checklist to enhance its use and effectiveness through better understanding of the intent of each item and why the information is important to report. Methods REMARK recommends including a transparent and full description of research goals and hypotheses, subject selection, specimen and assay considerations, marker measurement methods, statistical design and analysis, and study results. Each checklist item is explained and accompanied by published examples of good reporting, and relevant empirical evidence of the quality of reporting. We give prominence to discussion of the 'REMARK profile', a suggested tabular format for summarizing key study details. Summary The paper provides a comprehensive overview to educate on good reporting and provide a valuable reference for the many issues to consider when designing, conducting, and analyzing tumor marker studies and prognostic studies in medicine in general. To encourage dissemination of the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK): Explanation and Elaboration, this article has also been published in PLoS Medicine. PMID:22642691

[The Status of Higher Education and the College Environment. Collected Remarks.

ERIC Educational Resources Information Center

Boozer, Howard R.; And Others

Conference papers and panel remarks concerning the role of state coordinating or governing boards, trends in higher education since before World War II, and implications of the Bakke decision are presented as part of an inservice education program. In "Life in the Centrifuge--Panel Remarks," Howard R. Boozer suggests that higher…

A trade off between catalytic activity and protein stability determines the clinical manifestations of glucose-6-phosphate dehydrogenase (G6PD) deficiency.

PubMed

Boonyuen, Usa; Chamchoy, Kamonwan; Swangsri, Thitiluck; Junkree, Thanyaphorn; Day, Nicholas P J; White, Nicholas J; Imwong, Mallika

2017-11-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common polymorphism and enzymopathy in humans, affecting approximately 400 million people worldwide. It is responsible for various clinical manifestations, including favism, hemolytic anemia, chronic non-spherocytic hemolytic anemia, spontaneous abortion, and neonatal hyperbilirubinemia. Understanding the molecular mechanisms underlying the severity of G6PD deficiency is of great importance but that of many G6PD variants are still unknown. In this study, we report the construction, expression, purification, and biochemical characterization in terms of kinetic properties and stability of five clinical G6PD variants-G6PD Bangkok, G6PD Bangkok noi, G6PD Songklanagarind, G6PD Canton+Bangkok noi, and G6PD Union+Viangchan. G6PD Bangkok and G6PD Canton+Bangkok noi showed a complete loss of catalytic activity and moderate reduction in thermal stability when compared with the native G6PD. G6PD Bangkok noi and G6PD Union+Viangchan showed a significant reduction in catalytic efficiency, whereas G6PD Songklanagarind showed a catalytic activity comparable to the wild-type enzyme. The Union+Viangchan mutation showed a remarkable effect on the global stability of the enzyme. In addition, our results indicate that the location of mutations in G6PD variants affects their catalytic activity, stability, and structure. Hence, our results provide a molecular explanation for clinical manifestations observed in individuals with G6PD deficiency. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Peer assisted learning in the clinical setting: an activity systems analysis.

PubMed

Bennett, Deirdre; O'Flynn, Siun; Kelly, Martina

2015-08-01

Peer assisted learning (PAL) is a common feature of medical education. Understanding of PAL has been based on processes and outcomes in controlled settings, such as clinical skills labs. PAL in the clinical setting, a complex learning environment, requires fresh evaluation. Socio-cultural theory is proposed as a means to understand educational interventions in ways that are practical and meaningful. We describe the evaluation of a PAL intervention, introduced to support students' transition into full time clinical attachments, using activity theory and activity systems analysis (ASA). Our research question was How does PAL transfer to the clinical environment? Junior students on their first clinical attachments undertook a weekly same-level, reciprocal PAL activity. Qualitative data was collected after each session, and focus groups (n = 3) were held on completion. Data was analysed using ASA. ASA revealed two competing activity systems on clinical attachment; Learning from Experts, which students saw as the primary function of the attachment and Learning with Peers, the PAL intervention. The latter took time from the first and was in tension with it. Tensions arose from student beliefs about how learning takes place in clinical settings, and the importance of social relationships, leading to variable engagement with PAL. Differing perspectives within the group were opportunities for expansive learning. PAL in the clinical environment presents challenges specific to that context. Using ASA helped to describe student activity on clinical attachment and to highlight tensions and contradictions relating PAL in that setting. Planning learning opportunities on clinical placements, must take account of how students learn in workplaces, and the complexity of the multiple competing activity systems related to learning and social activities.

Danish research-active clinical nurses overcome barriers in research utilization.

PubMed

Adamsen, Lis; Larsen, Kristian; Bjerregaard, Lene; Madsen, Jan K

2003-03-01

The aim of this study was to examine whether there was a difference between clinical nurses who were research-active, and clinical nurses who were nonresearch-active in utilization of research. A further aim was to identify the most significant barriers faced by a group of Danish clinical nurses in their use of research. Discrepancy between the improved quality of research results and the lack of implementing them was the starting point for a series of studies which showed the types of barriers clinical nurses found especially cumbersome when applying the research results of other researchers. This study investigates whether the clinical nurses' own engagement in research had any impact on their perception of research utilization. The study had an exploratory and descriptive design. Seventy-nine Danish clinical nurses participated and semi-structured interviewing was used as the research method. There was a statistically significant difference between the research-active and nonresearch-active nurses on various variables. The study showed that, to a larger extent, research-active nurses used evidence-based knowledge and were generally more internationally orientated. Furthermore, two important barriers for research utilization were identified by all 79 clinical nurses included in the study, i.e. 90% of the nurses explained that the quantity of research results was overwhelming, and 75% of them found that they were unable to evaluate the quality of the research. Clinical nurses, who were research-active themselves, experienced more success in overcoming some of the barriers, which existed in applying research to practice. The research potential found amongst clinical nurses in Denmark needed to be further supported through training and guidance in research methodology, establishing introductory stipends and part-time research positions. By doing so, some of the barriers affecting research utilization and the so-called theory-practice gap might be reduced. Further

Endophytic Nocardiopsis sp. from Zingiber officinale with both antiphytopathogenic mechanisms and antibiofilm activity against clinical isolates.

PubMed

Sabu, Rohini; Soumya, K R; Radhakrishnan, E K

2017-06-01

Novel and potential antimicrobial compounds are essential to tackle the frequently emerging multidrug-resistant pathogens and also to develop environment friendly agricultural practices. In the current study, endophytic actinomycetes from rhizome of Zingiber officinale were explored in terms of its diversity and bioactive properties. Fourteen different organisms were isolated, identified and screened for activity against Pythium myriotylum and human clinical pathogens. Among these, Nocardiopsis sp. ZoA1 was found to have highest inhibition with excellent antibacterial effects compared to standard antibiotics. Remarkable antibiofilm property was also shown by the extract of ZoA1. Its antifungal activity against Pythium and other common phytopathogens was also found to be promising as confirmed by scanning electron microscopic analysis. By PCR-based sequence analysis of phz E gene, the organism was confirmed for the genetic basis of phenazine biosynthesis. Further GC-MS analysis of Nocardiopsis sp. revealed the presence of various compounds including Phenol, 2,4-bis (1,1-dimethylethyl) and trans cinnamic acid which can have significant role in the observed result. The current study is the first report on endophytic Nocardiopsis sp. from ginger with promising applications. In vivo treatment of Nocardiopsis sp. on ginger rhizome has revealed its inhibition towards the colonization of P. myriotylum which makes the study to have promises to manage the severe diseases in ginger like rhizome rot.

[Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--I. Gram-positive bacteria].

PubMed

Igari, Jun; Oguri, Toyoko; Hiramatsu, Nobuyoshi; Akiyama, Kazumitsu; Koyama, Tsuneo

2002-02-01

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, and carbapenems. Changes in the bacterial sensitivity for CZOP were also evaluated with the resistance ratio calculated with breakpoint MIC. Sixteen species (1,913 strains) of Gram-positive bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA; n = 178), methicillin-resistant S. aureus (MRSA; n = 199), methicillin-susceptible Staphylococcus epidermidis (MSSE; n = 98), methicillin-resistant S. epidermidis (MRSE; n = 164), Staphylococcus haemolyticus (n = 72), Staphylococcus saprophyticus (n = 28), Enterococcus faecalis (n = 206), Enterococcus faecium (n = 91), Enterococcus avium (n = 72), Streptococcus pyogenes (n = 133), Streptococcus agalactiae (n = 138), penicillin-susceptible Streptococcus pneumoniae (PSSP; n = 133), penicillin-intermediate resistant S. pneumoniae (PISP; n = 100), penicillin-resistant S. pneumoniae (PRSP; n = 29), Streptococcus milleri group (n = 135) and Peptostreptococcus spp. (n = 137). CZOP possessed comparable antibacterial activities against MSSA and MSSE to other cephems, and was also effective on MRSE but not on MRSA. An antibacterial activity of CZOP against S. saprophyticus was comparable to or higher than other cephems. CZOP, however, did not indicate an antibacterial activity against S. haemolyticus, just like other cephems. An antibacterial activity of CZOP against E. faecalis was comparable to cefpirome (CPR) and higher than other cephems. No antibacterial activity of CZOP against E. faecium and E. avium was observed, just like other drugs. An antibacterial activity of CZOP against S. pyogenes was as potent as that of cefotiam (CTM), cefepime (CFPM) and CPR, and that against S. agalactiae was

Remarkable Reproducibility of Enzyme Activity Profiles in Tomato Fruits Grown under Contrasting Environments Provides a Roadmap for Studies of Fruit Metabolism1[W][OPEN

PubMed Central

Biais, Benoît; Bénard, Camille; Beauvoit, Bertrand; Colombié, Sophie; Prodhomme, Duyên; Ménard, Guillaume; Bernillon, Stéphane; Gehl, Bernadette; Gautier, Hélène; Ballias, Patricia; Mazat, Jean-Pierre; Sweetlove, Lee; Génard, Michel; Gibon, Yves

2014-01-01

To assess the influence of the environment on fruit metabolism, tomato (Solanum lycopersicum ‘Moneymaker’) plants were grown under contrasting conditions (optimal for commercial, water limited, or shaded production) and locations. Samples were harvested at nine stages of development, and 36 enzyme activities of central metabolism were measured as well as protein, starch, and major metabolites, such as hexoses, sucrose, organic acids, and amino acids. The most remarkable result was the high reproducibility of enzyme activities throughout development, irrespective of conditions or location. Hierarchical clustering of enzyme activities also revealed tight relationships between metabolic pathways and phases of development. Thus, cell division was characterized by high activities of fructokinase, glucokinase, pyruvate kinase, and tricarboxylic acid cycle enzymes, indicating ATP production as a priority, whereas cell expansion was characterized by enzymes involved in the lower part of glycolysis, suggesting a metabolic reprogramming to anaplerosis. As expected, enzymes involved in the accumulation of sugars, citrate, and glutamate were strongly increased during ripening. However, a group of enzymes involved in ATP production, which is probably fueled by starch degradation, was also increased. Metabolites levels seemed more sensitive than enzymes to the environment, although such differences tended to decrease at ripening. The integration of enzyme and metabolite data obtained under contrasting growth conditions using principal component analysis suggests that, with the exceptions of alanine amino transferase and glutamate and malate dehydrogenase and malate, there are no links between single enzyme activities and metabolite time courses or levels. PMID:24474652

The Remarkable Amphoteric Nature of Defective UiO‐66 in Catalytic Reactions

PubMed Central

Hajek, Julianna; Bueken, Bart; Waroquier, Michel; De Vos, Dirk

2017-01-01

Abstract One of the major requirements in solid acid and base catalyzed reactions is that the reactants, intermediates or activated complexes cooperate with several functions of catalyst support. In this work the remarkable bifunctional behavior of the defective UiO‐66(Zr) metal organic framework is shown for acid‐base pair catalysis. The active site relies on the presence of coordinatively unsaturated zirconium sites, which may be tuned by removing framework linkers and by removal of water from the inorganic bricks using a dehydration treatment. To elucidate the amphoteric nature of defective UiO‐66, the Oppenauer oxidation of primary alcohols has been theoretically investigated using density functional theory (DFT) and the periodic approach. The presence of acid and basic centers within molecular distances is shown to be crucial for determining the catalytic activity of the material. Hydrated and dehydrated bricks have a distinct influence on the acidity and basicity of the active sites. In any case both functions need to cooperate in a concerted way to enable the chemical transformation. Experimental results on UiO‐66 materials of different defectivity support the theoretical observations made in this work. PMID:28736581

Remarkable-Tracking, Experiential Education of the Ecological Imagination

ERIC Educational Resources Information Center

Payne, Phillip G.

2010-01-01

Imagination might be understood as letting our senses, perceptions and sensibilities run free for no apparent reason. Here, for this special edition what might be "remarkable" is the "opening" of our imagination provided orally through storytelling. This opening involves the "placing" of our own and our listeners'…

Extremophilic Acinetobacter strains from high-altitude lakes in Argentinean Puna: remarkable UV-B resistance and efficient DNA damage repair.

PubMed

Albarracín, Virginia Helena; Pathak, Gopal P; Douki, Thierry; Cadet, Jean; Borsarelli, Claudio Darío; Gärtner, Wolfgang; Farias, María Eugenia

2012-06-01

High-Altitude Andean Lakes (HAAL) of the South American Andes are almost unexplored ecosystems of shallow lakes. The HAAL are recognized by a remarkably high UV exposure, strong changes in temperature and salinity, and a high content of toxic elements, especially arsenic. Being exposed to remarkably extreme conditions, they have been classified as model systems for the study of life on other planets. Particularly, Acinetobacter strains isolated from the HAAL were studied for their survival competence under strong UV-B irradiation. Clinical isolates, Acinetobacter baumannii and Acinetobacter johnsonii, served as reference material. Whereas the reference strains rapidly lost viability under UV-B irradiation, most HAAL-derived strains readily survived this exposure and showed less change in cell number after the treatment. Controls for DNA repair activity, comparing dark repair (DR) or photo repair (PR), gave evidence for the involvement of photolyases in the DNA repair. Comparative measurements by HPLC-mass spectrometry detected the number of photoproducts: bipyrimidine dimers under both PR and DR treatments were more efficiently repaired in the HAAL strains (up to 85 % PR and 38 % DR) than in the controls (31 % PR and zero DR ability). Analysis of cosmid-cloned total genomic DNA from the most effective DNA-photorepair strain (Ver3) yielded a gene (HQ443199) encoding a protein with clear photolyase signatures belonging to class I CPD-photolyases. Despite the relatively low sequence similarity of 41 % between the enzymes from Ver3 and from E. coli (PDB 1DNPA), a model-building approach revealed a high structural homology to the CPD-photolyase of E. coli.

Remarkable resilience of teeth.

PubMed

Chai, Herzl; Lee, James J-W; Constantino, Paul J; Lucas, Peter W; Lawn, Brian R

2009-05-05

Tooth enamel is inherently weak, with fracture toughness comparable with glass, yet it is remarkably resilient, surviving millions of functional contacts over a lifetime. We propose a microstructural mechanism of damage resistance, based on observations from ex situ loading of human and sea otter molars (teeth with strikingly similar structural features). Section views of the enamel implicate tufts, hypomineralized crack-like defects at the enamel-dentin junction, as primary fracture sources. We report a stabilization in the evolution of these defects, by "stress shielding" from neighbors, by inhibition of ensuing crack extension from prism interweaving (decussation), and by self-healing. These factors, coupled with the capacity of the tooth configuration to limit the generation of tensile stresses in largely compressive biting, explain how teeth may absorb considerable damage over time without catastrophic failure, an outcome with strong implications concerning the adaptation of animal species to diet.

Remarkable recoveries: research and practice from a patient's perspective.

PubMed

Barasch, Marc Ian

2008-08-01

Mind-body therapies are often portrayed in the literature as self-palliative, adjunctive, and complementary, but rarely as contributive to cure. Many physicians continue to view them as acceptable indulgences so long as they are harmless and the patient remains fully compliant with a standard treatment regimen. The possibility that such modalities might help drive the healing process itself is infrequently acknowledged. This article addresses the topic of such therapies, examining remarkable recoveries in cancer, and suggesting the need for a "Remarkable Recovery Registry" to expand the literature on these cases. The author discusses the importance of complementary alternative medicine, and emotional and pyschologic support in the treatment regimen, and the need for health care providers and patients to work together to provide the best emotional environment for the healing process.

Communication—Electrolysis at High Efficiency with Remarkable Hydrogen Production Rates

DOE PAGES

Wood, Anthony; He, Hongpeng; Joia, Tahir; ...

2016-01-20

Solid Oxide Electrolysis (SOE) can be used to produce hydrogen with very high efficiencies at remarkable hydrogen production rates. Through microstructural and compositional modification, conventional low cost Solid Oxide Fuel Cell (SOFC) materials have been used to create a Solid Oxide Electrolysis Cell (SOEC) that can achieve remarkable current density at cell voltages allowing higher conversion efficiency than current commercial electrolysers. Current densities in excess of 6 A/cm2 have been achieved at 800°C with a cell voltage of < 1.67 V. This cell shows a more than 3-fold increase in hydrogen production rate at higher efficiency than established commercial electrolysers.

Do Urinary Cystine Parameters Predict Clinical Stone Activity?

PubMed

Friedlander, Justin I; Antonelli, Jodi A; Canvasser, Noah E; Morgan, Monica S C; Mollengarden, Daniel; Best, Sara; Pearle, Margaret S

2018-02-01

An accurate urinary predictor of stone recurrence would be clinically advantageous for patients with cystinuria. A proprietary assay (Litholink, Chicago, Illinois) measures cystine capacity as a potentially more reliable estimate of stone forming propensity. The recommended capacity level to prevent stone formation, which is greater than 150 mg/l, has not been directly correlated with clinical stone activity. We investigated the relationship between urinary cystine parameters and clinical stone activity. We prospectively followed 48 patients with cystinuria using 24-hour urine collections and serial imaging, and recorded stone activity. We compared cystine urinary parameters at times of stone activity with those obtained during periods of stone quiescence. We then performed correlation and ROC analysis to evaluate the performance of cystine parameters to predict stone activity. During a median followup of 70.6 months (range 2.2 to 274.6) 85 stone events occurred which could be linked to a recent urine collection. Cystine capacity was significantly greater for quiescent urine than for stone event urine (mean ± SD 48 ± 107 vs -38 ± 163 mg/l, p <0.001). Cystine capacity significantly correlated inversely with stone activity (r = -0.29, p <0.001). Capacity also correlated highly negatively with supersaturation (r = -0.88, p <0.001) and concentration (r = -0.87, p <0.001). Using the suggested cutoff of greater than 150 mg/l had only 8.0% sensitivity to predict stone quiescence. Decreasing the cutoff to 90 mg/l or greater improved sensitivity to 25.2% while maintaining specificity at 90.9%. Our results suggest that the target for capacity should be lower than previously advised. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Applying Active Learning to Assertion Classification of Concepts in Clinical Text

PubMed Central

Chen, Yukun; Mani, Subramani; Xu, Hua

2012-01-01

Supervised machine learning methods for clinical natural language processing (NLP) research require a large number of annotated samples, which are very expensive to build because of the involvement of physicians. Active learning, an approach that actively samples from a large pool, provides an alternative solution. Its major goal in classification is to reduce the annotation effort while maintaining the quality of the predictive model. However, few studies have investigated its uses in clinical NLP. This paper reports an application of active learning to a clinical text classification task: to determine the assertion status of clinical concepts. The annotated corpus for the assertion classification task in the 2010 i2b2/VA Clinical NLP Challenge was used in this study. We implemented several existing and newly developed active learning algorithms and assessed their uses. The outcome is reported in the global ALC score, based on the Area under the average Learning Curve of the AUC (Area Under the Curve) score. Results showed that when the same number of annotated samples was used, active learning strategies could generate better classification models (best ALC – 0.7715) than the passive learning method (random sampling) (ALC – 0.7411). Moreover, to achieve the same classification performance, active learning strategies required fewer samples than the random sampling method. For example, to achieve an AUC of 0.79, the random sampling method used 32 samples, while our best active learning algorithm required only 12 samples, a reduction of 62.5% in manual annotation effort. PMID:22127105

Convocation: Opening Day Remarks, Fashion Institute of Technology.

ERIC Educational Resources Information Center

Feldman, Marvin

These opening day remarks by the Fashion Institute of Technology's (FIT's) retiring president focus on the Institute's educational history, mission, and future. First, the paper discusses FIT's finances which are undergoing a period of retrenchment due to a $700,000 cut in state aid, and an anticipated $500,000 reduction in city funds. The next…

Clinical markers of vitiligo activity.

PubMed

Benzekri, Laila; Gauthier, Yvon

2017-05-01

Current modalities of understanding disease state (active/stable) are limited when considering treatment of vitiligo. We sought to develop a rapid, accurate, and noninvasive assessment of vitiligo state. In daylight and Wood's light examinations, 2 common clinical types of vitiligo were identified as amelanotic with sharply demarcated borders and hypomelanotic with poorly defined borders. Photographs were taken at the time of examination and a skin biopsy at the edge of a vitiligo lesion was performed. One year after the initial visit, the vitiligo was classified as stable if no new lesions had appeared, and as active if the number, size, or both of existing vitiligo lesions were increased. Skin biopsy specimens from 71 patients were stained and immunostained for melanocytes, CD8 + T lymphocytes, and E-cadherin. The active lesions were associated with hypomelanotic appearance with poorly defined borders (P < .001), and histologically with an infiltration of CD8 + T lymphocytes in the epidermis and dermis (P = .017), with a strong expression of E-cadherin (P = .044). The fact that this was a single-center study and that activity was sometimes site-dependent are limitations. The hypomelanotic with poorly defined borders type could be a good indicator of the actual activity of a vitiligo lesion. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Thiamin Pyrimidine Biosynthesis in Candida albicans: A Remarkable Reaction between Histidine and Pyridoxal Phosphate

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

Lai, Rung-Yi; Huang, Siyu; Fenwick, Michael K.

2012-06-26

In Saccharomyces cerevisiae, thiamin pyrimidine is formed from histidine and pyridoxal phosphate (PLP). The origin of all of the pyrimidine atoms has been previously determined using labeling studies and suggests that the pyrimidine is formed using remarkable chemistry that is without chemical or biochemical precedent. Here we report the overexpression of the closely related Candida albicans pyrimidine synthase (THI5p) and the reconstitution and preliminary characterization of the enzymatic activity. A structure of the C. albicans THI5p shows PLP bound at the active site via an imine with Lys62 and His66 in close proximity to the PLP. Our data suggest thatmore » His66 of the THI5 protein is the histidine source for pyrimidine formation and that the pyrimidine synthase is a single-turnover enzyme.« less

Clinical features of adult-onset chronic active Epstein-Barr virus infection: a retrospective analysis.

PubMed

Arai, Ayako; Imadome, Ken-Ichi; Watanabe, Yuko; Yoshimori, Mayumi; Koyama, Takatoshi; Kawaguchi, Takeharu; Nakaseko, Chiaki; Fujiwara, Shigeyoshi; Miura, Osamu

2011-05-01

We performed a retrospective analysis of patients with adult-onset chronic active Epstein-Barr virus infection (CAEBV). First, we analyzed five patients (aged 28-72) diagnosed at our hospitals with EBV-infected clonally proliferating T cells. Four patients were administered cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) chemotherapy, but no remarkable decrease of viral load was observed in three of the patients. The other patient died 19 days after initiation of CHOP treatment due to disease progression. Addition of high-dose cytarabine to the regimens of two of the patients was discontinued shortly after administration, due to the development of grade 4 pericardial effusion. Together, these regimens may be insufficient for treating adult-onset CAEBV. We next reviewed 23 adult-onset CAEBV patients, adding 18 previously reported patients to the five patients described in the present study. T cells were frequently infected (87%), whereas NK- and T-cell types are known to be almost equally prevalent in childhood-onset cases. The time duration from the onset of disease to initiation of treatment averaged 20 months. Reports showed that 12 patients died; seven patients died at an average of 8 months after initiation of treatment. Patients' disease courses seemed to be rapidly progressive and more aggressive than those of childhood-onset cases. More cases must be studied to clarify clinical features and establish an optimal treatment strategy.

In vitro activity of AT-4140 against clinical bacterial isolates.

PubMed

Kojima, T; Inoue, M; Mitsuhashi, S

1989-11-01

The activity of AT-4140, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with those of existing analogs. AT-4140 had a broad spectrum and a potent activity against gram-positive and -negative bacteria, including Legionella spp. and Bacteroides fragilis. The activity of AT-4140 against gram-positive and -negative cocci, including Acinetobacter calcoaceticus, was higher than those of ciprofloxacin, ofloxacin, and norfloxacin. Its activity against gram-negative rods was generally comparable to that of ciprofloxacin. Some isolates of methicillin-resistant Staphylococcus aureus (MIC of methicillin, greater than or equal to 12.5 micrograms/ml) were resistant to existing quinolones, but many of them were still susceptible to AT-4140 at concentrations below 0.39 micrograms/ml. The MICs of AT-4140, ciprofloxacin, ofloxacin, and norfloxacin for 90% of clinical isolates of methicillin-resistant S. aureus were 0.2, 12.5, 6.25, and 100 micrograms/ml, respectively. AT-4140 was bactericidal for each of 20 clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa at concentrations near the MICs. AT-4140 inhibited the supercoiling activity of DNA gyrase from E. coli.

The Remarkable History Of Hypnosis In New Orleans (Société Du Magnétisme De La Nouvelle Orléans): A Tribute to Dabney Ewin.

PubMed

Tramontana, Joseph

2016-01-01

Dr. Dabney Ewin was a major factor in the revitalization of the New Orleans Society for Clinical Hypnosis (NOSCH) after it had been dormant for many years. This article briefly presents the fascinating history of the society as a tribute to Dr. Ewin, a remarkable physician.

Comparative hazard analysis of processes leading to remarkable flash floods (France, 1930-1999)

NASA Astrophysics Data System (ADS)

Boudou, M.; Lang, M.; Vinet, F.; Cœur, D.

2016-10-01

Flash flood events are responsible for large economic losses and lead to fatalities every year in France. This is especially the case in the Mediterranean and oversea territories/departments of France, characterized by extreme hydro-climatological features and with a large part of the population exposed to flood risks. The recurrence of remarkable flash flood events, associated with high hazard intensity, significant damage and socio-political consequences, therefore raises several issues for authorities and risk management policies. This study aims to improve our understanding of the hazard analysis process in the case of four remarkable flood events: March 1930, October 1940, January 1980 and November 1999. Firstly, we present the methodology used to define the remarkability score of a flood event. Then, to identify the factors leading to a remarkable flood event, we explore the main parameters of the hazard analysis process, such as the meteorological triggering conditions, the return period of the rainfall and peak discharge, as well as some additional factors (initial catchment state, flood chronology, cascade effects, etc.). The results contribute to understanding the complexity of the processes leading to flood hazard and highlight the importance for risk managers of taking additional factors into account.

Iranian Clinical Nurses’ Activities for Self-Directed Learning: A Qualitative Study

PubMed Central

Ghiyasvandian, Shahrzad; Malekian, Morteza; Cheraghi, Mohammad Ali

2016-01-01

Background: Clinical nurses need lifelong learning skills for responding to the rapid changes of clinical settings. One of the best strategies for lifelong learning is self-directed learning. The aim of this study was to explore Iranian clinical nurses’ activities for self-directed learning. Methods: In this qualitative study, 23 semi-structured personal interviews were conducted with nineteen clinical nurses working in all four hospitals affiliated to Isfahan Social Security Organization, Isfahan, Iran. Study data were analyzed by using the content analysis approach. The study was conducted from June 2013 to October 2014. Findings: Study participants’ activities for self-directed learning fell into two main categories of striving for knowledge acquisition and striving for skill development. The main theme of the study was ‘Revising personal performance based on intellectual-experiential activities’. Conclusions: Study findings suggest that Iranian clinical nurses continually revise their personal performance by performing self-directed intellectual and experiential activities to acquire expertise. The process of acquiring expertise is a linear process which includes two key steps of knowledge acquisition and knowledge development. In order to acquire and advance their knowledge, nurses perform mental learning activities such as sensory perception, self-evaluation, and suspended judgment step-by-step. Moreover, they develop their skills through doing activities like apprenticeship, masterly performance, and self-regulation. The absolute prerequisite to expertise acquisition is that a nurse needs to follow these two steps in a sequential manner. PMID:26652072

Epileptic activity in Alzheimer’s disease: causes and clinical relevance

PubMed Central

Vossel, Keith A; Tartaglia, Maria C; Nygaard, Haakon B; Zeman, Adam Z; Miller, Bruce L

2018-01-01

Epileptic activity is frequently associated with Alzheimer’s disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer’s disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer’s disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment. Some evidence indicates that subclinical epileptiform activity in patients with Alzheimer’s disease, detected by extended neurophysiological monitoring, can also lead to accelerated cognitive decline. Treatment of clinical seizures in patients with Alzheimer’s disease with select antiepileptic drugs (AEDs), in low doses, is usually well tolerated and efficacious. Moreover, studies in mouse models of Alzheimer’s disease suggest that certain classes of AEDs that reduce network hyperexcitability have disease-modifying properties. These AEDs target mechanisms of epileptogenesis involving amyloid β and tau. Clinical trials targeting network hyperexcitability in patients with Alzheimer’s disease will identify whether AEDs or related strategies could improve their cognitive symptoms or slow decline. PMID:28327340

Engaging clinical nurses in quality and performance improvement activities.

PubMed

Albanese, Madeline P; Evans, Dietra A; Schantz, Cathy A; Bowen, Margaret; Disbot, Maureen; Moffa, Joseph S; Piesieski, Patricia; Polomano, Rosemary C

2010-01-01

Nursing performance measures are an integral part of quality initiatives in acute care; however, organizations face numerous challenges in developing infrastructures to support quality improvement processes and timely dissemination of outcomes data. At the Hospital of the University of Pennsylvania, a Magnet-designated organization, extensive work has been conducted to incorporate nursing-related outcomes in the organization's quality plan and to integrate roles for clinical nurses into the Department of Nursing and organization's core performance-based programs. Content and strategies that promote active involvement of nurses and prepare them to be competent and confident stakeholders in quality initiatives are presented. Engaging clinical nurses in the work of quality and performance improvement is essential to achieving excellence in clinical care. It is important to have structures and processes in place to bring meaningful data to the bedside; however, it is equally important to incorporate outcomes into practice. When nurses are educated about performance and quality measures, are engaged in identifying outcomes and collecting meaningful data, are active participants in disseminating quality reports, and are able to recognize the value of these activities, data become one with practice.

The content of the work of clinical nurse specialists described by use of daily activity diaries.

PubMed

Oddsdóttir, Elín Jakobína; Sveinsdóttir, Herdís

2011-05-01

Evaluate the usefulness of the role of clinical nurse specialists and the content of their work by mapping their activities. The clinical work of advanced practice nursing differs in different countries, and a clear picture is lacking on what exactly advanced practice nurses do. Prospective exploratory study. The setting of the study was the largest hospital in Iceland where over half of the country's active nursing workforce are employed, including the only clinical nurse specialists. Of 19 clinical nurse specialists working at the hospital, 15 participated. Data were collected over seven days with a structured activity diary that lists 65 activities, classified into six roles and three domains. In 17 instances, the 'role activities' and 'domain activities' overlap and form 17 categories of practice. The clinical nurse specialists coded their activities at 15-minutes interval and could code up to four activities simultaneously. Daily, the clinical nurse specialists evaluated their clinical nurse specialist background. The roles that occupied the greatest proportion of the clinical nurse specialists' time were education, expert practice and 'other' activities, while the smallest proportions were in counselling, research and practice development. The domain they worked in most was the institutional domain, followed by the client/family domain and the clinical outcome management domain. All of the clinical nurse specialists reported working on two activities simultaneously, 11 of them on three activities and six on four activities. They self-assessed their background as clinical nurse specialists as being very useful. The activity diary is a useful tool for assessing the content of practice. Clinical nurse specialists spend too much time on activities related to the institution. Nurse managers are advised to provide clinical nurse specialists with ample time to develop the direct practice role in the client/family domain. The development of advanced nursing practice

Carbon nanocages: a new support material for Pt catalyst with remarkably high durability.

PubMed

Wang, Xiao Xia; Tan, Zhe Hua; Zeng, Min; Wang, Jian Nong

2014-03-24

Low durability is the major challenge hindering the large-scale implementation of proton exchange membrane fuel cell (PEMFC) technology, and corrosion of carbon support materials of current catalysts is the main cause. Here, we describe the finding of remarkably high durability with the use of a novel support material. This material is based on hollow carbon nanocages developed with a high degree of graphitization and concurrent nitrogen doping for oxidation resistance enhancement, uniform deposition of fine Pt particles, and strong Pt-support interaction. Accelerated degradation testing shows that such designed catalyst possesses a superior electrochemical activity and long-term stability for both hydrogen oxidation and oxygen reduction relative to industry benchmarks of current catalysts. Further testing under conditions of practical fuel cell operation reveals almost no degradation over long-term cycling. Such a catalyst of high activity, particularly, high durability, opens the door for the next-generation PEMFC for "real world" application.

Carbon nanocages: A new support material for Pt catalyst with remarkably high durability

PubMed Central

Wang, Xiao Xia; Tan, Zhe Hua; Zeng, Min; Wang, Jian Nong

2014-01-01

Low durability is the major challenge hindering the large-scale implementation of proton exchange membrane fuel cell (PEMFC) technology, and corrosion of carbon support materials of current catalysts is the main cause. Here, we describe the finding of remarkably high durability with the use of a novel support material. This material is based on hollow carbon nanocages developed with a high degree of graphitization and concurrent nitrogen doping for oxidation resistance enhancement, uniform deposition of fine Pt particles, and strong Pt-support interaction. Accelerated degradation testing shows that such designed catalyst possesses a superior electrochemical activity and long-term stability for both hydrogen oxidation and oxygen reduction relative to industry benchmarks of current catalysts. Further testing under conditions of practical fuel cell operation reveals almost no degradation over long-term cycling. Such a catalyst of high activity, particularly, high durability, opens the door for the next-generation PEMFC for “real world” application. PMID:24658614

[Clinical research activity of the French cancer cooperative network: Overview and perspectives].

PubMed

Dubois, Claire; Morin, Franck; Moro-Sibilot, Denis; Langlais, Alexandra; Seitz, Jean-François; Girault, Cécile; Salles, Gilles; Haioun, Corinne; Deschaseaux, Pascal; Casassus, Philippe; Mathiot, Claire; Pujade-Lauraine, Éric; Votan, Bénédicte; Louvet, Christophe; Delpeut, Christine; Bardet, Étienne; Vintonenko, Nadejda; Hoang Xuan, Khê; Vo, Maryline; Michon, Jean; Milleron, Bernard

The French Cancer Plan 2014-2019 stresses the importance of strengthening collaboration between all stakeholders involved in the fight against cancer, including cancer cooperative groups and intergroups. This survey aimed to describe the basics characteristics and clinical research activity among the Cancer Cooperative Groups (Groupes coopérateurs en oncologie). The second objective was to identify facilitators and barriers to their research activity. A questionnaire was sent to all the clinicians involved in 2014 as investigators in a clinical trial sponsored by one of the ten members of the Cancer Cooperative Groups network. The questions were related to their profile, research activity and the infrastructure existing within their healthcare center to support clinical research and related compliance activities. In total, 366 investigators responded to our survey. The academic clinical trials sponsored by the Cancer Cooperative Groups represented an important part of the research activity of the investigators in France in 2014. These academic groups contributed to the opening of many research sites throughout all regions in France. Factors associated with a higher participation of investigators (more than 10 patients enrolled in a trial over a year) include the existing support of healthcare professionals (more than 2 clinical research associate (CRA) OR=11.16 [3.82-32.6] compared to none) and the practice of their research activity in a University Hospital Center (CHU) rather than a Hospital Center (CH) (OR=2.15 [1.20-3.83]). This study highlighted factors that can strengthen investigator clinical research activities and subsequently improve patient access to evidence-based new cancer therapies in France. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Remarks by the President at Princeton University Commencement Address.

ERIC Educational Resources Information Center

Clinton, William

This speech by President William Clinton addresses the 1996 graduating class of Princeton University on the occasion of Princeton's 250th anniversary. After his opening remarks, the President touches on the importance of the graduating seniors' education as well as the importance of education in general to the nation's future. He compares the…

[A report on clinical PET activities in Germany].

PubMed

Tashiro, M; Kubota, K; Itoh, M; Sasaki, H; Moser, E

1999-09-01

Clinical diagnostic procedure using positron emission tomography (PET) requires high costs. To promote clinical use of PET, sociomedical evaluation is necessary. In this paper, sociomedical situations concerning clinical use of PET in Germany is reported. Some comparisons are made between Japan and this country putting emphases on several points such as 1) number of cyclotron and PET facilities, 2) social restriction to transportation of radioisotopes, 3) activities of satellite PET facilities, and 4) clinical indications for PET studies. Number of cyclotron was larger in Japan (29) than in Germany (17), but number of PET facilities was larger in Germany (47) than in Japan (29). The reason seems that in Germany transportation and buying of radioisotopes is less restricted. Hence, more than half of PET facilities in Germany are "satellite facilities" which do not have their own cyclotrons. Radioisotope distribution seems to serve as a backbone of "satellite concept." Additionally in Germany, list of clinical indications for PET study is almost completed and now is widely in applied to most cases. To promote clinical use of PET in Japan, the German system might serve as an important socioeconomic model in Europe instead of the United States.

Patient centered integrated clinical resource management.

PubMed

Hofdijk, Jacob

2011-01-01

The impact of funding systems on the IT systems of providers has been enormous and have prevented the implementation of designs to focused on the health issue of patients. The paradigm shift the Dutch Ministry of Health has taken in funding health care has a remarkable impact on the orientation of IT systems design. Since 2007 the next step is taken: the application of the funding concept on chronic diseases using clinical standards as the norm. The focus on prevention involves the patient as an active partner in the care plan. The impact of the new dimension in funding has initiated a process directed to the development of systems to support collaborative working and an active involvement of the patient and its informal carers. This national approach will be presented to assess its international potential, as all countries face the long term care crisis lacking resources to meet the health needs of the population.

The remarkable Dr Robertson.

PubMed

Hammarton, Tansy C

2017-10-01

Muriel Robertson (1883-1973) was a pioneering protozoologist who made a staggering number of important contributions to the fields of parasitology, bacteriology and immunology during her career, which spanned nearly 60 years. These contributions were all the more remarkable given the scientific and social times in which she worked. While Muriel is perhaps best known for her work on the life cycle and transmission of the African trypanosome, Trypanosoma brucei, which she carried out in Uganda at the height of a major Sleeping Sickness epidemic, her work on the Clostridia during the First and Second World Wars made significant contributions to the understanding of anaerobes and to the development of anti-toxoid vaccines, and her work on the immunology of Trichomonas foetus infections in cattle, carried out in collaboration with the veterinarian W. R. Kerr, resulted in changes in farming practices that very quickly eradicated trichomoniasis from cattle herds in Northern Ireland. The significance of her work was recognized with the award of Fellow of the Royal Society in 1947 and an Honorary Doctorate of Law from the University of Glasgow, where she had earlier studied, in 1948.

CLINICAL SURFACES - Activity-Based Computing for Distributed Multi-Display Environments in Hospitals

NASA Astrophysics Data System (ADS)

Bardram, Jakob E.; Bunde-Pedersen, Jonathan; Doryab, Afsaneh; Sørensen, Steffen

A multi-display environment (MDE) is made up of co-located and networked personal and public devices that form an integrated workspace enabling co-located group work. Traditionally, MDEs have, however, mainly been designed to support a single “smart room”, and have had little sense of the tasks and activities that the MDE is being used for. This paper presents a novel approach to support activity-based computing in distributed MDEs, where displays are physically distributed across a large building. CLINICAL SURFACES was designed for clinical work in hospitals, and enables context-sensitive retrieval and browsing of patient data on public displays. We present the design and implementation of CLINICAL SURFACES, and report from an evaluation of the system at a large hospital. The evaluation shows that using distributed public displays to support activity-based computing inside a hospital is very useful for clinical work, and that the apparent contradiction between maintaining privacy of medical data in a public display environment can be mitigated by the use of CLINICAL SURFACES.

A great pioneer of clinical science remembered: introduction to the special issue in honor of Paul E. Meehl.

PubMed

Lilienfeld, Scott O; Waller, Niels G

2005-10-01

In this special issue, the seminal contributions to clinical psychology of Paul E. Meehl, who passed away in 2003, are commemorated. The nine articles comprising this special issue chronicle Meehl's remarkable intellectual biography and examine his influence on diverse domains of psychology, including the clinical versus actuarial prediction debate, the cognitive activity of the clinician, personality assessment and trait theory, the etiology of schizophrenia, the shortcomings of statistical significance testing, and the use of metascientific methods to evaluate competing models of human nature. These articles illustrate not only Meehl's legendary brilliance but also his pivotal role in forcing clinical psychologists to think more clearly and incisively about their subject matter. 2005 Wiley Periodicals, Inc.

Nitrogen-Doped Porous Carbons from Ionic Liquids@MOF: Remarkable Adsorbents for Both Aqueous and Nonaqueous Media.

PubMed

Ahmed, Imteaz; Panja, Tandra; Khan, Nazmul Abedin; Sarker, Mithun; Yu, Jong-Sung; Jhung, Sung Hwa

2017-03-22

Porous carbons were prepared from a metal-organic framework (MOF, named ZIF-8), with or without modification, via high-temperature pyrolysis. Porous carbons with high nitrogen content were obtained from the calcination of MOF after introducing an ionic liquid (IL) (IL@MOF) via the ship-in-bottle method. The MOF-derived carbons (MDCs) and IL@MOF-derived carbons (IMDCs) were characterized using various techniques and used for liquid-phase adsorptions in both water and hydrocarbon to understand the possible applications in purification of water and fuel, respectively. Adsorptive performances for the removal of organic contaminants, atrazine (ATZ), diuron, and diclofenac, were remarkably enhanced with the modification/conversion of MOFs to MDC and IMDC. For example, in the case of ATZ adsorption, the maximum adsorption capacity of IMDC (Q 0 = 208 m 2 /g) was much higher than that of activated carbon (AC, Q 0 = 60 m 2 /g) and MDC (Q 0 = 168 m 2 /g) and was found to be the highest among the reported results so far. The results of adsorptive denitrogenation and desulfurization of fuel were similar to that of water purification. The IMDCs are very useful in the adsorptions since these new carbons showed remarkable performances in both the aqueous and nonaqueous phases. These results are very meaningful because hydrophobic and hydrophilic adsorbents are usually required for the adsorptions in the water and fuel phases, respectively. Moreover, a plausible mechanism, H-bonding, was also suggested to explain the remarkable performance of the IMDCs in the adsorptions. Therefore, the IMDCs derived from IL@MOF might have various applications, especially in adsorptions, based on high porosity, mesoporosity, doped nitrogen, and functional groups.

Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network.

PubMed

Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi

2016-07-11

Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to

A Study of the Use of Family Practice Physicians in Troop Health Clinics of the MEDDAC (Medical Department Activity), Fort Belvoir, Virginia.

DTIC Science & Technology

1981-04-01

Department. The questionnaire, devised by Major Merle Preble, MD and Colonel Llewellyn Legters , MD, gathered demographic data as well as infor- mation on...that it must surely have 7 evolved from the questionnaire devised by Preble and Legters , for the similarities are too remarkable to be merely a...M.D., and Llewellyn Legters , M.D. "Patient Satisfaction Studies in Ambulatory Patient Care Areas: Comparison of General Medical Clinic to Acute Minor

Age at first sexual activity: Clinical and cognitive associations.

PubMed

Harries, Michael D; Paglia, Helen A; Redden, Sarah A; Grant, Jon E-Mail

2018-05-01

Engagement in sexual activity is common among adolescents and can be considered part of adolescent development, but it carries potential life-changing consequences. This study examined if clinical and cognitive differences existed between adolescents who engaged in voluntary sexual behavior before age 15, between ages 15 to 18, and after age 18. All participants were part of a larger study examining impulsive behavior in young adults. Participants were assessed on measures including demographics, comorbid psychiatric disorders, and clinical scales and cognitive tasks assessing impulsivity, obsessive-compulsive traits, emotion regulation, depression, anxiety, and quality of life. Those who engaged in voluntary sexual activity before age 15 were more likely to have increased depression and anxiety symptoms, to score higher on the Yale Brown Obsessive-Compulsive Scale for Pathologic Gambling, and to make poorer decisions on the Cambridge Gambling Task. The results of this study suggest that the decision to engage in sexual activity at a young age is not an act of thinking before acting or impatience, but rather a decision to engage in sensation-seeking behavior. This finding carries implications for interventions targeting healthy sexual activity in adolescents.

Dr Albert L. Rhoton Jr's Time at the Mayo Clinic: The Beginnings of a Remarkable Career.

PubMed

Rayan, Tarek; Carlson, Matthew L; Piepgras, David G; Link, Michael J; Van Gompel, Jamie J

2017-08-09

Dr Albert L. Rhoton Jr became the focal point of neurosurgery's evolution in understanding the intricate and complex microanatomy of the human brain over the last 4 decades. His pioneering work on cadaveric specimens proved to be a pivotal endeavor in the pursuit to better understand the complex microsurgical anatomy of cranial surgery. This paper details his early career at the Mayo Clinic in Rochester, Minnesota. A comprehensive review and synthesis of data acquired from the institutional historical archives including the Annual Reports to the Executive Committee, the Reports to the Board of Directors, the MAYOVOX Newsletter, the illustration archives of the Mayo Clinic Division of Creative Media, staff biographies, curriculum vitae, personal interviews, as well as full-text journal articles, and book publications was performed. Dr Rhoton was engaged in a busy clinical practice as a young staff at the Mayo Clinic. Records show he focused on tackling complex intracranial pathologies along with numerous basic research and neuroanatomy projects that became a major part of his life's work and passion. He was a great teacher and friend to countless individuals and his work will continue to impact and improve the care provided to neurosurgery patients for generations to come. Copyright © 2017 by the Congress of Neurological Surgeons.

Running Memory for Clinical Handoffs: A Look at Active and Passive Processing.

PubMed

Anderson-Montoya, Brittany L; Scerbo, Mark W; Ramirez, Dana E; Hubbard, Thomas W

2017-05-01

The goal of the present study was to examine the effects of domain-relevant expertise on running memory and the ability to process handoffs of information. In addition, the role of active or passive processing was examined. Currently, there is little research that addresses how individuals with different levels of expertise process information in running memory when the information is needed to perform a real-world task. Three groups of participants differing in their level of clinical expertise (novice, intermediate, and expert) performed an abstract running memory span task and two tasks resembling real-world activities, a clinical handoff task and an air traffic control (ATC) handoff task. For all tasks, list length and the amount of information to be recalled were manipulated. Regarding processing strategy, all participants used passive processing for the running memory span and ATC tasks. The novices also used passive processing for the clinical task. The experts, however, appeared to use more active processing, and the intermediates fell in between. Overall, the results indicated that individuals with clinical expertise and a developed mental model rely more on active processing of incoming information for the clinical task while individuals with little or no knowledge rely on passive processing. The results have implications about how training should be developed to aid less experienced personnel identify what information should be included in a handoff and what should not.

NHS Trusts' clinical research activity and overall CQC performance - Is there a correlation?

PubMed

Jonker, L; Fisher, S J

2015-11-01

Since the late 2000's, the creation of the National Institute for Health Research (NIHR) has transformed clinical research activity in the United Kingdom. This study sought to establish if there is a link between clinical research activity and overall NHS Trust performance. Retrospective cohort study. Data for NHS Trust performance were obtained from public databases, namely the Care Quality Commission (CQC) 2013 risk rating for overall performance, and 2012-13 NIHR records for clinical research activity. Applying Spearman's rank analysis, none of the Trust categories showed a correlation with CQC risk rating: small hospitals, r = -0.062 (P = 0.76; n = 27); medium, r = -0.224 (P = 0.13; n = 47); large, r = -0.008 (P = 0.96; n = 57); academic, r = -0.18 (P = 0.41; n = 24). Similar results were observed when CQC risk rating was compared with the number of different clinical research studies conducted per Trust. The degree of NIHR National Portfolio clinical research activity is not significantly related to CQC risk rating, used as an indicator of overall NHS Trust performance. Other studies have previously shown that increased research activity correlates with improved mortality rates, one component of CQC risk rating scores. Alternative tools may have to be explored to evaluate the impact of clinical research on NHS Trusts and its patients. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Iodoform gauze removes necrotic tissue from pressure ulcer wounds by fibrinolytic activity.

PubMed

Mizokami, Fumihiro; Murasawa, Yusuke; Furuta, Katsunori; Isogai, Zenzo

2012-01-01

Iodoform gauze is used in clinical practice for treatment of infected wounds. However, effectiveness and action mechanism of iodoform gauze for removal of necrotic tissue are unknown. We therefore employed case control and biochemical studies in order to clarify the pharmacological activity of iodoform gauze. A clinical study demonstrated that treatment with iodoform gauze removed necrotic tissue more effectively than treatment with conventional ointments. More than 60% of iodoform gauze-treated wounds were completely debrided within 2 weeks. Consistent with the clinical observation, biochemical analyses revealed clear differences in wound fluid proteins after treatment with iodoform gauze or conventional gauze. The amount of macroaggregates of type I collagen from wounds were remarkably decreased in iodoform gauze. Moreover, iodoform gauze and iodoform itself released non-aggregative type I collagen from necrotic debris in vitro. Taken together, we conclude that iodoform gauze efficiently removes necrotic tissue by its lytic activity for collagen fibers.

Revisioning the Clinical Relationship: Heinz Kohut and the Viewpoint of Self-Psychology.

ERIC Educational Resources Information Center

Masek, Robert J.

Psychoanalysis is undergoing rapid and remarkable changes in its basic metapsychology, theoretical reflections, and concrete, clinical interventions. Through self-psychology, Heinz Kohut's alternative views on the clinical relationship have contributed to this restructuring of psychoanalysis. Traditionally, mainstream psychoanalysis has viewed the…

In Vitro Activities of Panduratin A against Clinical Staphylococcus Strains▿

PubMed Central

Rukayadi, Yaya; Lee, Kwanghyung; Han, Sunghwa; Yong, Dongeun; Hwang, Jae-Kwan

2009-01-01

In vitro antistaphylococcal activities of panduratin A, a natural chalcone compound isolated from Kaempferia pandurata Roxb, were compared to those of commonly used antimicrobials against clinical staphylococcal isolates. Panduratin A had a MIC at which 90% of bacteria were inhibited of 1 μg/ml for clinical staphylococcal isolates and generally was more potent than commonly used antimicrobials. PMID:19651906

[Chronic active hepatitis: clinical, biochemical, and histopathologic correlation].

PubMed

Subauste, M C

1989-01-01

A retrospective study over 26 female patients with chronic active hepatitis was made. The mean age was 39 years old, the mean length of illness of 8 months; 5 patients had positive markers for hepatitis B. Patients were selected with the grade of histological activity: 8 patients had a mild form from disease (2A) and 16 with a severe one (2B). The predominant group was 2B. Severe inflammatory infiltration was the hallmark and multiobulillar necrosis, bridging, eosinophils and hiperplasia of kuppfer cells were found only in this group. Clinical features range from hepatic manifestations to systemic ones. Chronic active hepatitis may present with cholestasis, but the latter is not always related with the grade of activity. Group 2B had elevated aminotransferases and a low concentration for protrobine.

The truly remarkable universality of half a standard deviation: confirmation through another look.

PubMed

Norman, Geoffrey R; Sloan, Jeff A; Wyrwich, Kathleen W

2004-10-01

In this issue of Expert Review of Pharmacoeconomics and Outcomes Research, Farivar, Liu, and Hays present their findings in 'Another look at the half standard deviation estimate of the minimally important difference in health-related quality of life scores (hereafter referred to as 'Another look') . These researchers have re-examined the May 2003 Medical Care article 'Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation' (hereafter referred to as 'Remarkable') in the hope of supporting their hypothesis that the minimally important difference in health-related quality of life measures is undoubtedly closer to 0.3 standard deviations than 0.5. Nonetheless, despite their extensive wranglings with the exclusion of many articles that we included in our review; the inclusion of articles that we did not include in our review; and the recalculation of effect sizes using the absolute value of the mean differences, in our opinion, the results of the 'Another look' article confirm the same findings in the 'Remarkable' paper.

Genomic biomarkers and clinical outcomes of physical activity.

PubMed

Izzotti, Alberto

2011-07-01

Clinical and experimental studies in humans provide evidence that moderate physical activity significantly decreases artery oxidative damage to nuclear DNA, DNA-adducts related to age and dyslipedemia, and mitochondrial DNA damage. Maintenance of adequate mitochondrial function is crucial for preventing lipid accumulation and peroxidation occurring in atherosclerosis. Studies performed on human muscle biopsies analyzing gene expression in living humans reveal that physically active subjects improve the expression of genes involved in mitochondrial function and of related microRNAs. The attenuation of oxidative damage to nuclear and mitochondrial DNA by physical activity resulted in beneficial effects due to polymorphisms of glutathione S-transferases genes. Subjects bearing null GSTM1/T1 polymorphisms have poor life expectancy in the case of being sedentary, which was increased 2.6-fold in case they performed physical activity. These findings indicate that the preventive effect of physical activity undergoes interindividual variation affected by genetic polymorphisms. © 2011 New York Academy of Sciences.

Studies on mimicry of naturally occurring annonaceous acetogenins: non-THF analogues leading to remarkable selective cytotoxicity against human tumor cells.

PubMed

Zeng, Bu-Bing; Wu, Yikang; Jiang, Sheng; Yu, Qian; Yao, Zhu-Jun; Liu, Zhong-Hai; Li, Hong-Yan; Li, Yan; Chen, Xiao-Guang; Wu, Yu-Lin

2003-01-03

A class of structurally simplified analogues of the naturally occurring annonaceous acetogenins were developed, amongst which some non-THF analogues showed remarkable cytotoxicities against tumor cell lines, as well as good selectivity between human tumor cells and normal cells. The synthetic routes were significantly shortened because of the removal of the chiral centers bearing the THF rings on the natural templates. This simplification also provides access to the parallel synthesis of these mimics by a combinatorial strategy. The remaining stereogenic centers at the positions alpha to the ethereal links were introduced by the Chiron approach from the easily accessible chiral building blocks 6a and/or 6b, made in turn from L-ascorbic acid or D-mannitol, while the one in the butenolide segment was taken from L-lactate. All four diastereomeric non-THF analogues 2a-2d showed remarkable activity against the HCT-8 cell line, and better differentiation was found when testing against the HT-29 cell line. It was also discovered that both the butenolide and ethylene glycol subunits play essential roles in the cytotoxicities against tumor cell lines, while the 10-substituted hydroxy group and the absolute configuration of methyl group at the butenolide moiety are less important for their activity.

Rheumatoid arthritis disease activity measures: American College of Rheumatology recommendations for use in clinical practice.

PubMed

Anderson, Jaclyn; Caplan, Liron; Yazdany, Jinoos; Robbins, Mark L; Neogi, Tuhina; Michaud, Kaleb; Saag, Kenneth G; O'Dell, James R; Kazi, Salahuddin

2012-05-01

Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice. The Rheumatoid Arthritis Clinical Disease Activity Measures Working Group conducted a systematic review of the literature to identify RA disease activity measures. Using exclusion criteria, input from an Expert Advisory Panel (EAP), and psychometric analysis, a list of potential measures was created. A survey was administered to rheumatologists soliciting input. The WG used these survey results in conjunction with the psychometric analyses to derive final recommendations. Systematic review of the literature resulted in identification of 63 RA disease activity measures. Application of exclusion criteria and ratings by the EAP narrowed the list to 14 measures for further evaluation. Practicing rheumatologists rated 9 of these 14 measures as most useful and feasible. From these 9 measures, the WG selected 6 with the best psychometric properties for inclusion in the final set of ACR-recommended RA disease activity measures. We recommend the Clinical Disease Activity Index, Disease Activity Score with 28-joint counts (erythrocyte sedimentation rate or C-reactive protein), Patient Activity Scale (PAS), PAS-II, Routine Assessment of Patient Index Data with 3 measures, and Simplified Disease Activity Index because they are accurate reflections of disease activity; are sensitive to change; discriminate well between low, moderate, and high disease activity states; have remission criteria; and are feasible to perform in clinical settings. Copyright © 2012 by the American College of Rheumatology.

Practical remarks on the heart rate and saturation measurement methodology

NASA Astrophysics Data System (ADS)

Kowal, M.; Kubal, S.; Piotrowski, P.; Staniec, K.

2017-05-01

A surface reflection-based method for measuring heart rate and saturation has been introduced as one having a significant advantage over legacy methods in that it lends itself for use in special applications such as those where a person’s mobility is of prime importance (e.g. during a miner’s work) and excluding the use of traditional clips. Then, a complete ATmega1281-based microcontroller platform has been described for performing computational tasks of signal processing and wireless transmission. In the next section remarks have been provided regarding the basic signal processing rules beginning with raw voltage samples of converted optical signals, their acquisition, storage and smoothing. This chapter ends with practical remarks demonstrating an exponential dependence between the minimum measurable heart rate and the readout resolution at different sampling frequencies for different cases of averaging depth (in bits). The following section is devoted strictly to the heart rate and hemoglobin oxygenation (saturation) measurement with the use of the presented platform, referenced to measurements obtained with a stationary certified pulsoxymeter.

Clinical development of platinum complexes in cancer therapy: an historical perspective and an update.

PubMed

Lebwohl, D; Canetta, R

1998-09-01

The vast amount of basic research on platinum coordination complexes has produced, over the past 25 years, several thousand new molecules for preclinical screening and 28 compounds which have entered clinical development. The goals of these research activities have been to identify compounds with superior efficacy, reduced toxicity, lack of cross-resistance or improved pharmacological characteristics as compared with the parent compound, cisplatin. After the remarkable therapeutic effects of cisplatin had been established, only a few other platinum compounds succeeded in reaching general availability. Whereas carboplatin is an analogue with an improved therapeutic index (mostly driven by reduced organ toxicity) over that of cisplatin, new compounds clearly more active than or non-cross-resistant with cisplatin have not yet been identified. The platinum analogues that remain under investigation are focusing on expanding the utilisation of platinum therapy to tumour types not usually treated with, or responsive to, cisplatin or carboplatin. In addition, novel routes of administration constitute another avenue of research. The clinical development of platinum coordination complexes, with emphasis on those compounds still under active development, is reviewed.

Clinical and financial burden of active lupus in Greece: a nationwide study.

PubMed

Bertsias, G; Karampli, E; Sidiropoulos, P; Gergianaki, I; Drosos, A; Sakkas, L; Garyfallos, A; Tzioufas, A; Vassilopoulos, D; Tsalapaki, C; Sfikakis, P; Panopoulos, S; Athanasakis, K; Perna, A; Psomali, D; Kyriopoulos, J; Boumpas, D

2016-10-01

Analyses of the medical and economic burden of chronic disorders such as systemic lupus erythematosus (SLE) are valuable for clinical and health policy decisions. We performed a chart-based review of 215 adult SLE patients with active autoantibody-positive disease at the predefined ratio of 30% severe (involvement of major organs requiring treatment) and 70% non-severe, followed at seven hospital centres in Greece. We reviewed 318 patients consecutively registered over three months (sub-study). Disease activity, organ damage, flares and healthcare resource utilization were recorded. Costs were assessed from the third-party payer perspective. Severe SLE patients had chronic active disease more frequently (22.4% vs 4.7%), higher average SLE disease activity index (SLEDAI) (10.5 vs 6.1) and systemic lupus international collaborating clinics (SLICC) damage index (1.1 vs 0.6) than non-severe patients. The mean annual direct medical cost was €3741 for severe vs €1225 for non-severe patients. Severe flares, active renal disease and organ damage were independent cost predictors. In the sub-study, 19% of unselected patients were classified as severe SLE, and 30% of them had chronic active disease. In conclusion, this is the first study to demonstrate the significant clinical and financial burden of Greek SLE patients with active major organ disease. Among them, 30% display chronic activity, in spite of standard care, which represents a significant unmet medical need. © The Author(s) 2016.

Nationwide Genomic Study in Denmark Reveals Remarkable Population Homogeneity

PubMed Central

Athanasiadis, Georgios; Cheng, Jade Y.; Vilhjálmsson, Bjarni J.; Jørgensen, Frank G.; Als, Thomas D.; Le Hellard, Stephanie; Espeseth, Thomas; Sullivan, Patrick F.; Hultman, Christina M.; Kjærgaard, Peter C.; Schierup, Mikkel H.; Mailund, Thomas

2016-01-01

Denmark has played a substantial role in the history of Northern Europe. Through a nationwide scientific outreach initiative, we collected genetic and anthropometrical data from ∼800 high school students and used them to elucidate the genetic makeup of the Danish population, as well as to assess polygenic predictions of phenotypic traits in adolescents. We observed remarkable homogeneity across different geographic regions, although we could still detect weak signals of genetic structure reflecting the history of the country. Denmark presented genomic affinity with primarily neighboring countries with overall resemblance of decreasing weight from Britain, Sweden, Norway, Germany, and France. A Polish admixture signal was detected in Zealand and Funen, and our date estimates coincided with historical evidence of Wend settlements in the south of Denmark. We also observed considerably diverse demographic histories among Scandinavian countries, with Denmark having the smallest current effective population size compared to Norway and Sweden. Finally, we found that polygenic prediction of self-reported adolescent height in the population was remarkably accurate (R2 = 0.639 ± 0.015). The high homogeneity of the Danish population could render population structure a lesser concern for the upcoming large-scale gene-mapping studies in the country. PMID:27535931

Activities of Intellectual Disability Clinical Nurse Specialists in Ireland.

PubMed

Doody, Owen; Slevin, Eamonn; Taggart, Laurence

The aim of this study was to identify the contribution of Irish intellectual disability clinical nurse specialists (ID CNSs) to service delivery. A nonexperimental descriptive design was selected to survey ID CNSs presently working in Ireland. The questionnaire was developed based on focus group interviews, available literature, and expert panel views. Ethical approval and access were granted to all ID CNSs in Ireland. Thirty-two responded (33.68% response rate) from all work areas (voluntary organizations or health service executive) practicing within residential, community, or school services. Respondents were surveyed across a range of areas (demographic details and support to client, staff, family, organization, community, other agencies, and professional development). Findings identify that ID CNSs are active in all aspects of their roles as clinical specialist, educator, communicator, researcher, change agent, and leader, thus supporting person-centered care and improving service delivery. To meet changing healthcare demands, promote person-centered care, and improve service delivery, the CNS role in ID should be developed and supported. The findings merit a further study on ID CNS role activity, possible variables influencing role activity, and team members' views.

[Purine and pyrimidine nucleoside phosphorylases - remarkable enzymes still not fully understood].

PubMed

Bzowska, Agnieszka

2015-01-01

Purine and pyrimidine nucleoside phosphorylases catalyze the reversible phosphorolytic cleavage of the glycosidic bond of purine and pyrimidine nucleosides, and are key enzymes of the nucleoside salvage pathway. This metabolic route is the less costly alternative to the de novo synthesis of nucleosides and nucleotides, supplying cells with these important building blocks. Interest in nucleoside phosphorylases is not only due to their important role in metabolism of nucleosides and nucleotides, but also due to the potential medical use of the enzymes (all phosphorylases in activating prodrugs - nucleoside and nucleic base analogs, high-molecular mass purine nucleoside phosphorylases in gene therapy of some solid tumors) and their inhibitors (as selective immunosuppressive, anticancer and antiparasitic agents, and preventing inactivation of other nucleoside drugs). Phosphorylases are also convenient tools for efficient enzymatic synthesis of otherwise inaccessible nucleoside analogues. In this paper the contribution of Professor David Shugar and some of his colleagues and coworkers in studies of these remarkable enzymes carried out over nearly 40 years is discussed on the background of global research in this field.

Ligand Fishing: A Remarkable Strategy for Discovering Bioactive Compounds from Complex Mixture of Natural Products.

PubMed

Zhuo, Rongjie; Liu, Hao; Liu, Ningning; Wang, Yi

2016-11-11

Identification of active compounds from natural products is a critical and challenging task in drug discovery pipelines. Besides commonly used bio-guided screening approaches, affinity selection strategy coupled with liquid chromatography or mass spectrometry, known as ligand fishing, has been gaining increasing interest from researchers. In this review, we summarized this emerging strategy and categorized those methods as off-line or on-line mode according to their features. The separation principles of ligand fishing were introduced based on distinct analytical techniques, including biochromatography, capillary electrophoresis, ultrafiltration, equilibrium dialysis, microdialysis, and magnetic beads. The applications of ligand fishing approaches in the discovery of lead compounds were reviewed. Most of ligand fishing methods display specificity, high efficiency, and require less sample pretreatment, which makes them especially suitable for screening active compounds from complex mixtures of natural products. We also summarized the applications of ligand fishing in the modernization of Traditional Chinese Medicine (TCM), and propose some perspectives of this remarkable technique.

Sexual Activity as a Risk Factor for the Spontaneous Rupture of Cerebral Aneurysms.

PubMed

Blanke-Roeser, Constantin; Matschke, Jakob; Püschel, Klaus

2016-06-01

Subarachnoid hemorrhages from ruptured cerebral aneurysms have a high clinical relevance and often lead to death. Approximately 2% to 5% of the people worldwide, even of younger age, are said to have aneurysms at cerebral arteries. In many cases, they remain clinically unapparent for decades. However, there are numerous risk factors for the rupture of an aneurysm, including temporary raises of the blood pressure. Such changes of the blood pressure can be induced even by several everyday behaviors. For example, any sort of sexual activities may cause extensive raises of the blood pressure because of several physical and psychological factors. The term "sexual activity" covers sexual intercourse as well as masturbation. In this article, the remarkable case of a 24-year-old woman with a ruptured cerebral aneurysm in the context of masturbation is presented. It is discussed with respect to the possible pathophysiological effects of sexual activity on cerebral aneurysms.

Activities of Tannins--From In Vitro Studies to Clinical Trials.

PubMed

Sieniawska, Elwira

2015-11-01

Tannins are considered as valuable plant secondary metabolites providing many benefits for human health. In this review information was gathered about bioactivity in vitro and in vivo, as well as about conducted clinical trials. The literature research was based on ScienceDirect, Scopus, and Cochrane databases and presents a wide range of tested activities of tannins. The described clinical trials verify laboratory tests and show the effective health benefits taken from supplementation with tannins.

Analysis of immune activation and clinical events in acute infectious mononucleosis.

PubMed

Williams, Hilary; Macsween, Karen; McAulay, Karen; Higgins, Craig; Harrison, Nadine; Swerdlow, Anthony; Britton, Kate; Crawford, Dorothy

2004-07-01

The symptoms of infectious mononucleosis (IM) are thought to be caused by T cell activation and cytokine production. Surface lymphocyte activation marker (SLAM)-associated protein (SAP) regulates lymphocyte activation via signals from cell-surface CD244 (2B4) and SLAM (CD150). We followed T cell activation via this SAP/SLAM/CD244 pathway in IM and analyzed whether the results were associated with clinical severity. At diagnosis, SAP, SLAM, and CD244 were significantly up-regulated on CD4 and CD8 T cells; expression decreased during IM, but CD244 and SLAM levels remained higher on CD8 cells 40 days later. There were significantly more lymphocytes expressing CD8 and CD244/CD8 in patients with severe sore throat. The expression of CD8 alone and CD244 on CD8 cells correlated with increased virus load. We suggest that T cells expressing CD244 and SLAM are responsible for the clinical features of IM but that the control of activation is maintained by parallel increased expression of SAP.

[Diagnostic (STARD) and prognostic (REMARK) studies].

PubMed

Altman, Douglas G; Bossuyt, Patrick Mm

2005-12-01

Deficiencies in how research studies are reported are both well-documented and widespread across all medical specialties and study designs. Although randomised trials have received the most attention in this regard, similar concerns have been expressed about reporting of other types of research including diagnostic and epidemiological studies. If a journal article describes in enough detail what was done at each stage of a study, readers will have enough information to allow them to decide on the merits of the results for themselves. From this simple idea comes the scientific rationale of developing guidelines on how to report research. Recommended processes to produce reporting guidelines have evolved over several years during the preparation of a sequence of reporting guidelines starting with CONSORT and QUOROM in the 1990s. We describe initiatives to develop reporting guidelines for diagnostic accuracy studies (STARD) and tumour marker prognostic studies (REMARK).

Active Interventions in Clinical Practice: Contributions of Gestalt Therapy.

ERIC Educational Resources Information Center

Lammert, Marilyn; Dolan, Mary M.

1983-01-01

Describes two dimensions of Gestalt therapy that can enhance clinical practice--orientation to the present and active-experimental style--and examines them in relation to some traditional principles of practice. Gestalt theory offers a method of discovery that is a combination of phenomenology and behaviorism. (JAC)

[In-vitro activity of panipenem against clinical isolates in 2006].

PubMed

Yoshida, Sanae; Koga, Tetsufumi; Kakuta, Masayo; Kobayashi, Intetsu; Matsuzaki, Kaoru; Urabe, Eriko; Omika, Kaoru; Hasegawa, Miyuki; Sato, Yumie

2008-02-01

The antimicrobial activity of various antibiotics against clinical bacterial isolates recovered from patients with infectious diseases at the medical facilities in the Kanto region between March and September 2006 was evaluated. A total of 1030 clinical isolates were available for susceptibility tests: 420 aerobic Gram-positive organisms, 520 aerobic Gram-negative organisms, 30 anaerobic Gram-positive organisms and 60 anaerobic Gram-negative pathogens. Antimicrobial susceptibility data for Streptococcus pneumoniae and Haemophilus influenzae isolates from pediatric and adult patients were analyzed separately. Panipenem (PAPM), imipenem (IPM), meropenem (MEPM), biapenem (BIPM), doripenem (DRPM), cefozopran (CZOP), cefepime (CFPM), and sulbactam/cefoperazone (SBT/CPZ) were used as test antibiotics. PAPM, IPM and DRPM exhibited excellent in vitro antibacterial activities against methicillin-susceptible Staphylococcus, with all isolates exhibiting a MIC of < or =0.06 microg/mL. Against Streptococcus including penicillin-resistant S. pneumoniae, PAPM demonstrated the strongest antibacterial activity among the carbapenems with a MIC range of < or =0.06 to 0.12 microg/mL. Against Enterobacteriaceae, MEPM showed the strongest antibacterial activity, and PAPM had comparable activity to IPM. Against the extended-spectrum beta-lactamase producing Escherichia coli, Klebsiella species and Proteus species, the MICs for the cephems were high, however, those for the carbepenems were low. Against H. influenzae, PAPM had comparable activity to IPM. With respect to anaerobes, each of the carbapenems tested demonstrated almost the same strong antibacterial activity. In conclusion, 13 years has passed since PAPM was launched in 1993, PAPM still maintains potent antibacterial activity and is considered an effective antimicrobial agent for various types of infectious diseases.

Exploring the Role of Conventionality in Children's Interpretation of Ironic Remarks

ERIC Educational Resources Information Center

Burnett, Debra L.

2015-01-01

Irony comprehension in seven- and eight-year-old children with typically developing language skills was explored under the framework of the graded salience hypothesis. Target ironic remarks, either conventional or novel/situation-specific, were presented following brief story contexts. Children's responses to comprehension questions were used to…

Improving management of student clinical placements: insights from activity theory.

PubMed

O'Keefe, Maree; Wade, Victoria; McAllister, Sue; Stupans, Ieva; Burgess, Teresa

2016-08-24

An approach to improve management of student clinical placements, the Building Teams for Quality Learning project, was trialed in three different health services. In a previous paper the authors explored in some detail the factors associated with considerable success of this approach at one of these services. In this paper, the authors extend this work with further analysis to determine if the more limited outcomes observed with participants at the other two services could be explained by application of activity theory and in particular the expansive learning cycle. Staff at three health services participated in the Building Teams for Quality Learning project: a dental clinic, a community aged care facility and a rural hospital. At each site a team of seven multi-disciplinary staff completed the project over 9 to 12 months (total 21 participants). Evaluation data were collected through interviews, focus groups and direct observation of staff and students. Following initial thematic analysis, further analysis was conducted to compare the processes and outcomes at each participating health service drawing on activity theory and the expansive learning cycle. Fifty-one interview transcripts, 33 h of workplace observation and 31 sets of workshop field notes (from 36 h of workshops) were generated. All participants were individually supportive of, and committed to, high quality student learning experiences. As was observed with staff at the dental clinic, a number of potentially effective strategies were discussed at the aged care facility and the rural hospital workshops. However, participants in these two health services could not develop a successful implementation plan. The expansive learning cycle element of modeling and testing new solutions was not achieved and participants were unable, collectively to reassess and reinterpret the object of their activities. The application of activity theory and the expansive learning cycle assisted a deeper understanding of

Developing Clinical Competency in Crisis Event Management: An Integrated Simulation Problem-Based Learning Activity

ERIC Educational Resources Information Center

Liaw, S. Y.; Chen, F. G.; Klainin, P.; Brammer, J.; O'Brien, A.; Samarasekera, D. D.

2010-01-01

This study aimed to evaluate the integration of a simulation based learning activity on nursing students' clinical crisis management performance in a problem-based learning (PBL) curriculum. It was hypothesized that the clinical performance of first year nursing students who participated in a simulated learning activity during the PBL session…

[Tyramine and serotonin syndromes. Pharmacological, medical and legal remarks].

PubMed

Toro-Martínez, Esteban

2005-01-01

The tyramine syndrome and the serotonin syndrome are a complex of signs and symptoms that are thought to be largely attributable to drug - drug interactions or drug - food interactions that enhances norepinephrine o serotonin activity. This article reviews: pharmacological basis of those syndromes; clinical features; forbidden foods, drug-drug interactions, and treatment options. Finally a set of legal recommendations are proposed to avoid liability litigations.

Hematopoietic cell transplantation activity of Turkey in 2014: Ongoing increase in HCT rates.

PubMed

Tekgündüz, Emre; Şencan, İrfan; Kapuağası, Arif; Ünal, Doğan; Öztürk, Murat; Gümüş, Eyüp; Göker, Hakan; Tavil, Emine Betül; Ertem, Mehmet; Çetin, Mustafa; Arat, Mutlu; Soysal, Teoman; Karakaşlı, Osman; Sur, Halil Yılmaz; Yeşilipek, Akif; Ferhanoğlu, Burhan; Uçkan, Duygu; İlhan, Osman; Altuntaş, Fevzi

2016-02-01

Hematopoietic cell transplantation is an established treatment option with curative potential for a variety of clinical conditions. The last decade especially witnessed a remarkable increase in HCT activity in Turkey. In 2014, 696 pediatric and 2631 adult (total 3327) HCT were performed in Turkey. Corresponding transplant rates per 10 million inhabitants for autologous-HCT and allogeneic-HCT were 226 and 202, respectively. Total HCT procedures in Turkey increased 177% in the last 5 years and 791% in the last 14 years. This report focuses mainly on HCT activity of Turkey in 2014 based on the national HCT registry and presents a general picture of national HCT activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transsexuality: some remarks based on clinical experience.

PubMed

Hertoft, P; Sørensen, T

People with severe gender identity problems have always existed. Some hope to find a solution to their deep intrapersonal conflicts in a so-called sex transformation. The term 'transsexual' was coined by Cauldwell in 1949 and since then an unknown number of people all over the world, probably more biological men than women, have undergone a hormonal and surgical sex-transformation procedure. In this chapter we discuss the impossibility of real sex change from man to woman and vice versa. We briefly touch on two classical cases of sex transformation with some connection with Denmark: the Lili Elbe case of 1930 and the famous Chris Jorgensen case from the early fifties. We discuss the incidence of transsexuality and follow-up studies of patients, and give preliminary results from a Danish study of 110 people (81 men and 29 women) who during the past 25 years have applied for a sex-change operation. Of these, 56 individuals (42 men and 14 women) have had such operations. These are minimum figures since some transsexuals are known to have had operations in other countries but have not contacted Danish hospitals or health personnel.

Teachers' Remarks about Their Salaries in 1800 in the Helvetic Republic

ERIC Educational Resources Information Center

Brühwiler, Ingrid

2015-01-01

For centuries, teachers have complained about their salaries. In the Stapfer inquiry of 1799, some teachers made remarks about financial issues, particularly their low incomes. This inquiry is the main source for the arguments presented here regarding teachers' low salary during this period of the Helvetic Republic. The disparity between the…

Story of a Mediation in the Clinical Setting.

PubMed

Morreim, Haavi

2016-01-01

Conflicts in the clinical setting can spiral downward with remarkable speed, as parties become ever more incensed and entrenched in their positions. Productive conversations seem unlikely at best. Nevertheless, such situations can sometimes be turned into collaborative problem solving with equally remarkable speed. For this to happen, those providing conflict-resolution services such as mediation need to bring, not just a set of skills, but also some key norms: the process must be voluntary for all; the mediator must abjure giving advice or taking sides, and must honor the privacy of privately offered thoughts. This article describes a conflict that had reached the point of a hospital's requesting judicial coercion. However, a conflict-resolution process was then initiated that, in the end, led to amicable resolution and mended relationships, obviating the need for court orders. This article describes that conflict and the resolution process in detail, along the way annotating specific strategies that are often highly effective. Copyright 2016 The Journal of Clinical Ethics. All rights reserved.

Improving surveillance of sexually transmitted infections using mandatory electronic clinical reporting: the genitourinary medicine clinic activity dataset, England, 2009 to 2013.

PubMed

Savage, E J; Mohammed, H; Leong, G; Duffell, S; Hughes, G

2014-12-04

A new electronic surveillance system for sexually transmitted infections (STIs) was introduced in England in 2009. The genitourinary medicine clinic activity dataset (GUMCAD) is a mandatory, disaggregated, pseudo-anonymised data return submitted by all STI clinics across England. The dataset includes information on all STI diagnoses made and services provided alongside demographic characteristics for every patient attendance at a clinic. The new system enables the timely analysis and publication of routine STI data, detailed analyses of risk groups and longitudinal analyses of clinic attendees. The system offers flexibility so new codes can be introduced to help monitor outbreaks or unusual STI activity. From January 2009 to December 2013 inclusive, over twenty-five million records from a total of 6,668,648 patients of STI clinics have been submitted. This article describes the successful implementation of this new surveillance system and the types of epidemiological outputs and analyses that GUMCAD enables. The challenges faced are discussed and forthcoming developments in STI surveillance in England are described.

Factors Related to Healthy Diet and Physical Activity in Hospital-Based Clinical Nurses.

PubMed

Albert, Nancy M; Butler, Robert; Sorrell, Jeanne

2014-09-30

Hospitals often promote healthy lifestyles, but little is known about nurses' actual diet and physical activity. Greater understanding about these lifestyle choices for clinical nurses may improve existing hospital-based programs and/or create desirable services. This article discusses a study that considered diet and physical activity of clinical nurses, using elements of Pender's self-care theory as a conceptual framework. Study methods included a cross-sectional, correlational design and a convenience sample of 278 nurses who worked on units with 24 hours/day and seven days-per-week responsibilities. Participants completed diet and exercise questionnaires about perceptions of attitudes and opinions, barriers, diet benefits/exercise motivators, self-efficacy, and locus of control, and personal and work characteristics. Diet and activity categories were created. Study results demonstrated that over 50% of nurses had moderately healthy diets but were insufficiently active. Healthy diet and physical activity levels were associated with higher self-efficacy, more diet benefits and physical activity motivators, fewer perceived barriers, and confidence in body image. The article discussion and conclusion sections note areas for future research and suggest that focused interventions that address benefits, motivators, and self-efficacy may increase participation in hospital-based programs and enhance healthy lifestyle for hospital-based clinical nurses.

Student and staff opinion of electronic capture of data related to clinical activity.

PubMed

Oliver, R G

1997-02-01

To seek the opinion of staff and students of a new electronic method for collection of data related to student clinical activity. Questionnaire survey. Staff and students in the Department of Child Dental Health, Dental School, Cardiff, and staff in the Community Dental Service who undertake clinical supervision. A questionnaire was circulated to all 2nd and 3rd clinical year dental undergraduate students seeking their opinion on a range of issues associated with the recently introduced bar code system of data gathering of their clinical activity and achievement. A similar questionnaire was circulated to staff who have responsibility for clinical supervision of these students. A total of 102 replies were received. With the exception of 2 aspects, there was no disagreement between staff and students. An overall majority preferred the use of bar codes to other methods of data collection; bar codes were perceived to be more accurate and reliable than other methods; students were satisfied with the method of quality assessment; staff were dissatisfied (P < 0.05). Staff were strongly in favour of extension of the use of bar codes to other clinics, whereas students were less strongly in favour (P < 0.001); there was little enthusiasm to extend bar codes for recording attendance at lectures, seminars and other such activity. The new system has been accepted by staff and students alike. It has proven to be satisfactory for its intended purpose. As a result of this survey, minor adjustments to procedures will take place, and the method of assessment of clinical work will be reconsidered.

Research nurse manager perceptions about research activities performed by non-nurse clinical research coordinators.

PubMed

Jones, Carolynn Thomas; Hastings, Clare; Wilson, Lynda Law

2015-01-01

There has been limited research to document differences in roles between nurses and non-nurses who assume clinical research coordination and management roles. Several authors have suggested that there is no acknowledged guidance for the licensure requirements for research study coordinators and that some non-nurse research coordinators may be assuming roles that are outside of their legal scopes of practice. There is a need for further research on issues related to the delegation of clinical research activities to non-nurses. This study used nominal group process focus groups to identify perceptions of experienced research nurse managers at an academic health science center in the Southern United States about the clinical research activities that are being performed by non-nurse clinical research coordinators without supervision that they believed should only be performed by a nurse or under the supervision of a nurse. A total of 13 research nurse managers volunteered to be contacted about the study. Of those, 8 participated in two separate nominal group process focus group sessions. The group members initially identified 22 activities that they felt should only be performed by a nurse or under the direct supervision of a nurse. After discussion and clarification of results, activities were combined into 12 categories of clinical research activities that participants believed should only be performed by a nurse or under the direct supervision of a nurse. Copyright © 2015 Elsevier Inc. All rights reserved.

A Remarkable World

NASA Image and Video Library

2015-07-03

This image of Pluto and its big moon Charon was taken by NASA's New Horizons spacecraft at 04:15 (UTC) on July 1, 2015, and shows the clearest view yet of the sides of Pluto and Charon that will be studied in great detail during New Horizons' closest approach to the dwarf planet on July 14, 2015. There will be just two more rotations of Pluto and Charon, and two more orbits about their mutual center of gravity, between the time of this image and closest approach (the rotation period of the system is 6.4 days). The image, which has been sharpened by the image processing technique known as deconvolution, shows details as small as about 160 kilometers (100 miles). The highest-resolution images of this side of Pluto, taken on July 14, will show details that are 1,000 times smaller. New Horizons is revealing Pluto to be a world that, at this point, looks like no other in the solar system. Its equatorial regions are occupied by a discontinuous band of very dark material, which is interrupted on this hemisphere by a very bright region which appears sharp-edged at the resolution of the image. The north polar region is blander, but shows a distinctive darker southern boundary where it meets the higher-contrast equatorial regions. The origin of these remarkable features is still unknown, though some of them might be related to seasonal movement of frost across Pluto's surface. Charon, in contrast, still shows few details other than the dark polar region. The image was taken by New Horizons' Long Range Reconnaissance Imager (LORRI ) at a distance from Pluto of 15.8 million kilometers (9.8 million miles) and has a central longitude of 177 degrees on Pluto and 357 degrees on Charon. The inset shows the orientation of Pluto- the solid lines mark the equator and the prime meridian, which is defined to be the longitude that always faces Charon. http://photojournal.jpl.nasa.gov/catalog/PIA19694

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease

PubMed Central

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-01-01

Abstract This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity. We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters. Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016). E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD. PMID:27684872

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease.

PubMed

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-09-01

This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity.We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters.Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016).E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD.

Remarks on neurocybernetics and its links to computing science. To the memory of Prof. Luigi M. Ricciardi.

PubMed

Moreno-Díaz, Roberto; Moreno-Díaz, Arminda

2013-06-01

This paper explores the origins and content of neurocybernetics and its links to artificial intelligence, computer science and knowledge engineering. Starting with three remarkable pieces of work, we center attention on a number of events that initiated and developed basic topics that are still nowadays a matter of research and inquire, from goal directed activity theories to circular causality and to reverberations and learning. Within this context, we pay tribute to the memory of Prof. Ricciardi documenting the importance of his contributions in the mathematics of brain, neural nets and neurophysiological models, computational simulations and techniques. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

PubMed

Mordekar, S R; Guthrie, P; Bonham, J R; Olpin, S E; Hargreaves, I; Baxter, P S

2006-03-01

Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.

Remarkable rates of lightning strike mortality in Malawi.

PubMed

Mulder, Monique Borgerhoff; Msalu, Lameck; Caro, Tim; Salerno, Jonathan

2012-01-01

Livingstone's second mission site on the shore of Lake Malawi suffers very high rates of consequential lightning strikes. Comprehensive interviewing of victims and their relatives in seven Traditional Authorities in Nkhata Bay District, Malawi revealed that the annual rate of consequential strikes was 419/million, more than six times higher than that in other developing countries; the rate of deaths from lightning was 84/million/year, 5.4 times greater than the highest ever recorded. These remarkable figures reveal that lightning constitutes a significant stochastic source of mortality with potential life history consequences, but it should not deflect attention away from the more prominent causes of mortality in this rural area.

Antimicrobial activity of solithromycin against clinical isolates of Legionella pneumophila serogroup 1.

PubMed

Mallegol, Julia; Fernandes, Prabhavathi; Melano, Roberto G; Guyard, Cyril

2014-01-01

The activity of solithromycin was evaluated against clinical Legionella pneumophila serogroup 1 (Lp1) isolates (n = 196) collected in Ontario, Canada, from 1980 to 2011. Its in vitro activity was compared to that of azithromycin (AZM) using the broth microdilution method. Solithromycin had a MIC50 of ≤0.015 μg/ml and a MIC90 of 0.031 μg/ml, making its activity at least 8-fold to 32-fold higher than that of AZM (MIC50 and MIC90, 0.125 μg/ml and 1 μg/ml, respectively). Ninety-nine percent of the isolates had MICs for solithromycin ranging from ≤0.015 μg/ml to 0.031 μg/ml, whereas 83.6% of the isolates showed MICs for AZM ranging from 0.062 μg/ml to 0.25 μg/ml. Interestingly, 96.7% (30 out of 31 clinical isolates) identified with higher AZM MICs (0.5 μg/ml to 2 μg/ml) belonged to the clinically prevalent sequence type 1. To investigate the intracellular activity of solithromycin, in vitro invasion assays were also performed against a subset of representative Lp1 isolates internalized within human lung epithelial cells. Solithromycin and AZM both inhibited growth of all intracellular Lp1 isolates at 1× or 8× MICs, displaying bacteriostatic effects, as would be expected with protein synthesis inhibitor rather than bactericidal activity. Solithromycin demonstrated the highest in vitro and intracellular potency against all Lp1 isolates compared to AZM. Given the rapid spread of resistance mechanisms among respiratory pathogens and the reported treatment failures in legionellosis, the development of this new fluoroketolide, already in phase 3 oral clinical studies, constitutes a promising alternative option for the treatment of legionellosis.

Antimicrobial Activity of Solithromycin against Clinical Isolates of Legionella pneumophila Serogroup 1

PubMed Central

Mallegol, Julia; Fernandes, Prabhavathi

2014-01-01

The activity of solithromycin was evaluated against clinical Legionella pneumophila serogroup 1 (Lp1) isolates (n = 196) collected in Ontario, Canada, from 1980 to 2011. Its in vitro activity was compared to that of azithromycin (AZM) using the broth microdilution method. Solithromycin had a MIC50 of ≤0.015 μg/ml and a MIC90 of 0.031 μg/ml, making its activity at least 8-fold to 32-fold higher than that of AZM (MIC50 and MIC90, 0.125 μg/ml and 1 μg/ml, respectively). Ninety-nine percent of the isolates had MICs for solithromycin ranging from ≤0.015 μg/ml to 0.031 μg/ml, whereas 83.6% of the isolates showed MICs for AZM ranging from 0.062 μg/ml to 0.25 μg/ml. Interestingly, 96.7% (30 out of 31 clinical isolates) identified with higher AZM MICs (0.5 μg/ml to 2 μg/ml) belonged to the clinically prevalent sequence type 1. To investigate the intracellular activity of solithromycin, in vitro invasion assays were also performed against a subset of representative Lp1 isolates internalized within human lung epithelial cells. Solithromycin and AZM both inhibited growth of all intracellular Lp1 isolates at 1× or 8× MICs, displaying bacteriostatic effects, as would be expected with protein synthesis inhibitor rather than bactericidal activity. Solithromycin demonstrated the highest in vitro and intracellular potency against all Lp1 isolates compared to AZM. Given the rapid spread of resistance mechanisms among respiratory pathogens and the reported treatment failures in legionellosis, the development of this new fluoroketolide, already in phase 3 oral clinical studies, constitutes a promising alternative option for the treatment of legionellosis. PMID:24277019

Closing remarks: A visit to Dr. Stout's and Dr. Murphy's forest health clinic

Treesearch

Russell T. Graham; Theresa B. Jain

1995-01-01

Two years ago I attended a camp with fellow silviculturists in central North Carolina. Camp Kanuga provided all kinds of fun activities. We described ecosystems and designed silvicultural systems for a variety of objectives; and as our camp scribe (Phil Aune) noted, the central camp theme evolved into ecosystem management. I am not sure exactly how or what happened but...

Clinical management of musculoskeletal injuries in active children and youth.

PubMed

Mazer, Barbara; Shrier, Ian; Feldman, Debbie Ehrmann; Swaine, Bonnie; Majnemer, Annette; Kennedy, Eileen; Chilingaryan, Gevorg

2010-07-01

To describe how different health care specialists manage musculoskeletal injury in children and examine factors influencing return to play decisions. National survey. Secure Web site hosting online questionnaire. Medical doctors, physical therapists, and athletic therapists who were members of their respective sport medicine specialty organizations. Professional affiliation and the effect of the following factors were examined: pushy parent, cautious parent, protective equipment, previous injury, musculoskeletal maturity, game importance, position played, team versus individual sport, and time since injury. Recommendation of return to activity after common injuries seen in children and adolescents as described in 5 vignettes; consistency of responses across vignettes. The survey was completed by 464 respondents (34%). There were several differences between the professional groups in their recommendations to return to activity. Most factors studied did not tend to influence the decision to return to activity, although protective equipment often increased the response to return sooner. The number of participants who would return a child to activity sooner or later for each factor varied greatly across the 5 vignettes, except for pushy parent or cautious parent. Management practices of sport medicine clinicians vary according to profession, child, clinical factors, and sport-related factors. Decisions regarding return to play vary according to 5 specific characteristics of each clinical case. These findings help establish areas of consensus and disagreement in the management of children with injuries and safe return to physical activity.

Hydroisomerization of n-hexadecane: remarkable selectivity of mesoporous silica post-synthetically modified with aluminum

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

Sabyrov, Kairat; Musselwhite, Nathan; Melaet, Gérôme

As the impact of acids on catalytically driven chemical transformations is tremendous, fundamental understanding of catalytically relevant factors is essential for the design of more efficient solid acid catalysts. In this work, we employed a post-synthetic doping method to synthesize a highly selective hydroisomerization catalyst and to demonstrate the effect of acid strength and density, catalyst microstructure, and platinum nanoparticle size on the reaction rate and selectivity. Aluminum doped mesoporous silica catalyzed gas-phase n-hexadecane isomerization with remarkably high selectivity to monobranched isomers (~95%), producing a substantially higher amount of isomers than traditional zeolite catalysts. Mildly acidic sites generated by post-syntheticmore » aluminum grafting were found to be the main reason for its high selectivity. The flexibility of the post-synthetic doping method enabled us to systematically explore the effect of the acid site density on the reaction rate and selectivity, which has been extremely difficult to achieve with zeolite catalysts. We found that a higher density of Brønsted acid sites leads to higher cracking of n-hexadecane presumably due to an increased surface residence time. Furthermore, regardless of pore size and microstructure, hydroisomerization turnover frequency linearly increased as a function of Brønsted acid site density. In addition to strength and density of acid sites, platinum nanoparticle size affected catalytic activity and selectivity. The smallest platinum nanoparticles produced the most effective bifunctional catalyst presumably because of higher percolation into aluminum doped mesoporous silica, generating more 'intimate' metallic and acidic sites. Finally, the aluminum doped silica catalyst was shown to retain its remarkable selectivity towards isomers even at increased reaction conversions.« less

Hydroisomerization of n-hexadecane: remarkable selectivity of mesoporous silica post-synthetically modified with aluminum

DOE PAGES

Sabyrov, Kairat; Musselwhite, Nathan; Melaet, Gérôme; ...

2017-01-01

As the impact of acids on catalytically driven chemical transformations is tremendous, fundamental understanding of catalytically relevant factors is essential for the design of more efficient solid acid catalysts. In this work, we employed a post-synthetic doping method to synthesize a highly selective hydroisomerization catalyst and to demonstrate the effect of acid strength and density, catalyst microstructure, and platinum nanoparticle size on the reaction rate and selectivity. Aluminum doped mesoporous silica catalyzed gas-phase n-hexadecane isomerization with remarkably high selectivity to monobranched isomers (~95%), producing a substantially higher amount of isomers than traditional zeolite catalysts. Mildly acidic sites generated by post-syntheticmore » aluminum grafting were found to be the main reason for its high selectivity. The flexibility of the post-synthetic doping method enabled us to systematically explore the effect of the acid site density on the reaction rate and selectivity, which has been extremely difficult to achieve with zeolite catalysts. We found that a higher density of Brønsted acid sites leads to higher cracking of n-hexadecane presumably due to an increased surface residence time. Furthermore, regardless of pore size and microstructure, hydroisomerization turnover frequency linearly increased as a function of Brønsted acid site density. In addition to strength and density of acid sites, platinum nanoparticle size affected catalytic activity and selectivity. The smallest platinum nanoparticles produced the most effective bifunctional catalyst presumably because of higher percolation into aluminum doped mesoporous silica, generating more 'intimate' metallic and acidic sites. Finally, the aluminum doped silica catalyst was shown to retain its remarkable selectivity towards isomers even at increased reaction conversions.« less

Constitutive RET tyrosine kinase activation in hereditary medullary thyroid cancer: clinical opportunities.

PubMed

Machens, A; Lorenz, K; Dralle, H

2009-07-01

The ground-breaking discovery of genotype-phenotype relationships in hereditary medullary thyroid cancer has greatly facilitated early prophylactic thyroidectomy. Its timing depends not solely on a positive gene test but, more importantly, on the type of the REarranged during Transfection (RET) mutation and its underlying mode of RET receptor tyrosine kinase activation. In the past decade, the therapeutic corridor opened by molecular information has been defined down to a remarkable level of detail. Based on mutational risk profiles, preemptive thyroidectomy is recommended at 6 months of age for carriers of highest-risk mutations, before the age of 5 years for carriers of high-risk mutations, and before the age of 5 or 10 years for carriers of least-high-risk mutations. Additional lymph node dissection may not be needed in the absence of increased preoperative basal calcitonin levels. Better comprehension of RET function should enable the design of targeted therapies for RET carriers beyond surgical cure in whom the DNA-based 'window of opportunity' has been missed.

Lessons from a remarkable family with dopa-responsive dystonia.

PubMed Central

Harwood, G; Hierons, R; Fletcher, N A; Marsden, C D

1994-01-01

A family is described in which dopa-responsive dystonia affected six members and segregated in an autosomal dominant fashion. Patients either presented in childhood with dystonia of the legs, going to develop parkinsonism and pseudo-pyramidal deficits, or in adult life with parkinsonian tremor and rigidity, with pseudo-pyramidal signs. Remarkably, in the three cases with childhood onset the symptoms and signs of the condition were abolished 36 to 52 years later by small doses of levodopa. No long term side effects of levodopa have appeared after 15 years of treatment. PMID:8163996

Checkpoint inhibitors in endometrial cancer: preclinical rationale and clinical activity.

PubMed

Mittica, Gloria; Ghisoni, Eleonora; Giannone, Gaia; Aglietta, Massimo; Genta, Sofia; Valabrega, Giorgio

2017-10-27

Treatment of advanced and recurrent endometrial cancer (EC) is still an unmet need for oncologists and gynecologic oncologists. The Cancer Genome Atlas Research Network (TCGA) recently provided a new genomic classification, dividing EC in four subgroups. Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors. We analyzed all available evidence supporting the role of tumor microenvironment (TME) in EC development and the therapeutic implications offered by immune checkpoint inhibitors in this setting. We performed a review on Pubmed with Mesh keywords 'endometrial cancer' and the name of each checkpoint inhibitor discussed in the article. The same search was operated on clinicaltrial.gov to identify ongoing clinical trials exploring PD-1/PD-L1 and CTLA-4 axis in EC, particularly focusing on POLE-ultra-muted and MSI-H cancer types. POLE-ultra-mutated and MSI-H ECs showed an active TME expressing high number of neo-antigens and an elevated amount of tumor infiltrating lymphocytes (TILs). Preliminary results from a phase-1 clinical trial (KEYNOTE-028) demonstrated antitumor activity of Pembrolizumab in EC. Moreover, both Pembrolizumab and Nivolumab reported durable clinical responses in POLE-ultra-mutated patients. Immune checkpoint inhibitors are an attractive option in POLE-ultra-mutated and MSI-H ECs. Future investigations in these subgroups include combinations of checkpoints inhibitors with chemotherapy and small tyrosine kinase inhibitors (TKIs) to enhance a more robust intra-tumoral immune response.

The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial.

PubMed

Rodríguez, P C; Prada, D M; Moreno, E; Aira, L E; Molinero, C; López, A M; Gómez, J A; Hernández, I M; Martínez, J P; Reyes, Y; Milera, J M; Hernández, M V; Torres, R; Avila, Y; Barrese, Y; Viada, C; Montero, E; Hernández, P

2018-02-01

Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients. © 2017 British Society for Immunology.

Flexible statistical modelling detects clinical functional magnetic resonance imaging activation in partially compliant subjects.

PubMed

Waites, Anthony B; Mannfolk, Peter; Shaw, Marnie E; Olsrud, Johan; Jackson, Graeme D

2007-02-01

Clinical functional magnetic resonance imaging (fMRI) occasionally fails to detect significant activation, often due to variability in task performance. The present study seeks to test whether a more flexible statistical analysis can better detect activation, by accounting for variance associated with variable compliance to the task over time. Experimental results and simulated data both confirm that even at 80% compliance to the task, such a flexible model outperforms standard statistical analysis when assessed using the extent of activation (experimental data), goodness of fit (experimental data), and area under the operator characteristic curve (simulated data). Furthermore, retrospective examination of 14 clinical fMRI examinations reveals that in patients where the standard statistical approach yields activation, there is a measurable gain in model performance in adopting the flexible statistical model, with little or no penalty in lost sensitivity. This indicates that a flexible model should be considered, particularly for clinical patients who may have difficulty complying fully with the study task.

Edward Miner Gallaudet's "Remarks on the Combined System": An Analysis of the "Preservative" Function of Rhetoric of Education.

ERIC Educational Resources Information Center

Sharkey, William F.; Hikins, James W.

1993-01-01

Examines Edward Miner Gallaudet's speech, "Remarks on the Combined System," to illustrate the power of the rhetorical knowledge thesis to account for paradoxes in Gallaudet's discourse on educating the deaf student. Contends that Gallaudet offered his remarks to preserve his ideas for a later age when they might receive sympathetic…

Remarkable Rates of Lightning Strike Mortality in Malawi

PubMed Central

Borgerhoff Mulder, Monique; Msalu, Lameck; Caro, Tim; Salerno, Jonathan

2012-01-01

Livingstone's second mission site on the shore of Lake Malawi suffers very high rates of consequential lightning strikes. Comprehensive interviewing of victims and their relatives in seven Traditional Authorities in Nkhata Bay District, Malawi revealed that the annual rate of consequential strikes was 419/million, more than six times higher than that in other developing countries; the rate of deaths from lightning was 84/million/year, 5.4 times greater than the highest ever recorded. These remarkable figures reveal that lightning constitutes a significant stochastic source of mortality with potential life history consequences, but it should not deflect attention away from the more prominent causes of mortality in this rural area. PMID:22253708

Supporting and activating clinical governance development in Ireland: sharing our learning.

PubMed

Flynn, Maureen A; Burgess, Thora; Crowley, Philip

2015-01-01

The purpose of this paper is to present a description of the Irish national clinical governance development initiative and an evaluation of the initiative with the purpose of sharing the learning and proposing actions to activate structures and processes for quality and safety. The Quality and Patient Safety Division of the Health Service Executive established the initiative to counterbalance a possible focus on finances during the economic crisis in Ireland and bring attention to the quality of clinical care. A clinical governance framework for quality in healthcare in Ireland was developed to clearly articulate the fundamentals of clinical governance. The project plan involved three overlapping phases. The first was designing resources for practice; the second testing the implementation of the national resources in practice; and the third phase focused on gathering feedback and learning. Staff responded positively to the clinical governance framework. At a time when there are a lot of demands (measurement and scrutiny) the health services leads and responds well to focused support as they improve the quality and safety of services. Promoting the use of the term "governance for quality and safety" assisted in gaining an understanding of the more traditional term "clinical governance". The experience and outcome of the initiative informed the identification of 12 key learning points and a series of recommendations The initial evaluation was conducted at 24 months so at this stage it is not possible to assess the broader impact of the clinical governance framework beyond the action project hospitals. The single most important obligation for any health system is patient safety and improving the quality of care. The easily accessible, practical resources assisted project teams to lead changes in structures and processes within their services. This paper describes the fundamentals of the clinical governance framework which might serve as a guide for more integrative

Cytotoxicity of Cyclometalated Platinum Complexes Based on Tridentate NCN and CNN-coordinating ligands: Remarkable Coordination Dependence

PubMed Central

Vezzu, Dileep A. k.; Lu, Qun; Chen, Yan-Hua; Huo, Shouquan

2014-01-01

A series of cyclometalated platinum complexes with diverse coordination patterns and geometries were screened for their anticancer activity. It was discovered that the NʌCʌN-coordinated platinum complex based on 1,3-di(pyridyl)benzene displayed much higher cytotoxicity against human lung cancer cells NCI-H522, HCC827, and NCI-H1299, and human prostate cancer cell RV1 than cisplatin. In a sharp contrast, the CʌNʌN-coordinated platinum complex based on 6-phenyl-2,2′-bipyridine was ineffective on these cancer cells. This remarkable difference in cytotoxicity displayed by NʌCʌN- and CʌNʌN-coordinated platinum complexes was related to the trans effect of the carbon donor in the cyclometalated platinum complexes, which played a crucial role in facilitating the dissociation of the chloride ligand to create an active binding site. The DNA binding was studied for the NʌCʌN-coordinated platinum complex using electrophoresis and emission titration. The cellular uptake observed by fluorescent microscope showed the complex is largely concentrated in the cytoplasm. The possible pathways for the cell apoptosis was studied by western blot analysis and the activation of PARP via caspase 7 was observed. PMID:24531534

Exploring Patient Activation in the Clinic: Measurement from Three Perspectives

ERIC Educational Resources Information Center

Ledford, Christy J. W.; Ledford, Christopher C.; Childress, Marc A.

2013-01-01

Objective. To further conceptualize and operationalize patient activation (PA), using measures from patient, physician, and researcher perspectives. Data Source/Study Setting. Multimethod observation in 2010 within a family medicine clinic. Study Design. Part of an intervention with 130 patients with type 2 diabetes, this observational study…

PPARs: Interference with Warburg' Effect and Clinical Anticancer Trials

PubMed Central

Vamecq, Joseph; Colet, Jean-Marie; Vanden Eynde, Jean Jacques; Briand, Gilbert; Porchet, Nicole; Rocchi, Stéphane

2012-01-01

The metabolic/cell signaling basis of Warburg's effect (“aerobic glycolysis”) and the general metabolic phenotype adopted by cancer cells are first reviewed. Several bypasses are adopted to provide a panoramic integrated view of tumoral metabolism, by attributing a central signaling role to hypoxia-induced factor (HIF-1) in the expression of aerobic glycolysis. The cancer metabolic phenotype also results from alterations of other routes involving ras, myc, p53, and Akt signaling and the propensity of cancer cells to develop signaling aberrances (notably aberrant surface receptor expression) which, when present, offer unique opportunities for therapeutic interventions. The rationale for various emerging strategies for cancer treatment is presented along with mechanisms by which PPAR ligands might interfere directly with tumoral metabolism and promote anticancer activity. Clinical trials using PPAR ligands are reviewed and followed by concluding remarks and perspectives for future studies. A therapeutic need to associate PPAR ligands with other anticancer agents is perhaps an important lesson to be learned from the results of the clinical trials conducted to date. PMID:22654896

Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular analysis and histogenetic evaluation.

PubMed

Cambruzzi, Eduardo

2018-05-01

Medulloblastoma (MDB) is a small cell poorly differentiated embryonal tumor of the cerebellum, which more frequently compromises children. Overall prognosis is favorable, but dependent of stage, histopathological pattern and molecular group. Approximately 30% of the affected patients will die from the disease. WHO 2016 Classification of Tumors of the Central Nervous System (CNS) has been classified MDB into four principal groups: WNT-activated MDB, SHH-activated MDB, group 3 MDB, and group 4 MDB. WNT-activated MDB is associated to monosomy 6, CTNNB1, DDX3X and TP53 mutations, beta-catenin nuclear immunoexpression, and a better prognosis than SHH-activated MDB. WNT-activated tumors account approximately for 10% of cases of MDBs, and are thought to arise from cells in the dorsal brain stem/lower rhombic lip progenitor cells. SHH-activated MDB more frequently arises in the lateral hemispheres of the cerebellum, and clinical outcome in this group is variable. TP53-mutant SHHactivated MDB usually shows the large cell/anaplastic pattern, and can be related to MYCN amplification, GLI2 amplification and 17p loss. TP53-wildtype SHH-activated MDB is more commonly of desmoplastic/nodular morphology, and can be related to PTCH1 deletion and 10q loss. Gene expression and methylation profiling is the gold standard for defining molecular groups of MDB. In immunohistochemistry assays, anti-GAB1 antibody expression is positive in tumors showing SHH pathway activation or PTCH mutation, while positive immunoexpression for YAP1 antibody can be only found in WNT-activated and SHH-activated MDB.

Case Report: Activity Diagrams for Integrating Electronic Prescribing Tools into Clinical Workflow

PubMed Central

Johnson, Kevin B.; FitzHenry, Fern

2006-01-01

To facilitate the future implementation of an electronic prescribing system, this case study modeled prescription management processes in various primary care settings. The Vanderbilt e-prescribing design team conducted initial interviews with clinic managers, physicians and nurses, and then represented the sequences of steps carried out to complete prescriptions in activity diagrams. The diagrams covered outpatient prescribing for patients during a clinic visit and between clinic visits. Practice size, practice setting, and practice specialty type influenced the prescribing processes used. The model developed may be useful to others engaged in building or tailoring an e-prescribing system to meet the specific workflows of various clinic settings. PMID:16622168

A remark on the energy conditions for Hawking's area theorem

NASA Astrophysics Data System (ADS)

Lesourd, Martin

2018-06-01

Hawking's area theorem is a fundamental result in black hole theory that is universally associated with the null energy condition. That this condition can be weakened is illustrated by the formulation of a strengthened version of the theorem based on an energy condition that allows for violations of the null energy condition. With the semi-classical context in mind, some brief remarks pertaining to the suitability of the area theorem and its energy condition are made.

Recombination activity of human RAG2 mutations and correlation with the clinical phenotype.

PubMed

Tirosh, Irit; Yamazaki, Yasuhiro; Frugoni, Francesco; Ververs, Francesca A; Allenspach, Eric J; Zhang, Yu; Burns, Siobhan; Al-Herz, Waleed; Noroski, Lenora; Walter, Jolan E; Gennery, Andrew R; van der Burg, Mirjam; Notarangelo, Luigi D; Lee, Yu Nee

2018-05-14

Mutations in the Recombinase Activating Gene 1 and 2 (RAG1, RAG2) are associated with a broad range of clinical and immunological phenotypes in humans. Using a flow cytometry-based assay, we aimed to measure the recombinase activity of naturally occurring RAG2 mutant proteins, and to correlate results with the severity of the clinical and immunological phenotype. Abelson virus-transformed Rag2 -/- pro-B cells engineered to contain an inverted GFP cassette flanked by recombination signal sequences (RSS) were transduced with retroviruses encoding either wild-type or 41 naturally occurring RAG2 variants. Bicistronic vectors were used to introduce compound heterozygous RAG2 variants.The percentage of GFP-expressing cells was evaluated by flow cytometry, and high throughput sequencing was used to analyze rearrangements at the endogenous Igh locus.. The RAG2 variants showed a wide range of recombination activity. Mutations associated with severe combined immune deficiency (SCID) and Omenn syndrome had significantly lower activity than those detected in patients with less severe clinical presentations. Four variants (P253R, F386L, N474S, and M502V) previously thought to be pathogenic were found to have wild-type levels of activity. Use of bicistronic vectors permitted to assess more carefully the effect of compound heterozygous mutations, with good correlation between GFP expression and number and diversity of Igh rearrangements. Our data support genotype-phenotype correlation in RAG2 deficiency. The assay described can be used to define the possible disease-causing role of novel RAG2 variants and may help predict the severity of the clinical phenotype. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

[Treatment regulations and treatment limits: factors influencing clinical decision-making].

PubMed

Baberg, H T; Kielstein, R; de Zeeuw, J; Sass, H-M

2002-08-02

Providing or withholding of treatment is based on a variety of factors. We sought for criteria in clinical decision making and reviewed attitudes towards clinical intuition and the patient's will. 503 physicians (25.6 % females; mean age 36.3) in 49 departments at nine hospitals of the universities Bochum and Magdeburg filled in a validated questionnaire. The most important factors in the decision to carry out a therapy were "international standards" and "own experience". The decision to omit a therapy was mainly influenced by the "patient's wish". Physicians with a higher status judged their own experience higher than young physicians, who considered the experience of colleagues more important. "Severe accompanying illnesses" and "multimorbidity" were the most frequently named reasons to withdraw a therapy. Intuitive decision-making was rare, especially in young physicians, although these decisions were seldom risky and often successful. A patient's will plays a prominent role in clinical decision making, especially in decisions to withdraw or to withhold treatment. Cost containment and research interest have been called less important, a remarkable response from research-based university hospitals. Also remarkable is the recognition and importance of clinical intuition in situations of complex or missing information. This important aspect is rarely discussed in the literature or in medical education. The widely voiced concern that priorities in clinical care are guided by scientific interest, financial or technical possibilities could not be confirmed.

Mass spectrometric detection of ricin and its activity in food and clinical samples.

PubMed

Kalb, Suzanne R; Barr, John R

2009-03-15

Ricin is a potent toxin capable of inhibiting protein synthesis and causing death or respiratory failure. Because of its high availability and lethality, ricin is considered a likely agent for bioterrorism. Rapidly determining contamination of food product with ricin and human exposure to ricin is therefore an important public health goal. In this work, we report the development of a method that detects ricin and its activity in food or clinical samples. This method involves immunocapture of the toxin, an examination of the activity of the ricin protein upon a DNA substrate that mimics the toxin's natural RNA target, and analysis of tryptic fragments of the toxin itself. It is the combination of these three techniques, all performed on the same sample, which allows for a sensitive and selective analysis of ricin isolated from a food or clinical sample. This measurement includes a measure of the toxin's activity. The utility of this method was demonstrated on ricin spiked into food and clinical samples consisting of milk, apple juice, serum, and saliva.

Innovative Clinical Assessment Technologies: Challenges and Opportunities in Neuroimaging

ERIC Educational Resources Information Center

Miller, Gregory A.; Elbert, Thomas; Sutton, Bradley P.; Heller, Wendy

2007-01-01

The authors review the reasons for the contrast between the remarkable advances that hemodynamic and electromagnetic imaging of the human brain appear capable of delivering in clinical practice in psychology and their very limited penetration into practice to date. Both the heritages of the relevant technologies and the historical orientation of…

A rare complication with remarkable stent shortening and successful recovery from the trouble.

PubMed

Goto, Yoshitaka; Kawasaki, Tomohiro; Koga, Hisashi

2012-05-01

Deployed coronary stent distortion is a rare complication, but can potentially occur during coronary intervention. We herein report a rare complicated case with remarkable stent distortion of longitudinal stent shortening and successful recovery from a trouble using a Corsair microcatheter.

Active video games to promote physical activity in children with cancer: a randomized clinical trial with follow-up.

PubMed

Kauhanen, Lotta; Järvelä, Liisa; Lähteenmäki, Päivi M; Arola, Mikko; Heinonen, Olli J; Axelin, Anna; Lilius, Johan; Vahlberg, Tero; Salanterä, Sanna

2014-04-05

Low levels of physical activity, musculoskeletal morbidity and weight gain are commonly reported problems in children with cancer. Intensive medical treatment and a decline in physical activity may also result in reduced motor performance. Therefore, simple and inexpensive ways to promote physical activity and exercise are becoming an increasingly important part of children's cancer treatment. The aim of this study is to evaluate the effect of active video games in promotion of physical activity in children with cancer. The research is conducted as a parallel randomized clinical trial with follow-up. Patients between 3 and 16 years old, diagnosed with cancer and treated with vincristine in two specialized medical centers are asked to participate. Based on statistical estimates, the target enrollment is 40 patients. The intervention includes playing elective active video games and, in addition, education and consultations for the family. The control group will receive a general recommendation for physical activity for 30 minutes per day. The main outcomes are the amount of physical activity and sedentary behavior. Other outcomes include motor performance, fatigue and metabolic risk factors. The outcomes are examined with questionnaires, diaries, physical examinations and blood tests at baseline and at 2, 6, 12 and 30 months after the baseline. Additionally, the children's perceptions of the most enjoyable activation methods are explored through an interview at 2 months. This trial will help to answer the question of whether playing active video games is beneficial for children with cancer. It will also provide further reasoning for physical activity promotion and training of motor skills during treatment. ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012).

Two-year efficacy of tocilizumab in patients with active rheumatoid arthritis in clinical practice.

PubMed

Notario Ferreira, Irene; Ferrer González, Miguel Angel; Morales Garrido, Pilar; González Utrilla, Alfonso; García Sanchez, Antonio; Soto Pino, María José; Suero Rosario, Evelyn; Caro Hernández, Cristina; Añón Oñate, Isabel; Pérez Albaladejo, Lorena; Cáliz Cáliz, Rafael

To evaluate the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in clinical practice, retention rates of the drug and predictors of response. We performed a descriptive, prospective, longitudinal, open-label study in patients receiving TCZ (8mg/kg/4 weeks) in a clinical practice setting. The clinical responses were evaluated using the European League Against Rheumatism (EULAR) response criteria, and the low activity and remission rates according to the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI). The EULAR response rate was 86.63% and the DAS28 remission rate was 53.7% after 6 months of treatment; rates of low disease activity were 52.9% on CDAI and 47.1% on DAS28 at month 24. There were no statistically significant differences in EULAR response, rates of low activity and remission on DAS28 between patients receiving TCZ alone and those receiving TCZ in combination therapy, or between patients positive or negative for rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies. The naïve biological therapy patients showed better remission and low activity rates after 6 months of treatment. The retention rate was 61% at month 24. Adverse events were among the most frequent causes of discontinuation. Tocilizumab is effective in RA, has a similar efficacy when used alone or in combination with synthetic disease-modifying antirheumatic drugs (DMARDs) and shows high retention rates. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Clinical pharmacists in general practice: an initial evaluation of activity in one English primary care organisation.

PubMed

Bush, Joseph; Langley, Christopher A; Jenkins, Duncan; Johal, Jaspal; Huckerby, Clair

2017-12-27

This aim of this research was to characterise the breadth and volume of activity conducted by clinical pharmacists in general practice in Dudley Clinical Commissioning Group (CCG), and to provide quantitative estimates of both the savings in general practitioner (GP) time and the financial savings attributable to such activity. This descriptive observational study retrospectively analysed quantitative data collected by Dudley CCG concerning the activity of clinical pharmacists in GP practices during 2015. Over the 9-month period for which data were available, the 5.4 whole time equivalent clinical pharmacists operating in GP practices within Dudley CCG identified 23 172 interventions. Ninety-five per cent of the interventions identified were completed within the study period saving the CCG in excess of £1 000 000. During the 4 months for which resource allocation data were available, the clinical pharmacists saved 628 GP appointments plus an additional 647 h that GPs currently devote to medication review and the management of repeat prescribing. This research suggests that clinical pharmacists in general practice in Dudley CCG are able to deliver clinical interventions efficiently and in high volume. In doing so, clinical pharmacists were able to generate considerable financial returns on investment. Further work is recommended to examine the effectiveness and cost-effectiveness of clinical pharmacists in general practice in improving outcomes for patients. © 2017 Royal Pharmaceutical Society.

Clinical experience of integrative cancer immunotherapy with GcMAF.

PubMed

Inui, Toshio; Kuchiike, Daisuke; Kubo, Kentaro; Mette, Martin; Uto, Yoshihiro; Hori, Hitoshi; Sakamoto, Norihiro

2013-07-01

Immunotherapy has become an attractive new strategy in the treatment of cancer. The laboratory and clinical study of cancer immunotherapy is rapidly advancing. However, in the clinical setting, the results of cancer immunotherapy are mixed. We therefore contend that cancer immunotherapy should be customized to each patient individually based on their immune status and propose an integrative immunotherapy approach with second-generation group-specific component macrophage activating factor (GcMAF)-containing human serum. The standard protocol of our integrative cancer immunotherapy is as follows: i) 0.5 ml GcMAF-containing human serum is administered intramuscularly or subcutaneously once or twice per week for the duration of cancer therapy until all cancer cells are eradicated; ii) hyper T/natural killer (NK) cell therapy is given once per week for six weeks; iii) high-dose vitamin C is administered intravenously twice per week; iv) alpha lipoic acid (600 mg) is administered orally daily; v) vitamin D3 (5,000-10,000 IU) is administered orally daily. By March 2013, Saisei Mirai have treated over 345 patients with GcMAF. Among them we here present the cases of three patients for whom our integrative immunotherapy was remarkably effective. The results of our integrative immunotherapy seem hopeful. We also plan to conduct a comparative clinical study.>

Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia.

PubMed

Tissino, Erika; Benedetti, Dania; Herman, Sarah E M; Ten Hacken, Elisa; Ahn, Inhye E; Chaffee, Kari G; Rossi, Francesca Maria; Dal Bo, Michele; Bulian, Pietro; Bomben, Riccardo; Bayer, Elisabeth; Härzschel, Andrea; Gutjahr, Julia Christine; Postorino, Massimiliano; Santinelli, Enrico; Ayed, Ayed; Zaja, Francesco; Chiarenza, Annalisa; Pozzato, Gabriele; Chigaev, Alexandre; Sklar, Larry A; Burger, Jan A; Ferrajoli, Alessandra; Shanafelt, Tait D; Wiestner, Adrian; Del Poeta, Giovanni; Hartmann, Tanja Nicole; Gattei, Valter; Zucchetto, Antonella

2018-02-05

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors. © 2018 Tissino et al.

Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia

PubMed Central

Tissino, Erika; Benedetti, Dania; Herman, Sarah E.M.; ten Hacken, Elisa; Rossi, Francesca Maria; Dal Bo, Michele; Bulian, Pietro; Bomben, Riccardo; Bayer, Elisabeth; Härzschel, Andrea; Gutjahr, Julia Christine; Postorino, Massimiliano; Santinelli, Enrico; Zaja, Francesco; Pozzato, Gabriele; Chigaev, Alexandre; Sklar, Larry A.; Burger, Jan A.; Ferrajoli, Alessandra; Shanafelt, Tait D.; Wiestner, Adrian; Del Poeta, Giovanni; Hartmann, Tanja Nicole

2018-01-01

The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, which antagonizes B cell receptor (BCR) signals, demonstrates remarkable clinical activity in chronic lymphocytic leukemia (CLL). The lymphocytosis experienced by most patients under ibrutinib has previously been attributed to inhibition of BTK-dependent integrin and chemokine cues operating to retain the tumor cells in nodal compartments. Here, we show that the VLA-4 integrin, as expressed by CD49d-positive CLL, can be inside-out activated upon BCR triggering, thus reinforcing the adhesive capacities of CLL cells. In vitro and in vivo ibrutinib treatment, although reducing the constitutive VLA-4 activation and cell adhesion, can be overcome by exogenous BCR triggering in a BTK-independent manner involving PI3K. Clinically, in three independent ibrutinib-treated CLL cohorts, CD49d expression identifies cases with reduced lymphocytosis and inferior nodal response and behaves as independent predictor of shorter progression-free survival, suggesting the retention of CD49d-expressing CLL cells in tissue sites via activated VLA-4. Evaluation of CD49d expression should be incorporated in the characterization of CLL undergoing therapy with BCR inhibitors. PMID:29301866

Gamete activation: basic knowledge and clinical applications

PubMed Central

Tosti, Elisabetta; Ménézo, Yves

2016-01-01

changes in gamete morphology and behavior, the regulatory molecules triggering gamete activation and the intracellular ions and second messengers involved in active metabolic pathways in different species. Recent scientific advances suggest that artificial gamete activation may represent a novel technique to improve human IVF outcomes, but this approach requires caution. Wider implications Although controversial, manipulation of gamete activation represents a promising tool for ameliorating the fertilization rate in assisted reproductive technologies. A better knowledge of mechanisms that transform the quiescent oocyte into a pluripotent cell may also provide new insights for the clinical use of stem cells. PMID:27278231

Headache associated with sexual activity: demography, clinical features, and comorbidity.

PubMed

Frese, A; Eikermann, A; Frese, K; Schwaag, S; Husstedt, I-W; Evers, S

2003-09-23

S: To provide data on the demography, clinical features, and comorbidity of headache associated with sexual activity (HSA). Between 1996 and 2001, 51 patients with the diagnosis of HSA were questioned using a structured interview. The mean age at onset was 39.2 (+/-11.1) years. There was a clear male preponderance (2.9:1). The age at onset had two peaks, with a first peak between the 20th and 24th (n = 13) years of life and a second peak between the 35th and 44th (n = 20) years of life. Eleven patients had HSA type 1 (dull subtype), which gradually increased with increasing sexual excitement. The remaining (n = 40) had HSA type 2 (explosive subtype). The pain was predominantly bilateral (67%), and diffuse or occipital (76%). The quality was nearly equally distributed among dull, throbbing, and stabbing. HSA was not dependent on specific sexual habits and most often occurred during sexual activity with the usual partner (94%) and during masturbation (35%). There was a high comorbidity with migraine (25%), benign exertional headache (29%), and tension-type headache (45%). HSA types 1 and 2 did not significantly differ in demography, clinical features, or comorbidity, except for a higher probability of stopping the attack by breaking off sexual activity in HSA type 1. There were no cases with HSA type 3 (postural subtype). Mean age at onset, a male preponderance, a predominantly bilateral and occipital pain, and a high comorbidity with other primary headaches are in concordance with case reports in the literature. The authors found two peaks for the age at onset, however. There was no clinical evidence proving subtypes 1 and 2 to be distinct disorders. HSA types 1 and 2 may be different manifestations of the same disease rather than distinct entities.

A Few Observations and Remarks on Time Effectiveness of Interactive Electronic Testing

ERIC Educational Resources Information Center

Magdin, Martin; Turcáni, Milan

2015-01-01

In the paper, we point out several observations and remarks on time effectiveness of electronic testing, in particular of its new form (interactive tests). A test is often used as an effective didactic tool for evaluating the extent of gained cognitive capabilities. According to authors Rudman (1989) and Wang (2003) it is provable that the…

Olfactory Hallucinations without Clinical Motor Activity: A Comparison of Unirhinal with Birhinal Phantosmia

PubMed Central

Henkin, Robert I.; Potolicchio, Samuel J.; Levy, Lucien M.

2013-01-01

Olfactory hallucinations without subsequent myoclonic activity have not been well characterized or understood. Herein we describe, in a retrospective study, two major forms of olfactory hallucinations labeled phantosmias: one, unirhinal, the other, birhinal. To describe these disorders we performed several procedures to elucidate similarities and differences between these processes. From 1272, patients evaluated for taste and smell dysfunction at The Taste and Smell Clinic, Washington, DC with clinical history, neurological and otolaryngological examinations, evaluations of taste and smell function, EEG and neuroradiological studies 40 exhibited cyclic unirhinal phantosmia (CUP) usually without hyposmia whereas 88 exhibited non-cyclic birhinal phantosmia with associated symptomology (BPAS) with hyposmia. Patients with CUP developed phantosmia spontaneously or after laughing, coughing or shouting initially with spontaneous inhibition and subsequently with Valsalva maneuvers, sleep or nasal water inhalation; they had frequent EEG changes usually ipsilateral sharp waves. Patients with BPAS developed phantosmia secondary to several clinical events usually after hyposmia onset with few EEG changes; their phantosmia could not be initiated or inhibited by any physiological maneuver. CUP is uncommonly encountered and represents a newly defined clinical syndrome. BPAS is commonly encountered, has been observed previously but has not been clearly defined. Mechanisms responsible for phantosmia in each group were related to decreased gamma-aminobutyric acid (GABA) activity in specific brain regions. Treatment which activated brain GABA inhibited phantosmia in both groups. PMID:24961619

Network Analysis of Associations between Serum Interferon Alpha Activity, Autoantibodies, and Clinical Features in Systemic Lupus Erythematosus

PubMed Central

Weckerle, Corinna E.; Franek, Beverly S.; Kelly, Jennifer A.; Kumabe, Marissa; Mikolaitis, Rachel A.; Green, Stephanie L.; Utset, Tammy O.; Jolly, Meenakshi; James, Judith A.; Harley, John B.; Niewold, Timothy B.

2010-01-01

Background Interferon-alpha (IFN-α) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFN-α levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. We used multivariate and network analyses to detect associations between clinical and serologic disease manifestations and serum IFN-α activity in a large diverse SLE cohort. Methods 1089 SLE patients were studied (387 African-American, 186 Hispanic-American, and 516 European-American). Presence or absence of ACR clinical criteria for SLE, autoantibodies, and serum IFN-α activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each background separately to establish the network of associations between variables that were independently significant following Bonferroni correction. Results In all ancestral backgrounds, high IFN-α activity was associated with anti-Ro and anti-dsDNA antibodies (p-values 4.6×10−18 and 2.9 × 10−16 respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFN-α activity (p≤6.7×10−4). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared by more than one ancestral background. Associations between clinical criteria were different in different ancestral backgrounds, while autoantibody-IFN-α relationships were similar across backgrounds. IFN-α activity and autoantibodies were not associated with ACR clinical features in multivariate models. Conclusions Serum IFN-α activity was strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFN-α may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations. PMID:21162028

Exercise is medicine: some cautionary remarks in principle as well as in practice.

PubMed

Neville, Ross D

2013-08-01

On the basis of extensive research on the relationship between physical activity, exercise and health, as well as strong support from policymakers and practitioners, the "Exercise is Medicine" initiative has become something of a linchpin in the agenda for modern healthcare reform and reflects a broader acceptance that the philosophy of health politics must shift from social engineering to performativity. However, in spite of the avowed commitment to encouraging individuals to take on a more reflexive relation to their health, it remains unclear as to whether an initiative such as this is, unambiguously, a good thing. In this paper, a number of cautionary remarks are made with respect to "Exercise is Medicine" in principle as well as in practice. Firstly, it is argued that equating exercise with medicine is to equate it with a definition of and relation to the body to which it is not entirely akin. And secondly, it is argued that any proposed alignment of the fitness and healthcare industries needs further critical examination, a realigning of interests, and a thorough reconsideration of their suitability of fit.

Lack of Interferon and Proinflammatory Cyto/chemokines in Serologically Active Clinically Quiescent Systemic Lupus Erythematosus.

PubMed

Steiman, Amanda J; Gladman, Dafna D; Ibañez, Dominique; Noamani, Babak; Landolt-Marticorena, Carolina; Urowitz, Murray B; Wither, Joan E

2015-12-01

Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) remain clinically quiescent for prolonged periods despite anti-dsDNA antibodies and/or low complements, indicating the presence of immune complexes. The immune mechanisms leading to this quiescence are unknown. However, in addition to activating complement, immune complex uptake by various cells leads to the production of interferon (IFN)-α and other proinflammatory factors that are also involved in tissue damage. Here we investigate whether production of these factors is reduced in SACQ patients. The levels of 5 IFN-induced genes and 19 cyto/chemokines were measured in SACQ patients and were compared with those in serologically and clinically active (SACA) and serologically and clinically quiescent (SQCQ) patients. SACQ and SQCQ were defined as ≥ 2 years without clinical activity, with/without persistent serologic activity, respectively, and off corticosteroids/immunosuppressives. SACA was defined as disease activity compelling immunosuppression. Levels of OAS1, IFIT1, MX1, LY6E, and ISG15 were measured by quantitative real-time polymerase chain reaction (PCR) and a composite score (IFN-5) derived from this. Plasma cyto/chemokines were measured by Luminex assay. Nonparametric univariate and logistic regression analyses were conducted. There were no differences in gene expression or cyto/chemokine levels between SACQ and SQCQ patients. The SACQ IFN-5 score was significantly lower than that of SACA (p = 0.003) and was driven by SACQ status, not by autoantibody profile or disease duration. Levels of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 6, IL-10, IFN-γ-inducible protein 10, monocyte chemoattractant protein 1, and tumor necrosis factor-α were significantly lower in SACQ than SACA. The levels of proinflammatory factors in SACQ mirror those of SQCQ patients, indicating reduced production of these factors despite the presence of immune

Antibiofilm Activity of the Brown Alga Halidrys siliquosa against Clinically Relevant Human Pathogens

PubMed Central

Busetti, Alessandro; Thompson, Thomas P.; Tegazzini, Diana; Megaw, Julianne; Maggs, Christine A.; Gilmore, Brendan F.

2015-01-01

The marine brown alga Halidrys siliquosa is known to produce compounds with antifouling activity against several marine bacteria. The aim of this study was to evaluate the antimicrobial and antibiofilm activity of organic extracts obtained from the marine brown alga H. siliquosa against a focused panel of clinically relevant human pathogens commonly associated with biofilm-related infections. The partially fractionated methanolic extract obtained from H. siliquosa collected along the shores of Co. Donegal; Ireland; displayed antimicrobial activity against bacteria of the genus Staphylococcus; Streptococcus; Enterococcus; Pseudomonas; Stenotrophomonas; and Chromobacterium with MIC and MBC values ranging from 0.0391 to 5 mg/mL. Biofilms of S. aureus MRSA were found to be susceptible to the algal methanolic extract with MBEC values ranging from 1.25 mg/mL to 5 mg/mL respectively. Confocal laser scanning microscopy using LIVE/DEAD staining confirmed the antimicrobial nature of the antibiofilm activity observed using the MBEC assay. A bioassay-guided fractionation method was developed yielding 10 active fractions from which to perform purification and structural elucidation of clinically-relevant antibiofilm compounds. PMID:26058011

Cytotoxicity of cyclometalated platinum complexes based on tridentate NCN and CNN-coordinating ligands: remarkable coordination dependence.

PubMed

Vezzu, Dileep A K; Lu, Qun; Chen, Yan-Hua; Huo, Shouquan

2014-05-01

A series of cyclometalated platinum complexes with diverse coordination patterns and geometries were screened for their anticancer activity. It was discovered that the N^C^N-coordinated platinum complex based on 1,3-di(pyridyl)benzene displayed much higher cytotoxicity against human lung cancer cells NCI-H522, HCC827, and NCI-H1299, and human prostate cancer cell RV1 than cisplatin. In a sharp contrast, the C^N^N-coordinated platinum complex based on 6-phenyl-2,2'-bipyridine was ineffective on these cancer cells. This remarkable difference in cytotoxicity displayed by N^C^N- and C^N^N-coordinated platinum complexes was related to the trans effect of the carbon donor in the cyclometalated platinum complexes, which played a crucial role in facilitating the dissociation of the chloride ligand to create an active binding site. The DNA binding was studied for the N^C^N-coordinated platinum complex using electrophoresis and emission titration. The cellular uptake observed by fluorescent microscope showed that the complex is largely concentrated in the cytoplasm. The possible pathways for the cell apoptosis were studied by western blot analysis and the activation of PARP via caspase 7 was observed. Copyright © 2014 Elsevier Inc. All rights reserved.

Adaptive optics retinal imaging: emerging clinical applications.

PubMed

Godara, Pooja; Dubis, Adam M; Roorda, Austin; Duncan, Jacque L; Carroll, Joseph

2010-12-01

The human retina is a uniquely accessible tissue. Tools like scanning laser ophthalmoscopy and spectral domain-optical coherence tomography provide clinicians with remarkably clear pictures of the living retina. Although the anterior optics of the eye permit such non-invasive visualization of the retina and associated pathology, the same optics induce significant aberrations that obviate cellular-resolution imaging in most cases. Adaptive optics (AO) imaging systems use active optical elements to compensate for aberrations in the optical path between the object and the camera. When applied to the human eye, AO allows direct visualization of individual rod and cone photoreceptor cells, retinal pigment epithelium cells, and white blood cells. AO imaging has changed the way vision scientists and ophthalmologists see the retina, helping to clarify our understanding of retinal structure, function, and the etiology of various retinal pathologies. Here, we review some of the advances that were made possible with AO imaging of the human retina and discuss applications and future prospects for clinical imaging.

Resveratrol-Induced AMP-Activated Protein Kinase Activation Is Cell-Type Dependent: Lessons from Basic Research for Clinical Application.

PubMed

Lan, Fan; Weikel, Karen A; Cacicedo, Jose M; Ido, Yasuo

2017-07-14

Despite the promising effects of resveratrol, its efficacy in the clinic remains controversial. We were the first group to report that the SIRT1 activator resveratrol activates AMP-activated protein kinase (AMPK) (Diabetes 2005; 54: A383), and we think that the variability of this cascade may be responsible for the inconsistency of resveratrol's effects. Our current studies suggest that the effect of SIRT1 activators such as resveratrol may not be solely through activation of SIRT1, but also through an integrated effect of SIRT1-liver kinase B1 (LKB1)-AMPK. In this context, resveratrol activates SIRT1 (1) by directly binding to SIRT1; and (2) by increasing NAD⁺ levels by upregulating the salvage pathway through Nampt activation, an effect mediated by AMPK. The first mechanism promotes deacetylation of a limited number of SIRT1 substrate proteins (e.g., PGC-1). The second mechanism (which may be more important than the first) activates other sirtuins in addition to SIRT1, which affects a broad spectrum of substrates. Despite these findings, detailed mechanisms of how resveratrol activates AMPK have not been reported. Here, we show that (1) resveratrol-induced activation of AMPK requires the presence of functional LKB1; (2) Resveratrol increases LKB1 activity, which involves translocation and phosphorylation at T336 and S428; (3) Activation of LKB1 causes proteasomal degradation of LKB1; (4) At high concentrations (50-100 µM), resveratrol also activates AMPK through increasing AMP levels; and (5) The above-mentioned activation mechanisms vary among cell types, and in some cell types, resveratrol fails to activate AMPK. These results suggest that resveratrol-induced activation of AMPK is not a ubiquitous phenomenon. In addition, AMPK-mediated increases in NAD⁺ in the second mechanism require several ATPs, which may not be available in many pathological conditions. These phenomena may explain why resveratrol is not always consistently beneficial in a clinical

Novel inhibitors of HIV discovered among existing classes of pharmaceutical compounds indicated for unrelated clinical indications.

PubMed

Kucherov, I I; Rytik, P G; Podol'skaya, I A; Mistryukova, L O; Korjev, M O

2009-01-01

In vitro screening of 307 drugs with various clinical indications (cardiotropic, neurotropic, antibacterial, etc.) has revealed 6 compounds which displayed remarkable antiretroviral activity. Three of these drugs had a tendency to have undesirable side effects and were thus excluded from further consideration. Remaining three, i.e., Xantinol Nicotinate, Tardiferon, and Trental may become valid candidates for inclusion into antiviral regimens such as HAART. In vitro tests have shown that xantinol and trental display synergistic effect with azidothymidine, inhibit the replication AZT-resistant strains of HIV, and have no competing undesirable activities. These compounds should be evaluated in safety studies to determine optimal doses for patients with HIV. If these studies confirm in vitro results these compounds may become valid candidates as safe and affordable means to be added into the arsenal of antiretroviral drugs.

The remarkable convergence of skull shape in crocodilians and toothed whales

PubMed Central

Evans, Alistair R.; Fitzgerald, Erich M. G.; Adams, Justin W.; Clausen, Philip D.; McHenry, Colin R.

2017-01-01

The striking resemblance of long-snouted aquatic mammals and reptiles has long been considered an example of morphological convergence, yet the true cause of this similarity remains untested. We addressed this deficit through three-dimensional morphometric analysis of the full diversity of crocodilian and toothed whale (Odontoceti) skull shapes. Our focus on biomechanically important aspects of shape allowed us to overcome difficulties involved in comparing mammals and reptiles, which have fundamental differences in the number and position of skull bones. We examined whether diet, habitat and prey size correlated with skull shape using phylogenetically informed statistical procedures. Crocodilians and toothed whales have a similar range of skull shapes, varying from extremely short and broad to extremely elongate. This spectrum of shapes represented more of the total variation in our dataset than between phylogenetic groups. The most elongate species (river dolphins and gharials) are extremely convergent in skull shape, clustering outside of the range of the other taxa. Our results suggest the remarkable convergence between long-snouted river dolphins and gharials is driven by diet rather than physical factors intrinsic to riverine environments. Despite diverging approximately 288 million years ago, crocodilians and odontocetes have evolved a remarkably similar morphological solution to feeding on similar prey. PMID:28275142

The remarkable convergence of skull shape in crocodilians and toothed whales.

PubMed

McCurry, Matthew R; Evans, Alistair R; Fitzgerald, Erich M G; Adams, Justin W; Clausen, Philip D; McHenry, Colin R

2017-03-15

The striking resemblance of long-snouted aquatic mammals and reptiles has long been considered an example of morphological convergence, yet the true cause of this similarity remains untested. We addressed this deficit through three-dimensional morphometric analysis of the full diversity of crocodilian and toothed whale (Odontoceti) skull shapes. Our focus on biomechanically important aspects of shape allowed us to overcome difficulties involved in comparing mammals and reptiles, which have fundamental differences in the number and position of skull bones. We examined whether diet, habitat and prey size correlated with skull shape using phylogenetically informed statistical procedures. Crocodilians and toothed whales have a similar range of skull shapes, varying from extremely short and broad to extremely elongate. This spectrum of shapes represented more of the total variation in our dataset than between phylogenetic groups. The most elongate species (river dolphins and gharials) are extremely convergent in skull shape, clustering outside of the range of the other taxa. Our results suggest the remarkable convergence between long-snouted river dolphins and gharials is driven by diet rather than physical factors intrinsic to riverine environments. Despite diverging approximately 288 million years ago, crocodilians and odontocetes have evolved a remarkably similar morphological solution to feeding on similar prey. © 2017 The Author(s).

Active video games to promote physical activity in children with cancer: a randomized clinical trial with follow-up

PubMed Central

2014-01-01

Background Low levels of physical activity, musculoskeletal morbidity and weight gain are commonly reported problems in children with cancer. Intensive medical treatment and a decline in physical activity may also result in reduced motor performance. Therefore, simple and inexpensive ways to promote physical activity and exercise are becoming an increasingly important part of children’s cancer treatment. Methods The aim of this study is to evaluate the effect of active video games in promotion of physical activity in children with cancer. The research is conducted as a parallel randomized clinical trial with follow-up. Patients between 3 and 16 years old, diagnosed with cancer and treated with vincristine in two specialized medical centers are asked to participate. Based on statistical estimates, the target enrollment is 40 patients. The intervention includes playing elective active video games and, in addition, education and consultations for the family. The control group will receive a general recommendation for physical activity for 30 minutes per day. The main outcomes are the amount of physical activity and sedentary behavior. Other outcomes include motor performance, fatigue and metabolic risk factors. The outcomes are examined with questionnaires, diaries, physical examinations and blood tests at baseline and at 2, 6, 12 and 30 months after the baseline. Additionally, the children’s perceptions of the most enjoyable activation methods are explored through an interview at 2 months. Discussion This trial will help to answer the question of whether playing active video games is beneficial for children with cancer. It will also provide further reasoning for physical activity promotion and training of motor skills during treatment. Trial registration ClinicalTrials.gov identifier: NCT01748058 (October 15, 2012). PMID:24708773

Clinical Advances of Hypoxia-Activated Prodrugs in Combination With Radiation Therapy.

PubMed

Mistry, Ishna N; Thomas, Matthew; Calder, Ewen D D; Conway, Stuart J; Hammond, Ester M

2017-08-01

With the increasing incidence of cancer worldwide, the need for specific, effective therapies is ever more urgent. One example of targeted cancer therapeutics is hypoxia-activated prodrugs (HAPs), also known as bioreductive prodrugs. These prodrugs are inactive in cells with normal oxygen levels but in hypoxic cells (with low oxygen levels) undergo chemical reduction to the active compound. Hypoxia is a common feature of solid tumors and is associated with a more aggressive phenotype and resistance to all modes of therapy. Therefore, the combination of radiation therapy and bioreductive drugs presents an attractive opportunity for synergistic effects, because the HAP targets the radiation-resistant hypoxic cells. Hypoxia-activated prodrugs have typically been precursors of DNA-damaging agents, but a new generation of molecularly targeted HAPs is emerging. By targeting proteins associated with tumorigenesis and survival, these compounds may result in greater selectivity over healthy tissue. We review the clinical progress of HAPs as adjuncts to radiation therapy and conclude that the use of HAPs alongside radiation is vastly underexplored at the clinical level. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical pancreatic islet transplantation.

PubMed

Shapiro, A M James; Pokrywczynska, Marta; Ricordi, Camillo

2017-05-01

Clinical pancreatic islet transplantation can be considered one of the safest and least invasive transplant procedures. Remarkable progress has occurred in both the technical aspects of islet cell processing and the outcomes of clinical islet transplantation. With >1,500 patients treated since 2000, this therapeutic strategy has moved from a curiosity to a realistic treatment option for selected patients with type 1 diabetes mellitus (that is, those with hypoglycaemia unawareness, severe hypoglycaemic episodes and glycaemic lability). This Review outlines the techniques required for human islet isolation, in vitro culture before the transplant and clinical islet transplantation, and discusses indications, optimization of recipient immunosuppression and management of adjunctive immunomodulatory and anti-inflammatory strategies. The potential risks, long-term outcomes and advances in treatment after the transplant are also discussed to further move this treatment towards becoming a more widely available option for patients with type 1 diabetes mellitus and eventually a potential cure.

Clinical medicine between science, ethics and economy: a complex activity.

PubMed

Federspil, Giovanni

2004-01-01

Until recently the common opinion was that medicine was substantially a natural science. In recent years, this has completely changed because two non-naturalistic disciplines have become part of the physician's activity; ethics and economy. These new disciplines have evidenced many problems to which doctors did not pay much attention before; however, they had an impact on the clinician's sensibility. At present, clinical medicine represents a complex knowledge as well as an activity: it is both a "historical" and a "technological" science characterized by a specific goal, the recovery or maintenance of health, and by a series of values.

All-nanoparticle self-assembly ZnO/TiO₂ heterojunction thin films with remarkably enhanced photoelectrochemical activity.

PubMed

Yuan, Sujun; Mu, Jiuke; Mao, Ruiyi; Li, Yaogang; Zhang, Qinghong; Wang, Hongzhi

2014-04-23

The multilaminated ZnO/TiO2 heterojunction films were successfully deposited on conductive substrates including fluorine-doped tin oxide (FTO) glass and flexible indium tin oxide coated poly(ethylene terephthalate) via the layer-by-layer (LBL) self assembly method from the oxide colloids without using any polyelectrolytes. The positively charged ZnO nanoparticles and the negatively charged TiO2 nanoparticles were directly used as the components in the consecutive deposition process to prepare the heterojunction thin films by varying the thicknesses. Moreover, the crystal growth of both oxides could be efficiently inhibited by the good connection between ZnO and TiO2 nanoparticles even after calcination at 500 °C, especially for ZnO which was able to keep the crystallite size under 25 nm. The as-prepared films were used as the working electrodes in the three-electrode photoelectrochemical cells. Because the well-contacted nanoscale heterojunctions were formed during the LBL self-assembling process, the ZnO/TiO2 all-nanoparticle films deposited on both substrates showed remarkably enhanced photoelectrochemical properties compared to that of the well-established TiO2 LBL thin films with similar thicknesses. The photocurrent response collected from the ZnO/TiO2 electrode on the FTO glass substrate was about five times higher than that collected from the TiO2 electrode. Owing to the absence of the insulating layer of dried polyelectrolytes, the ZnO/TiO2 all-nanoparticle heterojunction films were expected to be used in the photoelectrochemical device before calcination.

Some remarks on the numerical solution of parabolic partial differential equations

NASA Astrophysics Data System (ADS)

Campagna, R.; Cuomo, S.; Leveque, S.; Toraldo, G.; Giannino, F.; Severino, G.

2017-11-01

Numerous environmental/engineering applications relying upon the theory of diffusion phenomena into chaotic environments have recently stimulated the interest toward the numerical solution of parabolic partial differential equations (PDEs). In the present paper, we outline a formulation of the mathematical problem underlying a quite general diffusion mechanism in the natural environments, and we shortly emphasize some remarks concerning the applicability of the (straightforward) finite difference method. An illustration example is also presented.

Additional Remarks on Designing Category-Level Attributes for Discriminative Visual Recognition

DTIC Science & Technology

2013-01-01

Discriminative Visual Recognition ∗ Felix X. Yu†, Liangliang Cao§, Rogerio S. Feris§, John R. Smith§, Shih-Fu Chang† † Columbia University § IBM T. J...for Designing Category-Level Attributes for Dis- criminative Visual Recognition [3]. We first provide an overview of the proposed ap- proach in...2013 to 00-00-2013 4. TITLE AND SUBTITLE Additional Remarks on Designing Category-Level Attributes for Discriminative Visual Recognition 5a

Closing remarks at the symposium in honour of Daniel Bellus. Pharmacenter, University of Basel, February 6, 2009.

PubMed

Ganter, Camille

2010-01-01

In the Closing Remarks at the Symposium on 'Frontiers in Bioorganic Chemistry' (Friday, February 6, 2009, Pharmacenter, University of Basel) in honour of Daniel Bellus, his arrival in Zürich in fall 1967 and especially his postdoctoral work at the Laboratorium für Organische Chemie at the Eidgenössische Technische Hochschule (ETH) in Zürich throughout the year 1967/68 were mentioned. In his most remarkable paper (published in 1969 in Helv. Chim. Acta), the photochemistry of the alpha,beta-unsaturated cyclohexenones O-acetyl-testosterone and 10-methy-delta1,9-octalon-(2) is described in detail. Change of solvent leads to lowering or increasing of the n,pi*- and (pi,pi*)-triplet energies, resulting in a crossing of the two energy levels. Personal remarks on Daniel Bellus and warmest thanks to him, to Profs. Beat Ernst and Bernd Giese (the organizers of the symposium) and to all the speakers concluded this most special event.

Correlation of alkaline phosphatase activity to clinical parameters of inflammation in smokers suffering from chronic periodontitis.

PubMed

Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Bither, Rupika; Sachdeva, Sonia

2016-01-01

Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. To evaluate the correlation of alkaline phosphatase (ALP) activity in gingival crevicular fluid (GCF) to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Study population included 15 smoker male patients in the age group of 35-55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD), relative attachment level (RAL), and GCF ALP activity. Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy.

21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

21 CFR 312.87 - Active monitoring of conduct and evaluation of clinical trials.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Active monitoring of conduct and evaluation of clinical trials. 312.87 Section 312.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... to Treat Life-threatening and Severely-debilitating Illnesses § 312.87 Active monitoring of conduct...

Characterization of remarkable floods in France, a transdisciplinary approach applied on generalized floods of January 1910

NASA Astrophysics Data System (ADS)

Boudou, Martin; Lang, Michel; Vinet, Freddy; Coeur, Denis

2014-05-01

The 2007 Flood Directive promotes the integration and valorization of historical and significant floods in flood risk management (Flood Directive Text, chapter II, and article 4). Taking into account extreme past floods analysis seems necessary in the mitigation process of vulnerability face to flooding risk. In France, this aspect of the Directive was carried out through the elaboration of Preliminary Flood Risk Assessment (PFRA) and the establishment of a 2000 floods list. From this first list, a sample of 176 floods, considered as remarkable has been selected. These floods were compiled in discussion with local authorities in charge of flood management (Lang et al., 2012) and have to be integrated in priority in local risk management policies. However, a consideration emerges about this classification: how a remarkable flood can be defined? According which criteria can it be considered as remarkable? To answer these questions, a methodology has been established by building an evaluation grid of remarkable floods in France. The primary objective of this grid is to analyze the remarkable flood's characteristics (hydrological and meteorological characteristics, sociological- political and economic impacts), and secondly to propose a classification of significant floods selected in the 2011 PFRA. To elaborate this evaluation grid, several issues had to be taken into account. First, the objective is to allow the comparison of events from various periods. These temporal disparities include the integration of various kinds of data and point out the importance of historical hydrology. It is possible to evaluate accurately the characteristics of recent floods by interpreting quantitative data (for example hydrological records. However, for floods that occurred before the 1960's it is necessary resorting to qualitative information such as written sources is necessary (Coeur, Lang, 2008). In a second part the evaluation grid requires equitable criteria in order not to

Wearable Internet of Things - from human activity tracking to clinical integration.

PubMed

Kumari, Poonam; Lopez-Benitez, Miguel; Gyu Myoung Lee; Tae-Seong Kim; Minhas, Atul S

2017-07-01

Wearable devices for human activity tracking have been emerging rapidly. Most of them are capable of sending health statistics to smartphones, smartwatches or smart bands. However, they only provide the data for individual analysis and their data is not integrated into clinical practice. Leveraging on the Internet of Things (IoT), edge and cloud computing technologies, we propose an architecture which is capable of providing cloud based clinical services using human activity data. Such services could supplement the shortage of staff in primary healthcare centers thereby reducing the burden on healthcare service providers. The enormous amount of data created from such services could also be utilized for planning future therapies by studying recovery cycles of existing patients. We provide a prototype based on our architecture and discuss its salient features. We also provide use cases of our system in personalized and home based healthcare services. We propose an International Telecommunication Union based standardization (ITU-T) for our design and discuss future directions in wearable IoT.

Premna grandipaniculata (Lamiaceae, Premnoideae), a remarkable new species from north Myanmar

PubMed Central

Tan, Yun-Hong; Li, De-Rong; Zhou, Shi-Shun; Chen, Yong-Jun; Bramley, Gemma L.C.; Li, Bo

2018-01-01

Abstract A remarkable new Premna species from Myanmar, P. grandipaniculata Y.H.Tan & Bo Li (Lamiaceae), is here described and illustrated. It differs from all known congeneric taxa by having huge complicated panicles which have tertiary branches formed by spike-like thyrses. In Premna, such a spike-like thyrse is found in P. bracteata and P. interrupta, but those species can be easily distinguished from P. grandipaniculata by their habit, indumentum, leaf size and inflorescence structure. PMID:29416426

Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

PubMed Central

Weygandt, Martin; Meyer-Arndt, Lil; Behrens, Janina Ruth; Wakonig, Katharina; Bellmann-Strobl, Judith; Ritter, Kerstin; Scheel, Michael; Brandt, Alexander U.; Labadie, Christian; Hetzer, Stefan; Gold, Stefan M.; Paul, Friedemann; Haynes, John-Dylan

2016-01-01

Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was related to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, stress responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to impairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy (i.e., positively to GM volume) in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone. PMID:27821732

Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities

PubMed Central

Schweizer, Frank

2017-01-01

Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV), leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant fluoroquinolones display a remarkable selectivity for prokaryotic topoisomerase II, with excellent safety records in humans. Typical agents that target human topoisomerases (such as etoposide, doxorubicin and mitoxantrone) are associated with significant toxicities and secondary malignancies, whereas clinically relevant fluoroquinolones are not known to exhibit such propensities. Although many fluoroquinolones have been shown to display topoisomerase-independent antiproliferative effects against various human cancer cells, those that are significantly active against eukaryotic topoisomerase show the same DNA damaging properties as other topoisomerase poisons. Empirical models also show that fluoroquinolones mediate some unique immunomodulatory activities of suppressing pro-inflammatory cytokines and super-inducing interleukin-2. This article reviews the extended roles of fluoroquinolones and their prospects as lead for the unmet needs of “small and safe” multimodal-targeting drug scaffolds. PMID:29112154

Medicinal Mushrooms in Human Clinical Studies. Part I. Anticancer, Oncoimmunological, and Immunomodulatory Activities: A Review.

PubMed

Wasser, Solomon P

2017-01-01

More than 130 medicinal functions are thought to be produced by medicinal mushrooms (MMs) and fungi, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, antihypercholesterolemic, antiviral, antibacterial, antiparasitic, antifungal, detoxification, hepatoprotective, antidiabetic, and other effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelia, and cultured broth. Special attention has been paid to mushroom polysaccharides. Numerous bioactive polysaccharides or polysaccharide-protein complexes from MMs seem to enhance innate and cell-mediated immune responses, and they exhibit antitumor activities in animals and humans. While the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds seems to be central. Most important for modern medicine are polysaccharides and low-molecular weight secondary metabolites with antitumor and immunostimulating properties. More than 600 studies have been conducted worldwide, and numerous human clinical trials on MMs have been published. Several of the mushroom compounds have proceeded through phase I, II, and III clinical studies and are used extensively and successfully in Asia to treat various cancers and other diseases. The aim of this review is to provide an overview of and analyze the literature on clinical trials using MMs with human anticancer, oncoimmunological, and immunomodulatory activities. High-quality, long-term, randomized, double-blind, placebo-controlled clinical studies of MMs, including well-sized population studies are definitely needed in order to yield statistical power showing their efficacy and safety. Clinical trials must obtain sufficient data on the efficacy and safety of MM-derived drugs and preparations. Discussion of results based on clinical studies of the anticancer, oncoimmunological, and

Antifungal activity of low molecular weight chitosan against clinical isolates of Candida spp.

PubMed

Alburquenque, Claudio; Bucarey, Sergio A; Neira-Carrillo, Andrónico; Urzúa, Blanca; Hermosilla, Germán; Tapia, Cecilia V

2010-12-01

Chitosan is a natural polymer derived from chitin, a structural component of fungi, insects and shrimp, which exerts antimicrobial effects against bacteria and fungi. The aim of this study was to investigate the in vitro antifungal activity of low molecular weight chitosan (LMWC), and the potential synergy between chitosan and a currently used antifungal drug, fluconazole. The in vitro minimal inhibitory concentrations (MICs) of chitosan and fluconazole against 105 clinical Candida isolates were measured by the broth microdilution method. LMWC exhibited a significant antifungal activity, inhibiting over 89.9% of the clinical isolates examined (68.6% of which was completely inhibited). The species included several fluconazole-resistant strains and less susceptible species such as C. glabrata, which was inhibited at a concentration of 4.8 mg/l LMWC. Although some strains were susceptible at pH 7.0, a greater antifungal activity of LMWC was observed at pH 4.0. There was no evidence of a synergistic effect of the combination of LMWC and fluconazole at pH 7.0. This is the first report in which the antifungal activity of LMWC was investigated with clinical Candida strains. The use of LMWC as an antifungal compound opens new therapeutic perspectives, as the low toxicity of LMWC in humans supports its use in new applications in an environment of pH 4.0-4.5, such as a topical agent for vulvovaginal candidiasis.

The effect of active video games on cognitive functioning in clinical and non-clinical populations: A meta-analysis of randomized controlled trials.

PubMed

Stanmore, Emma; Stubbs, Brendon; Vancampfort, Davy; de Bruin, Eling D; Firth, Joseph

2017-07-01

Physically-active video games ('exergames') have recently gained popularity for leisure and entertainment purposes. Using exergames to combine physical activity and cognitively-demanding tasks may offer a novel strategy to improve cognitive functioning. Therefore, this systematic review and meta-analysis was performed to establish effects of exergames on overall cognition and specific cognitive domains in clinical and non-clinical populations. We identified 17 eligible RCTs with cognitive outcome data for 926 participants. Random-effects meta-analyses found exergames significantly improved global cognition (g=0.436, 95% CI=0.18-0.69, p=0.001). Significant effects still existed when excluding waitlist-only controlled studies, and when comparing to physical activity interventions. Furthermore, benefits of exergames where observed for both healthy older adults and clinical populations with conditions associated with neurocognitive impairments (all p<0.05). Domain-specific analyses found exergames improved executive functions, attentional processing and visuospatial skills. The findings present the first meta-analytic evidence for effects of exergames on cognition. Future research must establish which patient/treatment factors influence efficacy of exergames, and explore neurobiological mechanisms of action. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Enhanced platelet/endothelial activation in depressed patients with acute coronary syndromes: evidence from recent clinical trials.

PubMed

Serebruany, Victor L; Glassman, Alexander H; Malinin, Alex I; Sane, David C; Finkel, Mitchell S; Krishnan, Ranga R; Atar, Dan; Lekht, Vladimir; O'Connor, Christopher M

2003-09-01

Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective

Concluding remarks: Faraday Discussion on chemistry in the urban atmosphere.

PubMed

Jimenez, Jose L

2016-07-18

This article summarises the Concluding remarks from the Faraday Discussion on Chemistry in the Urban Atmosphere. The following themes are addressed: (a) new results that inform our understanding of the evolving sources and composition of the urban atmosphere ("News"); (b) results that identify gaps in our understanding that necessitate further work ("Gaps"); (c) the emerging instrumentation revolution and some of the challenges that it brings; (d) the structural issues of insufficient support for the analysis of field campaigns; and (e) some important areas that were missing from this Faraday Discussion and that should receive an increasing focus in the future.

Active learning reduces annotation time for clinical concept extraction.

PubMed

Kholghi, Mahnoosh; Sitbon, Laurianne; Zuccon, Guido; Nguyen, Anthony

2017-10-01

To investigate: (1) the annotation time savings by various active learning query strategies compared to supervised learning and a random sampling baseline, and (2) the benefits of active learning-assisted pre-annotations in accelerating the manual annotation process compared to de novo annotation. There are 73 and 120 discharge summary reports provided by Beth Israel institute in the train and test sets of the concept extraction task in the i2b2/VA 2010 challenge, respectively. The 73 reports were used in user study experiments for manual annotation. First, all sequences within the 73 reports were manually annotated from scratch. Next, active learning models were built to generate pre-annotations for the sequences selected by a query strategy. The annotation/reviewing time per sequence was recorded. The 120 test reports were used to measure the effectiveness of the active learning models. When annotating from scratch, active learning reduced the annotation time up to 35% and 28% compared to a fully supervised approach and a random sampling baseline, respectively. Reviewing active learning-assisted pre-annotations resulted in 20% further reduction of the annotation time when compared to de novo annotation. The number of concepts that require manual annotation is a good indicator of the annotation time for various active learning approaches as demonstrated by high correlation between time rate and concept annotation rate. Active learning has a key role in reducing the time required to manually annotate domain concepts from clinical free text, either when annotating from scratch or reviewing active learning-assisted pre-annotations. Copyright © 2017 Elsevier B.V. All rights reserved.

Multifunctional biosynthesized silver nanoparticles exhibiting excellent antimicrobial potential against multi-drug resistant microbes along with remarkable anticancerous properties.

PubMed

Jha, Diksha; Thiruveedula, Prasanna Kumar; Pathak, Rajiv; Kumar, Bipul; Gautam, Hemant K; Agnihotri, Shrish; Sharma, Ashwani Kumar; Kumar, Pradeep

2017-11-01

This study demonstrates the therapeutic potential of silver nanoparticles (AgNPs), which were biosynthesized using the extracts of Citrus maxima plant. Characterization through UV-Vis spectrophotometry, Dynamic Light Scattering (DLS), Fourier Transform Infrared spectroscopy (FTIR), X-ray Diffraction (XRD) and Transmission Electron Microscopy (TEM) confirmed the formation of AgNps in nano-size range. These nanoparticles exhibited enhanced antioxidative activity and showed commendable antimicrobial activity against wide range of microbes including multi-drug resistant bacteria that were later confirmed by TEM. These particles exhibited minimal toxicity when cytotoxicity study was performed on normal human lung fibroblast cell line as well as human red blood cells. It was quite noteworthy that these particles showed remarkable cytotoxicity on human fibrosarcoma and mouse melanoma cell line (B16-F10). Additionally, the apoptotic topographies of B16-F10 cells treated with AgNps were confirmed by using acridine orange and ethidium bromide dual dye staining, caspase-3 assay, DNA fragmentation assay followed by cell cycle analysis using fluorescence-activated cell sorting. Taken together, these results advocate promising potential of the biosynthesized AgNps for their use in therapeutic applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural, Functional, and Clinical Characterization of a Novel PTPN11 Mutation Cluster Underlying Noonan Syndrome.

PubMed

Pannone, Luca; Bocchinfuso, Gianfranco; Flex, Elisabetta; Rossi, Cesare; Baldassarre, Giuseppina; Lissewski, Christina; Pantaleoni, Francesca; Consoli, Federica; Lepri, Francesca; Magliozzi, Monia; Anselmi, Massimiliano; Delle Vigne, Silvia; Sorge, Giovanni; Karaer, Kadri; Cuturilo, Goran; Sartorio, Alessandro; Tinschert, Sigrid; Accadia, Maria; Digilio, Maria C; Zampino, Giuseppe; De Luca, Alessandro; Cavé, Hélène; Zenker, Martin; Gelb, Bruce D; Dallapiccola, Bruno; Stella, Lorenzo; Ferrero, Giovanni B; Martinelli, Simone; Tartaglia, Marco

2017-04-01

Germline mutations in PTPN11, the gene encoding the Src-homology 2 (SH2) domain-containing protein tyrosine phosphatase (SHP2), cause Noonan syndrome (NS), a relatively common, clinically variable, multisystem disorder. Here, we report on the identification of five different PTPN11 missense changes affecting residues Leu 261 , Leu 262 , and Arg 265 in 16 unrelated individuals with clinical diagnosis of NS or with features suggestive for this disorder, specifying a novel disease-causing mutation cluster. Expression of the mutant proteins in HEK293T cells documented their activating role on MAPK signaling. Structural data predicted a gain-of-function role of substitutions at residues Leu 262 and Arg 265 exerted by disruption of the N-SH2/PTP autoinhibitory interaction. Molecular dynamics simulations suggested a more complex behavior for changes affecting Leu 261 , with possible impact on SHP2's catalytic activity/selectivity and proper interaction of the PTP domain with the regulatory SH2 domains. Consistent with that, biochemical data indicated that substitutions at codons 262 and 265 increased the catalytic activity of the phosphatase, while those affecting codon 261 were only moderately activating but impacted substrate specificity. Remarkably, these mutations underlie a relatively mild form of NS characterized by low prevalence of cardiac defects, short stature, and cognitive and behavioral issues, as well as less evident typical facial features. © 2017 WILEY PERIODICALS, INC.

Five years of experience with the DSM-III system in clinical work and research: some concluding remarks.

PubMed

Malt, U

1986-01-01

The reliability of the DSM-III is superior to other classification systems available in psychiatry. However, reliability depends on proper knowledge of the system. Some pitfalls reducing reliability of axis 1 diagnosis which commonly are overlooked are discussed. Secondly, some problems of validity of axis 1 and 2 are considered. This is done by discussing the differential diagnosis of organic mental disorders and other psychiatric disorders with concomittant physical dysfunction, and the diagnoses of post-traumatic stress disorders and adjustment disorders among others. The emphasis on health care seeking behaviour as a diagnostic criteria in the DSM-III system, may cause a social, racial and sexual bias in DSM-III diagnoses. The present discussion of the DSM-III system from a clinical point of view indicates the need for validation studies based on clinical experience with the DSM-III. These studies should include more out-patients and patients with psychopathology who do not seek psychiatric treatment. Such studies must also apply alternative diagnostic standards like the ICD-9 and not only rely on structured psychiatric interviews constructed for DSM-III diagnoses. The discussion of axis 4 points to the problem of wanting to combine reliable rating with clinically meaningful information. It is concluded that the most important issue to be settled regarding axis 4 in the future revisions is the aim of including this axis. The discussion of axis 5 concludes that axis 5 is biased toward poor functioning and thus may be less usefull when applied on patients seen outside hospitals. Despite these problems of the DSM-III, our experiences indicate that the use of the DSM-III is fruitful both for the patient, the clinician and the researcher. Thus, the cost of time and effort needed to learn to use the DSM-III properly are small compared to the benefits achieved by using the system.

Active multimodal psychotherapy in children and adolescents with suicidality: description, evaluation and clinical profile.

PubMed

Högberg, Goran; Hällström, Tore

2008-07-01

The aim of this study was to describe and evaluate the clinical pattern of 14 youths with presenting suicidality, to describe an integrative treatment approach, and to estimate therapy effectiveness. Fourteen patients aged 10 to 18 years from a child and adolescent outpatient clinic in Stockholm were followed in a case series. The patients were treated with active multimodal psychotherapy. This consisted of mood charting by mood-maps, psycho-education, wellbeing practice and trauma resolution. Active techniques were psychodrama and body-mind focused techniques including eye movement desensitization and reprocessing. The patients were assessed before treatment, immediately after treatment and at 22 months post treatment with the Global Assessment of Functioning Scale. The clinical pattern of the group was observed. After treatment there was a significant change towards normality in the Global Assessment of Functioning scale both immediately post-treatment and at 22 months. A clinical pattern, post trauma suicidal reaction, was observed with a combination of suicidality, insomnia, bodily symptoms and disturbed mood regulation. We conclude that in the post trauma reaction suicidality might be a presenting symptom in young people. Despite the shortcomings of a case series the results of this study suggest that a mood-map-based multimodal treatment approach with active techniques might be of value in the treatment of children and youth with suicidality.

Biochemical and antimicrobial activity of phloretin and its glycosilated derivatives present in apple and kumquat.

PubMed

Barreca, Davide; Bellocco, Ersilia; Laganà, Giuseppina; Ginestra, Giovanna; Bisignano, Carlo

2014-10-01

Phloretin and its glycosylated derivatives (phlorizin and phloretin 3',5'-di-C-glucoside) are dihydrochalcones that have many interesting biological properties. The results obtained showed that the dihydrochalcones are able to inhibit growth of Gram positive bacteria, in particular Staphylococcus aureus ATCC 6538, Listeria monocytogenes ATCC 13932 and methicillin-resistant S. aureus clinical strains. Moreover, phloretin is active also against the Gram negative bacteria Salmonella typhimurium ATCC 13311. The determination of the enzymatic activity of key metabolic enzymes allowed us to shed some light on the biochemical mechanism of aglycon cell growth inhibition, showing as it remarkably influences the energetic metabolism of S. aureus. In addition, structure/activity determinations highlighted that the presence of a glycosyl moiety bound to the chalcone structure dramatically decreases the antimicrobial activity of phloretin. Copyright © 2014 Elsevier Ltd. All rights reserved.

Physical Activity of Nurse Clinical Practitioners and Managers.

PubMed

Jirathananuwat, Areeya; Pongpirul, Krit

2017-11-01

This study was aimed (1) to compare the level of physical activity (PA) between working and nonworking hours and (2) to compare the level of PA during working hours of nurse clinical practitioners (NCPs) with that of nurse managers (NMs). This cross-sectional survey was conducted at a Thai university hospital from October 2015 to March 2016. All randomly selected participants wore an activity tracker on their hip for 5 days, except during bathing and sleeping periods, to record step counts and time points. Of 884 nurses, 289 (142 NCPs and 147 NMs) were randomly selected. The average age was 35.87 years. They spent 9.76 and 6.01 hours on work and nonwork activities, respectively. Daily steps per hour were significantly lower during work than nonwork periods (P < .001). An NCP had significantly higher overall hourly PA (P = .002). The number of steps per hour during work period of NCP was significantly higher than that of NM even after adjusting for age, work experience, and body mass index (P = .034). NCP had higher overall PA than NM, which was partly contributed by work-related PA. Level of PA for a professional with variation of actual work hours should be measured on hourly basis.

Remarkable response with pembrolizumab plus albumin-bound paclitaxel in 2 cases of HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy.

PubMed

Li, Bian; Tao, Wang; Shao-Hua, Zhang; Ze-Rui, Qu; Fu-Quan, Jin; Fan, Li; Ze-Fei, Jiang

2018-04-03

In clinical practice, one subgroup patients of breast cancer might have developed resistance to multi-anti-HER2 targeted drugs(trastuzumab, lapatinib and/or T-DM1) and can not benefit from the anti-HER2 targeted therapy continuously. We attempt to change the next therapic way for these patients. Two patients with metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy were treated with pembrolizumab (2 mg/Kg, day1) plus albumin-bound paclitaxel (125 mg/m 2 , day1,8) every 3 weeks. CT evaluation and HER2 ECD test were performed every 2 cycles. Both of the two patients achieved remarkable response with Partial Remission (PR), meanwhile serum HER2 ECD levels (the upper normal limit is 15 ng/ml) showed a remarkable decreases(compared to the base line decreases 75% and 60% respectively). The results indicate that regimen of pembrolizumab combination with albumin-bound paclitaxel might produce response in patients with HER2-positive metastatic breast cancer who have failed to multi-anti-HER2 targeted therapy.

Developing a primary dental care outreach (PDCO) course--part 1: practical issues and evaluation of clinical activity.

PubMed

Hind, V; Waterhouse, P J; Maguire, A; Tabari, D; Lloyd, J

2009-11-01

The primary dental care outreach (PDCO) course in Newcastle, UK commenced in September 2004 with dental undergraduates attending outreach clinics on a fortnightly rotation over a 2 year continuous placement. To evaluate the PDCO with respect to practical issues and clinical activity. Clinical activity data were collected using data sheets and Access software together with data on patient attendances and Structured Clinical Operative Tests (SCOTs). Comparative clinical data were collected from the same group of students in Child Dental Health (CDH) in the School of Dental Sciences. In 2004/2005, 1683 clinical procedures were undertaken in PDCO and 1362 in CDH. Of the treatment undertaken in PDCO, 37.1% was examination and treatment planning, 17.1% basic intracoronal restorations and 13.1% fissure sealing, the activity representative of day to day in general practice. Completion rates for the five piloted SCOTs in cross infection control, writing a prescription, writing a referral letter, taking a valid consent and taking a radiograph ranged from 74% to 97% in 2004/2006. The practical issues and challenges of delivering a new clinical course broadly related to induction of new PDCO staff, support of staff, establishing effective communication, timetabling logistics, delivery of clinical teaching and quality assurance. Once the practical issues and challenges of setting up a new clinical course have been overcome PDCO has a valuable role to play in preparing undergraduates for their future practising careers.

Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy

PubMed Central

Rodriguez, Isaac A.; Growney Kalaf, Emily A.; Bowlin, Gary L.; Sell, Scott A.

2014-01-01

Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both in vitro and in vivo scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use. PMID:25050347

Frictional wave dissipation on a remarkably rough reef

NASA Astrophysics Data System (ADS)

Monismith, Stephen G.; Rogers, Justin S.; Koweek, David; Dunbar, Robert B.

2015-05-01

We present a week of observations of wave dissipation on the south forereef of Palmyra Atoll. Using wave measurements made in 6.2 m and 11.2 m of water offshore of the surf zone, we computed energy fluxes and near-bottom velocity. Equating the divergence of the shoreward energy flux to its dissipation by bottom friction and parameterizating dissipation in terms of the root-mean-square velocity cubed, we find that the wave friction factor, fw, for this reef is 1.80 ± 0.07, nearly an order of magnitude larger than values previously found for reefs. We attribute this remarkably high value of fw to the complex canopy structure of the reef, which we believe may be characteristic of healthy reefs. This suggests that healthy reefs with high coral cover may provide greater coastal protection than do degraded reefs with low coral cover.

Australian doctors' non-clinical activities: results from the Medicine in Australia: Balancing Employment and Life (MABEL) survey of doctors.

PubMed

Joyce, Catherine; Eyre, Harris; Wang, Wei Chun; Laurence, Caroline

2015-11-01

The aim of the present study was to investigate non-clinical work conducted by Australian doctors. This study was an exploratory descriptive study using data from Wave 5 of the Medicine in Australia: Balancing Employment and Life (MABEL) longitudinal survey, collected in 2012 from Australian medical practitioners (2200 general practitioners (GPs), 3455 specialists, 1270 specialists in training and 1656 hospital non-specialists). The main outcome measure was the number of hours worked per week in non-clinical work. Regression analysis was used to determine associations between non-clinical activities (i.e. education-related, management and administration and other) and personal and professional characteristics, including age, gender, job and life satisfaction, total clinical working hours, sector of practice (public or private) and doctor type. Australian doctors spend an average of just under 7 h per week, or 16% of their working time, on non-clinical activities. Doctors who worked more hours on non-clinical activities overall, and in education-related and management and administration specifically, were male, younger, had lower life satisfaction and generally spent fewer hours on clinical work. Lower job satisfaction was associated with longer management and administration hours, but not with time spent in education-related activities. Specialists were more likely to work long non-clinical hours, whereas GPs were more likely to report none. Hospital non-specialists reported relatively high management and administration hours. Further work is required to better understand the full range of non-clinical activities doctors are involved in and how this may impact future workforce projections.

14 CFR 151.15 - Federal-aid Airport Program: Policy affecting runway or taxiway remarking.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Federal-aid Airport Program: Policy... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS General Requirements § 151.15 Federal-aid Airport Program: Policy affecting runway or taxiway remarking. No project for...

14 CFR 151.15 - Federal-aid Airport Program: Policy affecting runway or taxiway remarking.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Federal-aid Airport Program: Policy... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS General Requirements § 151.15 Federal-aid Airport Program: Policy affecting runway or taxiway remarking. No project for...

14 CFR 151.15 - Federal-aid Airport Program: Policy affecting runway or taxiway remarking.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Federal-aid Airport Program: Policy... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS General Requirements § 151.15 Federal-aid Airport Program: Policy affecting runway or taxiway remarking. No project for...

Pharmacological Activity and Clinical Use of PDRN

PubMed Central

Squadrito, Francesco; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Minutoli, Letteria; Altavilla, Domenica

2017-01-01

PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects. PMID:28491036

Survey of occupational therapy students' attitudes towards sexual issues in clinical practice.

PubMed

Jones, Mairwen K; Weerakoon, Patricia; Pynor, Rosemary A

2005-01-01

The purpose of this study was to examine the level of comfort of 340 occupational therapy students during clinical interactions that have sexual implications. Participants completed the Comfort Scale Questionnaire to indicate their anticipated level of comfort. More than half of the students anticipated that they would not feel comfortable in dealing with sexual issues. The three items that students indicated as being most uncomfortable with were 'Walking in on a patient/client who is masturbating' (91.7%), 'Dealing with a patient/client who makes an overt sexual remark' (82.1%) and 'Dealing with a patient/client who makes a covert sexual remark' (77.2%). The three items which students felt relatively comfortable with were 'Homosexual male' (26.4%), '14-year-old female seeking contraception' (26.4%) and 'Handicapped individual who is inquiring about sexual options' (33.5%). At least half the senior students believed that their educational programme had not dealt adequately with sexual issues. Further research investigating the nature and origin of discomfort in clinical settings is recommended as well as research examining the effectiveness of sexuality education in increasing comfort in dealing with sexual issues in clinical settings.

A meta-meta-analysis of the effect of physical activity on depression and anxiety in non-clinical adult populations.

PubMed

Rebar, Amanda L; Stanton, Robert; Geard, David; Short, Camille; Duncan, Mitch J; Vandelanotte, Corneel

2015-01-01

Amidst strong efforts to promote the therapeutic benefits of physical activity for reducing depression and anxiety in clinical populations, little focus has been directed towards the mental health benefits of activity for non-clinical populations. The objective of this meta-meta-analysis was to systematically aggregate and quantify high-quality meta-analytic findings of the effects of physical activity on depression and anxiety for non-clinical populations. A systematic search identified eight meta-analytic outcomes of randomised trials that investigated the effects of physical activity on depression or anxiety. The subsequent meta-meta-analyses were based on a total of 92 studies with 4310 participants for the effect of physical activity on depression and 306 study effects with 10,755 participants for the effect of physical activity on anxiety. Physical activity reduced depression by a medium effect [standardised mean difference (SMD) = -0.50; 95% CI: -0.93 to -0.06] and anxiety by a small effect (SMD = -0.38; 95% CI: -0.66 to -0.11). Neither effect showed significant heterogeneity across meta-analyses. These findings represent a comprehensive body of high-quality evidence that physical activity reduces depression and anxiety in non-clinical populations.

The EXCITE Trial: Predicting a Clinically Meaningful Motor Activity Log Outcome

PubMed Central

Park, Si-Woon; Wolf, Steven L.; Blanton, Sarah; Winstein, Carolee; Nichols-Larsen, Deborah S.

2013-01-01

Background and Objective This study determined which baseline clinical measurements best predicted a predefined clinically meaningful outcome on the Motor Activity Log (MAL) and developed a predictive multivariate model to determine outcome after 2 weeks of constraint-induced movement therapy (CIMT) and 12 months later using the database from participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial. Methods A clinically meaningful CIMT outcome was defined as achieving higher than 3 on the MAL Quality of Movement (QOM) scale. Predictive variables included baseline MAL, Wolf Motor Function Test (WMFT), the sensory and motor portion of the Fugl-Meyer Assessment (FMA), spasticity, visual perception, age, gender, type of stroke, concordance, and time after stroke. Significant predictors identified by univariate analysis were used to develop the multivariate model. Predictive equations were generated and odds ratios for predictors were calculated from the multivariate model. Results Pretreatment motor function measured by MAL QOM, WMFT, and FMA were significantly associated with outcome immediately after CIMT. Pretreatment MAL QOM, WMFT, proprioception, and age were significantly associated with outcome after 12 months. Each unit of higher pretreatment MAL QOM score and each unit of faster pretreatment WMFT log mean time improved the probability of achieving a clinically meaningful outcome by 7 and 3 times at posttreatment, and 5 and 2 times after 12 months, respectively. Patients with impaired proprioception had a 20% probability of achieving a clinically meaningful outcome compared with those with intact proprioception. Conclusions Baseline clinical measures of motor and sensory function can be used to predict a clinically meaningful outcome after CIMT. PMID:18780883

The EXCITE Trial: Predicting a clinically meaningful motor activity log outcome.

PubMed

Park, Si-Woon; Wolf, Steven L; Blanton, Sarah; Winstein, Carolee; Nichols-Larsen, Deborah S

2008-01-01

This study determined which baseline clinical measurements best predicted a predefined clinically meaningful outcome on the Motor Activity Log (MAL) and developed a predictive multivariate model to determine outcome after 2 weeks of constraint-induced movement therapy (CIMT) and 12 months later using the database from participants in the Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial. A clinically meaningful CIMT outcome was defined as achieving higher than 3 on the MAL Quality of Movement (QOM) scale. Predictive variables included baseline MAL, Wolf Motor Function Test (WMFT), the sensory and motor portion of the Fugl-Meyer Assessment (FMA), spasticity, visual perception, age, gender, type of stroke, concordance, and time after stroke. Significant predictors identified by univariate analysis were used to develop the multivariate model. Predictive equations were generated and odds ratios for predictors were calculated from the multivariate model. Pretreatment motor function measured by MAL QOM, WMFT, and FMA were significantly associated with outcome immediately after CIMT. Pretreatment MAL QOM, WMFT, proprioception, and age were significantly associated with outcome after 12 months. Each unit of higher pretreatment MAL QOM score and each unit of faster pretreatment WMFT log mean time improved the probability of achieving a clinically meaningful outcome by 7 and 3 times at posttreatment, and 5 and 2 times after 12 months, respectively. Patients with impaired proprioception had a 20% probability of achieving a clinically meaningful outcome compared with those with intact proprioception. Baseline clinical measures of motor and sensory function can be used to predict a clinically meaningful outcome after CIMT.

Measures of rheumatoid arthritis disease activity in Australian clinical practice.

PubMed

Taylor, Andrew; Bagga, Hanish

2011-01-01

Objectives. To investigate which rheumatoid arthritis (RA) disease activity measures are being collected in patients receiving glucocorticoids, non-biologic or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian rheumatology practice. Methods. A retrospective audit of medical records was conducted from eight rheumatology practices around Australia. Each rheumatologist recruited 30 consecutive eligible patients into the review, 10 of whom must have been receiving a biological agent for rheumatoid arthritis. Disease activity measures and radiographic assessments were collected from each patient's last consultation. For biologic patients, disease activity measures were also collected from when the patient was first initiated on the biological agent. Results. At last consultation, the disease measures that were recorded most often were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently recorded (16.3%). The rate of recording disease activity measures for patients receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This review has shown inconsistency of RA activity measures being recorded in Australian rheumatology clinical practice. An accurate assessment of the disease process is necessary to effectively target rheumatoid arthritis patients to treat in order to achieve optimal outcomes.

Exploring function activated chlorins using MCD spectroscopy and DFT methods: design of a chlorin with a remarkably intense, red Q band.

PubMed

Zhang, Angel; Stillman, Martin J

2018-05-09

The electronic structures of three previously synthesized Ni-coordinated chlorins with β-substituents of thioketone, fluorene, and ketone were investigated using magnetic circular dichroism spectroscopy (MCD) and density functional theory (DFT) for potential application as sensitizers for dye-sensitized solar cells (DSSCs). Computational studies on modeled Zn-coordinated chlorins allowed identification of charge transfer and d-d transitions of the Ni2+ coordinated chlorins. Two fictive Zn chlorins, M1 and M2, were designed with thiophene units based on the fluorene substituted chlorin. Substitution with thiophene altered the typical arrangement of the four Gouterman molecular orbitals (MOs) and red-shifted and greatly intensified the lowest energy absorption band (the Q band). The introduction of the thiophene-based MO as the LUMO below the usual Gouterman LUMO is predicted to increase the efficiency of electron transfer from the dye to the conduction band of the semiconductor in DSSCs. The addition of a donor group on the opposite pyrrole (M2) red-shifted the Q band further and introduced a donor-based MO between the typical Gouterman HOMO and HOMO-1. Despite the relatively small ΔHOMO, M1 and M2 exhibited remarkably intense Q bands. M2 would be a possible candidate for application in DSSCs due to its panchromatic absorption, intense and red-shifted Q band, and the presence of the substituent based MO properties. Another indicator of a successful dye is the alignment of the ground state and excited state oxidation potentials (GSOP and ESOP, respectively) with respect to the conduction band of the semiconductor. The GSOP for M2 lies 0.55 eV below the I-/I3- redox potential and the ESOP lies 0.48 eV above the TiO2 conduction band. The impact of the thiophene dominance in the LUMO also supports the prediction of efficient sensitization properties. The remarkably intense Q band of M2 predicted to be at 777 nm with a ΔHOMO of just 1.04 eV provides a synthetic route

Ecto-Nucleotidase Activities of Promastigotes from Leishmania (Viannia) braziliensis Relates to Parasite Infectivity and Disease Clinical Outcome

PubMed Central

Leite, Pauline M.; Gomes, Rodrigo S.; Figueiredo, Amanda B.; Serafim, Tiago D.; Tafuri, Wagner L.; de Souza, Carolina C.; Moura, Sandra A. L.; Fietto, Juliana L. R.; Melo, Maria N.; Ribeiro-Dias, Fátima; Oliveira, Milton A. P.; Rabello, Ana; Afonso, Luís C. C.

2012-01-01

Background Leishmania (Viannia) braziliensis has been associated with a broad range of clinical manifestations ranging from a simple cutaneous ulcer to destructive mucosal lesions. Factors leading to this diversity of clinical presentations are not clear, but parasite factors have lately been recognized as important in determining disease progression. Given the fact that the activity of ecto-nucleotidases correlates with parasitism and the development of infection, we evaluated the activity of these enzymes in promastigotes from 23 L. braziliensis isolates as a possible parasite-related factor that could influence the clinical outcome of the disease. Methodology/Principal Findings Our results show that the isolates differ in their ability to hydrolyze adenine nucleotides. Furthermore, we observed a positive correlation between the time for peak of lesion development in C57BL/6J mice and enzymatic activity and clinical manifestation of the isolate. In addition, we found that L. (V.) braziliensis isolates obtained from mucosal lesions hydrolyze higher amounts of adenine nucleotides than isolates obtained from skin lesions. One isolate with high (PPS6m) and another with low (SSF) ecto-nucleotidase activity were chosen for further studies. Mice inoculated with PPS6m show delayed lesion development and present larger parasite loads than animals inoculated with the SSF isolate. In addition, PPS6m modulates the host immune response by inhibiting dendritic cell activation and NO production by activated J774 macrophages. Finally, we observed that the amastigote forms from PPS6m and SSF isolates present low enzymatic activity that does not interfere with NO production and parasite survival in macrophages. Conclusions/Significance Our data suggest that ecto-nucleotidases present on the promastigote forms of the parasite may interfere with the establishment of the immune response with consequent impaired ability to control parasite dissemination and this may be an important

Reduced susceptibility of clinical strains of Mycobacterium tuberculosis to reactive nitrogen species promotes survival in activated macrophages

PubMed Central

Idh, Jonna; Andersson, Blanka; Lerm, Maria; Raffetseder, Johanna; Eklund, Daniel; Woksepp, Hanna; Werngren, Jim; Mansjö, Mikael; Sundqvist, Tommy; Stendahl, Olle

2017-01-01

Background Drugs such as isoniazid (INH) and pretomanid (PRT), used against Mycobacterium tuberculosis are active partly through generation of reactive nitrogen species (RNS). The aim of this study was to explore variability in intracellular susceptibility to nitric oxide (NO) in clinical strains of M. tuberculosis. Method Luciferase-expressing clinical M. tuberculosis strains with or without INH resistance were exposed to RNS donors (DETA/NO and SIN-1) in broth cultures and bacterial survival was analysed by luminometry. NO-dependent intracellular killing in a selection of strains was assessed in interferon gamma/lipopolysaccharide-activated murine macrophages using the NO inhibitor L-NMMA. Results When M. tuberculosis H37Rv was compared to six clinical isolates and CDC1551, three isolates with inhA mediated INH resistance showed significantly reduced NO-susceptibility in broth culture. All strains showed a variable but dose-dependent susceptibility to RNS donors. Two clinical isolates with increased susceptibility to NO exposure in broth compared to H37Rv were significantly inhibited by activated macrophages whereas there was no effect on growth inhibition when activated macrophages were infected by clinical strains with higher survival to NO exposure in broth. Furthermore, the most NO-tolerant clinical isolate showed increased resistance to PRT both in broth culture and the macrophage model compared to H37Rv in the absence of mutational resistance in genes associated to reduced susceptibility against PRT or NO. Conclusion In a limited number of clinical M. tuberculosis isolates we found a significant difference in susceptibility to NO between clinical isolates, both in broth cultures and in macrophages. Our results indicate that mycobacterial susceptibility to cellular host defence mechanisms such as NO need to be taken into consideration when designing new therapeutic strategies. PMID:28704501

Daily activity level improvement with antidepressant medications predicts long-term clinical outcomes in outpatients with major depressive disorder.

PubMed

Jha, Manish K; Teer, Raymond B; Minhajuddin, Abu; Greer, Tracy L; Rush, A John; Trivedi, Madhukar H

2017-01-01

Major depressive disorder (MDD) significantly impacts performance of both work- and nonwork-related routine daily activities. We have shown that work productivity is significantly impaired in employed MDD patients, but the extent of impairments in nonwork-related routine activities and its association with antidepressant treatment outcomes has not been established. Activity impairment was measured using the sixth item of Work Productivity and Activity Impairment Scale in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (n=665). Published norms were used to define activity impairment levels. The relationship between activity impairment and baseline sociodemographic and clinical characteristics was evaluated along with changes in activity impairment and its relationship with other clinical outcomes such as symptom severity, function, and side effect burden. Remission status at 3 and 7 months was predicted based on week 6 activity impairment level. Higher psychosocial and cognitive impairments and greater number of comorbid medical conditions were associated with greater activity impairment at baseline. Proportion of participants with severe activity impairment declined from 47.6% at baseline to 18.7% at 3 months, while mean activity impairment decreased from 57.1 at baseline to 32.8 at 3 months. During course of treatment, levels of activity impairment correlated most strongly with psychosocial function among measures of symptom severity, function, quality of life, and side effect burden. No or minimal activity impairment at week 6 was associated with two to three times higher rates of remission at 3 and 7 months as compared to moderate or severe activity impairment levels even after controlling for remission status at week 6 and select baseline variables. Depressed patients have high levels of nonwork-related activity impairment at baseline that improves significantly with treatment and independently predicts long-term clinical outcomes. Brief

Exercise and physical activity in mental disorders: clinical and experimental evidence.

PubMed

Zschucke, Elisabeth; Gaudlitz, Katharina; Ströhle, Andreas

2013-01-01

Several epidemiological studies have shown that exercise (EX) and physical activity (PA) can prevent or delay the onset of different mental disorders, and have therapeutic benefits when used as sole or adjunct treatment in mental disorders. This review summarizes studies that used EX interventions in patients with anxiety, affective, eating, and substance use disorders, as well as schizophrenia and dementia/mild cognitive impairment. Despite several decades of clinical evidence with EX interventions, controlled studies are sparse in most disorder groups. Preliminary evidence suggests that PA/EX can induce improvements in physical, subjective and disorder-specific clinical outcomes. Potential mechanisms of action are discussed, as well as implications for psychiatric research and practice.

Charles Hard Townes: Remarkable Scientist and Inspiring Teacher

NASA Astrophysics Data System (ADS)

Goldsmith, P. F.

2015-05-01

Charles Townes is renowned for his work elucidating the structure of molecules through microwave spectroscopy and for his invention of the maser and the laser. He also had a lifelong interest in astronomy, and in the later portion of his remarkable and long career devoted himself to astronomical research, pioneering the study of molecules in interstellar space and the development of infrared spectroscopy, first from the ground and then from airborne facilities. His interest in high angular resolution, as well as high spectral resolution observations, led to development of the first infrared spatial interferometer employing coherent signal processing techniques. In this short review I will only touch on some of Townes' many scientific contributions, concentrating on astronomy, and will also give some personal thoughts about how he inspired students in their research, helping to make the "Townes Group" at the University of California, Berkeley, an ideal environment in which to start a career in research.

[Clinical research evolution. In parallel with the current changes in welfare expectations and information technology incorporation, study designs and data collection and analysis are quickly changing as well].

PubMed

Tavazzi, Luigi

2015-10-01

The development of both technology, biological, and clinical knowledge leads to remarkable changes of scientific research methodology, including the clinical research. Major changes deal with the pragmatic approach of trial designs, an explosive diffusion of observational research which is becoming a usual component of clinical practice, and an active modelling of new research design. Moreover, a new healthcare landscape could be generated from the information technology routinely used to collect clinical data in huge databases, the management and the analytic methodology of big data, and the development of biological sensors compatible with the daily life delivering signals remotely forwardable to central databases. Precision medicine and individualized medicine seem to be the big novelties of the coming years, guiding to a shared pattern of patient/physician relationship. In healthcare, a huge business related mainly, but not exclusively, to the implementation of information technology is growing. This development will favor radical changes in the health systems, also reshaping the clinical activity. A new governance of the research strategies is needed and the application of the results should be based on shared ethical foundations. This new evolving profile of medical research and practice is discussed in this paper.

ASSESSMENT OF UPPER EXTREMITY IMPAIRMENT, FUNCTION, AND ACTIVITY FOLLOWING STROKE: FOUNDATIONS FOR CLINICAL DECISION MAKING

PubMed Central

Lang, Catherine E.; Bland, Marghuretta D.; Bailey, Ryan R.; Schaefer, Sydney Y.; Birkenmeier, Rebecca L.

2012-01-01

The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common upper extremity impairments and how to assess them are briefly discussed. While multiple UE impairments are typically present after stroke, the severity of one impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed in order to optimize the provision of stroke rehabilitation services. PMID:22975740

[Laparoscopic aspect and clinical relevance of cholangiofibromas].

PubMed

Henning, H; Friedrich, K; Lüders, C J

1982-12-01

In a current series of 1160 laparoscopies in 38 cases (3.2%) we found cholangiofibromas. The picture of single, sporadic and multiple cholangiofibromas as well as cholangiofibromatosis is both described and documented by laparoscopic photography. Clinically it seems remarkable that only patients with alcohol- or drug-induced liver injury showed such alterations. The prevalence of cholangiofibromas in toxic liver damage suggests that we are here not dealing with embryonal aberrations (hamartomas) but apparently with cellular inductive phenomena.

MRI and clinical manifestations of delayed encephalopathy after carbon monoxide poisoning.

PubMed

Wang, Xiahong; Li, Zhenyu; Berglass, Jacqueline; He, Wenlong; Zhao, Jianmin; Zhang, Min; Gao, Chongyang; Zhang, Caixia; Zhang, Huimin; Yi, Xuewei

2016-11-01

To explore the relationship between the clinical manifestations and functional magnetic resonance images of delayed encephalopathy after carbon monoxide intoxication. Six patients received the MRI were diagnosed with delayed encephalopathy after carbon monoxide (CO) poisoning. Clinical manifestations were observed in each patient. MRI revealed multiple lesions. The majority of the lesions were located in the globus pallidus, sub cortical white matter, and basal ganglia. The cognitive injury, akinetic mutism, fecal and uroclepsia, forced crying, forced laughing and extra pyramidal syndromes such as chorea and parkinsonism were manifested in clinic. Cognitive impairment improved greatly while involuntary movements only improved slightly after several months. Meanwhile brain MRI suggested remarkable improvement. Neuroimaging directly correlated with the clinical manifestations.

Mating disruption of citrus leafminer mediated by a noncompetitive mechanism at a remarkably low pheromone release rate.

PubMed

Stelinski, L L; Miller, J R; Rogers, M E

2008-08-01

The citrus leafminer, Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae), is a worldwide pest of citrus. A season-long investigation was conducted that evaluated mating disruption for this pest. Effective disruption of the male P. citrella orientation to pheromone traps (98%) and reduced flush infestation by larvae was achieved for 221 d with two deployments of a 3:1 blend of (Z,Z,E)-7,11,13-hexadecatrienal/(Z,Z)-7,11-hexadecadienal at a remarkably low rate of 1.5 g active ingredient (AI)/ha per deployment. To gain insight into the mechanism that mediates the disruption of P. citrella, male moth catch was quantified in replicated plots of citrus treated with varying densities of pheromone dispensers. The densities of septum dispensers compared were: 0 (0/ha, 0.0 g AI/ha), 0.2 (one every fifth tree or 35/ha, 0.05 g AI/ha), 1 (215/ha, 0.29 g AI/ha), and 5 per tree (1,100/ha, 1.5 g AI/ha). Profile analysis by previously published mathematical methods matched predictions of noncompetitive mating disruption. Behavioral observations of male P. citrella in the field revealed that males did not approach mating disruption dispensers in any of the dispenser density treatments. The current report presents the first set of profile analyses combined with direct behavioral observations consistent with previously published theoretical predictions for a noncompetitive mechanism of mating disruption. The results suggest that disruption of P. citrella should be effective even at high population densities given the density-independent nature of disruption for this species and the remarkably low rate of pheromone per hectare required for efficacy.

Each Belongs: The Remarkable Story of the First School System to Move to Inclusion

ERIC Educational Resources Information Center

Hansen, Jim

2012-01-01

The Hamilton-Wentworth Catholic District School Board has just celebrated 30 Years of Fully Inclusive Education for All. Their mission statement: "EACH BELONGS". This remarkable book by Jim Hansen collects the history--including an extensive collection of documents and letters from teachers and families--that tell the stories of the…

REMARKS ON THE MAXIMUM ENTROPY METHOD APPLIED TO FINITE TEMPERATURE LATTICE QCD.

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

UMEDA, T.; MATSUFURU, H.

2005-07-25

We make remarks on the Maximum Entropy Method (MEM) for studies of the spectral function of hadronic correlators in finite temperature lattice QCD. We discuss the virtues and subtlety of MEM in the cases that one does not have enough number of data points such as at finite temperature. Taking these points into account, we suggest several tests which one should examine to keep the reliability for the results, and also apply them using mock and lattice QCD data.

Seasonality of clinical isolation of rapidly growing mycobacteria.

PubMed

Han, X Y

2008-09-01

Rapidly growing mycobacteria (RGM) are environmental organisms that have emerged as significant human pathogens. RGM infections show remarkable geographic variations. In this study, based on data from Houston, Texas, RGM were isolated from clinical cultures year-round, although peaks in the summer and autumn correlating with the seasonal variation of temperature and rainfall also were noted. These results may offer some explanation for the summer occurrence of RGM outbreaks at diverse locations.

Seasonality of clinical isolation of rapidly growing mycobacteria

PubMed Central

HAN, X. Y.

2008-01-01

SUMMARY Rapidly growing mycobacteria (RGM) are environmental organisms that have emerged as significant human pathogens. RGM infections show remarkable geographic variations. In this study, based on data from Houston, Texas, RGM were isolated from clinical cultures year-round, although peaks in the summer and autumn correlating with the seasonal variation of temperature and rainfall also were noted. These results may offer some explanation for the summer occurrence of RGM outbreaks at diverse locations. PMID:18005476

R124C mutation of the betaIGH3 gene leads to remarkable phenotypic variability in a Greek four-generation family with lattice corneal dystrophy type 1.

PubMed

Hellenbroich, Y; Tzivras, G; Neppert, B; Schwinger, E; Zühlke, C

2001-01-01

Five autosomal dominantly inherited corneal dystrophies are caused by missense mutations in the betaIGH3 gene on chromosome 5q31. Here we describe the clinical features and the analysis of the betaIGH3 gene in a Greek four-generation family with lattice corneal dystrophy type 1 (CDL1). Sequencing of the betaIGH3 cDNA from an affected family member revealed the R124C mutation. More recent data indicate that this is probably a mutation hot spot in CDL1. We could not find a common haplotype with another CDL1 family with the R124C mutation demonstrating that this mutation occurs independently in different families. The clinical course of the disease showed a remarkable variability between the affected family members. To investigate a possible role between the phenotypic variability and apolipoprotein E (ApoE), which co-localises with amyloid deposits in CDL1, we determined the ApoE genotype of all family members. The resulting data revealed no association with the variable clinical course. Copyright 2001 S. Karger AG, Basel

[Activities of women's consultation clinics in prevention of unplanned pregnancy].

PubMed

Allenova, I A

1990-01-01

The data on women of reproductive age residing in the area serviced by an obstetrician-gynaecologist were provided; the proportion of women requiring the prevention of unintended pregnancy was determined, their socio-hygienic characteristics were established. The peculiarities in the activities of an obstetrician-gynaecologist in the field of preventing abortions and regulating women's reproductive functions were identified. On the basis of these data measures to improve the performance of women's consultation clinic in preventing the unintended pregnancy were determined.

The value of power Doppler ultrasound in patients with rheumatoid arthritis in clinical remission: Reclassifying disease activity?

PubMed

Vergara, Facundo; Ruta, Santiago; Rosa, Javier; Marín, Josefina; García-Mónaco, Ricardo; Soriano, Enrique R

2017-03-18

The aim of the present study was to describe the ultrasound (US) findings in patients with rheumatoid arthritis (RA) in clinical remission, and to evaluate the ability of power Doppler (PD) US to reclassify disease activity in these patients. We included consecutive patients with RA according to 2010 American College of Rheumatology/European League Against Rheumatism criteria, who were in clinical remission by the Disease Activity Score (DAS28<2.6). Twenty joints of both hands were assessed by US. PD signal was evaluated on a semi-quantitative scale from 0 to 3. Three different US-modified DAS28 (US-DAS28) were constructed, replacing the clinical swollen joint count by the PD US joint count using PD score ≥1, ≥2 or ≥3, respectively. Eighty-six patients were included. Twenty-three (26.7%) patients had at least one joint with abnormal US-positive PD signal. Thirteen percent of patients were reclassified to low disease activity by applying the US-DAS28 when joints were considered active with a PD signal ≥1; 12%, when a PD signal ≥2 was considered, and 2% of the patients were reclassified when a PD score of 3 was considered. No patients were reclassified to a level of moderate or high activity applying US-DAS28. Although around a quarter of patients with RA in clinical remission showed PD US features indicating residual activity, only a small percentage were reclassified to a state of low activity and none to a level of moderate or high activity, applying the proposed US-DAS28. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

What prevents youth at clinical high risk for psychosis from engaging in physical activity? An examination of the barriers to physical activity.

PubMed

Newberry, Raeana E; Dean, Derek J; Sayyah, Madison D; Mittal, Vijay A

2018-06-13

Exercise has increasingly been proposed as a healthful intervention prior to and after the onset of psychosis. There is some evidence to suggest that youth at clinical high risk (CHR) for psychosis are less physically active and report more barriers to engaging in exercise; however, there has been relatively limited empirical work documenting this phenomenon, and to date, relationships between physical activity, barriers, and clinical phenomenology have been unclear. CHR (N = 51) and healthy control (N = 37) participants completed a structured clinical interview assessing attenuated psychotic symptoms and substance use, and an exercise survey that assessed current exercise practices, perceived physical fitness, and barriers related to engaging in exercise. CHR youth engaged in less physical activity, exhibited lower perception of fitness, and endorsed more barriers related to motivation for exercise. The CHR group showed significant negative correlations where lower perceptions of fitness were associated with increased negative, disorganized, and general symptoms. Decreased frequency of activity was related to more barriers of motivation. Interestingly, greater symptomatology in the CHR group was associated with more barriers of self-perception and motivation for engaging in exercise. However, findings suggested a nuanced relationship in this area; for example, increased physical activity was associated with increased substance use. The results of the current study support the notion that sedentary behavior is common in CHR youth, and more broadly, provide an impetus to target motivation through supervised exercise and fitness tracking to promote the health and well-being of CHR individuals. Copyright © 2018. Published by Elsevier B.V.

Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

ERIC Educational Resources Information Center

Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

2011-01-01

Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

A study of active learning methods for named entity recognition in clinical text.

PubMed

Chen, Yukun; Lasko, Thomas A; Mei, Qiaozhu; Denny, Joshua C; Xu, Hua

2015-12-01

Named entity recognition (NER), a sequential labeling task, is one of the fundamental tasks for building clinical natural language processing (NLP) systems. Machine learning (ML) based approaches can achieve good performance, but they often require large amounts of annotated samples, which are expensive to build due to the requirement of domain experts in annotation. Active learning (AL), a sample selection approach integrated with supervised ML, aims to minimize the annotation cost while maximizing the performance of ML-based models. In this study, our goal was to develop and evaluate both existing and new AL methods for a clinical NER task to identify concepts of medical problems, treatments, and lab tests from the clinical notes. Using the annotated NER corpus from the 2010 i2b2/VA NLP challenge that contained 349 clinical documents with 20,423 unique sentences, we simulated AL experiments using a number of existing and novel algorithms in three different categories including uncertainty-based, diversity-based, and baseline sampling strategies. They were compared with the passive learning that uses random sampling. Learning curves that plot performance of the NER model against the estimated annotation cost (based on number of sentences or words in the training set) were generated to evaluate different active learning and the passive learning methods and the area under the learning curve (ALC) score was computed. Based on the learning curves of F-measure vs. number of sentences, uncertainty sampling algorithms outperformed all other methods in ALC. Most diversity-based methods also performed better than random sampling in ALC. To achieve an F-measure of 0.80, the best method based on uncertainty sampling could save 66% annotations in sentences, as compared to random sampling. For the learning curves of F-measure vs. number of words, uncertainty sampling methods again outperformed all other methods in ALC. To achieve 0.80 in F-measure, in comparison to random

Concluding Remarks

NASA Astrophysics Data System (ADS)

Bonnet, Roger M.

2010-01-01

Let me first express my warmest acknowledgements to Cesare Barbieri for having taken the initiative of convening this symposium. These two days offered a unique opportunity to celebrate the scientific achievements and the legacy of Galileo Galilei. It allowed not only celebrating the scientist but also the philosopher and the human being. It was a fantastic journey in the past, present and future exploration of our universe and a fantastic retrospection into the Renaissance world which no better city than Padova would be able to offer. During these two days we could listen to a well balanced and well prepared set of excellent papers and presentations. All participants should be congratulated for their very active interactions during the discussions in the aula and also during coffee and lunch breaks.

Ocimum basilicum: Antibacterial activity and association study with antibiotics against bacteria of clinical importance.

PubMed

Araújo Silva, Viviane; Pereira da Sousa, Janiere; de Luna Freire Pessôa, Hilzeth; Fernanda Ramos de Freitas, Andrea; Douglas Melo Coutinho, Henrique; Beuttenmuller Nogueira Alves, Larissa; Oliveira Lima, Edeltrudes

2016-01-01

Ocimum basilicum L. (Lamiaceae), popularly known as basil, is part of a group of medicinal plants widely used in cooking and known for its beneficial health properties, possessing significant antioxidant effects, antinociceptive, and others. The objective of this study is to determine the pharmacological effects produced on the bacterial strains Staphylococcus aureus and Pseudomonas aeruginosa when standard antibiotics and O. basilicum essential oil are combined. The extraction of O. basilicum (leaves) components was done by steam distillation. The Minimum inhibitory concentration (MIC) was calculated using microdilution technique, where the oil concentrations varied from 2 to 1024 μg/mL. The combinations of O. basilicum oil with ciprofloxacin or imipenem were analyzed by the checkerboard method where fractional inhibitory concentration (FIC) indices were calculated. Ocimum basilicum essential oil, imipenem, and ciprofloxacin showed respective MIC antibacterial activities of 1024, 4, and 2 μg/mL, against S. aureus. In S. aureus, the oil with imipenem association showed synergistic effect (FIC = 0.0625), while the oil with ciprofloxacin showed antagonism (FIC value = 4.25). In P. aeruginosa, the imipenem/oil association showed additive effect for ATCC strains, and synergism for the clinical strain (FIC values = 0.75 and 0.0625). The association of O. basilicum essential oil with ciprofloxacin showed synergism for clinical strains (FIC value = 0.09). Ocimum basilicum essential oil associated with existing standard antibiotics may increase their antibacterial activity, resulting in a synergistic activity against bacterial strains of clinical importance. The antibacterial activity of O. basilicum essential oil may be associated with linalool.

Histological Disease Activity as a Predictor of Clinical Relapse Among Patients With Ulcerative Colitis: Systematic Review and Meta-Analysis.

PubMed

Park, Sunhee; Abdi, Tsion; Gentry, Mark; Laine, Loren

2016-12-01

Endoscopic remission in ulcerative colitis (UC) is associated with improved clinical outcomes. We assessed whether histological remission predicts clinical outcomes, estimated the magnitude of effect, and determined whether histological remission provides additional prognostic utility beyond clinical or endoscopic remission. Bibliographic databases were searched for studies in inflammatory bowel disease providing baseline histological status and relation to an outcome of clinical relapse or exacerbation. Our primary analysis compared the proportion of patients with study-defined histological remission vs. the proportion with histological activity who developed clinical relapse/exacerbation. Additional analyses compared the proportion with relapse/exacerbation for the presence vs. absence of different histological features and for histological remission vs. endoscopic remission and clinical remission. A fixed-effect model was used for meta-analysis, with a random-effects model if statistical heterogeneity was present. Fifteen studies met inclusion criteria. The major methodological shortcoming was lack of blinding of the assessor of clinical relapse/exacerbation to baseline histological status in 13 of the 15 studies. Relapse/exacerbation was less frequent with baseline histological remission vs. histological activity (relative risk (RR)=0.48, 95% confidence interval (CI) 0.39-0.60) and vs. baseline clinical and endoscopic remission (RR=0.81, 95% CI 0.70-0.94). Relapse/exacerbation was also less common in the absence vs. presence of specific histological features: neutrophils in epithelium (RR=0.32, 95% CI 0.23-0.45), neutrophils in lamina propria (RR=0.43, 95% CI 0.32-0.59), crypt abscesses (RR=0.38, 95% CI 0.27-0.54), eosinophils in the lamina propria (RR=0.43, 95% CI 0.21-0.91), and chronic inflammatory cell infiltrate (RR=0.28, 95% CI 0.10-0.75). Histological remission was present in 964 (71%) of the 1360 patients with combined endoscopic and clinical remission

Evaluation of the activity of rheumatoid arthritis in clinical practice. Agreement between self-rated clinimetric evaluation and clinical evaluation with activity indexes: DAS28, CDAI and SDAI.

PubMed

Horta-Baas, Gabriel; Pérez Bolde-Hernández, Arturo; Hernández-Cabrera, María Fernanda; Vergara-Sánchez, Imelda; Romero-Figueroa, María Del Socorro

2017-10-11

To achieve control of rheumatoid arthritis (RA) it is necessary to be able to evaluate its activity. The American College of Rheumatology (ACR) recommends for this purpose indexes of activity that can be performed by the patient (PAS-II and RAPID-3) and IA including medical evaluation with laboratory studies (DAS28 and SDAI) or without them (CDAI). The objective was to analyze the concordance between self-rated clinimetric evaluation and clinimetric evaluation performed by the physician. Analytical cross-sectional study in 126 patients with RA. The agreement was evaluated through the weighted κ coefficient and the Krippendorff's α coefficient. The PAS-II and RAPID-3 significantly correlated with all variables included in the core set of measures recommended by the ACR/EULAR. The agreement between PAS-II and CDAI-SDAI was good (κ: 0.6, α: 0.61-0.62), and moderate with DAS28-ESR (κ: 0.53, α: 0.56). The concordance between RAPID-3 and CDAI-SDAI was moderate (κ: 0.55-0.57, α: 0.50-0.51), and moderate with DAS28-ESR (κ: 0.55, α: 0.53). When categorizing the activity in remission/low activity vs. moderate/severe activity, the agreement was greater with the PAS-II (0.59 vs. 0.34; P=.012). The good concordance between PAS-II and SDAI supports their use in clinical practice, especially if biomarkers of inflammation or the possibility of joint count are not available. However, in order to recommend its routine application in clinical practice, it is necessary to perform longitudinal studies that assess its responsiveness. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia

PubMed Central

Amsberg, Gunhild Keller-von; Koschmieder, Steffen

2013-01-01

Bosutinib (SKI-606) is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML). Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML. PMID:23493838

Review of Maxillary Expansion Appliance Activation Methods: Engineering and Clinical Perspectives

PubMed Central

Romanyk, D. L.; Lagravere, M. O.; Toogood, R. W.; Major, P. W.; Carey, J. P.

2010-01-01

Objective. Review the reported activation methods of maxillary expansion devices for midpalatal suture separation from an engineering perspective and suggest areas of improvement. Materials and Methods. A literature search of Scopus and PubMed was used to determine current expansion methods. A U.S. and Canadian patent database search was also conducted using patent classification and keywords. Any paper presenting a new method of expansion was included. Results. Expansion methods in use, or patented, can be classified as either a screw- or spring-type, magnetic, or shape memory alloy expansion appliance. Conclusions. Each activation method presented unique advantages and disadvantages from both clinical and engineering perspectives. Areas for improvement still remain and are identified in the paper. PMID:20948570

Surfing the best practice guidelines: national clinical guideline clearinghouse in development.

PubMed

1997-08-01

The growth in development and usage of clinical guidelines during the last five years has been remarkable. Not only are health care practitioners reaching for what's deemed to be the best in protocols and practice, consumers, too, are looking toward standards and guidelines as they become more educated about the quality and quantity of health care services they should be receiving.

Modifying the clinical research infrastructure at a dedicated clinical trials unit: assessment of trial development, activation, and participant accrual

PubMed Central

Tang, Chad; Hess, Kenneth R.; Sanders, Dwana; Davis, Suzanne; Buzdar, Aman; Kurzrock, Razelle; Lee, J. Jack; Meric-Bernstam, Funda; Hong, David

2017-01-01

Purpose Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center and analyzed their effects on the trial activation timeline and enrollment. Experimental Design Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results We identified 3 facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship (industry [133 ICT and 133 non-ICT trials] or institutional [68 ICT and 68 non-ICT trials]). ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrollment (median difference of 0.3 months for industry vs. 1.2 months for institutional) (all matched P<0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional) (all matched P<0.05). Conclusions Use of a clinical research–focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. PMID:27852698

Development and use of active clinical decision support for preemptive pharmacogenomics

PubMed Central

Bell, Gillian C; Crews, Kristine R; Wilkinson, Mark R; Haidar, Cyrine E; Hicks, J Kevin; Baker, Donald K; Kornegay, Nancy M; Yang, Wenjian; Cross, Shane J; Howard, Scott C; Freimuth, Robert R; Evans, William E; Broeckel, Ulrich; Relling, Mary V; Hoffman, James M

2014-01-01

Background Active clinical decision support (CDS) delivered through an electronic health record (EHR) facilitates gene-based drug prescribing and other applications of genomics to patient care. Objective We describe the development, implementation, and evaluation of active CDS for multiple pharmacogenetic test results reported preemptively. Materials and methods Clinical pharmacogenetic test results accompanied by clinical interpretations are placed into the patient's EHR, typically before a relevant drug is prescribed. Problem list entries created for high-risk phenotypes provide an unambiguous trigger for delivery of post-test alerts to clinicians when high-risk drugs are prescribed. In addition, pre-test alerts are issued if a very-high risk medication is prescribed (eg, a thiopurine), prior to the appropriate pharmacogenetic test result being entered into the EHR. Our CDS can be readily modified to incorporate new genes or high-risk drugs as they emerge. Results Through November 2012, 35 customized pharmacogenetic rules have been implemented, including rules for TPMT with azathioprine, thioguanine, and mercaptopurine, and for CYP2D6 with codeine, tramadol, amitriptyline, fluoxetine, and paroxetine. Between May 2011 and November 2012, the pre-test alerts were electronically issued 1106 times (76 for thiopurines and 1030 for drugs metabolized by CYP2D6), and the post-test alerts were issued 1552 times (1521 for TPMT and 31 for CYP2D6). Analysis of alert outcomes revealed that the interruptive CDS appropriately guided prescribing in 95% of patients for whom they were issued. Conclusions Our experience illustrates the feasibility of developing computational systems that provide clinicians with actionable alerts for gene-based drug prescribing at the point of care. PMID:23978487

Phenotypic characterization of enzymatic activity of clinical dermatophyte isolates from animals with and without skin lesions and humans.

PubMed

Gnat, Sebastian; Łagowski, Dominik; Nowakiewicz, Aneta; Zięba, Przemysław

2018-05-20

The pathogenesis of dermatophytoses is associated with the secretion of enzymes degrading the infected tissue components. Although many studies on enzymatic activity of dermatophytes have been conducted over the years, there have been no concrete proposals on construction of the profile of enzymes characteristic of individual species, genus, or ecological types of dermatophytes. The aim of this study was to assess the capability of clinical dermatophyte isolates from both symptomatic and asymptomatic animals and humans to produce different enzymes. Clinical isolates of 234 dermatophyte strains collected during routine examination of animal health were used in this study. The enzymatic production of keratinase, elastase, phospholipase, lipase, protease, DNase, and gelatinase as well as the haemolytic activity were evaluated using specific test media. The overall degree of enzymatic activity of the analysed clinical isolates of the dermatophytes was 67%. All tested clinical isolates of different species of dermatophytes showed keratinase activity and 96% additionally exhibited phospholipase activity. The weakest activity among the tested enzymes was demonstrated for elastase and gelatinase. 83% of the isolates of the dermatophytes showed haemolytic activity. Our data indicate that clinical isolates of dermatophytes from different species produce enzymes with different levels of activities. Profile of enzymes characteristic of individual species, genus, or ecological types of dermatophytes is possibly dependent upon factors related to the host. The relationship between each enzyme and the occurrence of skin lesions in animals and humans or asymptomatic animal carriers varies on whether the infection is caused by T. mentagrophytes, T. verrucosum, or M. canis. Interestingly, only keratinase seems to be correlated with the appearance of dermatophyte infections, irrespective of the pathogen species, and elastase is a characteristic enzyme for dermatophyte strains

Doubling Pharmacist Coverage in the Intensive Care Unit: Impact on the Pharmacists' Clinical Activities and Team Members' Satisfaction.

PubMed

McDaniel, Joshua; Bass, Lynn; Pate, Toni; DeValve, Michael; Miller, Susan

2017-09-01

Background: National professional organizations have recognized pharmacists as essential members of the intensive care unit (ICU) team. Critical care pharmacists' clinical activities have been categorized as fundamental, desirable, and optimal, providing a structure for gauging ICU pharmacy services being provided. Objective: To determine the impact the addition of a second ICU pharmacist covering 30 adult ICU beds at a large regional medical center has on the complexity of pharmacists' interventions, the types of clinical activities performed by the pharmacists, and the ICU team members' satisfaction. Methods: A prospective mixed-method descriptive study was conducted. Pharmacists recorded their interventions and clinical activities performed. A focus group composed of randomly selected ICU team members was held to qualitatively describe the impact of the additional pharmacist coverage on patient care, team dynamics, and pharmacy services provided. Results: The baseline period consisted of 33 days, and the intervention period consisted of 20 days. The average complexity of interventions was 1.72 during the baseline period (mode = 2) versus 1.69 (mode = 2) during the intervention period. The number of desirable and optimal clinical activities performed daily increased during the intervention from 8.4 (n = 279) to 16.4 (n = 328) and 2.3 (n = 75) to 8.6 (n = 171) compared with the baseline, respectively. Focus group members qualitatively described additional pharmacist coverage as beneficial. Conclusion: The additional critical care pharmacist did not increase pharmacy intervention complexity; however, more interventions were performed per day. Additional pharmacist coverage increased the daily number of desirable and optimal clinical activities performed and positively impacted ICU team members' satisfaction.

Allotropes of Phosphorus with Remarkable Stability and Intrinsic Piezoelectricity

NASA Astrophysics Data System (ADS)

Li, Zhenqing; He, Chaoyu; Ouyang, Tao; Zhang, Chunxiao; Tang, Chao; Römer, Rudolf A.; Zhong, Jianxin

2018-04-01

We construct a class of two-dimensional (2D) phosphorus allotropes by assembling a previously proposed ultrathin metastable phosphorus nanotube into planar structures in different stacking orientations. Based on first-principles methods, the structures, stabilities, and fundamental electronic properties of these allotropes are systematically investigated. Our results show that these 2D van der Waals phosphorene allotropes possess remarkable stabilities due to the strong intertube van der Waals interactions, which cause an energy release of about 30 - 70 meV /atom , depending on their stacking details. Most of them are confirmed to be energetically more favorable than the experimentally viable α -P and β -P . Three of them, showing a relatively higher probability of being synthesized in the future, are further confirmed to be dynamically stable semiconductors with strain-tunable band gaps and intrinsic piezoelectricity, which may have potential applications in nanosized sensors, piezotronics, and energy harvesting in portable electronic nanodevices.

Potentiating antibiotics in drug-resistant clinical isolates via stimuli-activated superoxide generation.

PubMed

Courtney, Colleen M; Goodman, Samuel M; Nagy, Toni A; Levy, Max; Bhusal, Pallavi; Madinger, Nancy E; Detweiler, Corrella S; Nagpal, Prashant; Chatterjee, Anushree

2017-10-01

The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics. To treat already pervasive MDR infections, new classes of antibiotics or antibiotic adjuvants are needed. Reactive oxygen species (ROS) have been shown to play a role during antibacterial action; however, it is not yet understood whether ROS contribute directly to or are an outcome of bacterial lethality caused by antibiotics. We show that a light-activated nanoparticle, designed to produce tunable flux of specific ROS, superoxide, potentiates the activity of antibiotics in clinical MDR isolates of Escherichia coli , Salmonella enterica , and Klebsiella pneumoniae . Despite the high degree of antibiotic resistance in these isolates, we observed a synergistic interaction between both bactericidal and bacteriostatic antibiotics with varied mechanisms of action and our superoxide-producing nanoparticles in more than 75% of combinations. As a result of this potentiation, the effective antibiotic concentration of the clinical isolates was reduced up to 1000-fold below their respective sensitive/resistant breakpoint. Further, superoxide-generating nanoparticles in combination with ciprofloxacin reduced bacterial load in epithelial cells infected with S. enterica serovar Typhimurium and increased Caenorhabditis elegans survival upon infection with S. enterica serovar Enteriditis, compared to antibiotic alone. This demonstration highlights the ability to engineer superoxide generation to potentiate antibiotic activity and combat highly drug-resistant bacterial pathogens.

Clinical Information Systems - From Yesterday to Tomorrow.

PubMed

Gardner, R M

2016-06-30

To review the history of clinical information systems over the past twenty-five years and project anticipated changes to those systems over the next twenty-five years. Over 250 Medline references about clinical information systems, quality of patient care, and patient safety were reviewed. Books, Web resources, and the author's personal experience with developing the HELP system were also used. There have been dramatic improvements in the use and acceptance of clinical computing systems and Electronic Health Records (EHRs), especially in the United States. Although there are still challenges with the implementation of such systems, the rate of progress has been remarkable. Over the next twenty-five years, there will remain many important opportunities and challenges. These opportunities include understanding complex clinical computing issues that must be studied, understood and optimized. Dramatic improvements in quality of care and patient safety must be anticipated as a result of the use of clinical information systems. These improvements will result from a closer involvement of clinical informaticians in the optimization of patient care processes. Clinical information systems and computerized clinical decision support have made contributions to medicine in the past. Therefore, by using better medical knowledge, optimized clinical information systems, and computerized clinical decision, we will enable dramatic improvements in both the quality and safety of patient care in the next twenty-five years.

Remarkable biomimetic chemoselective aerobic oxidation of flavano-ellagitannins found in oak-aged wine.

PubMed

Petit, Emilie; Lefeuvre, Dorothée; Jacquet, Rémi; Pouységu, Laurent; Deffieux, Denis; Quideau, Stéphane

2013-10-25

Under the auspices of Bacchus! Acutissimins, natural flavano-ellagitannins, occur in oak-aged wine as a result of a diastereoselective condensation reaction of the flavan-3-ol catechin, a component of grapes, with the C-glucosidic ellagitannin vescalagin, found in oak. The acutissimins are further converted into natural mongolicains and analogues of camelliatannin G in a remarkably chemoselective fashion by simple aerobic oxidation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Therapeutic horticulture in clinical depression: a prospective study of active components.

PubMed

Gonzalez, Marianne Thorsen; Hartig, Terry; Patil, Grete Grindal; Martinsen, Egil W; Kirkevold, Marit

2010-09-01

This paper is a report of a study conducted to assess change in depression severity, perceived attentional capacity and rumination (brooding) in individuals with clinical depression during a therapeutic horticulture programme and to investigate if the changes were mediated by experiences of being away and fascination. Individuals with clinical depression suffer from distortion of attention and rumination. Interventions can help to disrupt maladaptive rumination and promote restoration of depleted attentional capacity. A single-group study was conducted with a convenience sample of 28 people with clinical depression in 2009. Data were collected before, twice during, and immediately after a 12-week therapeutic horticulture programme, and at 3-month follow-up. Assessment instruments were the Beck Depression Inventory, Attentional Function Index, Brooding Scale, and Being Away and Fascination subscales from the Perceived Restorativeness Scale. Mean Beck Depression Inventory scores declined by 4.5 points during the intervention (F = 5.49, P = 0.002). The decline was clinically relevant for 50% of participants. Attentional Function Index scores increased (F = 4.14, P = 0.009), while Brooding scores decreased (F = 4.51, P = 0.015). The changes in Beck Depression Inventory and Attentional Function Index scores were mediated by increases in Being Away and Fascination, and decline in Beck Depression Inventory scores was also mediated by decline in Brooding. Participants maintained their improvements in Beck Depression Inventory scores at 3-month follow-up. Being away and fascination appear to work as active components in a therapeutic horticulture intervention for clinical depression.

Community Representatives’ Involvement in Clinical and Translational Science Awardee Activities

PubMed Central

Spofford, Mark; Williams, Neely; McKeever, Corliss; Allen, Shauntice; Brown, Jen; Opp, Jennifer; Richmond, Alan; Strelnick, A. Hal

2013-01-01

Abstract Objectives To understand the formal roles of community representatives (CRs) in Clinical and Translational Science Awardee (CTSA) activities, to evaluate the extent of integration into the organizational and governance structures and to identify barriers to effective integration. Methods The inventory tool was distributed to each of the 60 CTSAs using a secure web application. Results Forty‐seven (78%) completed the inventory. The mean number of CRs per CTSA is 21.4 (SD: 14.8). Most CTSAs had community advisory boards (89%) and 94% included CRs in Community Engagement (CE) cores. Only 11% reported a CR being a member of the CTSA leadership team and 19% reported that CRs advise core programs beyond CE. CRs are compensated by 79% of CTSAs. Mean annual compensation is $753 (median: $400). Compensation directly correlated with the number of hours that CRs worked in CTSA activities (r = 0.64; P = 0.001). Conclusions This inventory allows CTSAs to better understand how CRs have engaged in activities and brings attention to the limited representation among cores and in leadership roles. CTSAs should, with substantive input from CRs, develop strategies to provide the resources and compensation necessary to better integrate the community in CTSA activities and fully realize the goals of the CTSA vision. PMID:23919364

Preliminary investigation of Brain Network Activation (BNA) and its clinical utility in sport-related concussion.

PubMed

Reches, A; Kutcher, J; Elbin, R J; Or-Ly, H; Sadeh, B; Greer, J; McAllister, D J; Geva, A; Kontos, A P

2017-01-01

The clinical diagnosis and management of patients with sport-related concussion is largely dependent on subjectively reported symptoms, clinical examinations, cognitive, balance, vestibular and oculomotor testing. Consequently, there is an unmet need for objective assessment tools that can identify the injury from a physiological perspective and add an important layer of information to the clinician's decision-making process. The goal of the study was to evaluate the clinical utility of the EEG-based tool named Brain Network Activation (BNA) as a longitudinal assessment method of brain function in the management of young athletes with concussion. Athletes with concussion (n = 86) and age-matched controls (n = 81) were evaluated at four time points with symptom questionnaires and BNA. BNA scores were calculated by comparing functional networks to a previously defined normative reference brain network model to the same cognitive task. Subjects above 16 years of age exhibited a significant decrease in BNA scores immediately following injury, as well as notable changes in functional network activity, relative to the controls. Three representative case studies of the tested population are discussed in detail, to demonstrate the clinical utility of BNA. The data support the utility of BNA to augment clinical examinations, symptoms and additional tests by providing an effective method for evaluating objective electrophysiological changes associated with sport-related concussions.

Preliminary investigation of Brain Network Activation (BNA) and its clinical utility in sport-related concussion

PubMed Central

Reches, A.; Kutcher, J.; Elbin, R. J.; Or-Ly, H.; Sadeh, B.; Greer, J.; McAllister, D. J.; Geva, A.; Kontos, A. P.

2017-01-01

ABSTRACT Background: The clinical diagnosis and management of patients with sport-related concussion is largely dependent on subjectively reported symptoms, clinical examinations, cognitive, balance, vestibular and oculomotor testing. Consequently, there is an unmet need for objective assessment tools that can identify the injury from a physiological perspective and add an important layer of information to the clinician’s decision-making process. Objective: The goal of the study was to evaluate the clinical utility of the EEG-based tool named Brain Network Activation (BNA) as a longitudinal assessment method of brain function in the management of young athletes with concussion. Methods: Athletes with concussion (n = 86) and age-matched controls (n = 81) were evaluated at four time points with symptom questionnaires and BNA. BNA scores were calculated by comparing functional networks to a previously defined normative reference brain network model to the same cognitive task. Results: Subjects above 16 years of age exhibited a significant decrease in BNA scores immediately following injury, as well as notable changes in functional network activity, relative to the controls. Three representative case studies of the tested population are discussed in detail, to demonstrate the clinical utility of BNA. Conclusion: The data support the utility of BNA to augment clinical examinations, symptoms and additional tests by providing an effective method for evaluating objective electrophysiological changes associated with sport-related concussions. PMID:28055228

The Need to Objectively Measure Physical Activity During Pregnancy: Considerations for Clinical Research and Public Health Impact.

PubMed

Guérin, Eva; Ferraro, Zachary M; Adamo, Kristi B; Prud'homme, Denis

2018-05-01

Engaging in recommended levels of physical activity during pregnancy can provide a host of physical and mental health benefits for the expecting mother and her child. However, methodological issues related to physical activity measurement have plagued many studies examining the effects of physical activity during this important life stage. Burgeoning support exists for the more widespread use of objective methods, and accelerometers specifically, for an accurate appraisal of maternal physical activity. In this commentary, we highlight discrepancies between activity estimates obtained via self-report and objective measures and describe the implications of erroneous measurement when making clinical recommendations and in conducting future physical activity and pregnancy research. Most importantly, we aim to foster academic discussion and propose a call to action requiring a paradigm shift where we acknowledge the shortcomings of self-report and move toward an empirically driven approach for physical activity measurement. Results from more high-quality research studies will help support public health messaging and facilitate trust among health care providers, clinical researchers, and expecting mothers regarding the health benefits of physical activity recommendations.

Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

PubMed Central

Coelho, Tatiane; Machado, Diana; Couto, Isabel; Maschmann, Raquel; Ramos, Daniela; von Groll, Andrea; Rossetti, Maria L.; Silva, Pedro A.; Viveiros, Miguel

2015-01-01

Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA) to study single combinations between antituberculosis drugs and efflux inhibitors (EIs) against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC) indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates. PMID:25972842

The Public University in South Africa: Philosophical Remarks on the Notion of "Elitist Knowledge" Production

ERIC Educational Resources Information Center

Waghid, Yusef

2009-01-01

In my remarks about elitist knowledge production, I firstly try to adjust the perspective from which the university could be analysed; I specifically explore the functions of the university in relation to Habermas's categorisation of knowledge. Secondly, with reference to Derrida's reflections on the university, I reformulate a conception of the…

Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor, demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro.

PubMed

Zhu, Liancheng; Lopez, Salvatore; Bellone, Stefania; Black, Jonathan; Cocco, Emiliano; Zigras, Tiffany; Predolini, Federica; Bonazzoli, Elena; Bussi, Beatrice; Stuhmer, Zachary; Schwab, Carlton L; English, Diana P; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2015-07-01

Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer that carries an extremely poor prognosis. Up to 35 % of USC may overexpress the epidermal growth factor receptor-2 (HER2/neu) at strong (i.e., 3+) level by immunohistochemistry (IHC) or harbor HER2/neu gene amplification by fluorescence in situ hybridization (FISH). In this study, we assessed the sensitivity of a panel of USC cell lines with and without HER2/neu gene amplification to dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor tyrosine kinase inhibitor. Eight primary cell lines (i.e., four harboring HER2/neu gene amplification by FISH and four FISH- cell lines), all demonstrating similar in vitro growth rates, were evaluated in viability/proliferation assays. The effect of dacomitinib on cell growth, cell cycle distribution, and signaling was determined using flow cytometry-based assays. Dacomitinib caused a significantly stronger growth inhibition in HER2/neu FISH+ USC cell lines when compared to FISH- USC (dacomitinib half maximal inhibitory concentration (IC50) mean ± SEM = 0.02803 ± 0.003355 μM in FISH+ versus 1.498 ± 0.2209 μM in FISH- tumors, P < 0.0001). Dacomitinib growth inhibition was associated with a significant and dose-dependent decline in phosphorylated HER2/neu and S6 transcription factor and a dose-dependent and time-dependent cell cycle arrest in G0/G1 in FISH+ USC. Dacomitinib is remarkably effective against chemotherapy-resistant HER2/neu gene-amplified USC. Clinical studies with dacomitinib in HER2/neu FISH+ USC patients resistant to standard salvage chemotherapy are warranted.

The Caatinga endemic Manilkara rufula possesses remarkable activity against Trichomonas vaginalis and Tritrichomonas foetus.

PubMed

de Brum Vieira, Patrícia; Feijó Silva, Nícolas Luiz; Silva, Denise Brentan; Lopes, Norberto Peporine; da Silva, Alexandre Gomes; da Silva, Márcia Vanusa; Bastida, Jaume; Macedo, Alexandre José; Tasca, Tiana

2017-02-01

Tritrichomonas foetus infects the bovine urogenital tract, causing bovine trichomoniasis. Significant economic losses may occur due to infertility and abortion among cattle. Trichomonas vaginalis is the causative agent of trichomoniasis; the most common but overlooked non-viral sexually transmitted disease worldwide. Human and bovine trichomoniasis present treatment restrictions and efforts to identify new alternatives are essential. The present study evaluated the anti-trichomonads activities of seven fractions from northwest endemic plant Manilkara rufula. Flavonoids and condensed tannins were identified from these fractions by LC-DAD-MS/MS and MALDI-MS/MS. Altogether, the results demonstrated for the first time the structural description of tannins from leaves of M. rufula and the relation of these compounds with anti-T. vaginalis and anti-T. foetus activities. Overall, this report reveals the potential of M. rufula fractions against both parasites and shows new alternatives to treat the infection caused by trichomonads. Copyright © 2016 Elsevier Inc. All rights reserved.

Pinostrobin Derivatives from PrenylationReaction and their Antibacterial Activity against Clinical Bacteria

NASA Astrophysics Data System (ADS)

Marliyana, S. D.; Mujahidin, D.; Syah, Y. M.

2018-04-01

Kaempferia pandurata (syn. Boesenbergia rotunda, B. pandurata (Roxb.)Schltr), locally known as "TemuKunci"in Indonesia, is one of the medicinal plants of the family Zingiberaceae. Phytochemical studies on the rhizome of K. pandurata showed the presence of flavonoid derivative, namely flavanones, which constitute as the main components of this plant. Bioactivity studies on this species exhibited various biological activities, such as antibacteria, anti-inflammatory, antitumor, antidiarrhea, antidisentri, anti-HIV, antioxidant, antipyretic, analgesic and insecticides. Among the biological activities, the antibacterial activity results are important as an attempt to answer the emergence of resistance of some bacteria against existing drugs, as well as the emergence of a number of outbreaks of disease caused by bacteria. Therefore, a search to find new compounds that are potential as an antibacterial is an urgent matter. The present study was aimed at the chemical transformation of pinostrobin (1) from K. pandurata rhizome and an antibacterial activity.The chemical transformation was performed through a prenylation reaction of pinostrobin (1) which is the main component of K. pandurata rhizome. The prenylation reaction was carried out by reacting pinostrobin (1) with prenyl bromide and potassium carbonat (K2CO3). The purification of product was done using the radial chromatography with mix solvent n-hexane and ethyl acetate (97.5:2.5; 9.5:0.5; 9.0:1.0.; 8.0:2.0). The purity test of isolated compound was analysedby TLC using different types of eluent. The identification of compounds was determined based on NMR data and mass spectra analysis. Five compounds were obtained from the prenylation reaction, i.e. monooxyprenylated pinostrobin (2), monooxyprenylated chalcone (3), diprenylated chalcone (4), triprenylated chalcone (5), and triprenylated cyclohexene chalcone (6). These compounds were tested for antibacterial activities against four clinical bacteria, namely

A Brief History of the Most Remarkable Numbers "e," "i" and "?" in Mathematical Sciences with Applications

ERIC Educational Resources Information Center

Debnath, Lokenath

2015-01-01

This paper deals with a brief history of the most remarkable Euler numbers "e,"?"i"?and?"?" in mathematical sciences. Included are many properties of the constants "e,"?"i"?and?"?" and their applications in algebra, geometry, physics, chemistry, ecology, business and industry. Special…

Summary of International Guidelines for Physical Activity Following Pregnancy

PubMed Central

Evenson, Kelly R.; Mottola, Michelle F.; Owe, Katrine M.; Rousham, Emily K.; Brown, Wendy J.

2014-01-01

Postpartum physical activity can improve mood, maintain cardiorespiratory fitness, improve weight control, promote weight loss, and reduce depression and anxiety. This review summarizes current guidelines for postpartum physical activity worldwide. PubMed (MedLINE) was searched for country-specific government and clinical guidelines on physical activity following pregnancy through the year 2013. Only the most recent guideline was included in the review. An abstraction form facilitated extraction of key details and helped to summarize results. Six guidelines were identified from five countries (Australia, Canada, Norway, United Kingdom, United States). All guidelines were embedded within pregnancy-related physical activity recommendations. All provided physical activity advice related to breastfeeding and three remarked about physical activity following Caesarean delivery. Recommended physical activities mentioned in the guidelines included aerobic (3/6), pelvic floor exercise (3/6), strengthening (2/6), stretching (2/6), and walking (2/6). None of the guidelines discussed sedentary behavior. The guidelines that were identified lacked specificity for physical activity. Greater clarity in guidelines would be more useful to both practitioners and the women they serve. Postpartum physical activity guidelines have the potential to assist women to initiate or resume physical activity following childbirth, so that they can transition to meeting recommended levels of physical activity. Health care providers have a critical role in encouraging women to be active at this time, and the availability of more explicit guidelines may assist them to routinely include physical activity advice in their postpartum care. PMID:25112589

Modifying the Clinical Research Infrastructure at a Dedicated Clinical Trials Unit: Assessment of Trial Development, Activation, and Participant Accrual.

PubMed

Tang, Chad; Hess, Kenneth R; Sanders, Dwana; Davis, Suzanne E; Buzdar, Aman U; Kurzrock, Razelle; Lee, J Jack; Meric-Bernstam, Funda; Hong, David S

2017-03-15

Purpose: Information on processes for trials assessing investigational therapeutics is sparse. We assessed the trial development processes within the Department of Investigational Cancer Therapeutics (ICT) at MD Anderson Cancer Center (Houston, TX) and analyzed their effects on the trial activation timeline and enrolment. Experimental Design: Data were from a prospectively maintained registry that tracks all clinical studies at MD Anderson. From this database, we identified 2,261 activated phase I-III trials; 221 were done at the ICT. ICT trials were matched to trials from other MD Anderson departments by phase, sponsorship, and submission year. Trial performance metrics were compared with paired Wilcoxon signed rank tests. Results: We identified three facets of the ICT research infrastructure: parallel processing of trial approval steps; a physician-led research team; and regular weekly meetings to foster research accountability. Separate analyses were conducted stratified by sponsorship [industry (133 ICT and 133 non-ICT trials) or institutional (68 ICT and 68 non-ICT trials)]. ICT trial development was faster from IRB approval to activation (median difference of 1.1 months for industry-sponsored trials vs. 2.3 months for institutional) and from activation to first enrolment (median difference of 0.3 months for industry vs. 1.2 months for institutional; all matched P < 0.05). ICT trials also accrued more patients (median difference of 8 participants for industry vs. 33.5 for institutional) quicker (median difference 4.8 participants/year for industry vs. 11.1 for institutional; all matched P < 0.05). Conclusions: Use of a clinical research-focused infrastructure within a large academic cancer center was associated with efficient trial development and participant accrual. Clin Cancer Res; 23(6); 1407-13. ©2016 AACR . ©2016 American Association for Cancer Research.

Premature adrenarche: etiology, clinical findings, and consequences.

PubMed

Voutilainen, Raimo; Jääskeläinen, Jarmo

2015-01-01

Adrenarche means the morphological and functional change of the adrenal cortex leading to increasing production of adrenal androgen precursors (AAPs) in mid childhood, typically at around 5-8 years of age in humans. The AAPs dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the best serum markers of adrenal androgen (AA) secretion and adrenarche. Normal ACTH secretion and action are needed for adrenarche, but additional inherent and exogenous factors regulate AA secretion. Inter-individual variation in the timing of adrenarche and serum concentrations of DHEA(S) in adolescence and adulthood are remarkable. Premature adrenarche (PA) is defined as the appearance of clinical signs of androgen action (pubic/axillary hair, adult type body odor, oily skin or hair, comedones, acne, accelerated statural growth) before the age of 8 years in girls or 9 years in boys associated with AAP concentrations high for the prepubertal chronological age. To accept the diagnosis of PA, central puberty, adrenocortical and gonadal sex hormone secreting tumors, congenital adrenal hyperplasia, and exogenous source of androgens need to be excluded. The individually variable peripheral conversion of circulating AAPs to biologically more active androgens (testosterone, dihydrotestosterone) and the androgen receptor activity in the target tissues are as important as the circulating AAP concentrations as determinants of androgen action. PA has gained much attention during the last decades, as it has been associated with small birth size, the metabolic and polycystic ovarian syndrome (PCOS), and thus with an increased risk for type 2 diabetes and cardiovascular diseases in later life. The aim of this review is to describe the known hormonal changes and their possible regulators in on-time and premature adrenarche, and the clinical features and possible later health problems associating with PA. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brentuximab vedotin: clinical updates and practical guidance

PubMed Central

Yi, Jun Ho; Kim, Seok Jin

2017-01-01

Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted accelerated approval in 2011 by the US Food and Drug Administration. Thereafter, many large-scale trials in various situations have been performed, which led to extensions of the original indication. The aim of this review was to describe the latest updates on clinical trials of BV and the in-practice guidance for the use of BV. PMID:29333400

A neurologist's reflections on boxing. V. Conclude remarks.

PubMed

Unterharnscheidt, F

1995-01-01

reparation or restitution of the destroyed neural tissue of the brain. What is destroyed remains so, a restitution ad integrum does not occur. As the result of the diffuse loss of neurons in the brain a cerebral atrophy exists. The septum pellucidum, which consists of two thin lamellae, and is small or very small in a normal brain, forms a Cavum septi pellucidi, which is considerably enlarged. The walls of this structure, especially in its dorsal parts are considerably thinned; they show fenestrations and are, in dorsal parts no longer detectable, so that a direct connection between the two lateral ventricles exists. The clinically and morphologically existing permanent brain damage is the result of the boxing activity. Diagnostically, processes of another origin, such as alcoholism, luetic processes, other forms of dementia, etc. can undoubtedly be excluded. A permanent brain damage develops in professional and amateur boxers. The objection, which are voiced by members of the different Amateur Boxing Association, that such permanent brain damage in amateur boxers today no longer exists, after stricter protective measurements were introduced, is not tenable. Individuals who represent today the opinion, that a permanent brain damage or punch drunkenness in boxers does not occur, are not familiar with the pertinent medical literature. The argument, the injury quotient in boxing is lower than in all other athletic activities is not sound, since the statistics show only the inconsequential injuries of boxers, as lesions of the skin of the face, injuries of the hand, fractures, etc. but not the much more important and severe permanent brain damage, which is not taken into consideration in these so-called statistics. Besides of the permanent brain damage of former boxers as the result of the repeated and numerous blows against their head, severe permanent damage of the eyes and the hearing organ exists.

[The informatics: a remarkable tool for teaching general internal medicine].

PubMed

Ombelli, Julien; Pasche, Olivier; Sohrmann, Marc; Monti, Matteo

2015-05-13

INTERMED training implies a three week course, integrated in the "primary care module" for medical students in the first master year at the school of medicine in Lausanne. INTERMED uses an innovative teaching method based on repetitive sequences of e-learning-based individual learning followed by collaborative learning activities in teams, named Team-based learning (TBL). The e-learning takes place in a web-based virtual learning environment using a series of interactive multimedia virtual patients. By using INTERMED students go through a complete medical encounter applying clinical reasoning and choosing the diagnostic and therapeutic approach. INTERMED offers an authentic experience in an engaging and safe environment where errors are allowed and without consequences.

Activating and Encouraging Supervisees' Creativity and Intuition through the Clinical Supervisory Relationship

ERIC Educational Resources Information Center

Tolbert, Yvette R.

2017-01-01

The purpose of this study was to explore how creativity and intuition were activated and encouraged by counseling supervisors within the clinical supervisory relationship with supervisees. Past research in this area was limited in scope, and suggestions for future research included uncovering what worked to encourage creativity and intuition for…

Reviewing Clinical Effectiveness of Active Training Strategies of Platform-Based Ankle Rehabilitation Robots.

PubMed

Zeng, Xiangfeng; Zhu, Guoli; Zhang, Mingming; Xie, Sheng Q

2018-01-01

This review aims to provide a systematical investigation of clinical effectiveness of active training strategies applied in platform-based ankle robots. English-language studies published from Jan 1980 to Aug 2017 were searched from four databases using key words of "Ankle ∗ " AND "Robot ∗ " AND "Effect ∗ OR Improv ∗ OR Increas ∗ ." Following an initial screening, three rounds of discrimination were successively conducted based on the title, the abstract, and the full paper. A total of 21 studies were selected with 311 patients involved; of them, 13 studies applied a single group while another eight studies used different groups for comparison to verify the therapeutic effect. Virtual-reality (VR) game training was applied in 19 studies, while two studies used proprioceptive neuromuscular facilitation (PNF) training. Active training techniques delivered by platform ankle rehabilitation robots have been demonstrated with great potential for clinical applications. Training strategies are mostly combined with one another by considering rehabilitation schemes and motion ability of ankle joints. VR game environment has been commonly used with active ankle training. Bioelectrical signals integrated with VR game training can implement intelligent identification of movement intention and assessment. These further provide the foundation for advanced interactive training strategies that can lead to enhanced training safety and confidence for patients and better treatment efficacy.

Reinforcement of high-risk anastomoses using laser-activated protein solders: a clinical study

NASA Astrophysics Data System (ADS)

Libutti, Steven K.; Bessler, Marc; Chabot, J.; Bass, Lawrence S.; Oz, Mehmet C.; Auteri, Joseph S.; Kirsch, Andrew J.; Nowygrod, Roman; Treat, Michael R.

1993-07-01

Anastomotic leakage or breakdown can result in catastrophic complications and significantly increased post-operative morbidity and mortality. Certain anastomoses are subject to a higher incidence of disruption and are therefore termed high risk. In an attempt to decrease the risk of anastomotic leaks, we reinforced sutured anastomoses with a laser activated protein solder in patients undergoing esophagojejunostomies (n equals 2), lung transplantation (n equals 2), and pancreaticojejunostomies (Whipple procedure, n equals 5). The protein solder was composed of 1.0 ml of a 25% human albumin solution, 1.0 ml of sodium hyaluronate, and 0.1 ml of Cardiogreen dye. This composition was applied to the sutured anastomosis and activated with an 860 nm pulsed diode laser. Drains were placed when appropriate and patients were followed for up to 10 months post-operatively and assessed for clinical signs of anastomotic leaks. Results to data demonstrated that there were no immediate complications as a result of the procedure. Operative time was not significantly lengthened. There were no cases of clinically significant leakage from any of the reinforced anastomoses. Laser activated protein solders may help to reduce the incidence of leakage in high risk anastomoses. Large numbers of patients and longer follow-up is needed however, to draw significant conclusions.

Refining Video Game Use Questionnaires for Research and Clinical Application: Detection of Problematic Response Sets

ERIC Educational Resources Information Center

Faust, Kyle A.; Faust, David; Baker, Aaron M.; Meyer, Joseph F.

2012-01-01

Even when relatively infrequent, deviant response sets, such as defensive and careless responding, can have remarkably robust effects on individual and group data and thereby distort clinical evaluations and research outcomes. Given such potential adverse impacts and the widespread use of self-report measures when appraising addictions and…

Effects of Long-Term Acupuncture Treatment on Resting-State Brain Activity in Migraine Patients: A Randomized Controlled Trial on Active Acupoints and Inactive Acupoints

PubMed Central

Zhao, Ling; Liu, Jixin; Zhang, Fuwen; Dong, Xilin; Peng, Yulin; Qin, Wei; Wu, Fumei; Li, Ying; Yuan, Kai; von Deneen, Karen M.; Gong, Qiyong; Tang, Zili; Liang, Fanrong

2014-01-01

Background Acupuncture has been commonly used for preventing migraine attacks and relieving pain during a migraine, although there is limited knowledge on the physiological mechanism behind this method. The objectives of this study were to compare the differences in brain activities evoked by active acupoints and inactive acupoints and to investigate the possible correlation between clinical variables and brain responses. Methods and Results A randomized controlled trial and resting-state functional magnetic resonance imaging (fMRI) were conducted. A total of eighty migraineurs without aura were enrolled to receive either active acupoint acupuncture or inactive acupoint acupuncture treatment for 8 weeks, and twenty patients in each group were randomly selected for the fMRI scan at the end of baseline and at the end of treatment. The neuroimaging data indicated that long-term active acupoint therapy elicited a more extensive and remarkable cerebral response compared with acupuncture at inactive acupoints. Most of the regions were involved in the pain matrix, lateral pain system, medial pain system, default mode network, and cognitive components of pain processing. Correlation analysis showed that the decrease in the visual analogue scale (VAS) was significantly related to the increased average Regional homogeneity (ReHo) values in the anterior cingulate cortex in the two groups. Moreover, the decrease in the VAS was associated with increased average ReHo values in the insula which could be detected in the active acupoint group. Conclusions Long-term active acupoint therapy and inactive acupoint therapy have different brain activities. We postulate that acupuncture at the active acupoint might have the potential effect of regulating some disease-affected key regions and the pain circuitry for migraine, and promote establishing psychophysical pain homeostasis. Trial Registration Chinese Clinical Trial Registry ChiCTR-TRC-13003635 PMID:24915066

The Geology and Remarkable Thermal Activity of Norris Geyser Basin, Yellowstone National Park, Wyoming

USGS Publications Warehouse

White, Donald Edward; Hutchinson, Roderick A.; Keith, Terry E.C.

1988-01-01

Norris Geyser Basin, normally shortened to Norris Basin, is adjacent to the north rim of the Yellowstone caldera at the common intersection of the caldera rim and the Norris-Mammoth Corridor, a zone of faults, volcanic vents, and thermal activity that strikes north from the caldera rim to Mammoth Hot Springs. An east-west fault zone terminates the Gallatin Range at its southern end and extends from Hebgen Lake, west of the park, to Norris Basin. No local evidence exists at the surface in Norris Basin for the two oldest Yellowstone volcanic caldera cycles (~2.0 and 1.3 m.y.B.P.). The third and youngest cycle formed the Yellowstone caldera, which erupted the 600,000-year-old Lava Creek Tuff. No evidence is preserved of hydrothermal activity near Norris Basin during the first 300,000.years after the caldera collapse. Glaciation probably removed most of the early evidence, but erratics of hot-spring sinter that had been converted diagenetically to extremely hard, resistant chalcedonic sinter are present as cobbles in and on some moraines and till from the last two glacial stages, here correlated with the early and late stages of the Pinedale glaciation <150,000 years B.P.). Indirect evidence for the oldest hydrothermal system at Norris Basin indicates an age probably older than both stages of Pinedale glaciation. Stream deposits consisting mainly of rounded quartz phenocrysts of the Lava Creek Tuff were subaerial, perhaps in part windblown and redeposited by streams. A few small rounded pebbles are interpreted as chalcedonic sinter of a still older cycle. None of these are precisely dated but are unlikely to be more than 150,000 to 200,000 years old. ...Most studies of active hydrothermal areas have noted chemical differences in fluids and alteration products but have given little attention to differences and models to explain evolution in types. This report, in contrast, emphasizes the kinds of changes in vents and their changing chemical types of waters and then

The remarkably high excitation planetary nebula GC 6537

PubMed Central

Aller, Lawrence H.; Hung, Siek; Feibelman, Walter A.

1999-01-01

NGC 6537 is an unusually high excitation point symmetric planetary nebula with a rich spectrum. Its kinematical structures are of special interest. We are here primarily concerned with the high resolution spectrum as revealed by the Hamilton echelle Spectrograph at Lick Observatory (resolution ≈ 0.2 Å) and supplemented by UV and near-UV data. These extensive data permit a determination of interstellar extinction, plasma diagnostics, and ionic concentrations. The photoionization models that have been used successfully for many planetary nebulae are not entirely satisfactory here. The plasma electron temperature of a photoionization model cannot much exceed 20,000 K, but plasma diagnostics show that regions emitting radiation of highly ionized atoms such as [Neiv] and [Nev] are much hotter, showing that shock excitation must be important, as suggested by the remarkable kinematics of this object. Hence, instead of employing a strict photoionization model, we are guided by the nebular diagnostics, which reveal how electron temperature varies with ionization potential and accommodates density effects. The predictions of the photoionization model may be useful in estimating ionization correction factor. In effect, we have estimated the chemical composition by using both photoionization and shock considerations. PMID:10318889

The remarkably high excitation planetary nebula GC 6537.

PubMed

Aller, L H; Hung, S; Feibelman, W A

1999-05-11

NGC 6537 is an unusually high excitation point symmetric planetary nebula with a rich spectrum. Its kinematical structures are of special interest. We are here primarily concerned with the high resolution spectrum as revealed by the Hamilton echelle Spectrograph at Lick Observatory (resolution approximately 0.2 A) and supplemented by UV and near-UV data. These extensive data permit a determination of interstellar extinction, plasma diagnostics, and ionic concentrations. The photoionization models that have been used successfully for many planetary nebulae are not entirely satisfactory here. The plasma electron temperature of a photoionization model cannot much exceed 20,000 K, but plasma diagnostics show that regions emitting radiation of highly ionized atoms such as [NeIV] and [NeV] are much hotter, showing that shock excitation must be important, as suggested by the remarkable kinematics of this object. Hence, instead of employing a strict photoionization model, we are guided by the nebular diagnostics, which reveal how electron temperature varies with ionization potential and accommodates density effects. The predictions of the photoionization model may be useful in estimating ionization correction factor. In effect, we have estimated the chemical composition by using both photoionization and shock considerations.

Shared Voyage: Learning and Unlearning from Remarkable Projects

NASA Technical Reports Server (NTRS)

Laufer, Alexander; Post, Todd; Hoffman, Edward J.

2005-01-01

Shared Voyage is about four remarkable projects: the Advanced Composition Explorer (NASA), the Joint Air-to-Surface Standoff Missile (U.S. Air Force), the Pathfinder Solar-Powered Airplane (NASA), and the Advanced Medium Range Air-to-Air Missile (U.S.Air Force). Each project is presented as a case study comprised of stories collected from key members of the project teams. The stories found in the book are included with the purpose of providing an effective learning source for project management, encouraging the unlearning of outdated project management concepts, and enhancing awareness of the contexts surrounding different projects. Significantly different from project concepts found in most project management literature, Shared Voyage highlights concepts like a will to win, a results-oriented focus, and collaboration through trust. All four project teams researched in this study applied similar concepts; however, they applied them differently, tailoring them to fit the context of their own particular projects. It is clear that the one best way approach which is still the prevailing paradigm in project management literature should be replaced by a new paradigm: Even though general project management principles exist, their successful application depends on the specifics of the situation.

[Active tuberculosis in a cohort of HIV-infected inmates in a prison in Mexico City: clinical and epidemiological characteristics].

PubMed

Hernández-León, Christian; Badial-Hernández, Florentino; Ponce-de-León, Alfredo; Sierra-Madero, Juan G; Martínez-Gamboa, Areli; Crabtree-Ramírez, Brenda; Bautista-Arredondo, Sergio; González-Aguirre, Adrián; Guerrero-Almeida, María de Lourdes; del Valle, J Miriam Bobadilla; González-Rodríguez, Andrea; Sifuentes-Osornio, José

2012-01-01

To determine the clinical and epidemiological characteristics of prison inmates with active tuberculosis in HIV-positive prison populations. We conducted a cohort study in HIV-infected subjects in a prison in Mexico City, with the aim of determining clinical and epidemiological characteristics of cases with active TB. We detected 172 HIV infected inmates and TB in 28 of them (16.3%) - 21 (12.2) with pulmonary TB--with an incidence rate of 7.7/100 persons/year for active TB and 4.7/100 persons/year for pulmonary TB. No drug resistance was found. Two clusters (4 and 2 subjects) were observed after RFLP-typing of 18 isolates, with a transmission rate of 11% by molecular and clinical analysis. The prevalence of active TB was found to be a thousand times greater than in the general population. Evidence of transmission inside the prison was also found.

PGLa-H tandem-repeat peptides active against multidrug resistant clinical bacterial isolates.

PubMed

Rončević, Tomislav; Gajski, Goran; Ilić, Nada; Goić-Barišić, Ivana; Tonkić, Marija; Zoranić, Larisa; Simunić, Juraj; Benincasa, Monica; Mijaković, Marijana; Tossi, Alessandro; Juretić, Davor

2017-02-01

Antimicrobial peptides (AMPs) are promising candidates for new antibiotic classes but often display an unacceptably high toxicity towards human cells. A naturally produced C-terminal fragment of PGLa, named PGLa-H, has been reported to have a very low haemolytic activity while maintaining a moderate antibacterial activity. A sequential tandem repeat of this fragment, diPGLa-H, was designed, as well as an analogue with a Val to Gly substitution at a key position. These peptides showed markedly improved in vitro bacteriostatic and bactericidal activity against both reference strains and multidrug resistant clinical isolates of Gram-negative and Gram-positive pathogens, with generally low toxicity for human cells as assessed by haemolysis, cell viability, and DNA damage assays. The glycine substitution analogue, kiadin, had a slightly better antibacterial activity and reduced haemolytic activity, which may correlate with an increased flexibility of its helical structure, as deduced using molecular dynamics simulations. These peptides may serve as useful lead compounds for developing anti-infective agents against resistant Gram-negative and Gram-positive species. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the in vitro activity of levornidazole, its metabolites and comparators against clinical anaerobic bacteria.

PubMed

Hu, Jiali; Zhang, Jing; Wu, Shi; Zhu, Demei; Huang, Haihui; Chen, Yuancheng; Yang, Yang; Zhang, Yingyuan

2014-12-01

This study evaluated the in vitro anti-anaerobic activity and spectrum of levornidazole, its metabolites and comparators against 375 clinical isolates of anaerobic bacteria, including Gram-negative bacilli (181 strains), Gram-negative cocci (11 strains), Gram-positive bacilli (139 strains) and Gram-positive cocci (44 strains), covering 34 species. Minimum inhibitory concentrations (MICs) of levornidazole, its five metabolites and three comparators against these anaerobic isolates were determined by the agar dilution method. Minimum bactericidal concentrations (MBCs) of levornidazole and metronidazole were measured against 22 strains of Bacteroides fragilis. Levornidazole showed good activity against B. fragilis, other Bacteroides spp., Clostridium difficile, Clostridium perfringens and Peptostreptococcus magnus, evidenced by MIC90 values of 0.5, 1, 0.25, 2 and 1mg/L, respectively. The activity of levornidazole and the comparators was poor for Veillonella spp. Generally, levornidazole displayed activity similar to or slightly higher than that of metronidazole, ornidazole and dextrornidazole against anaerobic Gram-negative bacilli, Gram-positive bacilli and Gram-positive cocci, especially B. fragilis. Favourable anti-anaerobic activity was also seen with levornidazole metabolites M1 and M4 but not M2, M3 or M5. For the 22 clinical B. fragilis strains, MBC50 and MBC90 values of levornidazole were 2mg/L and 4mg/L, respectively. Both MBC50/MIC50 and MBC90/MIC90 ratios of levornidazole were 4, similar to those of metronidazole. Levornidazole is an important anti-anaerobic option in clinical settings in terms of its potent and broad-spectrum in vitro activity, bactericidal property, and the anti-anaerobic activity of its metabolites M1 and M4. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Differential activation of stress-response signaling in load-induced cardiac hypertrophy and failure

PubMed Central

Rothermel, Beverly A.; Berenji, Kambeez; Tannous, Paul; Kutschke, William; Dey, Asim; Nolan, Bridgid; Yoo, Ki-Dong; Demetroulis, Elaine; Gimbel, Michael; Cabuay, Barry; Karimi, Mohsen; Hill, Joseph A.

2014-01-01

Hypertrophic growth of the myocardium occurs in most forms of heart failure and may contribute to the pathogenesis of the failure state. Little is known about the regulatory mechanisms governing the often-coexisting phenotypes of hypertrophy, systolic failure, and diastolic stiffness that characterize clinical disease. We hypothesized that intracellular signaling pathways are differentially activated by graded degrees of hemodynamic stress. To test this, we developed models of graded pressure stress in mice and used them to directly compare compensated hypertrophy and pressure-overload heart failure. Surgical interventions were designed to be similar, on either side of a threshold separating compensated from decompensated responses. Our findings revealed two dramatically different hypertrophic phenotypes with only modest differences in the activation of relevant intracellular signaling pathways. Furthermore, we uncovered a functional requirement of calcineurin signaling in each model such that calcineurin suppression blunted hypertrophic growth. Remarkably, in each case, suppression of calcineurin signaling was not associated with clinical deterioration or increased mortality. Profiles of stress-response signaling and Ca2+ handling differ between the steady-state, maintenance phases of load-induced cardiac hypertrophy and failure. This information may be useful in identifying novel targets of therapy in chronic disease. PMID:16033866

Differential activation of stress-response signaling in load-induced cardiac hypertrophy and failure.

PubMed

Rothermel, Beverly A; Berenji, Kambeez; Tannous, Paul; Kutschke, William; Dey, Asim; Nolan, Bridgid; Yoo, Ki-Dong; Demetroulis, Elaine; Gimbel, Michael; Cabuay, Barry; Karimi, Mohsen; Hill, Joseph A

2005-09-21

Hypertrophic growth of the myocardium occurs in most forms of heart failure and may contribute to the pathogenesis of the failure state. Little is known about the regulatory mechanisms governing the often-coexisting phenotypes of hypertrophy, systolic failure, and diastolic stiffness that characterize clinical disease. We hypothesized that intracellular signaling pathways are differentially activated by graded degrees of hemodynamic stress. To test this, we developed models of graded pressure stress in mice and used them to directly compare compensated hypertrophy and pressure-overload heart failure. Surgical interventions were designed to be similar, on either side of a threshold separating compensated from decompensated responses. Our findings revealed two dramatically different hypertrophic phenotypes with only modest differences in the activation of relevant intracellular signaling pathways. Furthermore, we uncovered a functional requirement of calcineurin signaling in each model such that calcineurin suppression blunted hypertrophic growth. Remarkably, in each case, suppression of calcineurin signaling was not associated with clinical deterioration or increased mortality. Profiles of stress-response signaling and Ca2+ handling differ between the steady-state, maintenance phases of load-induced cardiac hypertrophy and failure. This information may be useful in identifying novel targets of therapy in chronic disease.

[Application of three compartment model and response surface model to clinical anesthesia using Microsoft Excel].

PubMed

Abe, Eiji; Abe, Mari

2011-08-01

With the spread of total intravenous anesthesia, clinical pharmacology has become more important. We report Microsoft Excel file applying three compartment model and response surface model to clinical anesthesia. On the Microsoft Excel sheet, propofol, remifentanil and fentanyl effect-site concentrations are predicted (three compartment model), and probabilities of no response to prodding, shaking, surrogates of painful stimuli and laryngoscopy are calculated using predicted effect-site drug concentration. Time-dependent changes in these calculated values are shown graphically. Recent development in anesthetic drug interaction studies are remarkable, and its application to clinical anesthesia with this Excel file is simple and helpful for clinical anesthesia.

The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study.

PubMed

Millward, M J; House, C; Bowtell, D; Webster, L; Olver, I N; Gore, M; Copeman, M; Lynch, K; Yap, A; Wang, Y; Cohen, P S; Zalcberg, J

2006-10-09

Midostaurin (PKC412A), N-benzoyl-staurosporine, potently inhibits protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and FLT3 tyrosine kinases. In mice, midostaurin slows growth and delays lung metastasis of melanoma cell lines. We aimed to test midostaurin's safety, efficacy and biologic activity in a Phase IIA clinical trial in patients with metastatic melanoma. Seventeen patients with advanced metastatic melanoma received midostaurin 75 mg p.o. t.i.d., unless toxicity or disease progression supervened. Patient safety was assessed weekly, and tumour response was assessed clinically or by CT. Tumour biopsies and plasma samples obtained at entry and after 4 weeks were analysed for midostaurin concentration, PKC activity and multidrug resistance. No tumour responses were seen. Two (12%) patients had stable disease for 50 and 85 days, with minor response in one. The median overall survival was 43 days. Seven (41%) discontinued treatment with potential toxicity, including nausea, vomiting, diarrhoea and/or fatigue. One patient had >50% reduction in PKC activity. Tumour biopsies showed two PKC isoforms relatively insensitive to midostaurin, out of three patients tested. No modulation of multidrug resistance was demonstrated. At this dose schedule, midostaurin did not show clinical or biologic activity against metastatic melanoma. This negative trial reinforces the importance of correlating biologic and clinical responses in early clinical trials of targeted therapies.

[Morphological signs of inflammatory activity in different clinical forms of drug-resistant pulmonary tuberculosis].

PubMed

Elipashev, A A; Nikolsky, V O; Shprykov, A S

to determine whether the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant pulmonary tuberculosis. The material taken from 310 patients operated on in 2010-2015 were retrospectively examined. The patients underwent economical lung resections of limited extent (typical and atypical ones of up to 3 segments) for circumscribed forms of tuberculosis with bacterial excretion. A study group consisted of 161 (51.9%) patients with drug-resistant variants of pulmonary tuberculosis. A control group included 149 (48.1%) patients with preserved susceptibility of Mycobacterium tuberculosis to anti-TB drugs. The activity of specific changes in tuberculosis was morphologically evaluated in accordance with the classification proposed by B.M. Ariel in 1998. The highest activity of fourth-to-fifth degree specific inflammation, including that outside the primary involvement focus, was obtained in the drug-resistant pulmonary tuberculosis group due to the predominance of patients with cavernous and fibrous-cavernous tuberculosis versus those in whom the susceptibility to chemotherapeutic agents was preserved. A macroscopic study showed that the primary lesion focus had a median size in one-half of the all the examinees; but large tuberculomas, caverns, and fibrous caverns over 4 cm in diameter were multiple and detected in the drug-resistant pulmonary tuberculosis group. Multidrug resistance was observed in more than 60% of the patients with fibrous-cavernous pulmonary tuberculosis, extensive drug resistance was seen in those with cavernous tuberculosis, which is an aggravating factor. The data obtained from the morphological study of the intraoperative material can specify the clinical form of tuberculosis and evaluate the efficiency of preoperative specific therapy. The highest activity of specific inflammation was observed in patients with multiple drug-resistant pulmonary tuberculosis, the prevalence of third-to-fourth degree

Self-esteem: a closer look at clinical interventions.

PubMed

Meisenhelder, J B

1985-01-01

Self-esteem, a positive regard for oneself, is a universal need for every human being and a key component in restoring and maintaining mental and physical health. Yet, this important concept is remarkably neglected in nursing literature and easily overlooked in clinical practice. This article examines the existing research on the antecedents of self-esteem and compiles a list of factors which can facilitate the nurse's therapeutic effect on her client's positive self-concept. From this list, specific nursing interventions are provided for raising and maintaining a client's self-esteem. Since the impact of nursing interventions varies with clinical circumstances, the nursing actions are correlated with their most effective health care settings. This article provides a global and practical approach to the enhancement of clients' self-esteem.

Clinical Study of Student Learning Using Mastery Style versus Immediate Feedback Online Activities

ERIC Educational Resources Information Center

Gladding, Gary; Gutmann, Brianne; Schroeder, Noah; Stelzer, Timothy

2015-01-01

This paper is part of a series of studies to improve the efficacy of online physics homework activities by integrating narrated animated solutions with mastery inspired exercises. In a clinical study using first- and second-year university students, the mastery group attempted question sets in four levels, with animated solutions between each…

Remarkably high apparent quantum yield of the overall photocatalytic H2O splitting achieved by utilizing Zn ion added Ga2O3 prepared using dilute CaCl2 solution.

PubMed

Sakata, Yoshihisa; Hayashi, Takuya; Yasunaga, Ryō; Yanaga, Nobuyuki; Imamura, Hayao

2015-08-21

Remarkably high photocatalytic activity for the overall H2O splitting, where the activity was 32 mmol h(-1) for H2 production and 16 mmol h(-1) for O2 production under irradiation from a 450 W high-pressure Hg lamp and the apparent quantum yield (AQY) was 71% under irradiation at 254 nm, was achieved by utilizing a Rh(0.5)Cr(1.5)O3(Rh; 0.5 wt%)/Zn(3 mol%)-Ga2O3 photocatalyst when Ga2O3 was prepared using dilute CaCl2 aqueous solution having a concentration of 0.001 mol l(-1).

[Medical safety in infectious disease--chairmen's introductory remarks].

PubMed

Shimetani, Naoto; Miida, Takashi

2012-10-01

"The National Joint Action of Risk Management" was started in May 2008. The Japanese Society of Laboratory Medicine took this opportunity to set up a Medical Safety Committee as a participant in this Action. The Society holds symposia concerning medical safety to educate the Society members. Nosocomial infections are medical accidents. Whereas community-acquired infections are likely to develop depending on a balance between pathogens and hosts, nosocomial infections are implicated with medical practices, so they develop depending on the interrelationship among pathogens, hosts, and medical practices. Medical practices are mostly indispensable for providing medical services; therefore, activities against nosocomial infections are critical for establishing medical safety, freedom from anxiety, and reliability. Hence, this symposium deals with five themes: Countermeasures against and the management of needle-stick and cut accidents, collaboration between the infection control team (ICT) and the bacteriology laboratory, information transmission from the clinical laboratory department to physicians engaged in infectious disease treatment, utilization of laboratory data for infection control, and medical safety against tuberculosis infection.

A remarkably stable TipE gene cluster: evolution of insect Para sodium channel auxiliary subunits

PubMed Central

2011-01-01

Background First identified in fruit flies with temperature-sensitive paralysis phenotypes, the Drosophila melanogaster TipE locus encodes four voltage-gated sodium (NaV) channel auxiliary subunits. This cluster of TipE-like genes on chromosome 3L, and a fifth family member on chromosome 3R, are important for the optional expression and functionality of the Para NaV channel but appear quite distinct from auxiliary subunits in vertebrates. Here, we exploited available arthropod genomic resources to trace the origin of TipE-like genes by mapping their evolutionary histories and examining their genomic architectures. Results We identified a remarkably conserved synteny block of TipE-like orthologues with well-maintained local gene arrangements from 21 insect species. Homologues in the water flea, Daphnia pulex, suggest an ancestral pancrustacean repertoire of four TipE-like genes; a subsequent gene duplication may have generated functional redundancy allowing gene losses in the silk moth and mosquitoes. Intronic nesting of the insect TipE gene cluster probably occurred following the divergence from crustaceans, but in the flour beetle and silk moth genomes the clusters apparently escaped from nesting. Across Pancrustacea, TipE gene family members have experienced intronic nesting, escape from nesting, retrotransposition, translocation, and gene loss events while generally maintaining their local gene neighbourhoods. D. melanogaster TipE-like genes exhibit coordinated spatial and temporal regulation of expression distinct from their host gene but well-correlated with their regulatory target, the Para NaV channel, suggesting that functional constraints may preserve the TipE gene cluster. We identified homology between TipE-like NaV channel regulators and vertebrate Slo-beta auxiliary subunits of big-conductance calcium-activated potassium (BKCa) channels, which suggests that ion channel regulatory partners have evolved distinct lineage-specific characteristics

Clinical significance of nailfold capillaroscopy in systemic lupus erythematosus: correlation with endothelial cell activation markers and disease activity.

PubMed

Kuryliszyn-Moskal, A; Ciolkiewicz, M; Klimiuk, P A; Sierakowski, S

2009-01-01

To evaluate whether nailfold capillaroscopy (NC) changes are associated with the main serum endothelial cell activation markers and the disease activity of systemic lupus erythematosus (SLE). Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), soluble E-selectin (sE-selectin), and soluble thrombomodulin (sTM) were determined by an enzyme-linked immunosorbent assay (ELISA) in 80 SLE patients and 33 healthy controls. Nailfold capillary abnormalities were seen in 74 out of 80 (92.5%) SLE patients. A normal capillaroscopic pattern or mild changes were found in 33 (41.25%) and moderate/severe abnormalities in 47 (58.75%) of all SLE patients. In SLE patients a capillaroscopic score >1 was more frequently associated with the presence of internal organ involvement (p < 0.001) as well as with immunosuppressive therapy (p < 0.01). Significant differences were found in VEGF (p < 0.001), ET-1 (p < 0.001), sE-selectin (p < 0.01), and sTM (p < 0.001) serum concentrations between SLE patients with a capillaroscopic score > 1 and controls. SLE patients with severe/moderate capillaroscopic abnormalities showed significantly higher VEGF serum levels than patients with mild changes (p < 0.001). Moreover, there was a significant positive correlation between the severity of capillaroscopic changes and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p < 0.005) as well as between capillaroscopic score and VEGF serum levels (p < 0.001). Our findings confirm the usefulness of NC as a non-invasive technique for the evaluation of microvascular involvement in SLE patients. A relationship between changes in NC, endothelial cell activation markers and clinical features of SLE suggest an important role for microvascular abnormalities in clinical manifestation of the disease.

Clinical case series: treatment of PTSD with transcendental meditation in active duty military personnel.

PubMed

Barnes, Vernon A; Rigg, John L; Williams, Jennifer J

2013-07-01

Active duty U.S. Army Service Members previously diagnosed with post-traumatic stress disorder (PTSD) were selected from review of patient records in the Traumatic Brain Injury Clinic at the Department of Defense Eisenhower Army Medical Center at Fort Gordon in Augusta, Georgia. Patients agreed to practice the Transcendental Meditation (TM) technique for 20 minutes twice a day for the duration of a 2-month follow-up period. Three cases are presented with results that show the feasibility of providing TM training to active duty soldiers with PTSD in a Department of Defense medical facility. Further investigation is suggested to determine if a TM program could be used as an adjunct for treatment of PTSD. Impact of this report is expected to expand the complementary and alternative evidence base for clinical care of PTSD. Reprint & Copyright © 2013 Association of Military Surgeons of the U.S.

Clinical Information Systems – From Yesterday to Tomorrow

PubMed Central

2016-01-01

Summary Objectives To review the history of clinical information systems over the past twenty-five years and project anticipated changes to those systems over the next twenty-five years. Methods Over 250 Medline references about clinical information systems, quality of patient care, and patient safety were reviewed. Books, Web resources, and the author’s personal experience with developing the HELP system were also used. Results There have been dramatic improvements in the use and acceptance of clinical computing systems and Electronic Health Records (EHRs), especially in the United States. Although there are still challenges with the implementation of such systems, the rate of progress has been remarkable. Over the next twenty-five years, there will remain many important opportunities and challenges. These opportunities include understanding complex clinical computing issues that must be studied, understood and optimized. Dramatic improvements in quality of care and patient safety must be anticipated as a result of the use of clinical information systems. These improvements will result from a closer involvement of clinical informaticians in the optimization of patient care processes. Conclusions Clinical information systems and computerized clinical decision support have made contributions to medicine in the past. Therefore, by using better medical knowledge, optimized clinical information systems, and computerized clinical decision, we will enable dramatic improvements in both the quality and safety of patient care in the next twenty-five years. PMID:27362589

Antifungal Activity of Hydroalcoholic Extract of Chrysobalanus icaco Against Oral Clinical Isolates of Candida Species

PubMed Central

Silva, João Paulo Bastos; Peres, Ana Regina Maués Noronha; Paixão, Thiago Portal; Silva, Andressa Santa Brígida; Baetas, Ana Cristina; Barbosa, Wagner Luiz Ramos; Monteiro, Marta Chagas; Andrade, Marcieni Ataíde

2017-01-01

Background: Chrysobalanus icaco is a medicinal plant commonly used to treat fungal infections in Brazilian Amazonian region. Objective: This work aimed to evaluate the antifungal activity of the hydroalcoholic extract of C. icaco (HECi) against oral clinical isolates of Candida spp. and to determine the pharmacognostic parameters of the herbal drug and the phytochemical characteristics of HECi. Materials and Methods: The pharmacognostic characterization was performed using pharmacopoeial techniques. Phytochemical screening, total flavonoid content, and high-performance liquid chromatography (HPLC) analysis were used to investigate the chemical composition of the HECi. A broth microdilution method was used to determine the antifungal activity of the extract against 11 oral clinical isolates of Candida spp. Results: Herbal drug presented parameters which were within the limits set forth in current Brazilian legislation. A high amount of flavonoid content (132,959.33 ± 12,598.23 μg quercetin equivalent/g of extract) was found in HECi. Flavonoids such as myricetin and rutin were detected in the extract by HPLC analyses. HECi showed antifungal activity against oral isolates of Candida albicans and Candida parapsilosis (minimum inhibitory concentrations [MIC] 3.12 and 6.25 mg/mL, respectively), and C. albicans American American Type Culture Collection (MIC <1.56 mg/mL). Conclusion: HECi was shown to possess antifungal activity against Candida species with clinical importance in the development of oral candidiasis, and these activities may be related to its chemical composition. The antifungal activity detected for C. icaco against Candida species with clinical importance in the development of oral candidiasis can be attributed to the presence of flavonoids in HECi, characterized by chromatographic and spectroscopic techniques. SUMMARY Chrysobalanus icaco presents a high amount of flavonoids in its constitutionLC analysis was able to identify the flavonoids myricetin

Synergistic Activity of Econazole-Nitrate and Chelerythrine against Clinical Isolates of Candida albicans.

PubMed

Chen, Zhibao; Li, Xinran; Wu, Xiuping; Wang, Wei; Wang, Wendong; Xin, Mingxun; Shen, Fengge; Liu, Lihui; Liang, Junchao; Li, Lei; Yu, Lu

2014-01-01

The aim of this investigation was to assess the in-vitro interaction of two antifungal agents, econazole-nitrate and chelerythrine, against ten fluconazole-resistant clinical isolates and one ATCC type strain 10231 of Candida albicans. The checkerboard microdilution method was performed according to the recommendations of the National Committee for Clinical Laboratory Standards, and the results were determined by visual examination. The interaction intensity was tested in all isolates using the fractional inhibitory concentration index (FICI). These experiments showed synergism between econazole-nitrate and chelerythrine in antifungal activity against C. albicans, and no antagonistic activity was observed in any of the strains tested. Moreover, time-kill curves were performed with selected strains to confirm the positive interactions. The similarity between the results of the FICI values and the time-kill curves revealed that chelerythrine greatly enhances the antifungal effects of econazole-nitrate against isolates of C. albicans. This synergistic effect may markedly reduce the dose of econazole-nitrate required to treat candidiasis, thereby decreasing the econazole-nitrate toxic side effects. This novel synergism might provide a potential combination treatment against fungal infections.

[Rule of Clinical Application of Auricular Acupuncture Based on Data Mining].

PubMed

Bao, Na; Wang, Qiong; Sun, Yan-Hui; Shi, Jing; Li, Xiao-Feng; Xu, Jing; Xing, Hai-Jiao; Zhang, Xuan-Ping; Zhang, Xin; Du, Yu-Zhu; Li, Jun-Lei; Yang, Qing-Qing; Feng, Xin-Xin; Jia, Chun-Sheng; Wang, Jian-Ling

2017-02-25

To explore the rule of clinical application of auricular acupuncture therapy by data mining in order to guide clinical practice. The data base about single auricular acupuncture therapy for different clinical diseases was established by collection, sorting, screening, recording, collation, data extraction, statistic analysis on data samples from journals, academic theses dissertations published in near 60 years. The application rules of auricular therapy including its predominant diseases, stimulus modality, therapeutic effect, and angle of needling were summarized by data mining technique. Auricular acupuncture therapy has been widely and mostly used in the internal medicine department, accounting for 48.56%. Of stimulus modalities, auricular point paste and pressure is applied with the highest frequency, accounting for 64%. The highest effective rate is found in the surgery department diseases(81.41%). Pressure is the most effective stimulus in the internal medi-cine department, and bloodletting combined with paste and pressure in the surgery department, auricular point injection in the gynecology and pediatrics departments, bloodletting in the ophthalmology and otorhinolaryngology department, and auricular point incision in the dermatology department. Auricular point injection has remarkable effect. Bloodletting combined with paste and pressure has nearly the same effect as bloodletting in the same medical department except dematology department. Otherwise, angle of needling is rarely studied. Auricular therapy is widely used and has remarkable effect in treating diseases by using different stimulus modalities. Whereas the angle of needling is rarely studied and future investigation is needed.

The effect of continuous passive motion and sling exercise training on clinical and functional outcomes following total knee arthroplasty: a randomized active-controlled clinical study.

PubMed

Mau-Moeller, Anett; Behrens, Martin; Finze, Susanne; Bruhn, Sven; Bader, Rainer; Mittelmeier, Wolfram

2014-05-09

The parallel-group randomized active-controlled clinical study was conducted to compare the effectiveness of two in-hospital range of motion (ROM) exercise programs following total knee arthroplasty (TKA). Continuous passive motion (CPM) is frequently used to increase ROM and improve postoperative recovery despite little conclusive scientific evidence. In contrast, a new active sling-based ROM therapy requires the activation of the knee joint muscles and dynamic joint stabilization. It was hypothesized that higher demands on muscle strength and muscle coordination during sling exercise training (ST) might be advantageous for early recovery following TKA. A total of 125 patients undergoing primary TKA were assessed for eligibility. Thirty-eight patients were randomly assigned to receive ST or CPM (control intervention) during hospital stay. Patients were assessed before TKA for baseline measurement (pretest), 1 day before discharge (posttest) and 3 months after TKA (follow-up). The passive knee flexion range of motion (pFL) was the primary outcome measure. Secondary outcome measures included active knee flexion range of motion, active and passive knee extension ROM, static postural control, physical activity, pain, length of hospital stay as well as clinical, functional and quality-of-life outcomes (SF-36, HSS and WOMAC scores). Data were analyzed according to the intention-to-treat principle. Differences between the groups were tested for significance by the unpaired Student's t test or an analysis of covariance (ANCOVA) adjusted for baseline, weight, sex, age, pain and physical activity. A between-group difference could be determined at posttest. The pFL was significantly higher by 6.0° (95% CI 0.9 to 11.2°; P = 0.022) in the ST group. No difference between groups in pFL was documented at follow-up. Furthermore, no significant differences could be observed for any secondary outcome measure at posttest and follow-up. ST seems to have a clinically relevant

Churg-Strauss syndrome and persistent heart failure: active disease or damage?

PubMed

Lin, Yih Chang; Oliveira, Guilherme H M; Villa-Forte, Alexandra

2013-10-01

Churg-Strauss syndrome (CSS) is a rare small-vessel vasculitis typically associated with adult-onset asthma, peripheral and tissue hypereosinophilia, migratory pulmonary infiltrates, upper respiratory tract symptoms, and clinical evidence of systemic vasculitis. Cardiac involvement is a well-recognized complication with an estimated prevalence of 60%. Heart disease is associated with poor prognosis, accounting for almost 50% mortality in CSS. We present a case of a 48-year-old woman with CSS complicated by congestive heart failure with left ventricular ejection fraction of 25%, who was initially treated with long course of high-dose steroids without any clinical or echocardiographic improvement. She was referred to our hospital 1 year later and was initiated with cyclophosphamide 2 mg/kg per day and prednisone 60 mg/d followed by slow taper. Subsequently, the patient had remarkable improvement. Patient was then transitioned to azathioprine for 1.5 years with sustained disease remission. It may be difficult to determine myocardial disease activity status versus tissue damage in CSS with prolonged duration of heart failure symptoms. This is the first case report demonstrating that CSS cardiac disease may remain active despite 1 year of corticosteroid therapy, and significant improvement or remission can still be achieved by administering more aggressive cytotoxic immunosuppressive therapy.

Effects and safety of 99Tc-MDP in patients with refractory ankylosing spondylitis: a 2-stage (30-week follow-up) clinical trial.

PubMed

Xu, Yunyun; Zhong, Yi; Zhao, Minjing; Tu, Liudan; Fan, Meida; Zhang, Pingping; Wei, Qiujing; Cao, Shuangyan; Li, Qiuxia; Liao, Zetao; Lin, Zhiming; Pan, Yunfeng; Jin, Ou; Gu, Jieruo

2018-01-01

To evaluate the clinical efficacy and safety in patients with refractory ankylosing spondylitis (AS) initiating 99Tc-MDP therapy and explore the mechanisms. Refractory AS patients were enrolled in the clinical trial and received 99Tc-MDP treatments for 3 or 5 courses according to ASAS improvement. Efficacy and safety evaluations were conducted during the follow-up. 37 cytokines were quantified by Luminex at baseline and week 30. p-values<0.05 were considered statistically significant. 51 refractory AS patients were included, with 20 healthy people serving as the control group. The patients were in an active disease state (mean (SD) ASDAS 3.66 (0.83), BASDAI 4.53 (1.92)), 42(82.35%) patients had syndesmophytes. Their cytokines were significantly higher than that in the control group. After 3 courses of 99Tc-MDP treatment, 32 (62.75%) patients achieved ASAS20 improvement, 24 (47.06%) patients achieved a clinically significant improvement (ΔASDAS-CRP≥1.1). 27 patients entered the second stage to complete 5 courses of the treatment, all of whom achieved ASAS20 improvement, 18 (66.67%) patients achieved a clinically significant improvement. All clinical parameters including ASAS and ASDAS significantly improved as the treatment was continued. Cytokines also had significant down-regulation after the treatment, and the reductions had positive correlations with the improvements of disease activity. No serious adverse event was observed. This investigation confirmed the remarkable efficacy of 99Tc-MDP in a large number of refractory AS patients, and highlighted the mechanism by dramatic regulation on cytokines. 99Tc-MDP was safe in clinical application.

Self-Reported Physical Activity in Medically Underserved Adults With Type 2 Diabetes in Clinical and Community Settings.

PubMed

Cooper, John; Stetson, Barbara; Bonner, Jason; Spille, Sean; Krishnasamy, Sathya; Mokshagundam, Sri Prakash

2015-07-01

This study assessed physical activity (PA) in community dwelling adults with Type 2 diabetes, using multiple instruments reflecting internationally normed PA and diabetes-specific self-care behaviors. Two hundred and fifty-three Black (44.8%) and White (55.2%) Americans [mean age = 57.93; 39.5% male] recruited at low-income clinic and community health settings. Participants completed validated PA self-report measures developed for international comparisons (International Physical Activity Questionnaire Short Form), characterization of diabetes self-care (Summary of Diabetes Self-Care Activities Measure; SDSCA) and exercise-related domains including provider recommendations and PA behaviors and barriers (Personal Diabetes Questionnaire; PDQ). Self-reported PA and PA correlates differed by instrument. BMI was negatively correlated with PA level assessed by the PDQ in both genders, and assessed with SDSCA activity items in females. PA levels were low, comparable to previous research with community and diabetes samples. Pain was the most frequently reported barrier; females reported more frequent PA barriers overall. When using self-report PA measures for PA evaluation of adults with diabetes in clinical settings, it is critical to consider population and setting in selecting appropriate tools. PA barriers may be an important consideration when interpreting PA levels and developing interventions. Recommendations for incorporating these measures in clinical and research settings are discussed.

Activation of Nrf2/HO-1signaling pathway involves the anti-inflammatory activity of magnolol in Porphyromonas gingivalis lipopolysaccharide-stimulated mouse RAW 264.7 macrophages.

PubMed

Lu, Sheng-Hua; Hsu, Wen-Lin; Chen, Tso-Hsiao; Chou, Tz-Chong

2015-12-01

Magnolol isolated from Magnolia officinalis, a Chinese medical herb, exhibits an anti-inflammatory activity and a protective effect against periodontitis. The inflammation caused by lipopolysaccharide (LPS) from Porphyromonas gingivalis (P. gingivalis) has been considered a key inducer in the development of periodontitis. In this study, we investigated whether magnolol inhibits P. gingivalis LPS-evoked inflammatory responses in RAW 264.7 macrophages and the involvement of heme oxygenase-1 (HO-1). Magnolol significantly activated p38 MAPK, Nrf-2/HO-1 cascade and reactive oxygen species (ROS) formation. Notably, the Nrf-2 activation and HO-1 induction by magnolol were greatly diminished by blocking p38 MAPK activity and ROS production. Furthermore, in P. gingivalis LPS-stimulated macrophages, magnolol treatment remarkably inhibited the inflammatory responses evidenced by suppression of pro-inflammatory cytokine, prostaglandin E2, nitrite formation, and the expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as NF-κB activation accompanied by a significant elevation of Nrf-2 nuclear translocation and HO-1 expression/activity. However, inhibiting HO-1 activity with tin protoporphyrin IX markedly reversed the anti-inflammatory effects of magnolol. Collectively, these findings provide a novel mechanism by which magnolol inhibits P. gingivalis LPS-induced inflammation in macrophages is at least partly mediated by HO-1 activation, and thereby promoting its clinical use in periodontitis. Copyright © 2015 Elsevier B.V. All rights reserved.

Acrosin activity in turkey spermatozoa: assay by clinical method and effect of zinc and benzamidine on the activity.

PubMed

Glogowski, J; Jankowski, J; Faruga, A; Ottobre, J S; Ciereszko, A

2001-09-15

We optimized a clinical assay developed for measuring total acrosin activity for mammalian and fish semen for use in turkey spermatozoa. The main modifications included dilution of semen to a final concentration of 25 to 1000 x 10(3) spermatozoa, an increase of Triton X-100 concentration to 0.05% and 1 hr preincubation without substrate, Acrosin activity in turkey spermatozoa was much higher than in human spermatozoa (about 100-times) but similar to that of boar sperm. To optimize this assay for turkey spermatozoa, it was necessary to use higher Triton X-100 concentrations in the reaction mixture. There was a better catalytic efficiency at higher temperatures and a special requirement for a preincubation period for proacrosin activation. We observed high inhibition of acrosin activity by zinc added during preincubation (90% at 0.01 mM of zinc chloride). Benzamidine also inhibited turkey acrosin, and the extent of inhibition was similar for the incubation or preincubation period. When zinc ions were added during incubation, this inhibition was lower (24%). The results suggest that zinc influences proacrosin activation of turkey spermatozoa. This influence may be important for successful long-term storage of spermatozoa in the hen's oviduct.

Physical activity monitoring in adolescents with juvenile fibromyalgia: findings from a clinical trial of cognitive-behavioral therapy.

PubMed

Kashikar-Zuck, Susmita; Flowers, Stacy R; Strotman, Daniel; Sil, Soumitri; Ting, Tracy V; Schikler, Kenneth N

2013-03-01

Juvenile fibromyalgia (JFM) is a chronic musculoskeletal pain condition that is associated with reduced physical function. Recent research has demonstrated that cognitive-behavioral therapy (CBT) is effective in improving daily functioning among adolescents with JFM. However, it is not known whether these improvements were accompanied by increased physical activity levels. Our objective was to analyze secondary data from a randomized clinical trial of CBT to examine whether CBT was associated with improvement in objectively measured physical activity and whether actigraphy indices corresponded with self-reported functioning among adolescents with JFM. Participants were 114 adolescents (ages 11-18 years) recruited from pediatric rheumatology clinics that met criteria for JFM and were enrolled in a clinical trial. Subjects were randomly (1:1) assigned to receive either CBT or fibromyalgia education (FE). Participants wore a hip-mounted accelerometer for 1 week as part of their baseline and posttreatment assessments. The final sample included 68 subjects (94% female, mean age 15.2 years) for whom complete actigraphy data were obtained. Actigraphy measures were not found to correspond with self-reported improvements in functioning. While self-reported functioning improved in the CBT condition compared to FE, no significant changes were seen in either group for activity counts, sedentary, moderate, or vigorous activity. The CBT group had significantly lower peak and light activity at posttreatment. Actigraphy monitoring provides a unique source of information about patient outcomes. CBT intervention was not associated with increased physical activity in adolescents with JFM, indicating that combining CBT with interventions to increase physical activity may enhance treatment effects. Copyright © 2013 by the American College of Rheumatology.

Reviewing Clinical Effectiveness of Active Training Strategies of Platform-Based Ankle Rehabilitation Robots

PubMed Central

2018-01-01

Objective This review aims to provide a systematical investigation of clinical effectiveness of active training strategies applied in platform-based ankle robots. Method English-language studies published from Jan 1980 to Aug 2017 were searched from four databases using key words of “Ankle∗” AND “Robot∗” AND “Effect∗ OR Improv∗ OR Increas∗.” Following an initial screening, three rounds of discrimination were successively conducted based on the title, the abstract, and the full paper. Result A total of 21 studies were selected with 311 patients involved; of them, 13 studies applied a single group while another eight studies used different groups for comparison to verify the therapeutic effect. Virtual-reality (VR) game training was applied in 19 studies, while two studies used proprioceptive neuromuscular facilitation (PNF) training. Conclusion Active training techniques delivered by platform ankle rehabilitation robots have been demonstrated with great potential for clinical applications. Training strategies are mostly combined with one another by considering rehabilitation schemes and motion ability of ankle joints. VR game environment has been commonly used with active ankle training. Bioelectrical signals integrated with VR game training can implement intelligent identification of movement intention and assessment. These further provide the foundation for advanced interactive training strategies that can lead to enhanced training safety and confidence for patients and better treatment efficacy. PMID:29675142

Energized Active Regions

NASA Image and Video Library

2017-06-02

A pair of relatively small (but frenetic) active regions rotated into view, spouting off numerous small flares and sweeping loops of plasma (May 31-June 2, 2017). At first, only the one active region was observed, but mid-way though the video clip a second one behind the first can be picked out. The dynamic regions were easily the most remarkable areas on the sun during this 42-hour period. The images were taken in a wavelength of extreme ultraviolet light. Movies are available at https://photojournal.jpl.nasa.gov/catalog/PIA21756

Prepared Remarks for Secretary of Education Arne Duncan, House Education and Labor Committee, May 20, 2009

ERIC Educational Resources Information Center

US Department of Education, 2009

2009-01-01

This document contains a transcript of prepared remarks for Secretary of Education Arne Duncan to the House Education and Labor Committee. The Secretary discussed provisions for education in the American Recovery and Reinvestment Act and the State Fiscal Stabilization Fund to supplement state budgets. The Secretary also noted an expanded…

Political and clinical developments in analytical psychology, 1972-2014: subjectivity, equality and diversity-inside and outside the consulting room.

PubMed

Samuels, Andrew

2014-11-01

Utilizing Jung's idea of theory as a 'personal confession', the author charts his own development as a theorist, establishing links between his personal history and his ideas. Such links include his relationship with both parents, his sexuality, his cultural heritage, and his fascination with Tricksters and with Hermes. There follows a substantial critical interrogation of what the author discerns as the two main lines of clinical theorizing in contemporary analytical psychotherapy: interpretation of transference-countertransference, and the relational approach. His conclusion is that neither is superior to the other and neither is in fact adequate as a basis for clinical work. The focus then shifts to explore a range of political and social aspects of the clinical project of analytical psychology: economic inequality, diversity within the professional field, and Jung's controversial ideas about Jews and Africans. The author calls for an apology from the 'Jungian community' for remarks about Africans analogous to the apology already issued for remarks about Jews. The paper is dedicated to the author's friend Fred Plaut (1913-2009). © 2014, The Society of Analytical Psychology.

[The in vitro antifungal activities of fluconazole against pathogenic yeasts recently isolated from clinical specimens].

PubMed

Yamaguchi, H; Igari, J; Kume, H; Abe, M; Oguri, T; Kanno, H; Kawakami, S; Okuzumi, K; Fukayama, M; Ito, A; Kawata, K; Uchida, K

1997-09-01

The emergence of Candida albicans resistance to azole antifungal agents have been reported in the U. S. and Europe. We examined the in vitro antifungal activities of fluconazole against clinical isolates collected by seven investigators in three years to examine if a tendency existed toward the development of azole-resistance among fungal isolates in Japan. The following results were obtained: 1. Sensitivities to fluconazole (FLCZ) were determined for yeast-like fungi, including 113 strains isolated in 1993, 149 strains isolated in 1994 and 205 strains isolated in 1995. No significant differences in sensitivities in the three years were detected. 2. Minimum inhibitory concentrations of FLCZ were 0.1-0.78 microgram/ml for C. albicans and 3.13-25 micrograms/ml for C. glabrata. Strains with 25 micrograms/ml of FLCZ's MIC were detected; two strains of C. krusei and one strain each of C. krusei, Trichospron beigelii and Hansenula anomala. No strains with higher than 50 micrograms/ml MIC of FLCZ were detected. 3. In vitro activities of FLCZ were compared between clinical strains isolated between 1993 and 1995 and clinical strains isolated before the marketing of FLCZ (up to December 1987) or clinical yeasts isolated between 1991 and 1992. No significant differences were observed, suggesting that no tendency existed toward azole resistance among fungal strains examined.

Clinical Feasibility of Continuously Monitored Data for Heart Rate, Physical Activity, and Sleeping by Wearable Activity Trackers in Patients with Thyrotoxicosis: Protocol for a Prospective Longitudinal Observational Study

PubMed Central

Lee, Jie-Eun; Lee, Dong Hwa; Oh, Tae Jung; Kim, Kyoung Min; Choi, Sung Hee; Lim, Soo; Park, Young Joo; Park, Do Joon; Jang, Hak Chul

2018-01-01

Background Thyrotoxicosis is a common disease caused by an excess of thyroid hormones. The prevalence of thyrotoxicosis about 2% and 70-90% of thyrotoxicosis cases are caused by Graves' disease, an autoimmune disease, which has a high recurrence rate when treated with antithyroid drugs such as methimazole or propylthiouracil. The clinical symptoms and signs of thyrotoxicosis include palpitation, weight loss, restlessness, and difficulty sleeping. Although these clinical changes in thyrotoxicosis can be detected by currently available wearable activity trackers, there have been few trials of the clinical application of wearable devices in patients with thyrotoxicosis. Objective The aim of this study is to investigate the clinical applicability of wearable device-generated data to the management of thyrotoxicosis. We are analyzing continuously monitored data for heart rate, physical activity, and sleep in patients with thyrotoxicosis during their clinical course after treatment. Methods Thirty thyrotoxic patients and 10 control subjects were enrolled in this study at Seoul National University Bundang Hospital. Heart rate, physical activity, and sleep are being monitored using a Fitbit Charge HR or Fitbit Charge 2. Clinical data including anthropometric measures, thyroid function test, and hyperthyroidism symptom scale are recorded. Results Study enrollment began in December 2016, and the intervention and follow-up phases are ongoing. The results of the data analysis are expected to be available by September 2017. Conclusions This study will provide a foundational feasibility trial of the clinical applications of biosignal measurements to the differential diagnosis, prediction of clinical course, early detection of recurrence, and treatment in patients with thyrotoxicosis. Trial Registration ClinicalTrials.gov NCT03009357; https://clinicaltrials.gov/ct2/show/NCT03009357 (Archived by WebCite at http://www.webcitation.org/6wh4MWPm2) PMID:29467121

Concluding Remarks: The Current Status and Future Prospects for GRB Astronomy

NASA Technical Reports Server (NTRS)

Gehrels, Neil

2009-01-01

We are in a remarkable period of discovery in GRB astronomy. The current satellites including Swift, Fermi. AGILE and INTEGRAL are detecting and observing bursts of all varieties. Increasing capabilities for follow-up observations on the ground and in space are leading to rapid and deep coverage across the electromagnetic spectrum, The future will see continued operation of the current experiments and with future missions like SVOM plus possible rni_Ssions like JANUS and EXIST. An exciting expansion of capabilities is occurring in areas of gravitational waves and neutrinos that could open new windows on the GRB phenomenon. Increased IR capabilities on the ground and with missions like JWST will enable further exploration of high redshift bursts. The future is bright.

Vision Restoration in Glaucoma by Activating Residual Vision with a Holistic, Clinical Approach: A Review.

PubMed

Sabel, Bernhard A; Cárdenas-Morales, Lizbeth; Gao, Ying

2018-01-01

How to cite this article: Sabel BA, Cárdenas-Morales L, Gao Y. Vision Restoration in Glaucoma by activating Residual Vision with a Holistic, Clinical Approach: A Review. J Curr Glaucoma Pract 2018;12(1):1-9.

[The antibacterial activity of oregano essential oil (Origanum heracleoticum L.) against clinical strains of Escherichia coli and Pseudomonas aeruginosa].

PubMed

Sienkiewicz, Monika; Wasiela, Małgorzata; Głowacka, Anna

2012-01-01

The aim of this study was to investigate the antibacterial properties of oregano (Origanum heracleoticum L.) essential oil against clinical strains of Escherichia coli and Pseudomonas aeruginosa. The antibacterial activity of oregano essential oil was investigate against 2 tested and 20 clinical bacterial strains of Escherichia coli and 20 clinical strains o Pseudomonas aeruginosa come from patients with different clinical conditions. The agar dilution method was used for microbial growth inhibition at various concentrations ofoil. Susceptibility testing to antibiotics was carried out using disc-diffusion method. The results of experiments showed that the tested oil was active against all of the clinical strains from both genus of bacteria, but strains of Escherichia coli were more sensitive to tested oil. Essential oil from Origanum heracleoticum L. inhibited the growth of Escherichia coli and Pseudomonas aeruginosa clinical strains with different patters of resistance. The obtained outcomes will enable further investigations using oregano essential oil obtained from Origanum heracleoticum L. as alternative antibacterial remedies enhancing healing process in bacterial infections and as an effective means for the prevention of antibiotic-resistant strain development.

mActive: A Randomized Clinical Trial of an Automated mHealth Intervention for Physical Activity Promotion.

PubMed

Martin, Seth S; Feldman, David I; Blumenthal, Roger S; Jones, Steven R; Post, Wendy S; McKibben, Rebeccah A; Michos, Erin D; Ndumele, Chiadi E; Ratchford, Elizabeth V; Coresh, Josef; Blaha, Michael J

2015-11-09

We hypothesized that a fully automated mobile health (mHealth) intervention with tracking and texting components would increase physical activity. mActive enrolled smartphone users aged 18 to 69 years at an ambulatory cardiology center in Baltimore, Maryland. We used sequential randomization to evaluate the intervention's 2 core components. After establishing baseline activity during a blinded run-in (week 1), in phase I (weeks 2 to 3), we randomized 2:1 to unblinded versus blinded tracking. Unblinding allowed continuous access to activity data through a smartphone interface. In phase II (weeks 4 to 5), we randomized unblinded participants 1:1 to smart texts versus no texts. Smart texts provided smartphone-delivered coaching 3 times/day aimed at individual encouragement and fostering feedback loops by a fully automated, physician-written, theory-based algorithm using real-time activity data and 16 personal factors with a 10 000 steps/day goal. Forty-eight outpatients (46% women, 21% nonwhite) enrolled with a mean±SD age of 58±8 years, body mass index of 31±6 kg/m(2), and baseline activity of 9670±4350 steps/day. Daily activity data capture was 97.4%. The phase I change in activity was nonsignificantly higher in unblinded participants versus blinded controls by 1024 daily steps (95% confidence interval [CI], -580 to 2628; P=0.21). In phase II, participants receiving texts increased their daily steps over those not receiving texts by 2534 (95% CI, 1318 to 3750; P<0.001) and over blinded controls by 3376 (95% CI, 1951 to 4801; P<0.001). An automated tracking-texting intervention increased physical activity with, but not without, the texting component. These results support new mHealth tracking technologies as facilitators in need of behavior change drivers. URL: http://ClinicalTrials.gov/. Unique identifier: NCT01917812. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Remarkable Second-Order Optical Nonlinearity of Nano-Sized Au Cluster: A TDDFT Study

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

Wu, Kechen; Li, Jun; Lin, Chensheng

2004-04-21

The dipole polarizability, static first hyperpolarizability, and UV-vis spectrum of the recently identified nano-sized tetrahedral cluster of Au have been investigated by using time-dependent density functional response theory. We have discovered that the Au cluster possesses remarkably large molecular second-order optical nonlinearity with the first hyperpolarizabilty (xyz) calculated to be 14.3 x 10 electrostatic unit (esu). The analysis of the low-energy absorption band suggests that the charge transfer from the edged gold atoms to the vertex ones plays the key role in nonlinear optical (NLO) response of Au.

Assessing student clinical learning experiences.

PubMed

Nehyba, Katrine; Miller, Susan; Connaughton, Joanne; Singer, Barbara

2017-08-01

This article describes the use of an activity worksheet and questionnaire to investigate the learning experience of students on clinical placement. The worksheet measures the amount of time students spend in different learning activities, and the questionnaire explores student satisfaction and preferred learning activities. An activity worksheet and questionnaire … investigate[d] the learning experiences of students on clinical placement METHODS: The activity worksheet and questionnaire were used in a cohort pilot study of physiotherapy students on clinical placement. The activity worksheet provides details of the amount of time students engage in a range of clinical and non-clinical tasks while on placement, such as time spent treating patients, working individually, working with their peers and engaging in reflective practice. In combination with the questionnaire results, it allows clinicians to gain an understanding of the clinical learning environment experienced by their students. The data collected using these tools provide a description of the students' activities while undertaking the clinical placement. This information may guide the refinement of the clinical experience, and offers an opportunity to individualise learning activities to match students' needs and preferences. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Antimicrobial resistance profile of Staphylococcus aureus isolated from clinical samples and foods of animal origin.

PubMed

Yucel, Nihal; Citak, Sumru; Bayhün, Sinem

2011-03-01

Staphylococcus aureus has been well established as a clinical and epidemiological pathogen and can cause infections at many anatomical sites. Increasing insusceptibility to β-lactams and the glycopeptides complicates the treatment of these infections. We isolated 584 strains of S. aureus from various clinical and animal origin food samples during (from January 2006 to December 2007) the survey. Resistance to 15 antibiotics frequently used in human medicine and veterinary practice was also determined. A remarkable level of penicillin resistance was detected in both clinical (98.3%) and food (92.0%) S. aureus isolates. But, there were no S. aureus strains that were resistant to vancomycin, teicoplanin, linezolid, and quinupristin/dalfobristin. The rate of resistance to tetracycline, ciprofloxacin, levofloxacin, methicillin, gentamicin, tobramycin, norfloxacin, and moxifloxacin among the human and foods S. aureus isolates ranged from 50.3% to 56.3% and 1.4% to 9.5%, respectively. In our survey, in vitro susceptibility data suggested that the incidence of resistance among the S. aureus strains isolated from food were not remarkably high, excluding penicillin. Although the transfer of antibiotic resistance of S. aureus from foods to humans probably occurs less frequently than is generally assumed, the increasing prevalence of resistance in the strains of human origin may have important therapeutic implications.

Increasing Recreational Physical Activity in Patients With Chronic Low Back Pain: A Pragmatic Controlled Clinical Trial.

PubMed

Ben-Ami, Noa; Chodick, Gabriel; Mirovsky, Yigal; Pincus, Tamar; Shapiro, Yair

2017-02-01

Study Design Prospective, pragmatic, nonrandomized controlled clinical trial. Background Clinical guidelines recommend physical activity for the treatment of chronic low back pain. But engaging patients in physical activity has proven difficult. Known obstacles to physical activity include low self-efficacy and fear avoidance. Objectives This study tested the effectiveness of an enhanced transtheoretical model intervention (ETMI) aimed at increasing recreational physical activity in patients with chronic low back pain, in comparison to usual physical therapy. Methods Patients (n = 220) referred to physical therapy for chronic low back pain were allocated to ETMI or to a control group. The ETMI was delivered by physical therapists and based on behavior-change principles, combined with increased reassurance, therapeutic alliance, and exposure to reduce fear avoidance. The primary outcome was back pain-related disability (Roland-Morris Disability Questionnaire). Secondary outcomes included pain intensity, mental and physical health, and levels of physical activity. Results Intention-to-treat analysis in 189 patients at 12 months indicated that patients in the ETMI group had significantly lower disability compared to usual physical therapy. The difference in mean change from baseline between the interventions was 2.7 points (95% confidence interval: 0.9, 4.5) on the Roland-Morris Disability Questionnaire. At 12 months, worst pain, physical activity, and physical health were all significantly better in patients receiving ETMI. The average number of sessions was 3.5 for the ETMI group and 5.1 for controls. Conclusion Targeting obstacles to physical activity with an intervention that includes components to address self-efficacy and fear avoidance appears to be more effective than usual physical therapy care in reducing long-term disability. Further research is needed to explore the mechanisms that impact outcomes in this intervention package. Level of Evidence Therapy

NCI Director Norman Sharpless’s ASCO 2018 Remarks

Cancer.gov

In this video, NCI Director Dr. Norman E. Sharpless discusses the future of cancer research at the 2018 American Society of Clinical Oncology (ASCO) annual meeting in Chicago. Learn more about his focus on basic science, workforce development, big data, and clinical trials.

The Diamond Light Source and the challenges ahead for structural biology: some informal remarks.

PubMed

Ramakrishnan, V

2015-03-06

The remarkable advances in structural biology in the past three decades have led to the determination of increasingly complex structures that lie at the heart of many important biological processes. Many of these advances have been made possible by the use of X-ray crystallography using synchrotron radiation. In this short article, some of the challenges and prospects that lie ahead will be summarized. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Transition From Clinical to Educator Roles in Nursing: An Integrative Review.

PubMed

Fritz, Elizabeth

This review identified barriers to and facilitators of nurses' transition from clinical positions into nursing professional development and other nurse educator roles. The author conducted literature searches using multiple databases. Twenty-one articles met search criteria, representing a variety of practice settings. The findings, both barriers and facilitators, were remarkably consistent across practice settings. Four practice recommendations were drawn from the literature to promote nurses' successful transition to nursing professional development roles.

Differences in activation of MAP kinases and variability in the polyglutamine tract of Slt2 in clinical and non-clinical isolates of Saccharomyces cerevisiae.

PubMed

de Llanos, Rosa; Hernández-Haro, Carolina; Barrio, Eladio; Querol, Amparo; Fernández-Espinar, María Teresa; Molina, María

2010-08-01

The concept of Saccharomyces cerevisiae as an emerging opportunistic pathogen is relatively new and it is due to an increasing number of human infections during the past 20 years. There are still few studies addressing the mechanisms of infection of this yeast species. Moreover, little is known about how S. cerevisiae cells sense and respond to the harsh conditions imposed by the host, and whether this response is different between clinical isolates and non-pathogenic strains. In this regard, mitogen-activated protein kinase (MAPK) pathways constitute one of the major mechanisms for controlling transcriptional responses and, in some cases, virulence in fungi. Here we show differences among clinical and non-clinical isolates of S. cerevisiae in the level of activation of the MAPKs Kss1, which controls pseudohyphal and invasive growth, and Slt2, which is required for maintaining the integrity of the cell wall under stress conditions and in the absence of stimulating conditions. Moreover, we report for the first time the existence of length variability in SLT2 alleles of strains with a clinical origin. This is due to the expansion in the number of glutamine-encoding triplets in the microsatellite region coding for the polyglutamine (poly-Q) tract of this gene, which range from 12 to more than 38 repetitions. We suggest that this variability may influence biological features of the Slt2 protein, allowing it to adapt swiftly in order to survive in unusual environments. Copyright (c) 2010 John Wiley & Sons, Ltd.

Remarkable Improvement of Shape-Memory Effect in a Co-31Ni-3Si Alloy by Ausforming

NASA Astrophysics Data System (ADS)

Sun, Jiangwei; Wang, Shanling; Yan, Zhiwei; Peng, Huabei; Wen, Yuhua

2015-04-01

In order to improve the shape-memory effect (SME) in Co-Ni alloys, the influence of ausforming temperature on the SME, microstructures, and mechanical behavior in a Co-31Ni-3Si alloy was studied. The results show that the ausforming at 1073 K (800 °C) could remarkably improve the SME in Co-31Ni-3Si alloy. A large recovery strain of 2.3 pct was obtained after bent by 3.7 pct at 77 K (-196 °C). The increase of yield strength and the decrease of the critical stress for the stress-induced gamma to epsilon martensitc transformation are responsible for the remarkable improvement of SME. The results indirectly showed that the SME in Co-Ni alloys results from the stress-induced gamma to epsilon martensitic transformation, and their low yield strength account for their poor SME. It can be expected that the strengthening of matrix by other methods, such as solution, dispersion, and grain refinement hardening, will improve the SME of Co-Ni alloys.

Clinical efficacy of EDTA ultrasonic activation in the reduction of endotoxins and cultivable bacteria.

PubMed

Herrera, D R; Martinho, F C; de-Jesus-Soares, A; Zaia, A A; Ferraz, C C R; Almeida, J F A; Gomes, B P F A

2017-10-01

This clinical study was conducted to investigate the influence of 17% ethylenediaminetetraacetic acid (EDTA) ultrasonic activation after chemomechanical preparation (CMP) on eliminating/reducing oral bacterial lipopolysaccharides (known as endotoxins) and cultivable bacteria in teeth with pulp necrosis and apical periodontitis. Samples were taken from 24 root canals at several clinical periods: S1 - before CMP; S2 - after CMP; S3 - after EDTA: G1 - with ultrasonic activation (n = 12) and G2 - without ultrasonic activation (n = 12). Root canals were instrumented using Mtwo rotary files. Culture techniques were used to determine the number of colony-forming units (CFU). Limulus amebocyte lysate (LAL) was used to measure endotoxin levels. Friedman's and Wilcoxon signed-rank tests were used to compare the amount of bacteria and endotoxin levels in each period (P < 0.05). Endotoxins and cultivable bacteria were recovered in 100% of the initial samples (S1). CMP was effective in reducing endotoxins and bacterial load (all with P < 0.05). Higher values of endotoxin reduction were achieved with EDTA ultrasonic activation [G1, 0.02 EU mL -1 (range 0.01-0.75)] compared with the no activation group [G2, 1.13 EU mL -1 (range 0.01-8.34)] (P < 0.05). Regarding bacterial reduction, no statistically significant difference was found in S3, regardless of the group (G1, G2, P > 0.05). Chemomechanical preparation was effective in reducing bacteria and endotoxins, but could not completely eliminate them. The ultrasonic activation of EDTA was effective in further reducing endotoxin levels in the root canals of teeth with pulp necrosis and apical periodontitis. © 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Interpretation of acid α-glucosidase activity in creatine kinase elevation: A case of Becker muscular dystrophy.

PubMed

Oitani, Yoshiki; Ishiyama, Akihiko; Kosuga, Motomichi; Iwasawa, Kentaro; Ogata, Ayako; Tanaka, Fumiko; Takeshita, Eri; Shimizu-Motohashi, Yuko; Komaki, Hirofumi; Nishino, Ichizo; Okuyama, Torayuki; Sasaki, Masayuki

2018-05-16

Diagnosis of Pompe disease is sometimes challenging because it exhibits clinical similarities to muscular dystrophy. We describe a case of Becker muscular dystrophy (BMD) with a remarkable reduction in activity of the acid α-glucosidase (GAA) enzyme, caused by a combination of pathogenic mutation and polymorphism variants resulting in pseudodeficiency in GAA. The three-year-old boy demonstrated asymptomatic creatine kinase elevation. Neither exon deletion nor duplication was detected on multiplex ligation-dependent probe amplification (MLPA) of DMD. GAA enzyme activity in both dried blood spots and lymphocytes was low, at 11.7% and 7.7% of normal, respectively. However, genetic analysis of GAA detected only heterozygosity for a nonsense mutation (c.118C > T, p.Arg40 ∗ ). Muscle pathology showed no glycogen deposits and no high acid phosphatase activity. Hematoxylin-eosin staining detected scattered regenerating fibers; the fibers were faint and patchy on immunochemistry staining of dystrophin. The amount of dystrophin protein was reduced to 11.8% of normal, on Western blotting analysis. Direct sequencing analysis of DMD revealed hemizygosity for a nonsense mutation (c.72G > A, p.Trp24 ∗ ). The boy was diagnosed with BMD, despite remarkable reduction in GAA activity; further, he demonstrated heterozygosity for [p.Gly576Ser; p.Glu689Lys] polymorphism variants that indicated pseudodeficiency on another allele in GAA. Pseudodeficiency alleles are detected in approximately 4% of the Asian population; these demonstrate low activity of acid α-glucosidase (GAA), similar to levels found in Pompe disease. Clinicians should be careful in their interpretations of pseudodeficiency alleles that complicate diagnosis in cases of elevated creatine kinase. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Comprehension of direct and indirect sarcastic remarks in children and adolescents with Tourette's syndrome.

PubMed

Drury, Helena; Shah, Shivani; Stern, Jeremy S; Crawford, Sarah; Channon, Shelley

2018-05-01

Previous research has reported that aspects of social cognition such as nonliteral language comprehension are impaired in adults with Tourette's syndrome (TS), but little is known about social cognition in children and adolescents with TS. The present study aims to evaluate a measure of sarcasm comprehension suitable for use with children and adolescents (Experiment 1), and to examine sarcasm comprehension in children and adolescents with TS-alone or TS and attention deficit hyperactivity disorder (ADHD; Experiment 2). In Experiment 1, the measure of sarcasm comprehension was found to be sensitive to differences in nonliteral language comprehension for typically-developing children aged 10 to 11 years old compared to children aged 8 to 9 years old; the older group performed significantly better on the comprehension of scenarios ending with either direct or indirect sarcastic remarks, whereas the two age groups did not differ on the comprehension of scenarios ending with sincere remarks. In Experiment 2, both the TS-alone and TS+ADHD groups performed below the level of the control participants on the comprehension of indirect sarcasm items but not on the comprehension of direct sarcasm items and sincere items. Those with TS+ADHD also performed below the level of the control participants on measures of interference control and fluency. The findings are discussed with reference to the possible contribution of executive functioning and mentalizing to the patterns of performance.

Impaired phagocytosis of apoptotic cell material in serologically active clinically quiescent patients with systemic lupus erythematosis.

PubMed

Huang, Wen-Nan; Tso, Tim K; Wu, Hsiao-Chih; Yang, Hsiu-Fen; Tsay, Gregory J

2016-12-01

Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) account for 8-12% of all patients with SLE, but there is disagreement about whether such patients are indeed clinically stable. Patients with clinically active SLE have decreased macrophage function, although the status of SACQ patients with SLE is unclear. This study compared 18 patients who met the diagnostic criteria for SACQ SLE with 18 healthy volunteers with regard to the capability of macrophages to clear apoptotic bodies by use of a modified serum-free phagocytosis test. Macrophages that naturally differentiated from monocytes were used to engulf apoptotic cells developed from polymorphonuclear neutrophils. The results showed that macrophages from SACQ patients with SLE had less phagocytotic capability than those from healthy controls. The significant reduction of macrophage phagocytotic capability in these patients suggests the potential for disease recurrence. The use of a serum-free method confirmed the presence of intrinsic factors that modulate the decrease of macrophage function in SLE. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Intracellular activity of clinical concentrations of phenothiazines including thioridiazine against phagocytosed Staphylococcus aureus.

PubMed

Ordway, Diane; Viveiros, Miguel; Leandro, Clara; Arroz, Maria Jorge; Amaral, Leonard

2002-07-01

The effect of thioridazine (TZ) was studied on the killing activity of human peripheral blood monocyte derived macrophages (HPBMDM) and of human macrophage cell line THP-1 at extracellular concentrations below those achievable clinically. These macrophages have nominal killing activity against bacteria and therefore, would not influence any activity that the compounds may have against intracellular localised Staphylococcus aureus. The results indicated that whereas TZ has an in vitro minimum inhibitory concentration (MIC) against the strains of S. aureus of 18, 0.1 mg/l of TZ in the medium completely inhibits the growth of S. aureus that has been phagocytosed by macrophages. The latter concentration was non-toxic to macrophages, did not cause cellular expression of activation marker CD69 nor induction of CD3+ T cell production of IFN-gamma, but blocked cellular proliferation and down-regulated the production of T cell-derived cytokines (IFN-gamma, IL-5). These results suggest that TZ induces intracellular bactericidal activities independent of the capacity to generate Type 1 responses against S. aureus.

Anti-tumor activity of calcitriol: pre-clinical and clinical studies.

PubMed

Trump, Donald L; Hershberger, Pamela A; Bernardi, Ronald J; Ahmed, Sharmilla; Muindi, Josephia; Fakih, Marwan; Yu, Wei-Dong; Johnson, Candace S

2004-05-01

1,25-Dihydroxycholecalciferol (calcitriol) is recognized widely for its effects on bone and mineral metabolism. Epidemiological data suggest that low Vitamin D levels may play a role in the genesis of prostate cancer and perhaps other tumors. Calcitriol is a potent anti-proliferative agent in a wide variety of malignant cell types. In prostate, breast, colorectal, head/neck and lung cancer as well as lymphoma, leukemia and myeloma model systems calcitriol has significant anti-tumor activity in vitro and in vivo. Calcitriol effects are associated with an increase in G0/G1 arrest, induction of apoptosis and differentiation, modulation of expression of growth factor receptors. Glucocorticoids potentiate the anti-tumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. Calcitriol potentiates the antitumor effects of many cytotoxic agents and inhibits motility and invasiveness of tumor cells and formation of new blood vessels. Phase I and II trials of calcitriol either alone or in combination with carboplatin, taxanes or dexamethasone have been initiated in patients with androgen dependent and independent prostate cancer and advanced cancer. Data indicate that high-dose calcitriol is feasible on an intermittent schedule, no dose-limiting toxicity has been encountered and optimal dose and schedule are being delineated. Clinical responses have been seen with the combination of high dose calcitriol+dexamethasone in androgen independent prostate cancer (AIPC) and apparent potentiation of the antitumor effects of docetaxel have been seen in AIPC. These results demonstrate that high intermittent doses of calcitriol can be administered to patients without toxicity, that the MTD is yet to be determined and that calcitriol has potential as an anti-cancer agent.

The use of functional neuroimaging to evaluate psychological and other non-pharmacological treatments for clinical pain

PubMed Central

Jensen, Karin B.; Berna, Chantal; Loggia, Marco L.; Wasan, Ajay; Edwards, Robert R.; Gollub, Randy L.

2013-01-01

A large number of studies have provided evidence for the efficacy of psychological and other non-pharmacological interventions in the treatment of chronic pain. While these methods are increasingly used to treat pain, remarkably few studies focused on the exploration of their neural correlates. The aim of this article was to review the findings from neuroimaging studies that evaluated the neural response to distraction-based techniques, cognitive behavioral therapy (CBT), clinical hypnosis, mental imagery, physical therapy/exercise, biofeedback, and mirror therapy. To date, the results from studies that used neuroimaging to evaluate these methods have not been conclusive and the experimental methods have been suboptimal for assessing clinical pain. Still, several different psychological and non-pharmacological treatment modalities were associated with increased painrelated activations of executive cognitive brain regions, such as the ventral- and dorsolateral prefrontal cortex. There was also evidence for decreased pain-related activations in afferent pain regions and limbic structures. If future studies will address the technical and methodological challenges of today’s experiments, neuroimaging might have the potential of segregating the neural mechanisms of different treatment interventions and elucidate predictive and mediating factors for successful treatment outcomes. Evaluations of treatment-related brain changes (functional and structural) might also allow for sub-grouping of patients and help to develop individualized treatments. PMID:22445888

Developing a Cognition Endpoint for Traumatic Brain Injury Clinical Trials

PubMed Central

Crane, Paul K.; Dams-O'Connor, Kristen; Holdnack, James; Ivins, Brian J.; Lange, Rael T.; Manley, Geoffrey T.; McCrea, Michael; Iverson, Grant L.

2017-01-01

Abstract Cognitive impairment is a core clinical feature of traumatic brain injury (TBI). After TBI, cognition is a key determinant of post-injury productivity, outcome, and quality of life. As a final common pathway of diverse molecular and microstructural TBI mechanisms, cognition is an ideal endpoint in clinical trials involving many candidate drugs and nonpharmacological interventions. Cognition can be reliably measured with performance-based neuropsychological tests that have greater granularity than crude rating scales, such as the Glasgow Outcome Scale-Extended, which remain the standard for clinical trials. Remarkably, however, there is no well-defined, widely accepted, and validated cognition endpoint for TBI clinical trials. A single cognition endpoint that has excellent measurement precision across a wide functional range and is sensitive to the detection of small improvements (and declines) in cognitive functioning would enhance the power and precision of TBI clinical trials and accelerate drug development research. We outline methodologies for deriving a cognition composite score and a research program for validation. Finally, we discuss regulatory issues and the limitations of a cognition endpoint. PMID:27188248

Unique and remarkable dilatometer measurements of pyroclastic flow generated tsunamis

NASA Astrophysics Data System (ADS)

Mattioli, G. S.; Voight, B.; Linde, A. T.; Sacks, I. S.; Watts, P.; Widiwijayanti, C.; Young, S. R.; Hidayat, D.; Elsworth, D.; Malin, P. E.; Shalev, E.; van Boskirk, E.; Johnston, W.; Sparks, R. S. J.; Neuberg, J.; Bass, V.; Dunkley, P.; Herd, R.; Syers, T.; Williams, P.; Williams, D.

2007-01-01

Pyroclastic flows entering the sea may cause tsunamis at coastal volcanoes worldwide, but geophysically monitored field occurrences are rare. We document the process of tsunami generation during a prolonged gigantic collapse of the Soufrière Hills volcano lava dome on Montserrat on 12 13 July 2003. Tsunamis were initiated by large-volume pyroclastic flows entering the ocean. We reconstruct the collapse from seismic records and report unique and remarkable borehole dilatometer observations, which recorded clearly the passage of wave packets at periods of 250 500 s over several hours. Strain signals are consistent in period and amplitude with water loading from passing tsunamis; each wave packet can be correlated with individual pyroclastic flow packages recorded by seismic data, proving that multiple tsunamis were initiated by pyroclastic flows. Any volcano within a few kilometers of water and capable of generating hot pyroclastic flows or cold debris flows with volumes greater than 5 × 106 m3 may generate significant and possibly damaging tsunamis during future eruptions.

One remarkable molecule: Filaggrin

PubMed Central

Brown, Sara J.; McLean, W. H. Irwin

2011-01-01

The discovery, in 2006, that loss-of-function mutations in the filaggrin gene (FLG) are the cause of ichthyosis vulgaris – the most common disorder of keratinization – and also a strong genetic risk factor for atopic eczema, marked a significant breakthrough in the understanding of eczema pathogenesis. Subsequent investigations of the role of FLG null mutations have identified a series of significant associations with atopic disease phenotypes, including atopic asthma, allergic rhinitis and peanut allergy. However, many questions remain to be answered in relation to the precise mechanisms by which deficiency of an intracellular protein expressed primarily in the differentiating epidermis may contribute to the development of cutaneous and systemic pathology. This review aims to highlight the key milestones in filaggrin research over the past 25 years, to discuss the mechanistic, clinical and therapeutic implications and to consider possible future directions for ongoing investigation. PMID:22158554

Quality assessment of osteoporosis clinical practice guidelines for physical activity and safe movement: an AGREE II appraisal.

PubMed

Armstrong, James Jacob; Rodrigues, Isabel Braganca; Wasiuta, Tom; MacDermid, Joy C

2016-01-01

Many osteoporosis clinical practice guidelines are published, and the extent to which physical activity and safe movement is addressed varies. To better inform clinical decision-making, a quality assessment and structured analysis of recommendations was undertaken. Guideline quality varied substantially, and improvement is necessary in physical activity and safe movement recommendations. The purpose of the present study is to survey available osteoporosis clinical practice guidelines (CPGs) containing physical activity and safe movement recommendations in order to assess the methodological quality with which they were developed. An analysis of the various physical activity and safe movement recommendations was conducted to determine variability between CPGs. An online literature search revealed 19 CPGs meeting our inclusion criteria. Three independent scorers evaluated CPG quality using the Appraisal of Guidelines for Research and Evaluation version II (AGREE II) instrument. Two separate individuals used a standard table to extract relevant recommendations. Intra-reviewer AGREE II score agreement ranged from fair to good (intra-class correlation coefficient (ICC) = 0.34 to 0.65). The quality of the 19 included CPGs was variable (AGREE sub-scores: 14 to 100%). CPGs scored higher in the "scope and purpose" and "clarity of presentation" domains. They scored the lowest in "applicability" and "editorial independence." Four CPGs were classified as high quality, ten average quality, and five low quality. Most CPGs recommended weight-bearing, muscle-strengthening, and resistance exercises. Information on exercise dosage, progression, and contraindications was often absent. Immobility and movements involving spinal flexion and/or torsion were discouraged. There were several high-quality CPGs; however, variability in quality and lack of specific parameters for implementation necessitates caution and critical examination by readers. CPG development groups should pay

Clinical Feasibility of Continuously Monitored Data for Heart Rate, Physical Activity, and Sleeping by Wearable Activity Trackers in Patients with Thyrotoxicosis: Protocol for a Prospective Longitudinal Observational Study.

PubMed

Lee, Jie-Eun; Lee, Dong Hwa; Oh, Tae Jung; Kim, Kyoung Min; Choi, Sung Hee; Lim, Soo; Park, Young Joo; Park, Do Joon; Jang, Hak Chul; Moon, Jae Hoon

2018-02-21

Thyrotoxicosis is a common disease caused by an excess of thyroid hormones. The prevalence of thyrotoxicosis about 2% and 70-90% of thyrotoxicosis cases are caused by Graves' disease, an autoimmune disease, which has a high recurrence rate when treated with antithyroid drugs such as methimazole or propylthiouracil. The clinical symptoms and signs of thyrotoxicosis include palpitation, weight loss, restlessness, and difficulty sleeping. Although these clinical changes in thyrotoxicosis can be detected by currently available wearable activity trackers, there have been few trials of the clinical application of wearable devices in patients with thyrotoxicosis. The aim of this study is to investigate the clinical applicability of wearable device-generated data to the management of thyrotoxicosis. We are analyzing continuously monitored data for heart rate, physical activity, and sleep in patients with thyrotoxicosis during their clinical course after treatment. Thirty thyrotoxic patients and 10 control subjects were enrolled in this study at Seoul National University Bundang Hospital. Heart rate, physical activity, and sleep are being monitored using a Fitbit Charge HR or Fitbit Charge 2. Clinical data including anthropometric measures, thyroid function test, and hyperthyroidism symptom scale are recorded. Study enrollment began in December 2016, and the intervention and follow-up phases are ongoing. The results of the data analysis are expected to be available by September 2017. This study will provide a foundational feasibility trial of the clinical applications of biosignal measurements to the differential diagnosis, prediction of clinical course, early detection of recurrence, and treatment in patients with thyrotoxicosis. ClinicalTrials.gov NCT03009357; https://clinicaltrials.gov/ct2/show/NCT03009357 (Archived by WebCite at http://www.webcitation.org/6wh4MWPm2). ©Jie-Eun Lee, Dong Hwa Lee, Tae Jung Oh, Kyoung Min Kim, Sung Hee Choi, Soo Lim, Young Joo Park, Do

Vedolizumab provides clinical benefit over 1 year in patients with active inflammatory bowel disease - a prospective multicenter observational study.

PubMed

Stallmach, A; Langbein, C; Atreya, R; Bruns, T; Dignass, A; Ende, K; Hampe, J; Hartmann, F; Neurath, M F; Maul, J; Preiss, J C; Schmelz, R; Siegmund, B; Schulze, H; Teich, N; von Arnim, U; Baumgart, D C; Schmidt, C

2016-12-01

Vedolizumab, a monoclonal antibody targeting the α4β7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials. To determine the long-term effectiveness of vedolizumab in a real-world clinical setting. This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60). Primary endpoint was clinical remission (HBI ≤ 4/pMayo ≤ 1) at week 54. Secondary endpoints included clinical response rates (HBI/pMayo score drop ≥3) and steroid-free clinical remission at weeks 30 and 54. Vedolizumab was stopped in 69/127 (56%) patients after a median time of 18 weeks (range 2-49) predominantly owing to lack or loss of response. Using nonresponder imputation analysis, clinical remission and steroid-free remission rates were 21% and 15% in Crohn's disease and 25% and 22% in ulcerative colitis, respectively. Lack of clinical remission was associated with prior treatment with anti-TNF or with steroids for more than 3 months in the last 6 months in ulcerative colitis. At week 14, the absence of remission in Crohn's disease or nonresponse in ulcerative colitis indicated a low likelihood of clinical remission at week 54 [2/31 (7%) in Crohn's disease, 4/41 (10%) in ulcerative colitis]. Accordingly, declining C-reactive protein in inflammatory bowel disease and/or lower faecal calprotectin in ulcerative colitis at week 14 predicted remission at week 54. Among patients who started vedolizumab for active inflammatory bowel disease, clinical remission rates are 21-25% after 54 weeks. © 2016 John Wiley & Sons Ltd.

The impact of clinical research activities on communities in rural Africa: the development of the Clinical Research Unit of Nanoro (CRUN) in Burkina Faso.

PubMed

Tinto, Halidou; Valea, Innocent; Sorgho, Hermann; Tahita, Marc Christian; Traore, Maminata; Bihoun, Biébo; Guiraud, Issa; Kpoda, Hervé; Rouamba, Jérémi; Ouédraogo, Sayouba; Lompo, Palpouguini; Yara, Sandrine; Kabore, William; Ouédraogo, Jean-Bosco; Guiguemdé, Robert Tinga; Binka, Fred N; Ogutu, Bernhards

2014-03-22

The opportunities for developing new drugs and vaccines for malaria control look brighter now than ten years ago. However, there are few places in sub-Saharan Africa with the necessary infrastructure and expertise to support such research in compliance to international standards of clinical research (ICH-GCP). The Clinical Research Unit of Nanoro (CRUN) was founded in 2008 to provide a much-needed GCP-compliant clinical trial platform for an imminent large-scale Phase 3 malaria vaccine trial. A dynamic approach was used that entailed developing the required infrastructure and human resources, while engaging local communities in the process as key stakeholders. This provided a better understanding and ownership of the research activities by the local population. Within five years (2008-2013), the CRUN set up a fully and well-equipped GCP-compliant clinical trial research facility, which enabled to attract 25 grants. The research team grew from ten health workers prior to 2008 to 254 in 2013. A Health and Demographic Surveillance System (HDSS), which covers a total population of about 60,000 people in 24 villages was set up in the district. The local community contributed to the development of the facility through the leadership of the king and the mayor of Nanoro. As a result of their active advocacy, the government extended the national electrical grid to the new research center, and later to the entire village. This produced a positive impact on the community's quality of life. The quality of health care improved substantially, due to the creation of more elaborate clinical laboratory services and the acquisition of state-of-the-art equipment. Involving the community in the key steps of establishing the centre provided the foundation for what was to become the CRUN success story. This experience demonstrates that when clinical trials research sites are carefully developed and implemented, they can have a positive and powerful impact on local communities in

A remarkable new genus of Protosmylinae (Neuroptera: Osmylidae) from late Eocene Florissant, Colorado.

PubMed

Makarkin, Vladimir N

2017-05-18

Pseudosmylidia relicta gen. et sp. nov. (Neuroptera: Osmylidae) is described from the late Eocene of Florissant (U.S.A., Colorado). It is assigned to the subfamily Protosmylinae based on the presence of two venational features characteristic of the subfamily: most crossveins in the radial to intramedial spaces of the forewing are arranged in four gradate series, and CuP is short and simple or forked only once in the hind wing. This genus is remarkable by CuP in the forewing bearing few pectinate branches. This is the only genus of extant and Cenozoic fossil Osmylidae in which this plesiomorphic condition is retained.

[Clinical and pharmacological aspects of rifaximin, local antibiotic therapy in intestinal disorders].

PubMed

Gasztonyi, Beáta; Hunyady, Béla

2004-10-24

The authors report pharmacokinetics and indications of rifaximin and the results of clinical studies. Rifaximin has a large antibacterial spectrum with a good therapeutic effect on both gram positive and gram negative aerob and anaerob bacteria. Practically there is no absorption (< 1%) following oral administration with a high concentration in gastrointestinal mucosa (8000 microg/g). No increase in absorption can be detected in intestinal damage caused by inflammatory bowel disease. The remarkable safety profile of rifaximin is due to its negligible quality of absorption. According to the clinical studies rifaximin could be an adequate therapeutic approach in all gastrointestinal diseases and interventions when antibacterial therapy is needed.

Preliminary clinical results: an analyzing tool for 2D optical imaging in detection of active inflammation in rheumatoid arthritis

NASA Astrophysics Data System (ADS)

Adi Aizudin Bin Radin Nasirudin, Radin; Meier, Reinhard; Ahari, Carmen; Sievert, Matti; Fiebich, Martin; Rummeny, Ernst J.; No"l, Peter B.

2011-03-01

Optical imaging (OI) is a relatively new method in detecting active inflammation of hand joints of patients suffering from rheumatoid arthritis (RA). With the high number of people affected by this disease especially in western countries, the availability of OI as an early diagnostic imaging method is clinically highly relevant. In this paper, we present a newly in-house developed OI analyzing tool and a clinical evaluation study. Our analyzing tool extends the capability of existing OI tools. We include many features in the tool, such as region-based image analysis, hyper perfusion curve analysis, and multi-modality image fusion to aid clinicians in localizing and determining the intensity of inflammation in joints. Additionally, image data management options, such as the full integration of PACS/RIS, are included. In our clinical study we demonstrate how OI facilitates the detection of active inflammation in rheumatoid arthritis. The preliminary clinical results indicate a sensitivity of 43.5%, a specificity of 80.3%, an accuracy of 65.7%, a positive predictive value of 76.6%, and a negative predictive value of 64.9% in relation to clinical results from MRI. The accuracy of inflammation detection serves as evidence to the potential of OI as a useful imaging modality for early detection of active inflammation in patients with rheumatoid arthritis. With our in-house developed tool we extend the usefulness of OI imaging in the clinical arena. Overall, we show that OI is a fast, inexpensive, non-invasive and nonionizing yet highly sensitive and accurate imaging modality.-

Miniaturization and globalization of clinical laboratory activities.

PubMed

Melo, Murilo R; Clark, Samantha; Barrio, Daniel

2011-04-01

Clinical laboratories provide an invaluable service to millions of people around the world in the form of quality diagnostic care. Within the clinical laboratory industry the impetus for change has come from technological development (miniaturization, nanotechnology, and their collective effect on point-of-care testing; POCT) and the increasingly global nature of laboratory services. Potential technological gains in POCT include: the development of bio-sensors, microarrays, genetics and proteomics testing, and enhanced web connectivity. In globalization, prospective opportunities lie in: medical tourism, the migration of healthcare workers, cross-border delivery of testing, and the establishment of accredited laboratories in previously unexplored markets. Accompanying these impressive opportunities are equally imposing challenges. Difficulty transitioning from research to clinical use, poor infrastructure in developing countries, cultural differences and national barriers to global trade are only a few examples. Dealing with the issues presented by globalization and the impact of developing technology on POCT, and on the clinical laboratory services industry in general, will be a daunting task. Despite such concerns, with appropriate countermeasures it will be possible to address the challenges posed. Future laboratory success will be largely dependent on one's ability to adapt in this perpetually shifting landscape.

Long-times series of infrasonic records at open-vents volcanoes (Yasur volcano, Vanuatu, 2003-2014): the remarkable temporal stability of magma viscosity

NASA Astrophysics Data System (ADS)

Vergniolle, S.; Souty, V.; Zielinski, C.; Bani, P.; LE Pichon, A.; Lardy, M.; Millier, P.; Herry, P.; Todman, S.; Garaebiti, E.

2017-12-01

Open-vents volcanoes, often presenting series of Strombolian explosions of various intensity, are responding, although with a delay, to any changes in the degassing pattern, providing a quasi-direct route to processes at depth. Open-vents volcanoes display a persistent volcanic activity, although of variable intensity. Long-times series at open-vents volcanoes could therefore be key measurements to unravel physical processes at the origin of Strombolian explosions and be crucial for monitoring. Continuous infrasonic records can be used to estimate the gas volume expelled at the vent during explosions (bursting of a long slug). The gas volume of each explosion is deduced from a series of two successive integrations of acoustic pressure (monopole). Here we analysed more than 4 years of infrasonic records at Yasur volcano (Vanuatu), spanning between 2003 and 2014 and organised into 8 main quasi-continuous periods. The relationship between the gas volume of each explosion and its associated maximum positive acoustic pressure, a proxy for the inner gas overpressure at bursting, shows a remarkably stable trend over the 8 periods. Two main trends exists, one which covers the full range of acoustic pressures (called « strong explosions ») and the second which represents explosions with a large gas volume and mild acoustic pressure. The class of « strong explosions » clearly follows the model of Del Bello et al. (2012), which shows that the inner gas overpressure at bursting, here empirically measured by the maximum acoustic pressure, is proportional to the gas volume. Constrains on magma viscosity and conduit radius, are deduced from this trend and from the gas volume at the transition passive-active degassing. The remarkable stability of this trend over time suggests that 1) the magma viscosity is stable at the depth where gas overpressure is produced within the slug and 2) any potential changes in magma viscosity occur very close to the top of the magma column.

Clinical manifestation and prognosis of active ocular toxoplasmosis in Iran.

PubMed

Kianersi, Farzan; Naderi Beni, Afsaneh; Naderi Beni, Zahra

2012-12-01

Toxoplasmosis is the most common cause of posterior uveitis in the world. This study described the clinical characteristics and visual outcome of 193 patients with ocular toxoplasmosis at Feiz Hospital (Isfahan, Iran) during the last six years. The setting and design used was a retrospective non-comparative observational case series. In this study, 193 patients with ocular toxoplasmosis (111 female, 82 male) were enrolled. The distribution of symptoms and fundoscopic findings were studied. The most-reported chief complaint was blurred vision in 96 % (184 patients) and floaters in 13.47 % (25 patients) of cases and most frequent clinical manifestations were chorioretinitis 98.48 % (190 patients), macular scars 50.7 % (98 patients), and atrophic optic papilla two (1.03 %) patients. Primary retinal lesions were observed in 16 (8.2 %) and combination of active lesions and old retinochoroidal scars in 177 (91.7 %) of the patients. Retinal detachment occurred in 11 (5.69 %) patients. Bilateral involvement was found in 27 % of patients. Blindness was 0.05 % after treatment. Recurrence rate was 14.5 %. In conclusion, ocular toxoplasmosis substantially varies among patients with different age, gender, site of lesion and other factors. Suddenly blurred vision, floater, and pain could be caused by Toxoplasma gondii. Flashing, may necessitate a more precise peripheral fundus examination.

Variable clinical presentations of secondary delusional infestation: an experience of six cases from a psychodermatology clinic.

PubMed

Altunay, Ilknur K; Ates, Bilge; Mercan, Sibel; Demirci, Gulsen Tukenmez; Kayaoglu, Semra

2012-01-01

Delusional Infestation (DI) is a relatively rare condition with a fixed belief of being infested with living organisms, despite a lack of medical evidence of such infestation. Although it seems to be a psychiatric disease, patients commonly are admitted to dermatology clinics because of skin findings. Psychiatrists can underestimate its prevalance, whereas dermatologists can miss the diagnosis. It should be managed as a psychodermatological disease. Our aim in the study was to evaluate six patients with different clinical presentations of DI and to emphasize some clinical features. All patients were internalized in the psychodermatology clinic for this study. Medical history and clinical data from dermatologic and psychiatric examinations were noted; Mini International Neuropsychiatric Interview (MINI-Plus) and laboratory investigations including blood and urine analyses, microscopic analysis of so-called pathogens, and skin biopsy if needed, were performed. The diagnosis was made based on detailed history, dermatologic and psychiatric examinations, and laboratory investigations. All patients had symptoms of itching, burning, or crawling sensations dermatologically and thus were admitted to dermatology clinic. They were all considered secondary DI to another medical condition or to psychiatric illness. Vitamin B12 deficiency, diabetes, and hypothyroidism were the underlying medical conditions. Related psychiatric illnesses were trichotillomania and schizoaffective disorder, schizophrenia, shared pychotic disorder, and brief psychotic disorder. Two patients had delusions of inanimate materials; four patients had partial and complete remissions; and two patients have dropped out. Each patient had different clinical characteristics creating diagnostic challenges. All complaints were related to the infestation of the skin. The presence of different psychiatric comorbidities is remarkable. It seems that both psychiatrists and dermatologists can face diagnostic and

First experience with clinical use of an original hemoperfusion system.

PubMed

Horký, J; Horák, J; Tlustáková, M; Kálal, J

1981-01-01

1. The authors present their experience with the use of an original charcoal hemoperfusion system Hemosorb in clinical application, in 9 patients with a heavy metabolic disturbance (failure of the liver and kidney) and after an intoxication with drugs. 2. In two patients the consciousness was remarkably recovered and in one patient it was improved already in the course of the hemoperfusion process, in further two cases the consciousness was recovered in short time after the Hemosorb was used, 7 were completely healed. 3. During the hemoperfusion with Hemosorb there were no symptoms of bad tolerance and no complications except for temporary pyretic reaction in one case. In unique cases manifestations of an enhanced bleeding occurred at the end of the long-term process, which were, however, rather easily corrected. The drop of thrombocytes was essentially reasonable and their restriction after the hemoperfusion was good. 4. Out of metabolic parameters of interest, in the patients with the heavy metabolic failure the drop of total phenol substances, uric acid and creatinine in the blood serum were observed at first stages of the hemoperfusion. The clearance of the total phenol substances and creatinine in the hemoperfusion system was ever rather high. 5. In a patient intoxicated with drugs, there was a remarkable drop of the metaqualone in the blood serum in the course of the hemoperfusion with Hemosorb; the clearance of this compound in the hemoperfusion system was still high after 4 hrs. 6. The first experiences with the clinical application of a new, original hemoperfusion system demonstrated its non-harmful character and biocompatibility as well as clinical, metabolic and toxicologic efficiency.

Association of Asian ethnicity with disease activity in SLE: an observational study from the Monash Lupus Clinic.

PubMed

Golder, V; Connelly, K; Staples, M; Morand, E; Hoi, A

2013-11-01

Systemic lupus erythematosus (SLE), an autoimmune condition with diverse clinical manifestations, is reported to have different expression in populations of different ancestry. Most previous studies compared patients of different ethnic groups from geographically distinct cohorts. In our study, we aimed to characterize disease manifestations in patients of different ethnic groups from a single centre, and studied patterns of disease activity over time. Demographics, baseline disease characteristics and autoantibody profiles, and disease activity (SLEDAI) measured at each visit, were captured from all consenting patients prospectively followed between 2007 and 2011 in an urban teaching hospital lupus clinic. Ethnicity was self-reported. Asian ethnicity was significantly associated with more clinically severe SLE. Time-adjusted mean SLEDAI (p = 0.01) and maximum SLEDAI (p = 0.0018) were significantly higher in Asian patients. Asians were more likely to have renal disease (OR 2.9, 95% CI 1.4-5.98; p = 0.004) and persistently active disease (PAD) (OR 2.14, 95% CI 1.05-4.38, p = 0.04). Asian lupus patients also had a significantly higher proportion of autoantibody positivity to anti-dsDNA, anti-RNP, anti-Sm, anti-Ro and anti-La, as well as increased likelihood of hypocomplementaemia and immunosuppressant use. In this single-cohort study, Asian ethnicity was found to be associated with increased SLE disease activity. This suggests significant inter-ethnic genetic contributions to the regulation of autoimmune responses and disease severity in SLE.

Opening remarks; special session 4. Burning issues and smoke screens: heat and light in southern forests

Treesearch

Peter J. Roussopoulos

1998-01-01

In Roussopoulos’ opening remarks he included nine assertions about southern forests: 1) that their characteristics are unique; 2) that they recovered from abusive agricultural practices and exploitive forest extraction in the 19th and early 20th centuries; 3) that they are brand new; 4) that social forces driving change will intensify at all scales; 5) that the...

Communities of clinical practice: the social organization of clinical learning.

PubMed

Egan, Tony; Jaye, Chrystal

2009-01-01

The social organization of clinical learning is under-theorized in the sociological literature on the social organization of health care. Professional scopes of practice and jurisdictions are formally defined by professional principles and standards and reflected in legislation; however, these are mediated through the day-to-day clinical activities of social groupings of clinical teams. The activities of health service providers typically occur within communities of clinical practice. These are also major sites for clinical curriculum delivery, where clinical students learn not only clinical skills but also how to be health professionals. In this article, we apply Wenger's model of social learning within organizations to curriculum delivery within a health service setting. Here, social participation is the basis of learning. We suggest that it offers a powerful framework for recognizing and explaining paradox and incongruence in clinical teaching and learning, and also for recognizing opportunities, and devising means, to add value to students' learning experiences.

Assessing the activity of perianal Crohn's disease: comparison of clinical indices and computer-assisted anal ultrasound.

PubMed

Losco, Alessandra; Viganò, Chiara; Conte, Dario; Cesana, Bruno Mario; Basilisco, Guido

2009-05-01

Assessing perianal disease activity is important for the treatment and prognosis of Crohn's disease (CD) patients, but the diagnostic accuracy of the activity indices has not yet been established. The aim of this study was to determine the accuracy and agreement of the Fistula Drainage Assessment (FDA), Perianal Disease Activity Index (PDAI), and computer-assisted anal ultrasound imaging (AUS). Sixty-two consecutive patients with CD and perianal fistulae underwent clinical, FDA, PDAI, and AUS evaluation. Perianal disease was considered active in the presence of visible fistula drainage and/or signs of local inflammation (induration and pain at digital compression) upon clinical examination. The AUS images were analyzed by calculating the mean gray-scale tone of the lesion. The PDAI and gray-scale tone values discriminating active and inactive perianal disease were defined using receiver operating characteristics statistics. Perianal disease was active in 46 patients. The accuracy of the FDA was 87% (confidence interval [CI]: 76%-94%). A PDAI of >4 and a mean gray-scale tone value of 117 maximized sensitivity and specificity; their diagnostic accuracy was, respectively, 87% (CI: 76%-94%) and 81% (CI: 69%-90%). The agreement of the 3 evaluations was fair to moderate. The addition of AUS to the PDAI or FDA increased their diagnostic accuracy to respectively 95% and 98%. The diagnostic accuracy of the FDA, PDAI, and computer-assisted AUS imaging was good in assessing perianal disease activity in patients with CD. The agreement between the techniques was fair to moderate. Overall accuracy can be increased by combining the FDA or PDAI with AUS.

[Perspectives on pharmacological and clinical benefits from sirtuin 1 activators in oxidative damage].

PubMed

Kutinová, Canová Nikolina; Gaier, Norbert; Farghali, Hassan

2012-01-01

Sirtuins, named after their homology to the Saccharomyces cerevisiae Silent Information Regulator Two, constitute a family of highly conserved nicotinamide adenine dinucleotide-dependent enzymes that deacetylate histones and residues of acetylated lysine. The main aim of this article is to put forward the pharmacological importance of major sirtuin 1 activators of natural or synthetic origin tested in last years in cases of oxidative tissue damage. The related bioactivity of these activators as "leading" compounds in the search for new drugs and remedies is also described. With the recent development of our knowledge on the cross talks between sirtuin 1 and its modulators (e.g. resveratrol), pharmacological and clinical research on this topic is getting a new horizon.

Definition of treatment response in rheumatoid arthritis based on the simplified and the clinical disease activity index.

PubMed

Aletaha, Daniel; Martinez-Avila, Jose; Kvien, Tore K; Smolen, Josef S

2012-07-01

The simplified disease activity index (SDAI) and the clinical disease activity index (CDAI) are established instruments to measure disease activity in rheumatoid arthritis (RA). To date, no validated response definitions for the SDAI and CDAI are available. The authors aimed to define minor, moderate and major response criteria for the SDAI. The authors used data from two clinical trials on infliximab versus methotrexate in early (ASPIRE) or established (ATTRACT) RA, and identified the three SDAI cutpoints based on the best agreement (by κ statistics) with the American College of Rheumatology (ACR)20/50/70 responses. Cutpoints were then tested for different aspects of validity in the trial datasets and in a Norwegian disease modifying antirheumatic drug prescription dataset (NOR-DMARD). Based on agreement with the ACR response, the minor, moderate and major responses were identified as SDAI 50%, 70% and 85% improvement. These cutpoints had good face validity concerning the disease activity states achieved by the different response definitions. Construct validity was shown by a clear association of increasing SDAI response categories with increasing levels of functional improvement, achievement of better functional states and lower annual radiographic progression. Across SDAI 50/70/85, the sensitivities regarding a patient-perceived improvement decreased (73%/39%/22%) and the specificities increased (61%/89%/96%) in a meaningful way. Further, the cutpoints discriminated the different treatment arms in ASPIRE and ATTRACT. The same cutpoints were used for the CDAI, with similar results in the validation analyses. These new response criteria expand the usefulness of the SDAI and CDAI for their use as endpoints in clinical trials beyond the definition of disease activity categories.

Reliability of Classifying Multiple Sclerosis Disease Activity Using Magnetic Resonance Imaging in a Multiple Sclerosis Clinic

PubMed Central

Altay, Ebru Erbayat; Fisher, Elizabeth; Jones, Stephen E.; Hara-Cleaver, Claire; Lee, Jar-Chi; Rudick, Richard A.

2013-01-01

Objective To assess the reliability of new magnetic resonance imaging (MRI) lesion counts by clinicians in a multiple sclerosis specialty clinic. Design An observational study. Setting A multiple sclerosis specialty clinic. Patients Eighty-five patients with multiple sclerosis participating in a National Institutes of Health–supported longitudinal study were included. Intervention Each patient had a brain MRI scan at entry and 6 months later using a standardized protocol. Main Outcome Measures The number of new T2 lesions, newly enlarging T2 lesions, and gadolinium-enhancing lesions were measured on the 6-month MRI using a computer-based image analysis program for the original study. For this study, images were reanalyzed by an expert neuroradiologist and 3 clinician raters. The neuroradiologist evaluated the original image pairs; the clinicians evaluated image pairs that were modified to simulate clinical practice. New lesion counts were compared across raters, as was classification of patients as MRI active or inactive. Results Agreement on lesion counts was highest for gadolinium-enhancing lesions, intermediate for new T2 lesions, and poor for enlarging T2 lesions. In 18% to 25% of the cases, MRI activity was classified differently by the clinician raters compared with the neuroradiologist or computer program. Variability among the clinical raters for estimates of new T2 lesions was affected most strongly by the image modifications that simulated low image quality and different head position. Conclusions Between-rater variability in new T2 lesion counts may be reduced by improved standardization of image acquisitions, but this approach may not be practical in most clinical environments. Ultimately, more reliable, robust, and accessible image analysis methods are needed for accurate multiple sclerosis disease-modifying drug monitoring and decision making in the routine clinic setting. PMID:23599930

Webcasts promote in-class active participation and learning in an engineering elective course

NASA Astrophysics Data System (ADS)

Freguia, Stefano

2017-09-01

This paper describes the design and outcomes of an educational intervention undertaken to improve the quality of delivery of a fourth-year engineering elective course - Industrial Wastewater and Solid Waste Management at the University of Queensland. The objective was to increase the level of active participation of students in planned active-learning classroom activities, including whole-class discussions and small group project-type work. According to a flipped classroom model, new online material in the form of webcasts was proposed to students before class. Students reacted very positively to the webcasts: the percentage of students viewing the webcast before planned workshop sessions ranged between 80% and 92% over the five weeks of the intervention. Enhanced engagement led also to increased attendance (85-92% at workshop sessions), and remarkable active participation in class (half of observed teams were ∼80% active). Remarkably, team performance as quantified by their report marks linearly correlated with the level of active participation in class.

Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study.

PubMed

Rasova, Kamila; Prochazkova, Marie; Tintera, Jaroslav; Ibrahim, Ibrahim; Zimova, Denisa; Stetkarova, Ivana

2015-03-01

There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.

Clinical activity of mTOR inhibition with sirolimus in malignant perivascular epithelioid cell tumors: targeting the pathogenic activation of mTORC1 in tumors.

PubMed

Wagner, Andrew J; Malinowska-Kolodziej, Izabela; Morgan, Jeffrey A; Qin, Wei; Fletcher, Christopher D M; Vena, Natalie; Ligon, Azra H; Antonescu, Cristina R; Ramaiya, Nikhil H; Demetri, George D; Kwiatkowski, David J; Maki, Robert G

2010-02-10

PURPOSE Perivascular epithelioid cell tumors (PEComas) represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. There is no known effective therapy for PEComa, and the molecular pathophysiology of aberrant mTOR signaling provided us with a scientific rationale to target this pathway therapeutically. On this mechanistic basis, we treated three consecutive patients with metastatic PEComa with an oral mTOR inhibitor, sirolimus. PATIENTS AND METHODS Patients with advanced PEComa were treated with sirolimus and consented to retrospective collection of data from their medical records and analysis of archival tumor specimens. Tumor response was determined by computed tomography scans obtained at the clinical discretion of the treating physicians. Tumors were assessed for immunohistochemical evidence of mTORC1 activation and genetic evidence of alterations in TSC1 and TSC2. Results Radiographic responses to sirolimus were observed in all patients. PEComas demonstrated loss of TSC2 protein expression and evidence of baseline mTORC1 activation. Homozygous loss of TSC1 was identified in one PEComa. CONCLUSION Inhibition of mTORC1, pathologically activated by loss of the TSC1/TSC2 tumor suppressor complex, is a rational mechanistic target for therapy in PEComas. The clinical activity of sirolimus in PEComa additionally strengthens the pathobiologic similarities linking PEComas to other neoplasms related to the tuberous sclerosis complex.

Clinical Activity of mTOR Inhibition With Sirolimus in Malignant Perivascular Epithelioid Cell Tumors: Targeting the Pathogenic Activation of mTORC1 in Tumors

PubMed Central

Wagner, Andrew J.; Malinowska-Kolodziej, Izabela; Morgan, Jeffrey A.; Qin, Wei; Fletcher, Christopher D.M.; Vena, Natalie; Ligon, Azra H.; Antonescu, Cristina R.; Ramaiya, Nikhil H.; Demetri, George D.; Kwiatkowski, David J.; Maki, Robert G.

2010-01-01

Purpose Perivascular epithelioid cell tumors (PEComas) represent a family of mesenchymal neoplasms, mechanistically linked through activation of the mTOR signaling pathway. There is no known effective therapy for PEComa, and the molecular pathophysiology of aberrant mTOR signaling provided us with a scientific rationale to target this pathway therapeutically. On this mechanistic basis, we treated three consecutive patients with metastatic PEComa with an oral mTOR inhibitor, sirolimus. Patients and Methods Patients with advanced PEComa were treated with sirolimus and consented to retrospective collection of data from their medical records and analysis of archival tumor specimens. Tumor response was determined by computed tomography scans obtained at the clinical discretion of the treating physicians. Tumors were assessed for immunohistochemical evidence of mTORC1 activation and genetic evidence of alterations in TSC1 and TSC2. Results Radiographic responses to sirolimus were observed in all patients. PEComas demonstrated loss of TSC2 protein expression and evidence of baseline mTORC1 activation. Homozygous loss of TSC1 was identified in one PEComa. Conclusion Inhibition of mTORC1, pathologically activated by loss of the TSC1/TSC2 tumor suppressor complex, is a rational mechanistic target for therapy in PEComas. The clinical activity of sirolimus in PEComa additionally strengthens the pathobiologic similarities linking PEComas to other neoplasms related to the tuberous sclerosis complex. PMID:20048174

Clinical and laboratory characteristics of active and healthy aging (AHA) in octogenarian men.

PubMed

Rantanen, Kirsi K; Strandberg, Timo E; Stenholm, Sari S; Strandberg, Arto Y; Pitkälä, Kaisu H; Salomaa, Veikko V; Tilvis, Reijo S

2015-10-01

To investigate clinical and laboratory variables associated with good subjective and objective health ("active and healthy aging", AHA) in a cohort of octogenarian men. Cross-sectional analyses of a longitudinal study. The Helsinki Businessmen Study in Finland. A socioeconomically homogenous cohort of men (baseline n = 3293), born in 1919-1934, has been followed up from the 1960s. From 2000, the men have been regularly sent mailed questionnaires and mortality has been retrieved from national registers. In 2010 survey, AHA was defined as independently responding to the mailed survey, feeling happy without cognitive or functional impairments and without major diseases. In 2010/11, a random subgroup men was clinically investigated and survivors with healthy and nonhealthy aging were compared. By 2010, 1788 men of the baseline cohort had died, and 894 men responded to the mailed survey. 154 (17.2 %) of those fulfilled the present AHA criteria. Increasing number of criteria were negatively (P < 0.001) related to short-term mortality. In 2011, a random sample of 458 men were clinically investigated, 90 of them with AHA. Men with AHA had higher serum LDL cholesterol and diastolic blood pressure (partially explained by less frequent drug use) but no significant difference was observed in other risk factors. Men with AHA had significantly faster walking speed (P < 0.001), stronger handgrip (P = 0.017), better self-rated health and less phenotypic frailty (P = 0.02). Less than 5 % enjoyed active and healthy aging over their life course, which was significantly related to markers of frailty but not to the traditional vascular risk factors.

In vitro activity of Citrus bergamia (bergamot) oil against clinical isolates of dermatophytes.

PubMed

Sanguinetti, M; Posteraro, B; Romano, L; Battaglia, F; Lopizzo, T; De Carolis, E; Fadda, G

2007-02-01

Recently, bergamot oil was shown to be a potent antifungal agent in vitro against clinically important Candida species. In this study, the activities of bergamot natural essence and its furocoumarin-free and distilled extracts on dermatophytes such as Trichophyton, Microsporum and Epidermophyton species were investigated. In vitro susceptibility testing assays on 92 clinical isolates of dermatophytes (Trichophyton mentagrophytes n = 20, Trichophyton rubrum n = 18, Trichophyton interdigitale n = 15, Trichophyton tonsurans n = 2, Microsporum canis n = 24, Microsporum gypseum n = 1 and Epidermophyton floccosum n = 12) were performed using the CLSI M38-A broth microdilution method, except for employing an inoculum of 1-3 x 10(3) cfu/mL. MICs were determined at a visual endpoint reading of 80% inhibition compared with the growth control. MICs (v/v) of all fungi ranged from 0.156% to 2.5% for the natural essence, from 0.02% to 2.5% for the distilled extract, and from 0.08% to 1.25% for the furocoumarin-free extract. The three isolates of T. tonsurans and M. gypseum exhibited the highest MIC values. Data from this study indicate that bergamot oil is active in vitro against several common species of dermatophytes, suggesting its potential use for topical treatment of dermatophytoses.

Highlights of 1978 activities

NASA Technical Reports Server (NTRS)

1978-01-01

General highlights of NASA's activities for 1978 are presented. The highlights are categorized into topics such as space science, space transportation systems, space and terrestrial applications, environment, technology utilization, aeronautics, space research and technology, energy programs, and international. A list of the 1978 launches including: (1) launch date; (2) payload designation; (3) launch vehicle; (4) launch site and (5) mission remarks is also presented.

Perception versus reality: a comparative study of the clinical judgment skills of nurses during a simulated activity.

PubMed

Fenske, Cynthia L; Harris, Margaret A; Aebersold, Michelle L; Hartman, Laurie S

2013-09-01

This study was conducted to determine how closely nurses' perceptions of their clinical judgment abilities matched their demonstrated clinical judgment skills during a simulation. Seventy-four registered nurses participated in a simulation using a video format. After the simulation, the nurses self-assessed their performance using the Lasater Clinical Judgment Rubric. This rubric was then used to rate the nurses' actual performance in the simulation activity. The study results showed a significant discrepancy between nurses' perceptions of their own clinical judgment abilities and their demonstrated clinical judgment skills. Age and length of nursing experience enhanced the difference between the findings of self-assessment and actual performance. Younger nurses and those with 1 year or less of nursing experience were significantly more likely to have self-assessed their abilities at a much higher level compared with their actual skills. Copyright 2013, SLACK Incorporated.

Targeted Delivery and Sustained Antitumor Activity of Triptolide through Glucose Conjugation.

PubMed

He, Qing-Li; Minn, Il; Wang, Qiaoling; Xu, Peng; Head, Sarah A; Datan, Emmanuel; Yu, Biao; Pomper, Martin G; Liu, Jun O

2016-09-19

Triptolide, a key ingredient from the traditional Chinese medicinal plant thunder god vine, which has been used to treat inflammation and autoimmune diseases for centuries, has been shown to be an irreversible inhibitor of the XPB subunit of the transcription factor TFIIH and initiation of RNA polymerase II mediated transcription. The clinical development of triptolide over the past two decades has been limited by its toxicity and low water solubility. Herein, we report the development of a glucose conjugate of triptolide, named glutriptolide, which was intended to target tumor cells overexpressing glucose transporters selectively. Glutriptolide did not inhibit XPB activity in vitro but demonstrated significantly higher cytotoxicity against tumor cells over normal cells with greater water solubility than triptolide. Furthermore, it exhibited remarkable tumor control in vivo, which is likely due to sustained stepwise release of active triptolide within cancer cells. These findings indicate that glutriptolide may serve as a promising lead for developing a new mechanistic class of anticancer drugs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Early Disease Activity or Clinical Response as Predictors of Long‐Term Outcomes With Certolizumab Pegol in Axial Spondyloarthritis or Psoriatic Arthritis

PubMed Central

Deodhar, A.; Fleischmann, R.; Mease, P. J.; Rudwaleit, M.; Nurminen, T.; Davies, O.

2017-01-01

Objective Early identification of patients unlikely to achieve good long‐term disease control with anti–tumor necrosis factor therapy in axial spondyloarthritis (SpA) and psoriatic arthritis (PsA) is important for physicians following treat‐to‐target recommendations. Here we assess associations between disease activity or clinical response during the first 12 weeks of treatment and attainment of treatment targets at week 48 in axial SpA and PsA patients receiving certolizumab pegol. Methods The relationship between disease activity or clinical response during the first 12 weeks of treatment and achievement of week‐48 targets (for axial SpA: inactive disease based on Ankylosing Spondylitis Disease Activity Score [ASDAS] using the C‐reactive protein [CRP] level, or Bath Ankylosing Spondylitis Disease Activity Index <2 with normal CRP level; and for PsA: minimal disease activity) was assessed post hoc using RAPID‐axSpA and RAPID‐PsA trial data. Results A clear relationship between disease activity from week 2 to 12 and achievement of week‐48 treatment targets was observed in both axial SpA and PsA populations. In axial SpA, week‐48 ASDAS inactive disease was achieved by 0% of patients (0 of 21) with ASDAS very high disease activity at week 12, compared to 68% of patients (34 of 50) with week‐12 ASDAS inactive disease. For PsA, week‐48 minimal disease activity was achieved by 0% of patients (0 of 26) with Disease Activity Score in 28 joints (DAS28) using the CRP level >5.1 at week 12, compared to 73% of patients (57 of 78) with DAS28‐CRP <2.6. Similar results were observed regardless of the disease activity measure used. Clinical response at week 12 also predicted week‐48 outcomes, though to a lesser extent than disease activity. Conclusion Using disease activity and the clinical response state during the first 12 weeks of certolizumab pegol treatment, it was possible to identify a subset of axial SpA and PsA patients unlikely to achieve

The anti-candidal activity of Satureja khuzistanica ethanol extract against clinical isolates of C. albicans.

PubMed

Mahboubi, M; Kazempour, N

2016-03-01

Candida albicans is the common cause of some infectious diseases such as vaginal candidiasis or candidemia. Due to the emergence of drug resistant isolates of C. albicans, finding a new anti-Candida agent is a new strategy for current treatments. This study evaluated the anti-candidal activity of Satureja khuzistanica ethanol extract against clinical isolates of C. albicans. S. khuzistanica ethanol extract from aerial parts of plant at full flowering stage was evaluated against 30 clinical isolates and two ATCC reference strains of C. albicans by disc diffusion and micro-broth dilution assay. Also, in this study we evaluated the synergistic effects of amphotericin B, clotrimazole and ketoconazole with S. khuzistanica ethanol extract. The means of MIC and MFC of S. khuzistanica ethanol extract against clinical isolates were 299.4 and 722.6 (μg/mL), respectively. S. khuzistanica ethanol extract increased the anti-candidal effect of amphotericin B and ketoconazole, while it had no synergistic effect on clotrimazole against clinical isolates of C. albicans. Therefore, S. khuzistanica ethanol extract can be introduced as a new source of anti-candidal agent against clinical isolates of C. albicans. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A multi-instructor, team-based, active-learning exercise to integrate basic and clinical sciences content.

PubMed

Kolluru, Srikanth; Roesch, Darren M; Akhtar de la Fuente, Ayesha

2012-03-12

To introduce a multiple-instructor, team-based, active-learning exercise to promote the integration of basic sciences (pathophysiology, pharmacology, and medicinal chemistry) and clinical sciences in a doctor of pharmacy curriculum. A team-based learning activity that involved pre-class reading assignments, individual-and team-answered multiple-choice questions, and evaluation and discussion of a clinical case, was designed, implemented, and moderated by 3 faculty members from the pharmaceutical sciences and pharmacy practice departments. Student performance was assessed using a multiple-choice examination, an individual readiness assurance test (IRAT), a team readiness assurance test (TRAT), and a subjective, objective, assessment, and plan (SOAP) note. Student attitudes were assessed using a pre- and post-exercise survey instrument. Students' understanding of possible correct treatment strategies for depression improved. Students were appreciative of this true integration of basic sciences knowledge in a pharmacotherapy course and to have faculty members from both disciplines present to answer questions. Mean student score on the on depression module for the examination was 80.4%, indicating mastery of the content. An exercise led by multiple instructors improved student perceptions of the importance of team-based teaching. Integrated teaching and learning may be achieved when instructors from multiple disciplines work together in the classroom using proven team-based, active-learning exercises.

Remarkable optical red shift and extremely high optical absorption coefficient of V-Ga co-doped TiO2

NASA Astrophysics Data System (ADS)

Deng, Quanrong; Han, Xiaoping; Gao, Yun; Shao, Guosheng

2012-07-01

A first attempt has been made to study the effect of codoping of transition metal and sp metal on the electronic structure and associated optical properties of TiO2, through V-Ga codoped thin films. V-Ga codoped rutile TiO2 films were fabricated on fused quartz substrates using pulsed laser ablation, followed by heat treatment at high temperatures. Gigantic redshift in the optical absorption edge was observed in V-Ga co-doped TiO2 materials, from UV to infrared region with high absorption coefficient. Through combined structural characterization and theoretical modeling, this is attributed to the p-d hybridization between the two metals. This leads to additional energy bands to overlap with the minimum of the conduction band, leading to remarkably narrowed band gap free of mid-gap states. The direct-gap of the co-doped phase is key to the remarkably high optical absorption coefficient of the coped titania.

Clinical descriptive measures of shoulder range of motion for a healthy, young and physically active cohort.

PubMed

Vairo, Giampietr L; Duffey, Michele L; Owens, Brett D; Cameron, Kenneth L

2012-09-10

The objective of this innovative research study was to describe clinical shoulder complex range of motion (ROM) measures for a young, healthy, and physically active population. This investigation represents a cross-sectional experiment conducted at a military academy-based sports medicine center. Military cadets with no history of shoulder complex injury were assessed within two months of enrollment in the academy; 548 men (18.8 ± 1.0 yr, 75.2 ± 12.2 kg, 178.3 ± 7.4 cm) and 74 women (18.7 ± 0.9 yr, 63.2 ± 8.9 kg, 165.2 ± 6.9 cm) participated. Descriptive measures included cross-body adduction (CAD), flexion (FLX), external rotation (ER0) with the shoulder complex in adduction and elbow flexed to 90°, internal and external rotation (IR, ER) with the shoulder complex at 90° of abduction and elbow flexed to 90° as well as arc (ARC) of IR-ER using standardized clinical quantification techniques. Bilateral and sex differences were evaluated using dependent and independent t-tests, respectively. Percentiles by arm dominance and sex were also calculated for all ROM measures. Data were normally distributed. Active and passive ROM measures indicated significant bilateral differences (P < 0.05) except for ARC. Sex differences (P < 0.05) were noted for active and passive CAD, FLX and ER0 for the dominant arm as well as active and passive CAD, FLX and ARC for the non-dominant arm. These original data provide descriptive measures for shoulder complex ROM excursions, assisting sports medicine practitioners in potentially identifying clinical deficiencies and functional outcomes following shoulder injury.

Remarkable convergent evolution in specialized parasitic Thecostraca (Crustacea)

PubMed Central

Pérez-Losada, Marcos; Høeg, Jens T; Crandall, Keith A

2009-01-01

Background The Thecostraca are arguably the most morphologically and biologically variable group within the Crustacea, including both suspension feeders (Cirripedia: Thoracica and Acrothoracica) and parasitic forms (Cirripedia: Rhizocephala, Ascothoracida and Facetotecta). Similarities between the metamorphosis found in the Facetotecta and Rhizocephala suggests a common evolutionary origin, but until now no comprehensive study has looked at the basic evolution of these thecostracan groups. Results To this end, we collected DNA sequences from three nuclear genes [18S rRNA (2,305), 28S rRNA (2,402), Histone H3 (328)] and 41 larval characters in seven facetotectans, five ascothoracidans, three acrothoracicans, 25 rhizocephalans and 39 thoracicans (ingroup) and 12 Malacostraca and 10 Copepoda (outgroup). Maximum parsimony, maximum likelihood and Bayesian analyses showed the Facetotecta, Ascothoracida and Cirripedia each as monophyletic. The better resolved and highly supported DNA maximum likelihood and morphological-DNA Bayesian analysis trees depicted the main phylogenetic relationships within the Thecostraca as (Facetotecta, (Ascothoracida, (Acrothoracica, (Rhizocephala, Thoracica)))). Conclusion Our analyses indicate a convergent evolution of the very similar and highly reduced slug-shaped stages found during metamorphosis of both the Rhizocephala and the Facetotecta. This provides a remarkable case of convergent evolution and implies that the advanced endoparasitic mode of life known from the Rhizocephala and strongly indicated for the Facetotecta had no common origin. Future analyses are needed to determine whether the most recent common ancestor of the Thecostraca was free-living or some primitive form of ectoparasite. PMID:19374762

Activation of QA devices and phantom materials under clinical scanning proton beams—a gamma spectrometry study

NASA Astrophysics Data System (ADS)

Hanušová, Tereza; Johnová, Kamila; Navrátil, Matěj; Valenta, Jiří; Müller, Lutz

2018-06-01

Activation of detectors and phantoms used for commissioning and quality assurance of clinical proton beams may lead to radiation protection issues. Good understanding of the activation nuclide vectors involved is necessary to assess radiation risk for the personnel working with these devices on a daily basis or to fulfill legal requirements regarding transport of radioactive material and its release to the public. 11 devices and material samples were irradiated with a 220 MeV proton pencil beam (PBS, Proton Therapy Center, Prague). This study focuses on devices manufactured by IBA Dosimetry GmbH: MatriXX PT, PPC05, Stingray, Zebra, Lynx, a Blue Phantom rail and samples of RW3, PMMA, titanium, copper and carbon fibre plastic. Monitor units (MU) were monitored during delivery. Gamma spectrometry was then performed for each item using a HPGe detector, with a focus on longer lived gamma emitting radionuclides. Activities were quantified for all found isotopes and compared to relevant legal limits for exemption and clearance of radioactive objects. Activation was found to be significant after long irradiation sessions, as done during commissioning of a proton therapy room. Some of the investigated devices may also cumulate activity in time, depending on the scenario of periodic irradiation in routine clinical practice. However, the levels of activity and resulting beta/gamma doses are more comparable to internationally recommended concentration limits for exemption than to dose limits for radiation workers. Results of this study will help to determine nuclide inventories required by some legal authorities for radiation protection purposes.

Activation of QA devices and phantom materials under clinical scanning proton beams-a gamma spectrometry study.

PubMed

Hanušová, Tereza; Johnová, Kamila; Navrátil, Matěj; Valenta, Jiří; Müller, Lutz

2018-06-07

Activation of detectors and phantoms used for commissioning and quality assurance of clinical proton beams may lead to radiation protection issues. Good understanding of the activation nuclide vectors involved is necessary to assess radiation risk for the personnel working with these devices on a daily basis or to fulfill legal requirements regarding transport of radioactive material and its release to the public. 11 devices and material samples were irradiated with a 220 MeV proton pencil beam (PBS, Proton Therapy Center, Prague). This study focuses on devices manufactured by IBA Dosimetry GmbH: MatriXX PT, PPC05, Stingray, Zebra, Lynx, a Blue Phantom rail and samples of RW3, PMMA, titanium, copper and carbon fibre plastic. Monitor units (MU) were monitored during delivery. Gamma spectrometry was then performed for each item using a HPGe detector, with a focus on longer lived gamma emitting radionuclides. Activities were quantified for all found isotopes and compared to relevant legal limits for exemption and clearance of radioactive objects. Activation was found to be significant after long irradiation sessions, as done during commissioning of a proton therapy room. Some of the investigated devices may also cumulate activity in time, depending on the scenario of periodic irradiation in routine clinical practice. However, the levels of activity and resulting beta/gamma doses are more comparable to internationally recommended concentration limits for exemption than to dose limits for radiation workers. Results of this study will help to determine nuclide inventories required by some legal authorities for radiation protection purposes.

Creation of the SAQ-COPD Questionnaire to Determine Physical Activity in COPD Patients in Clinical Practice.

PubMed

Soler-Cataluña, Juan José; Puente Maestu, Luis; Román-Rodríguez, Miguel; Esteban, Cristóbal; Gea, Joaquín; Bernabeu Mora, Roberto; Pleguezuelos Cobo, Eulogio; Ancochea, Julio; Monteagudo Ruiz, Gema; Garcia Rio, Francisco

2018-03-13

Physical activity (PA) is a significant clinical dimension in COPD, but no useful tools are available to determine this variable in routine clinical practice. To create a simple, easy-to-use, specific questionnaire to detect PA deficits. A multidisciplinary panel of COPD experts was formed to review PA, its determinants, and measuring methods. The methodology for selecting specific dimensions and items was agreed in rounds, and the aspects to be included in the preliminary version were determined. The questionnaire structure was defined according to applicability of these aspects in clinical practice. Agreements were reached by consensus of the members. A total of 148 items were reviewed, of which only 3 were directly selected. It was decided that the questionnaire should evaluate the intensity (low, moderate, or intense), amount, and frequency of PA, and inactivity or sedentary lifestyles. It also gathers information on the profile of inactive patients, and includes a measure of impact, defined as the patient's perception of their expectations regarding activity, their personal experience, characteristics of their environment, and their personality. The questionnaire is divided into 2blocks, one aimed at quantifying PA, and the other at collecting data for defining the profile and impact in patients with low PA only. The SAQ-COPD is a simple, short, specific questionnaire, designed to evaluate PA in COPD patients in clinical practice. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Critical factors influencing physicians' intention to use computerized clinical practice guidelines: an integrative model of activity theory and the technology acceptance model.

PubMed

Hsiao, Ju-Ling; Chen, Rai-Fu

2016-01-16

With the widespread use of information communication technologies, computerized clinical practice guidelines are developed and considered as effective decision supporting tools in assisting the processes of clinical activities. However, the development of computerized clinical practice guidelines in Taiwan is still at the early stage and acceptance level among major users (physicians) of computerized clinical practice guidelines is not satisfactory. This study aims to investigate critical factors influencing physicians' intention to computerized clinical practice guideline use through an integrative model of activity theory and the technology acceptance model. The survey methodology was employed to collect data from physicians of the investigated hospitals that have implemented computerized clinical practice guidelines. A total of 505 questionnaires were sent out, with 238 completed copies returned, indicating a valid response rate of 47.1 %. The collected data was then analyzed by structural equation modeling technique. The results showed that attitudes toward using computerized clinical practice guidelines (γ = 0.451, p < 0.001), organizational support (γ = 0.285, p < 0.001), perceived usefulness of computerized clinical practice guidelines (γ = 0.219, p < 0.05), and social influence (γ = 0.213, p < 0.05) were critical factors influencing physicians' intention to use computerized clinical practice guidelines, and these factors can explain 68.6 % of the variance in intention to use computerized clinical practice guidelines. This study confirmed that some subject (human) factors, environment (organization) factors, tool (technology) factors mentioned in the activity theory should be carefully considered when introducing computerized clinical practice guidelines. Managers should pay much attention on those identified factors and provide adequate resources and incentives to help the promotion and use of computerized clinical

Clinical study of student learning using mastery style versus immediate feedback online activities

NASA Astrophysics Data System (ADS)

Gladding, Gary; Gutmann, Brianne; Schroeder, Noah; Stelzer, Timothy

2015-06-01

This paper is part of a series of studies to improve the efficacy of online physics homework activities by integrating narrated animated solutions with mastery inspired exercises. In a clinical study using first- and second-year university students, the mastery group attempted question sets in four levels, with animated solutions between each attempt, until mastery was achieved on each level. This combined elements of formative assessment, the worked example effect, and mastery learning. The homework group attempted questions with immediate feedback and unlimited tries. The two groups took a similar amount of time to complete the activity. The mastery group significantly outperformed the homework group on a free response post-test that required students to show their work in solving near and far transfer problems.

Student's perceptions of effective clinical teaching revisited.

PubMed

Kelly, Claudette

2007-11-01

Despite a wealth of research on clinical teaching, the criteria for determining what constitutes effective clinical teaching remain poorly defined [Cholowski, K., 2002. Nursing students' and clinical educators' perceptions of characteristics of effective clinical educators in an Australian university school of nursing. Journal of Advanced Nursing 39 (5), 412-420]. This paper reports on two studies exploring second and third year nursing student's perceptions of effective clinical teaching over 14 years (1989-2003). The aim of the inquiry was to compare student's perceptions in diploma and baccalaureate programs within existing clinical contexts. This research used a generative approach to elicit learner's views of what teacher characteristics and contextual influences impact them in clinical settings. A convenience sample of 30 students at the end of second and third years volunteered to be interviewed in-depth for each study. The first study was conducted in a diploma program, whereas in the second study all but a few students were elected to complete a four year baccalaureate nursing degree. Findings from both studies are remarkably consistent. Students in both studies rated teacher knowledge as most important followed by feedback and communication skills. Teacher knowledge appeared critical in four areas: as it pertains to the clinical setting, the curriculum, the learner and teaching/learning theory. How well students perceived that they were accepted by staff, student-teacher ratios and peer support also appeared to impact student's views of effective clinical teaching. This research has implications for employment and evaluation practices for teachers in applied fields such as nursing. The study raises questions about the recent trend toward temporary employment of clinical teachers and in the separation of academic and clinical roles of nurse educators.

A remarkable adsorbent for removal of contaminants of emerging concern from water: Porous carbon derived from metal azolate framework-6.

PubMed

Bhadra, Biswa Nath; Jhung, Sung Hwa

2017-10-15

A series of metal-azolate frameworks or MAFs-MAF-4, -5, and -6-were synthesized and pyrolyzed to prepare porous carbons derived from MAFs (CDM-4, -5, -6, respectively). Not only the obtained carbons but also MAFs were characterized and applied for the adsorption of organic contaminants of emerging concern (CECs, including pharmaceuticals and personal care products) such as salicylic acid, clofibric acid, diclofenac sodium, bisphenol-A, and oxybenzone (OXB) from water. CDM-6 was found to be the most remarkable adsorbent among the tested ones (including activated carbon) for all the adsorbates. OXB was taken as a representative adsorbate for detailed adsorption studies as well as understanding the adsorption mechanism. H-bonding (H-acceptor: CDM; H-donor: CECs) was suggested as the principal mechanism for the adsorption of tested adsorbates. Finally, CDMs, especially CDM-6, were suggested as highly efficient and easily recyclable adsorbents for water purification. Copyright © 2017 Elsevier B.V. All rights reserved.

Remarkable Effect of Sodium Alginate Aqueous Binder on Anatase TiO2 as High-Performance Anode in Sodium Ion Batteries.

PubMed

Ling, Liming; Bai, Ying; Wang, Zhaohua; Ni, Qiao; Chen, Guanghai; Zhou, Zhiming; Wu, Chuan

2018-02-14

Sodium alginate (SA) is investigated as the aqueous binder to fabricate high-performance, low-cost, environmentally friendly, and durable TiO 2 anodes in sodium-ion batteries (SIBs) for the first time. Compared to the conventional polyvinylidene difluoride (PVDF) binder, electrodes using SA as the binder exhibit significant promotion of electrochemical performances. The initial Coulombic efficiency is as high as 62% at 0.1 C. A remarkable capacity of 180 mAh g -1 is achieved with no decay after 500 cycles at 1 C. Even at 10 C (3.4 A g -1 ), it remains 82 mAh g -1 after 3600 cycles with approximate 100% Coulombic efficiency. TiO 2 electrodes with SA binder display less electrolyte decomposition, fewer side reactions, high electrochemistry reaction activity, effective suppression of polarization, and good electrode morphology, which is ascribed to the rich carboxylic groups, high Young's modulus, and good electrochemical stability of SA binder.

Solar activity and the weather

NASA Technical Reports Server (NTRS)

Wilcox, J. M.

1975-01-01

The attempts during the past century to establish a connection between solar activity and the weather are discussed; some critical remarks about the quality of much of the literature in this field are given. Several recent investigations are summarized. Use of the solar/interplanetary magnetic sector structure in future investigations is suggested to add an element of cohesiveness and interaction to these investigations.

Road map for the clinical application of the basophil activation test in food allergy.

PubMed

Santos, A F; Shreffler, W G

2017-09-01

The diagnosis of IgE-mediated food allergy based solely on the clinical history and the documentation of specific IgE to whole allergen extract or single allergens is often ambiguous, requiring oral food challenges (OFCs), with the attendant risk and inconvenience to the patient, to confirm the diagnosis of food allergy. This is a considerable proportion of patients assessed in allergy clinics. The basophil activation test (BAT) has emerged as having superior specificity and comparable sensitivity to diagnose food allergy, when compared with skin prick test and specific IgE. BAT, therefore, may reduce the number of OFC required for accurate diagnosis, particularly positive OFC. BAT can also be used to monitor resolution of food allergy and the clinical response to immunomodulatory treatments. Given the practicalities involved in the performance of BAT, we propose that it can be applied for selected cases where the history, skin prick test and/or specific IgE are not definitive for the diagnosis of food allergy. In the cases that the BAT is positive, food allergy is sufficiently confirmed without OFC; in the cases that BAT is negative or the patient has non-responder basophils, OFC may still be indicated. However, broad clinical application of BAT demands further standardization of the laboratory procedure and of the flow cytometry data analyses, as well as clinical validation of BAT as a diagnostic test for multiple target allergens and confirmation of its feasibility and cost-effectiveness in multiple settings. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Rapid growth rate results in remarkably hardened breast in broilers during the middle stage of rearing: A biochemical and histopathological study

PubMed Central

Iwasaki, Tomohito; Yamada, Michi; Yoshida, Takashi

2018-01-01

The high incidence of meat of impaired quality poses a serious problem in the poultry industry. In recent years, the incidence of the pectoralis major muscle that appeared pale colored, remarkably hardened, and exudative, called “wooden breast” or “woody breast” has increased in slaughter houses. In the present study, 19-day-old Ross 308 broiler chickens affected (n = 10) and unaffected (n = 10) with remarkably hardened breast were selected from a commercial broiler farm, and reared to 55 days of age under a controlled environment. Among the affected birds, 5 of 10 birds appeared exhausted with markedly suppressed weight gain and 4 of 10 birds died during the rearing period. In contrast, all unaffected birds survived and most gained weight. Four of 10 unaffected birds lost the ability of back-to-back wing contact by the late stage of rearing. The biochemical analysis of blood plasma samples of 20-day-old birds revealed that creatine kinase and L-aspartate aminotransferase values in most affected birds were higher than those in unaffected birds; however, these values in unaffected birds increased rapidly with lost wing contactability and increasing age. Postmortem examinations revealed that the mean diameter of myofibers in affected birds was smaller than that in unaffected birds. Moreover, symptoms of degenerative and regenerative muscles were observed in most birds in both groups. Among them, a decrease in, or defect of, the characteristic polygonal shape of myofibers was the most common change within the pectoralis major muscles in both groups. The present study demonstrated that broilers affected with remarkably hardened breast during the middle stage of rearing would have suppressed physical status and weight gain, or would die. It was suggested that rapid growth in broilers might be a cause of remarkably hardened breast. PMID:29474396

Rapid growth rate results in remarkably hardened breast in broilers during the middle stage of rearing: A biochemical and histopathological study.

PubMed

Kawasaki, Takeshi; Iwasaki, Tomohito; Yamada, Michi; Yoshida, Takashi; Watanabe, Takafumi

2018-01-01

The high incidence of meat of impaired quality poses a serious problem in the poultry industry. In recent years, the incidence of the pectoralis major muscle that appeared pale colored, remarkably hardened, and exudative, called "wooden breast" or "woody breast" has increased in slaughter houses. In the present study, 19-day-old Ross 308 broiler chickens affected (n = 10) and unaffected (n = 10) with remarkably hardened breast were selected from a commercial broiler farm, and reared to 55 days of age under a controlled environment. Among the affected birds, 5 of 10 birds appeared exhausted with markedly suppressed weight gain and 4 of 10 birds died during the rearing period. In contrast, all unaffected birds survived and most gained weight. Four of 10 unaffected birds lost the ability of back-to-back wing contact by the late stage of rearing. The biochemical analysis of blood plasma samples of 20-day-old birds revealed that creatine kinase and L-aspartate aminotransferase values in most affected birds were higher than those in unaffected birds; however, these values in unaffected birds increased rapidly with lost wing contactability and increasing age. Postmortem examinations revealed that the mean diameter of myofibers in affected birds was smaller than that in unaffected birds. Moreover, symptoms of degenerative and regenerative muscles were observed in most birds in both groups. Among them, a decrease in, or defect of, the characteristic polygonal shape of myofibers was the most common change within the pectoralis major muscles in both groups. The present study demonstrated that broilers affected with remarkably hardened breast during the middle stage of rearing would have suppressed physical status and weight gain, or would die. It was suggested that rapid growth in broilers might be a cause of remarkably hardened breast.

Effects of probiotic supplementation over 5 months on routine haematology and clinical chemistry measures in healthy active adults.

PubMed

Cox, A J; West, N P; Horn, P L; Lehtinen, M J; Koerbin, G; Pyne, D B; Lahtinen, S J; Fricker, P A; Cripps, A W

2014-11-01

Use of probiotic-containing foods and probiotic supplements is increasing; however, few studies document safety and tolerability in conjunction with defined clinical end points. This paper reports the effects of 150 days of supplementation with either a single- (Bifidobacterium animalis subsp. lactis Bl-04) or a double-strain (Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bi-07) probiotic on routine haematology and clinical chemistry measures in healthy active adults. Pre- to post-intervention changes in laboratory measures were determined and compared between supplement and placebo groups. Overall there were few differences in routine haematology and clinical chemistry measures between supplement and placebo groups post-intervention. Exceptions included plasma calcium (P=0.03) and urea (P=0.015); however, observed changes were small and within assay-specific laboratory reference ranges. These data provide evidence supporting the use of these probiotic supplements over a period of 5 months in healthy active adults without obvious safety or tolerability issues.

Delafloxacin, a non-zwitterionic fluoroquinolone in Phase III of clinical development: evaluation of its pharmacology, pharmacokinetics, pharmacodynamics and clinical efficacy.

PubMed

Van Bambeke, Françoise

2015-01-01

Delafloxacin is a fluoroquinolone lacking a basic substituent in position 7. It shows MICs remarkably low against Gram-positive organisms and anaerobes and similar to those of ciprofloxacin against Gram-negative bacteria. It remains active against most fluoroquinolone-resistant strains, except enterococci. Its potency is further increased in acidic environments (found in many infection sites). Delafloxacin is active on staphylococci growing intracellularly or in biofilms. It is currently evaluated as an intravenous and intravenous/oral stepdown therapy in Phase III trials for the treatment of complicated skin/skin structure infections. It was also granted as Qualified Infectious Disease Product for the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, due to its high activity on pneumococci and atypical pathogens.

The Kadota Fund International Forum 2004-Clinical group consensus*

PubMed Central

van der Zee, J.; Vujaskovic, Z.; Kondo, M.; Sugahara, T.

2009-01-01

The results from experimental studies indicate that hyperthermia is both an effective complementary treatment to, and a strong sensitiser of, radiotherapy and many cytotoxic drugs. Since the first international hyperthermia conference in 1975, Washington DC, techniques to increase tumour temperature have been developed and tested clinically. Hyperthermia can be applied by several methods: local hyperthermia by external or internal energy sources, perfusion hyperthermia of organs, limbs, or body cavities, and whole body hyperthermia. The clinical value of hyperthermia in combination with other treatment modalities has been shown by randomised trials. Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck, breast, brain, bladder, cervix, rectum, lung, oesophagus, for melanoma and sarcoma. The addition of hyperthermia resulted in remarkably higher (complete) response rates, accompanied by improved local tumour control rates, better palliative effects, and/or better overall survival rates. Toxicity from hyperthermia cannot always be avoided, but is usually of limited clinical relevance. In spite of these good clinical results, hyperthermia has received little attention. Problems with acceptance concern the limited availability of equipment, the lack of awareness concerning clinical results, and the lack of financial resources. In this paper the most relevant literature describing the clinical effects of hyperthermia is reviewed and discussed, and means to overcome the lack of awareness and use of this modality is described. PMID:18283588

Hybrid molecule from O2-(2,4-dinitrophenyl)diazeniumdiolate and oleanolic acid: a glutathione S-transferase π-activated nitric oxide prodrug with selective anti-human hepatocellular carcinoma activity and improved stability.

PubMed

Fu, Junjie; Liu, Ling; Huang, Zhangjian; Lai, Yisheng; Ji, Hui; Peng, Sixun; Tian, Jide; Zhang, Yihua

2013-06-13

A series of hybrids from O(2)-(2,4-dinitrophenyl)diazeniumdiolate and oleanolic acid (OA) were designed, synthesized, and biologically evaluated as novel nitric oxide (NO)-releasing prodrugs that could be activated by glutathione S-transferase π (GSTπ) overexpressed in a number of cancer cells. It was discovered that the most active compound, 21, released high levels of NO selectively in HCC cells but not in the normal cells and exhibited potent antiproliferative activity in vitro as well as remarkable tumor-retarding effects in vivo. Compared with the reported GSTπ-activated prodrugs JS-K and PABA/NO, 21 exhibited remarkably improved stability in the absence of GSTπ. Importantly, the decomposition of 21 occurred in the presence of GSTπ and was much more effective than in glutathione S-transferase α. Additionally, 21 induced apoptosis in HepG2 cells by arresting the cell cycle at the G2/M phase, activating both the mitochondrion-mediated pathway and the MAPK pathway and enhancing the intracellular production of ROS.

Clinical Trial of Tailored Activity and Eating Newsletters with Older Rural Women

PubMed Central

Walker, Susan Noble; Pullen, Carol H.; Boeckner, Linda; Hageman, Patricia A.; Hertzog, Melody; Oberdorfer, Maureen K.; Rutledge, Matthew J.

2009-01-01

Background Unhealthy diet and lack of physical activity increase rural midlife and older women’s risk for chronic diseases and premature death, and they are behind urban residents in meeting Healthy People 2010 objectives. Objectives To compare a tailored intervention based on the Health Promotion Model (HPM) and a generic intervention to increase physical activity and healthy eating among rural women. Methods In a randomized by site community-based controlled clinical trial, Wellness for Women, 225 women aged 50 to 69 years were recruited in two similar rural areas. Over 12 months, women received by mail either 18 generic newsletters or 18 newsletters computer-tailored on HPM behavior-specific cognitions (benefits, barriers, self-efficacy, and interpersonal support), activity, and eating. Outcomes at 6 and 12 months included behavioral markers and biomarkers of physical activity and eating. Data were analyzed by repeated measures ANOVA and χ2 tests (α < .05). Results Both groups significantly increased stretching and strengthening exercise and fruit and vegetable servings and decreased % calories from fat, while only the tailored group increased ≥ moderate intensity activity and decreased % calories from saturated fat from baseline to 6 months. Both groups increased stretching and strengthening exercise, while only the tailored group increased ≥ moderate activity and fruit and vegetable servings and decreased % calories from fat from baseline to 12 months. Both groups had several changes in biomarkers over the study. A higher proportion of women receiving tailored newsletters met Healthy People 2010 criteria for ≥ moderate activity, fruit and vegetable servings, and % calories from fat at 12 months. Discussion Mailed computer-tailored and generic print newsletters facilitated the adoption of change in both activity and eating over 6 months. Tailored newsletters were more efficacious in facilitating change over 12 months. PMID:19289928

Evaluation of biofeedback seat insert for improving active sitting posture in children with cerebral palsy. A clinical report.

PubMed

Bertoti, D B; Gross, A L

1988-07-01

Biofeedback devices have been used successfully to improve head control and symmetrical standing in children with cerebral palsy. This clinical report describes a biofeedback seat insert developed to improve erect sitting posture in children with cerebral palsy who have inadequate trunk control. The seat insert is easily placed against the back of any seating device. A momentary-contact pressure switch on the seat insert is activated when the child exerts pressure on it by extending his trunk. The pressure switch then activates a videocassette recorder or can be adapted to activate a television or radio. Five children with spastic cerebral palsy participated in this evaluation of the biofeedback seat insert. The results of this evaluation show that the children used the biofeedback seat insert effectively to actively improve their sitting posture by voluntarily extending their trunk against the pressure switch. The biofeedback seat insert offers physical therapists a valuable therapeutic training tool to encourage carry-over of improved sitting posture away from the clinical setting for children with cerebral palsy.

Introduction to Metagenomics at DOE JGI (Opening Remarks for the Metagenomics Informatics Challenges Workshop: 10K Genomes at a Time)

ScienceCinema

Kyrpides, Nikos [DOE JGI

2018-05-30

After a quick introduction by DOE JGI Director Eddy Rubin, DOE JGI's Nikos Kyrpides delivers the opening remarks at the Metagenomics Informatics Challenges Workshop held at the DOE JGI on October 12-13, 2011.

Antibacterial activity of fresh pomegranate juice against clinical strains of Staphylococcus epidermidis

PubMed Central

Betanzos-Cabrera, Gabriel; Montes-Rubio, Perla Y.; Fabela-Illescas, Héctor E.; Belefant-Miller, Helen; Cancino-Diaz, Juan C.

2015-01-01

Background Polyphenols have received a great deal of attention due to their biological functions. Pomegranate (Punica granatum L.) is a polyphenol-rich fruit. In the past decade, studies testing the antimicrobial activity of pomegranates almost exclusively used solvent extracts instead of fresh pomegranate juice (FPJ). The use of FPJ instead of solvent extracts would reduce toxicity issues while increasing patient acceptance. We established a model to test FPJ as a natural antimicrobial agent. Objective To evaluate the antimicrobial activity of FPJ on clinical isolates of multidrug-resistant Staphylococcus epidermidis strains. Design Sixty strains of S. epidermidis isolated from ocular infections were grown in the presence of FPJ, and minimum inhibitory concentration (MIC) was determined by broth and agar dilution methods. Results FPJ at 20% had a MIC equal to 100% (MIC100%) on all 60 strains tested. This inhibition of FPJ was confirmed by the growth kinetics of a multidrug-resistant strain exposed to different concentrations of FPJ. Additionally, the antimicrobial activity of FPJ was compared against commercial beverages containing pomegranate: Ocean Spray® had a MIC100% at 20%, followed by Del Valle® with a MIC15% at 20% concentration only. The beverages Jumex® and Sonrisa® did not have any antimicrobial activity. FPJ had the highest polyphenol content and antioxidant capacity. Conclusions Overall, FPJ had antimicrobial activity, which might be attributed to its high polyphenol content and antioxidant capacity. PMID:25999265

Antifungal activity of oligochitosans (short chain chitosans) against some Candida species and clinical isolates of Candida albicans: molecular weight-activity relationship.

PubMed

Kulikov, Sergey N; Lisovskaya, Svetlana A; Zelenikhin, Pavel V; Bezrodnykh, Evgeniya A; Shakirova, Diana R; Blagodatskikh, Inesa V; Tikhonov, Vladimir E

2014-03-03

A series of oligochitosans (short chain chitosans) prepared by acidic hydrolysis of chitosan and characterized by their molecular weight, polydispersity and degree of deacetylation were used to determine their anticandidal activities. This study has demonstrated that oligochitosans show a high fungistatic activity (MIC 8-512 μg/ml) against Candida species and clinical isolates of Candida albicans, which are resistant to a series of classic antibiotics. Flow cytometry analysis showed that oligochitosan possessed a high fungicidal activity as well. For the first time it was shown that even sub-MIC oligochitosan concentration suppressed the formation of C. albicans hyphal structures, cause severe cell wall alterations, and altered internal cell structure. These results indicate that oligochitosan should be considered as a possible alternative/additive to known anti-yeast agents in pharmaceutical compositions. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pancreas cancer meets the thunder god.

PubMed

Hingorani, Sunil R; Potter, John D

2012-10-17

A new formulation of a natural product shows remarkable activity against pancreatic ductal adenocarcinoma across a number of preclinical model systems. These findings set the stage for a clinical trial.

Spectroscopic and asteroseismic analysis of the remarkable main-sequence A star KIC 11145123

NASA Astrophysics Data System (ADS)

Takada-Hidai, Masahide; Kurtz, Donald W.; Shibahashi, Hiromoto; Murphy, Simon J.; Takata, Masao; Saio, Hideyuki; Sekii, Takashi

2017-10-01

A spectroscopic analysis was carried out to clarify the properties of KIC 11145123 - the first main-sequence star with a directly measured core-to-surface rotation profile - based on spectra observed with the High Dispersion Spectrograph (HDS) of the Subaru telescope. The atmospheric parameters (Teff = 7600 K, log g = 4.2, ξ = 3.1 km s-1 and [Fe/H] = -0.71 dex), the radial and rotation velocities, and elemental abundances were obtained by analysing line strengths and fitting line profiles, which were calculated with a 1D LTE model atmosphere. The main properties of KIC 11145123 are: (1) a low [Fe/H] = -0.71 ± 0.11 dex and a high radial velocity of -135.4 ± 0.2 km s-1. These are remarkable among late-A stars. Our best asteroseismic models with this low [Fe/H] have slightly high helium abundance and low masses of 1.4 M⊙. All of these results strongly suggest that KIC 11145123 is a Population II blue straggler; (2) the projected rotation velocity confirms the asteroseismically predicted slow rotation of the star; (3) comparisons of abundance patterns between KIC 11145123 and Am, Ap, and blue stragglers show that KIC 11145123 is neither an Am star nor an Ap star, but has abundances consistent with a blue straggler. We conclude that the remarkably long 100-d rotation period of this star is a consequence of it being a blue straggler, but both pathways for the formation of blue stragglers - merger and mass loss in a binary system - pose difficulties for our understanding of the exceedingly slow rotation. In particular, we show that there is no evidence of any secondary companion star, and we put stringent limits on the possible mass of any such purported companion through the phase modulation technique.

Hospital clinical pharmacy services in Vietnam.

PubMed

Trinh, Hieu T; Nguyen, Huong T L; Pham, Van T T; Ba, Hai L; Dong, Phuong T X; Cao, Thao T B; Nguyen, Hanh T H; Brien, Jo-Anne

2018-04-07

Background Clinical pharmacy is key to the quality use of medicines. While there are different approaches in different countries, international perspectives may inform health service development. The Vietnamese Ministry of Health introduced a legal regulation of clinical pharmacy services in December 2012. Objective To describe the services, and to explore reported barriers and facilitators in implementing clinical pharmacy activities in Vietnamese hospitals after the introduction of Vietnamese Ministry of Health legal regulation. Setting Thirty-nine hospitals in Hanoi, Vietnam, including 22 provincial and 17 district hospitals. Method A mixed methods study was utilized. An online questionnaire was sent to the hospitals. In-depth interviews were conducted with pairs of nominated pharmacists at ten of these hospitals. The questionnaire focused on four areas: facilities, workforce, policies and clinical pharmacy activities. Main outcome measure Proportion of clinical pharmacy activities in hospitals. Themes in clinical pharmacy practice. Results 34/39 (87%) hospitals had established clinical pharmacy teams. Most activities were non-patient-specific (87%) while the preliminary patient-specific clinical pharmacy services were available in only 8/39 hospitals (21%). The most common non-patient-specific activities were providing medicines information (97%), reporting adverse drug reactions (97%), monitoring medication usage (97%). The patient specific activities varied widely between hospitals and were ad hoc. The main challenges reported were: lack of workforce and qualified clinical pharmacists. Conclusion While most hospitals had hospital-based pharmacy activities, the direct patient care was limited. Training, education and an expanded work forces are needed to improve clinical pharmacy services.

The cost of resident scholarly activity and its effect on resident clinical experience.

PubMed

Schott, Nicholas J; Emerick, Trent D; Metro, David G; Sakai, Tetsuro

2013-11-01

Scholarly activity is an important aspect of the academic training of future anesthesiologists. However, residents' scholarly activity may reduce training caseloads and increase departmental costs. We conducted this study within a large academic anesthesiology residency program with data from the 4 graduating classes of 2009 through 2012. Scholarly activity included peer-reviewed manuscripts, case reports, poster presentations at conferences, book chapters, or any other publications. It was not distinguished whether a resident was the principal investigator or a coinvestigator on a project. The following data were collected on each resident: months spent on a resident research rotation, number of scholarly projects completed, number of research conferences attended, and Accreditation Council for Graduate Medical Education case entries. Comparison was made between residents electing a resident research rotation with those who did not for (1) scholarly projects, (2) research conference attendance, and (3) Accreditation Council for Graduate Medical Education case numbers. Cost to the department for extra clinical coverage during residents' time spent on research activities was calculated using an estimated average cost of $675 ± $176 (mean ± SD) per day with local certified registered nurse anesthetist pay scales. Sixty-eight residents were included in the analyses. Twenty-four residents (35.3%) completed resident research rotations with an average duration of 3.7 months. Residents who elected resident research rotations completed more scholarly projects (5 projects [4-6]: median [25%-75% interquartile range] vs 2 [0-3]; P < 0.0001), attended more research conferences (2 conferences [2-4] vs 1 [0-2]; P < 0.0001), but experienced fewer cases (980 cases [886-1333] vs 1182 [930-1420]; P ≤ 0.002) compared with those who did not elect resident research rotations. The estimated average cost to the department per resident who elected a resident research rotation was $13

Performance on a Clinical Quadriceps Activation Battery Is Related to a Laboratory Measure of Activation and Recovery After Total Knee Arthroplasty.

PubMed

Bade, Michael; Struessel, Tamara; Paxton, Roger; Winters, Joshua; Baym, Carol; Stevens-Lapsley, Jennifer

2018-01-01

To determine the relation between performance on a clinical quadriceps activation battery with (1) activation measured by doublet interpolation and (2) recovery of quadriceps strength and functional performance after total knee arthroplasty (TKA). Planned secondary analysis of a randomized controlled trial. University research laboratory. Patients (N=162; mean age, 63±7y; 89 women) undergoing TKA. Patients were classified as high (quadriceps activation battery ≥4/6) or low (quadriceps activation battery ≤3/6) based on performance on the quadriceps activation battery measured 4 days after TKA. Differences between groups in activation and recovery at 1, 2, 3, 6, and 12 months after TKA were compared using a repeated-measures maximum likelihood model. The low quadriceps activation battery group demonstrated poorer quadriceps activation via doublet interpolation (P=.01), greater quadriceps strength loss (P=.01), and greater functional performance decline (all P<.001) at 1 month after TKA compared with the high quadriceps activation battery group. Differences between low and high quadriceps activation battery groups on all measures did not persist at 3 and 12 months (all P>.05). Poor performance on the quadriceps activation battery early after TKA is related to poor quadriceps activation and poor recovery in the early postoperative period. Patients in the low quadriceps activation battery group took 3 months to recover to the same level as the high quadriceps activation battery group. The quadriceps activation battery may be useful in identifying individuals who need specific interventions to target activation deficits or different care pathways in the early postoperative period to speed recovery after TKA. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Clinical-grade quality platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelet concentrates promoted expansion of mesenchymal stromal cells.

PubMed

Borghese, C; Agostini, F; Durante, C; Colombatti, A; Mazzucato, M; Aldinucci, D

2016-08-01

The aim of our study was to test a platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelets as a source of growth factors for the expansion of mesenchymal stromal cells (MSCs). PRP-R/SRGF, obtained with a low-cost procedure, is characterized by a reduced variability of growth factor release. PRP-R/SRGF is a clinical-grade quality solution obtained from CaCl2 -activated platelets. Its activity was evaluated by measuring the proliferation, the phenotype, the differentiation potential and the immunosuppressive properties of MSCs derived from bone marrow (BM) and adipose tissue (AT). PRP-R/SRGF was more active than FBS to expand BM- and AT-derived MSCs. PRP-R/SRGF treatment did not affect the expression of typical MSCs surface markers, neither MSCs differentiation potential nor their capability to inhibit activated T-cell proliferation. The clinical-grade PRP-R/SRGF may be used in the clinical setting for the expansion of MSCs. © 2016 International Society of Blood Transfusion.

A systematic review of measurement of endoscopic disease activity and mucosal healing in Crohn's disease: recommendations for clinical trial design.

PubMed

Khanna, Reena; Bouguen, Guillaume; Feagan, Brian G; DʼHaens, Geert; Sandborn, William J; Dubcenco, Elena; Baker, K Adam; Levesque, Barrett G

2014-10-01

Crohn's disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials. A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized. The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohn's Disease (SES-CD) are indices with the most extensively described operating properties. Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.

Activating Patients for Sustained Chronic Disease Self-Management: Thinking Beyond Clinical Outcomes.

PubMed

Dye, Cheryl J; Williams, Joel E; Evatt, Janet H

2016-04-01

This article describes the impact of an 8-week community program implemented by trained volunteers on the hypertension self-management of 185 patients who were batch randomized to intervention or wait-list control groups. Compared with control group participants, a higher proportion of treatment group participants moved from the cognitive to behavioral stages of motivational readiness for being physically active (P < .001), practicing healthy eating habits (P = .001), handling stress well (P = .001), and living an overall healthy lifestyle (P = .003). They also demonstrated a greater average increase in perceived competence for self-management, F(1.134) = 4.957, P = .028, η2 = .036, and a greater increase in mean hypertension-related knowledge, F(1.160) = 16.571, P < .0005, η(2) = .094. Enduring lifestyle changes necessary for chronic disease self-management require that psychosocial determinants of health behavior are instilled, which is typically beyond standard medical practice. We recommend peer-led, community-based programs as a complement to clinical care and support the increasing health system interest in promoting population health beyond clinical walls. © The Author(s) 2016.

The relationship of transversus abdominis and lumbar multifidus activation and prognostic factors for clinical success with a stabilization exercise program: a cross-sectional study.

PubMed

Hebert, Jeffrey J; Koppenhaver, Shane L; Magel, John S; Fritz, Julie M

2010-01-01

Hebert JJ, Koppenhaver SL, Magel JS, Fritz JM. The relationship of transversus abdominis and lumbar multifidus activation and prognostic factors for clinical success with a stabilization exercise program: a cross-sectional study. To examine the relationship between prognostic factors for clinical success with a stabilization exercise program and lumbar multifidus (LM) and transversus abdominis (TrA) muscle activation assessed using rehabilitative ultrasound imaging (RUSI). Cross-sectional study. Outpatient physical therapy clinic. Volunteers with current low back pain (N=40). Not applicable. We examined the relationship between prognostic factors associated with clinical success with a stabilization exercise program (positive prone instability test, age <40y, aberrant movements, straight leg raise >91 degrees , presence of lumbar hypermobility) and degree of TrA and LM muscle activation assessed by RUSI. Significant univariate relationships were identified between LM muscle activation and the number of prognostic factors present (Pearson correlation coefficient [r] =-.558, P=.001), as well as the individual factors of a positive prone instability test (point biserial correlation coefficient [r(pbis)]=.376, P=.018) and segmental hypermobility (r(pbis)=.358, P=.025). The multivariate analyses indicated that after controlling for other variables, the addition of the variable "number of prognostic factors present" resulted in a significant increase in R(2) (P=.006). No significant univariate or multivariate relationships were observed between the prognostic factors and TrA muscle activation. Decreased LM muscle activation, but not TrA muscle activation, is associated with the presence of factors predictive of clinical success with a stabilization exercise program. Our findings provide researchers and clinicians with evidence regarding the construct validity of the prognostic factors examined in this study, as well as the potential clinical importance of the LM muscle

Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects.

PubMed

Li, Yannan; Ning, Jing; Wang, Yan; Wang, Chao; Sun, Chengpeng; Huo, Xiaokui; Yu, Zhenlong; Feng, Lei; Zhang, Baojing; Tian, Xiangge; Ma, Xiaochi

2018-05-09

The high risk of herb-drug interactions (HDIs) mediated by the herbal medicines and dietary supplements which containing abundant flavonoids had become more and more frequent in our daily life. In our study, the inhibition activities of 44 different structures of flavonoids toward human CYPs were systemically evaluated for the first time. According to our results, a remarkable structure-dependent inhibition behavior toward CYP3A4 was observed in vitro. Some flavonoids such as licoflavone (12) and irilone (30) exhibited the selective inhibition toward CYP3 A4 rather than other major human CYPs. To illustrate the interaction mechanism, the inhibition kinetics of various compounds was further performed. Sophoranone (1), apigenin (10), baicalein (11), 5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone (15), myricetin (23) and kushenol K (38) remarkably inhibited the CYP3 A4-catalyzed bufalin 5'-hydroxylation reaction, with K i values of 2.17 ± 0.29, 6.15 ± 0.39, 9.18 ± 3.40, 2.30 ± 0.36, 5.00 ± 2.77 and 1.35 ± 0.25 μM, respectively. Importantly, compounds 1, 11, 15, 23 and 38 could significantly inhibit the metabolism of some clinical drugs in vitro, and these drug-drug interactions (DDIs) of myricetin (23) or kushenol K (38) with clinical drug diazepam were further verified in human primary hepatocytes, respectively. Finally, a quantitative structure-activity relationship (QSAR) of flavonoids with their inhibitory effects toward CYP3 A4 was established using computational methods. Our findings illustrated the high risk of herb-drug interactions (HDIs) caused by flavonoids and revealed the vital structures requirement of natural flavonoids for the HDIs with clinical drugs eliminated by CYP3 A4. Our research provided the useful guidance to safely and rationally use herbal medicines and dietary supplements containing rich natural flavonoids components. Copyright © 2018 Elsevier B.V. All rights reserved.

Improving physical activity in arthritis clinical trial (IMPAACT): study design, rationale, recruitment, and baseline data.

PubMed

Chang, Rowland W; Semanik, Pamela A; Lee, Jungwha; Feinglass, Joseph; Ehrlich-Jones, Linda; Dunlop, Dorothy D

2014-11-01

Over 21 million Americans report an arthritis-attributable activity limitation. Knee osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common/disabling forms of arthritis. Various forms of physical activity (PA) can improve a variety of health outcomes and reduce health care costs, but the proportion of the US population engaging in the recommended amount of PA is low and even lower among those with arthritis. The Improving Motivation for Physical Activity in Arthritis Clinical Trial (IMPAACT) is a randomized clinical trial that studied the effects of a lifestyle PA promotion intervention on pain and physical function outcomes. The IMPAACT intervention was based on a chronic care/disease management model in which allied health professionals promote patient self-management activities outside of traditional physician office encounters. The program was a motivational interviewing-based, individualized counseling and referral intervention, directed by a comprehensive assessment of individual patient barriers and strengths related to PA performance. The specific aims of IMPAACT were to test the efficacy of the IMPAACT intervention for persons with arthritis (N=185 persons with RA and 155 persons with knee OA) in improving arthritis-specific and generic self-reported pain and Physical Function outcomes, observed measures of function, and objectively measured and self-reported PA levels. Details of the stratified-randomized study design, subject recruitment, and data collection are described. The results from IMPAACT will generate empiric evidence pertaining to increasing PA levels in persons with arthritis and result in widely applicable strategies for health behavior change. Copyright © 2014 Elsevier Inc. All rights reserved.

Clinical spectrum of anorexia nervosa in children.

PubMed

Atkins, D M; Silber, T J

1993-08-01

A retrospective review of 21 patients ages 12 years and younger (age of onset range 7 to 12 years) with anorexia nervosa showed diagnostic delay in the youngest ones, high incidence of family psychiatric history, a remarkable severity of illness, and positive response to intensive treatment. Additional findings included significant comorbidity, a distinct subgroup with personality disorder and another with features of the "vulnerable child syndrome." This broad clinical spectrum of anorexia nervosa in children may explain the great variability in outcome. The development of anorexia nervosa in children relates to a complex combination of etiological and trigger factors. Precipitants identified in this study were physical maturation, entry into junior high, loss, or some combination thereof.

Spectrum and chemical composition of the remarkable planetary nebula NGC 6537

PubMed Central

Feibelman, Walter; Aller, Lawrence H.; Keyes, C. D.; Czyzak, S. J.

1985-01-01

Observations with the image tube scanner at the Shane 3-m telescope are combined with data obtained with the International Ultraviolet Explorer to assess the spectrum of the remarkable high-excitation planetary nebula NGC 6537. We have analyzed the spectrum of this nitrogen-rich object with the aid of the theoretical nebular models. The models permit one to estimate the fraction of unobservable ions of abundant elements. On the scale log N(H) = 12, the logarithmic abundance values for He, C, N, and O are as follows: [Table: see text] The abundances of Ne S, Cl, and Ar appear to be essentially solar to within a factor of 2. Our interpretation is that the progenitor of NGC 6537 had a chemical composition not differing greatly from that of the Sun. In the course of its prenebular evolution, C and probably O were converted to N and much H was converted to helium. PMID:16593550

Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

PubMed

Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

2015-08-01

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high. © The Author(s) 2015.

Clinical Activity of Alectinib in Advanced RET-Rearranged Non-Small Cell Lung Cancer.

PubMed

Lin, Jessica J; Kennedy, Elizabeth; Sequist, Lecia V; Brastianos, Priscilla K; Goodwin, Kelly E; Stevens, Sara; Wanat, Alexandra C; Stober, Lisa L; Digumarthy, Subba R; Engelman, Jeffrey A; Shaw, Alice T; Gainor, Justin F

2016-11-01

Chromosomal rearrangements involving rearranged during transfection gene (RET) occur in 1% to 2% of NSCLCs and may confer sensitivity to rearranged during transfection (RET) inhibitors. Alectinib is an anaplastic lymphoma kinase tyrosine kinase inhibitor (TKI) that also has anti-RET activity in vitro. The clinical activity of alectinib in patients with RET-rearranged NSCLC has not yet been reported. We have described four patients with advanced RET-rearranged NSCLC who were treated with alectinib (600 mg twice daily [n = 3] or 900 mg twice daily [n = 1]) as part of single-patient compassionate use protocols or off-label use of the commercially available drug. Four patients with metastatic RET-rearranged NSCLC were identified. Three of the four had received prior RET TKIs, including cabozantinib and experimental RET inhibitors. In total, we observed two (50%) objective radiographic responses after treatment with alectinib (one confirmed and one unconfirmed), with durations of therapy of 6 months and more than 5 months (treatment ongoing), respectively. Notably, one of these two patients had his dose of alectinib escalated to 900 mg twice daily and had clinical improvement in central nervous system metastases. In addition, one patient (25%) experienced a best response of stable disease lasting approximately 6 weeks (the drug discontinued for toxicity). A fourth patient who was RET TKI-naive had primary progression while receiving alectinib. Alectinib demonstrated preliminary antitumor activity in patients with advanced RET-rearranged NSCLC, most of whom had received prior RET inhibitors. Larger prospective studies with longer follow-up are needed to assess the efficacy of alectinib in RET-rearranged NSCLC and other RET-driven malignancies. In parallel, development of more selective, potent RET TKIs is warranted. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

[Differences between clinical trials according to the German law on pharmaceuticals (Arzneimittelgesetz) and trials according to the German law on medical products (Medizinproduktegesetz)].

PubMed

Krummenauer, F

2003-02-01

Similar to the registration process for pharmaceutical agents, medical devices have to undergo standardized clinical evaluation before being marketed and used in routine therapy or diagnostics. However, conduction, submission, and reporting of such clinical evaluations to authorities has to follow the German law on medical products(Medizinproduktegesetz,MPG), which in some central aspects differs remarkably from the German law on pharmaceuticals (Arzneimittelgesetz,AMG). Relevant deviations of MPG requirements from those of the AMG are reviewed with particular emphasis on submission, conduction, and reporting of trials to the authorities in charge. Whereas AMG-based trials focus on the proof of efficacy of pharmaceutical agents, the MPG demands instead proof of functionality of the medical devices; the MPG therefore concentrates more on technically satisfactory results in the context of function and patient safety. The aim of MPG trials is thus CE marking instead of AMG-based registration. However, this focus on functionality implies that medical devices need not necessarily be tested in a clinical trial--in some settings evidence-based evaluation alone will be sufficient. The decision on the necessity of a clinical trial is based mainly on the risk profile and invasive character of the device at hand. The early consideration of differences between AMG and MPG concerning the role and conduction of clinical trials will remarkably increase the (CE) certification process's outcome quality and juridical validity.

Acetyl aspartic acid, a novel active ingredient, demonstrates potential to improve signs of skin ageing: from consumer need to clinical proof.

PubMed

Mavon, A

2015-10-01

The megatrend of population ageing is leading to a growing demand for "anti-ageing" treatments, especially to prevent or treat skin ageing. Facing an increasing offer, consumers are choosing more and more skin care products supported by a scientific rationale, active ingredients and clinical proof of efficacy. Considering consumer expectations, this research led to the discovery of acetyl aspartic acid (A-A-A), a novel active ingredient to improve sagging skin and loss of skin firmness. This supplement is featuring seven manuscripts aiming at presenting the research and investigations from consumer insights, discovery of A-A-A, its in vitro activity confirmation, safety assessment, formulation and its dermal absorption to the clinical proof of efficacy, investigated through two pilots' double bind randomized and placebo controlled studies on photo-aged skin. This extensive research enabled us to discover A-A-A, as an active ingredient with potential to repair sign of skin ageing and supported by clinical proof of efficacy. This active ingredient will be soon launched in a commercial innovative skin care range, delivering desirable anti-wrinkle and skin lifting benefits. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Activity of innate antimicrobial peptides and ivacaftor against clinical cystic fibrosis respiratory pathogens.

PubMed

Payne, Joanna E; Dubois, Alice V; Ingram, Rebecca J; Weldon, Sinead; Taggart, Clifford C; Elborn, J Stuart; Tunney, Michael M

2017-09-01

There is a clear need for new antimicrobials to improve current treatment of chronic lung infection in people with cystic fibrosis (CF). This study determined the activities of antimicrobial peptides (AMPs) and ivacaftor, a novel CF transmembrane conductance regulator potentiator, for CF treatment. Antimicrobial activities of AMPs [LL37, human β-defensins (HβD) 1-4 and SLPI] and ivacaftor against clinical respiratory isolates (Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus spp., Achromobacter spp. and Stenotrophomonas maltophilia) were determined using radial diffusion and time-kill assays, respectively. Synergy of LL37 and ivacaftor with tobramycin was determined by time-kill, with in vivo activity of ivacaftor and tobramycin compared using a murine infection model. LL37 and HβD3 were the most active AMPs tested, with MICs ranging from 3.2- ≥ 200 mg/L and 4.8- ≥ 200 mg/L, respectively, except for Achromobacter that was resistant. HβD1 and SLPI demonstrated no antimicrobial activity. LL37 demonstrated synergy with tobramycin against 4/5 S. aureus and 2/5 Streptococcus spp. isolates. Ivacaftor demonstrated bactericidal activity against Streptococcus spp. (mean log 10 decrease 3.31 CFU/mL) and bacteriostatic activity against S. aureus (mean log 10 change 0.13 CFU/mL), but no activity against other genera. Moreover, ivacaftor demonstrated synergy with tobramycin, with mean log 10 decreases of 5.72 CFU/mL and 5.53 CFU/mL at 24 h for S. aureus and Streptococcus spp., respectively. Ivacaftor demonstrated immunomodulatory but no antimicrobial activity in a P. aeruginosa in vivo murine infection model. Following further modulation to enhance activity, AMPs and ivacaftor offer real potential as therapeutics to augment antibiotic therapy of respiratory infection in CF. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

[Objectives, organization and activities of a nurse-led clinic for outpatient cardiology care].

PubMed

Radini, Donatella; Sola, Gioia; Zeriali, Nadia; Grande, Eliana; Humar, Franco; Tarantini, Luigi; Pulignano, Giovanni; Stellato, Kira; Barbati, Giulia; Di Lenarda, Andrea

2016-05-01

Cardiovascular diseases are the first cause of death worldwide. In the last decades, therapeutic advances have determined an increase in survival rates, with a subsequent rise in the number of elderly people suffering from chronic cardiovascular diseases and associated comorbidities requiring comprehensive, team-based multidisciplinary care. The aim of this study is to describe the organization, purposes and activities of a nurse-led cardiology clinic. Between November 1, 2009 and October 31, 2014, the nurse-led clinics located within our Cardiology Outpatient Center provided care to 2081 out of 26 057 patients (8%) with complex healthcare needs, high cardiovascular risk and/or specific therapeutic indications or needs for reassessment; 1875 of these patients received nurse-led interventions: 451 (21.7%) in Chronic Heart Disease (CHD) care; 402 (19.3%) in Heart Failure (HF) care; 1022 (49.1%) at the Oral Anticoagulant Therapy (OAT) care, while 206 patients (9.9%) underwent Nurse Triage. Nursing assessment includes a clinical multidimensional analysis, with identification of relevant health issues and planning of a nursing intervention (education, intensified monitoring, and support to therapy) shared with the cardiologist in a joint report. The clinical characteristics and the social care needs of the patients who received nurse-led care were extremely heterogeneous. Patients with heart failure were the oldest (79 years), most severe (58.2% hospitalized last year), with Charlson index ≥3% (82.8 %); 72.4% were taking ≥7 drugs daily. The majority of them had medium-to-low education levels and more frequently lived alone, with disabilities, inadequate self-monitoring, and self-care behaviors. Patients on anticoagulant therapy were younger (71 years), in 75.9% of cases with atrial fibrillation, most frequently assisted by a caregiver and without functional limitations. The patients of these two nurse-led clinics (HF and OAT) were those who came most frequently

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.

Dendritic cells for active immunotherapy: optimizing design and manufacture in order to develop commercially and clinically viable products.

PubMed

Nicolette, C A; Healey, D; Tcherepanova, I; Whelton, P; Monesmith, T; Coombs, L; Finke, L H; Whiteside, T; Miesowicz, F

2007-09-27

Dendritic cell (DC) active immunotherapy is potentially efficacious in a broad array of malignant disease settings. However, challenges remain in optimizing DC-based therapy for maximum clinical efficacy within manufacturing processes that permit quality control and scale-up of consistent products. In this review we discuss the critical issues that must be addressed in order to optimize DC-based product design and manufacture, and highlight the DC based platforms currently addressing these issues. Variables in DC-based product design include the type of antigenic payload used, DC maturation steps and activation processes, and functional assays. Issues to consider in development include: (a) minimizing the invasiveness of patient biological material collection; (b) minimizing handling and manipulations of tissue at the clinical site; (c) centralized product manufacturing and standardized processing and capacity for commercial-scale production; (d) rapid product release turnaround time; (e) the ability to manufacture sufficient product from limited starting material; and (f) standardized release criteria for DC phenotype and function. Improvements in the design and manufacture of DC products have resulted in a handful of promising leads currently in clinical development.

Directional selection in temporally replicated studies is remarkably consistent.

PubMed

Morrissey, Michael B; Hadfield, Jarrod D

2012-02-01

Temporal variation in selection is a fundamental determinant of evolutionary outcomes. A recent paper presented a synthetic analysis of temporal variation in selection in natural populations. The authors concluded that there is substantial variation in the strength and direction of selection over time, but acknowledged that sampling error would result in estimates of selection that were more variable than the true values. We reanalyze their dataset using techniques that account for the necessary effect of sampling error to inflate apparent levels of variation and show that directional selection is remarkably constant over time, both in magnitude and direction. Thus we cannot claim that the available data support the existence of substantial temporal heterogeneity in selection. Nonetheless, we conject that temporal variation in selection could be important, but that there are good reasons why it may not appear in the available data. These new analyses highlight the importance of applying techniques that estimate parameters of the distribution of selection, rather than parameters of the distribution of estimated selection (which will reflect both sampling error and "real" variation in selection); indeed, despite availability of methods for the former, focus on the latter has been common in synthetic reviews of the aspects of selection in nature, and can lead to serious misinterpretations. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

[Clinical and laboratory characteristics of chronic active Epstein-Barr virus infection in children].

PubMed

Mao, Jun-Qing; Yang, Shi-Long; Song, Hua; Zhao, Fen-Ying; Xu, Xiao-Jun; Gu, Min-Er; Tang, Yong-Min

2014-11-01

To study the clinical and laboratory characteristics of chronic active Epstein-Barr virus (EBV) infection (CAEBV) in children and to provide a basis for the diagnosis and treatment of CAEBV. The clinical data of 13 children with CAEBV, as well as 15 cases of acute EBV infection (AEBV) as controls, were analyzed, including clinical manifestations, EBV antibodies, EBV DNA, and peripheral blood lymphocyte subsets. Both groups of patients had infectious mononucleosis-like symptoms such as fever, hepatomegaly, splenomegaly, and lymphadenectasis, but CAEBV patients had a longer course of disease and continuous and recurrent symptoms. Compared with the AEBV group, the CAEBV group had a significantly higher EBV DNA load in peripheral blood (P<0.05), a significantly higher VCA-IgG titer (P<0.05), and significantly lower numbers of white blood cells, lymphocytes, B cells, total T cells, CD4+ T cells, and CD8+ T cells in peripheral blood (P<0.05). Among 13 CAEBV patients followed up, 8 cases died, 2 cases showed an improvement, 2 cases had a recurrence, and 1 case was lost to follow-up after being transferred to another hospital. All the AEBV patients were cured and had no recurrence during the one-year follow-up. The clinical manifestations of CAEBV vary in children. It is difficult to distinguish CAEBV from AEBV early. More attention should be paid to CAEBV because of its severe complications, poor prognosis, and high mortality. Measurement of EBV DNA load, VCA-IgG titer, and lymphocyte subsets in peripheral blood may be helpful in the diagnosis and differential diagnosis of CAEBV.

Carfilzomib demonstrates broad anti-tumor activity in pre-clinical non-small cell and small cell lung cancer models.

PubMed

Baker, Amanda F; Hanke, Neale T; Sands, Barbara J; Carbajal, Liliana; Anderl, Janet L; Garland, Linda L

2014-12-31

Carfilzomib (CFZ) is a proteasome inhibitor that selectively and irreversibly binds to its target and has been approved in the US for treatment of relapsed and refractory multiple myeloma. Phase 1B studies of CFZ reported signals of clinical activity in solid tumors, including small cell lung cancer (SCLC). The aim of this study was to investigate the activity of CFZ in lung cancer models. A diverse panel of human lung cancer cell lines and a SHP77 small cell lung cancer xenograft model were used to investigate the anti-tumor activity of CFZ. CFZ treatment inhibited both the constitutive proteasome and the immunoproteasome in lung cancer cell lines. CFZ had marked anti-proliferative activity in A549, H1993, H520, H460, and H1299 non-small cell lung cancer (NSCLC) cell lines, with IC50 values after 96 hour exposure from <1.0 nM to 36 nM. CFZ had more variable effects in the SHP77 and DMS114 SCLC cell lines, with IC50 values at 96 hours from <1 nM to 203 nM. Western blot analysis of CFZ-treated H1993 and SHP77 cells showed cleavage of poly ADP ribose polymerase (PARP) and caspase-3, indicative of apoptosis, and induction of microtubule-associated protein-1 light chain-3B (LC3B), indicative of autophagy. In SHP77 flank xenograft tumors, CFZ monotherapy inhibited tumor growth and prolonged survival, while no additive or synergistic anti-tumor efficacy was observed for CFZ + cisplatin (CDDP). CFZ demonstrated anti-proliferative activity in lung cancer cell lines in vitro and resulted in a significant survival advantage in mice with SHP77 SCLC xenografts, supporting further pre-clinical and clinical investigations of CFZ in NSCLC and SCLC.

Autophagy inhibition sensitizes WYE-354-induced anti-colon cancer activity in vitro and in vivo.

PubMed

Wang, Lijun; Zhu, Yun-Rong; Wang, Shaowei; Zhao, Song

2016-09-01

Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 are frequently dysregulated in human colon cancers. In the present study, we evaluated the potential anti-colon cancer cell activity by a novel mTORC1/2 dual inhibitor WYE-354. We showed that WYE-354 was anti-survival and anti-proliferative when adding to primary (patient-derived) and established (HCT-116, HT-29, Caco-2, LoVo, and DLD-1 lines) colon cancer cells. In addition, WYE-354 treatment activated caspase-dependent apoptosis in the colon cancer cells. Mechanistically, WYE-354 blocked mTORC1 and mTORC2 activation. Meanwhile, it also induced autophagy activation in the colon cancer cells. Autophagy inhibitors (bafilomycin A1 and 3-methyladenine), or shRNA-mediated knockdown of autophagy elements (Beclin-1 and ATG-5), remarkably sensitized WYE-354-mediated anti-colon cancer cell activity in vitro. Further studies showed that WYE-354 administration inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Importantly, its activity in vivo was further potentiated with co-administration of the autophagy inhibitor 3-MA. Phosphorylations of Akt (Ser-473) and S6 were also decreased in WYE-354-treated HT-29 xenografts. Together, these pre-clinical results demonstrate the potent anti-colon cancer cell activity by WYE-354, and its activity may be further augmented with autophagy inhibition.

The Antimicrobial Activity of Annona emarginata (Schltdl.) H. Rainer and Most Active Isolated Compounds against Clinically Important Bacteria.

PubMed

Dolab, Juan G; Lima, Beatriz; Spaczynska, Ewelina; Kos, Jiri; Cano, Natividad H; Feresin, Gabriela; Tapia, Alejandro; Garibotto, Francisco; Petenatti, Elisa; Olivella, Monica; Musiol, Robert; Jampilek, Josef; Enriz, Ricardo D

2018-05-16

Annona emarginata (Schltdl.) H. Rainer, commonly known as "arachichú", "araticú", "aratigú", and "yerba mora", is a plant that grows in Argentina. Infusions and decoctions are used in folk medicine as a gargle against throat pain and for calming toothache; another way to use the plant for these purposes is chewing its leaves. Extracts from bark, flowers, leaves, and fruits from A. emarginata were subjected to antibacterial assays against a panel of Gram (+) and Gram (-) pathogenic bacteria according to Clinical and Laboratory Standards Institute protocols. Extracts from the stem bark and leaves showed moderate activity against the bacteria tested with values between 250⁻1000 µg/mL. Regarding flower extracts, less polar extracts (hexane, dichloromethane) showed very strong antibacterial activity against methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus ATCC 43300 with values between 16⁻125 µg/mL. Additionally, hexane extract showed activity against Klebsiella pneumoniae (MIC = 250 µg/mL). The global methanolic extract of the fruits (MeOHGEF) was also active against the three strains mentioned above, with MICs values 250⁻500 µg/mL. Bioassay-guided fractionation of MeOHGEF led to the isolation of a new main compound-( R )-2-(4-methylcyclohex-3-en-1-yl)propan-2-yl ( E )-3-(4-hydroxyphenyl)acrylate ( 1 ). The structure and relative configurations have been determined by means of 1D and 2D NMR techniques, including COSY, HMQC, HMBC, and NOESY correlations. Compound 1 showed strong antimicrobial activity against all Gram (+) species tested (MICs = 3.12⁻6.25 µg/mL). In addition, the synthesis and antibacterial activity of some compounds structurally related to compound 1 (including four new compounds) are reported. A SAR study for these compounds was performed based on the results obtained by using molecular calculations.

Organic Cations Might Not Be Essential to the Remarkable Properties of Band Edge Carriers in Lead Halide Perovskites.

PubMed

Zhu, Haiming; Trinh, M Tuan; Wang, Jue; Fu, Yongping; Joshi, Prakriti P; Miyata, Kiyoshi; Jin, Song; Zhu, X-Y

2017-01-01

A charge carrier in a lead halide perovskite lattice is protected as a large polaron responsible for the remarkable photophysical properties, irrespective of the cation type. All-inorganic-based APbX 3 perovskites may mitigate the stability problem for their applications in solar cells and other optoelectronics. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association of Resting Metabolism in the Fear Neural Network With Extinction Recall Activations and Clinical Measures in Trauma-Exposed Individuals.

PubMed

Marin, Marie-France; Song, Huijin; VanElzakker, Michael B; Staples-Bradley, Lindsay K; Linnman, Clas; Pace-Schott, Edward F; Lasko, Natasha B; Shin, Lisa M; Milad, Mohammed R

2016-09-01

Exposure-based therapy, an effective treatment for posttraumatic stress disorder (PTSD), relies on extinction learning principles. In PTSD patients, dysfunctional patterns in the neural circuitry underlying fear extinction have been observed using resting-state or functional activation measures. It remains undetermined whether resting activity predicts activations during extinction recall or PTSD symptom severity. Moreover, it remains unclear whether trauma exposure per se affects resting activity in this circuitry. The authors employed a multimodal approach to examine the relationships among resting metabolism, clinical symptoms, and activations during extinction recall. Three cohorts were recruited: PTSD patients (N=24), trauma-exposed individuals with no PTSD (TENP) (N=20), and trauma-unexposed healthy comparison subjects (N=21). Participants underwent a resting positron emission tomography scan 4 days before a functional MRI fear conditioning and extinction paradigm. Amygdala resting metabolism negatively correlated with clinical functioning (as measured by the Global Assessment of Functioning Scale) in the TENP group, and hippocampal resting metabolism negatively correlated with clinical functioning in the PTSD group. In the PTSD group, dorsal anterior cingulate cortex (dACC) resting metabolism positively correlated with PTSD symptom severity, and it predicted increased dACC activations but decreased hippocampal and ventromedial prefrontal cortex activations during extinction recall. The TENP group had lower amygdala resting metabolism compared with the PTSD and healthy comparison groups, and it exhibited lower hippocampus resting metabolism relative to the healthy comparison group. Resting metabolism in the fear circuitry correlated with functioning, PTSD symptoms, and extinction recall activations, further supporting the relevance of this network to the pathophysiology of PTSD. The study findings also highlight the fact that chronic dysfunction in the

Functional Brain Activation in Response to a Clinical Vestibular Test Correlates with Balance

PubMed Central

Noohi, Fatemeh; Kinnaird, Catherine; DeDios, Yiri; Kofman, Igor S.; Wood, Scott; Bloomberg, Jacob; Mulavara, Ajitkumar; Seidler, Rachael

2017-01-01

The current study characterizes brain fMRI activation in response to two modes of vestibular stimulation: Skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit either a vestibulo-spinal reflex [saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)], or an ocular muscle response [utricle-mediated ocular VEMP (oVEMP)]. Research suggests that the skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for subjects than the high decibel tones required to elicit VEMPs. However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of brain activity. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that pneumatically powered skull taps would elicit a similar pattern of brain activity as shown in previous studies. Our results provide the first evidence of using pneumatically powered skull taps to elicit vestibular activity inside the MRI scanner. A conjunction analysis revealed that skull taps elicit overlapping activation with auditory tone bursts in the canonical vestibular cortical regions. Further, our postural control assessments revealed that greater amplitude of brain activation in response to vestibular stimulation was associated with better balance control for both techniques. Additionally, we found that skull taps elicit more robust vestibular activity compared to auditory tone bursts, with less reported aversive effects, highlighting the utility of this approach for future clinical and basic science research. PMID:28344549

Psychological, interpersonal, and clinical factors predicting time spent on physical activity among Mexican patients with hypertension.

PubMed

Ybarra Sagarduy, José Luis; Camacho Mata, Dacia Yurima; Moral de la Rubia, José; Piña López, Julio Alfonso; Yunes Zárraga, José Luis Masud

2018-01-01

It is widely known that physical activity is the key to the optimal management and clinical control of hypertension. This research was conducted to identify factors that can predict the time spent on physical activity among Mexican adults with hypertension. This cross-sectional study was conducted among 182 Mexican patients with hypertension, who completed a set of self-administered questionnaires related to personality, social support, and medical adherence and health care behaviors, body mass index, and time since the disease diagnosis. Several path analyses were performed in order to test the predictors of the study behavior. Lower tolerance to frustration, more tolerance to ambiguity, more effective social support, and less time since the disease diagnosis predicted more time spent on physical activity, accounting for 13.3% of the total variance. The final model shows a good fit to the sample data ( p BS =0.235, χ 2 / gl =1.519, Jöreskog and Sörbom's Goodness of Fit Index =0.987, adjusted modality =0.962, Bollen's Incremental Fit Index =0.981, Bentler-Bonett Normed Fit Index =0.946, standardized root mean square residual =0.053). The performance of physical activity in patients with hypertension depends on a complex set of interactions between personal, interpersonal, and clinical variables. Understanding how these factors interact might enhance the design of interdisciplinary intervention programs so that quality of life of patients with hypertension improves and they might be able to manage and control their disease well.

Athletic Training Students' and Preceptors' Perceptions of Active Learning Time and Bug-in-Ear Technology during Clinical Education Experiences

ERIC Educational Resources Information Center

Nottingham, Sara L.; Kasamatsu, Tricia M.; Montgomery, Melissa M.

2017-01-01

Context: Engaging clinical experiences that allow extensive active learning and patient care interactions are important for the professional development of athletic training students. Understanding students' use of clinical time is important when attempting to improve these experiences. Objective: To gain participants' perspectives on active…

Clinical application of a modern high-definition head-mounted display in sonography.

PubMed

Takeshita, Hideki; Kihara, Kazunori; Yoshida, Soichiro; Higuchi, Saori; Ito, Masaya; Nakanishi, Yasukazu; Kijima, Toshiki; Ishioka, Junichiro; Matsuoka, Yoh; Numao, Noboru; Saito, Kazutaka; Fujii, Yasuhisa

2014-08-01

Because of the remarkably improved image quality and wearability of modern head-mounted displays, a monitoring system using a head-mounted display rather than a fixed-site monitor for sonographic scanning has the potential to improve the diagnostic performance and lessen the examiner's physical burden during a sonographic examination. In a preclinical setting, 2 head-mounted displays, the HMZ-T2 (Sony Corporation, Tokyo, Japan) and the Wrap1200 (Vuzix Corporation, Rochester, NY), were found to be applicable to sonography. In a clinical setting, the feasibility of the HMZ-T2 was shown by its good image quality and acceptable wearability. This modern device is appropriate for clinical use in sonography. © 2014 by the American Institute of Ultrasound in Medicine.

Clinical Supervision Skills: Managing the Clinical Environment. Health Occupations Clinical Teacher Education Series for Secondary and Post-Secondary Educators.

ERIC Educational Resources Information Center

Shea, Mary Lou; And Others

This learning module, which is part of a staff development program for health occupations clinical instructors, discusses the process of managing the physical clinical environment and students' experiences within the clinical environment. It includes learning activities dealing with various aspects of managing the physical environment and student…

Improvement of Clinical Skills through Pharmaceutical Education and Clinical Research.

PubMed

Ishizaki, Junko

2017-01-01

Professors and teaching staff in the field of pharmaceutical sciences should devote themselves to staying abreast of relevant education and research. Similarly those in clinical pharmacies should contribute to the advancement of pharmaceutical research and the development of next generation pharmacists and pharmaceuticals. It is thought that those who work in clinical pharmacies should improve their own skills and expertise in problem-finding and -solving, i.e., "clinical skills". They should be keen to learn new standard treatments based on the latest drug information, and should try to be in a position where collecting clinical information is readily possible. In the case of pharmacists in hospitals and pharmacies, they are able to aim at improving their clinical skills simply through performing their pharmaceutical duties. On the other hand, when a pharmaceutical educator aims to improve clinical skills at a level comparable to those of clinical pharmacists, it is necessary to devote or set aside considerable time for pharmacist duties, in addition to teaching, which may result in a shortage of time for hands-on clinical practice and/or in a decline in the quality of education and research. This could be a nightmare for teaching staff in clinical pharmacy who aim to take part in such activities. Nonetheless, I believe that teaching staff in the clinical pharmacy area could improve his/her clinical skills through actively engaging in education and research. In this review, I would like to introduce topics on such possibilities from my own experiences.

Active faulting at Delphi, Greece: Seismotectonic remarks and a hypothesis for the geologic environment of a myth

NASA Astrophysics Data System (ADS)

Piccardi, Luigi

2000-07-01

Historical data are fundamental to the understanding of the seismic history of an area. At the same time, knowledge of the active tectonic processes allows us to understand how earthquakes have been perceived by past cultures. Delphi is one of the principal archaeological sites of Greece, the main oracle of Apollo. It was by far the most venerated oracle of the Greek ancient world. According to tradition, the mantic proprieties of the oracle were obtained from an open chasm in the earth. Delphi is directly above one of the main antithetic active faults of the Gulf of Corinth Rift, which bounds Mount Parnassus to the south. The geometry of the fault and slip-parallel lineations on the main fault plane indicate normal movement, with minor right-lateral slip component. Combining tectonic data, archaeological evidence, historical sources, and a reexamination of myths, it appears that the Helice earthquake of 373 B.C. ruptured not only the master fault of the Gulf of Corinth Rift at Helice, but also the antithetic fault at Delphi, similarly to the Corinth earthquake of 1981. Moreover, the presence of an active fault directly below the temples of the oldest sanctuary suggests that the mythological oracular chasm might well have been an ancient tectonic surface rupture.

Changes in muscle activity determine progression of clinical symptoms in patients with chronic spine-related muscle pain. A complex clinical and neurophysiological approach

PubMed Central

Wytra̦żek, Marcin; Huber, Juliusz; Lisiński, Przemysław

Summary Spine-related muscle pain can affect muscle strength and motor unit activity. This study was undertaken to investigate whether surface electromyographic (sEMG) recordings performed during relaxation and maximal contraction reveal differences in the activity of muscles with or without trigger points (TRPs). We also analyzed the possible coexistence of characteristic spontaneous activity in needle electromyographic (eEMG) recordings with the presence of TRPs. Thirty patients with non-specific cervical and back pain were evaluated using clinical, neuroimaging and electroneurographic examinations. Muscle pain was measured using a visual analog scale (VAS), and strength using Lovett’s scale; trigger points were detected by palpation. EMG was used to examine motor unit activity. Trigger points were found mainly in the trapezius muscles in thirteen patients. Their presence was accompanied by increased pain intensity, decreased muscle strength, increased resting sEMG amplitude, and decreased sEMG amplitude during muscle contraction. eEMG revealed characteristic asynchronous discharges in TRPs. The results of EMG examinations point to a complexity of muscle pain that depends on progression of the myofascial syndrome PMID:22152435

Ultrasound-detected bone erosion is a relapse risk factor after discontinuation of biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis whose ultrasound power Doppler synovitis activity and clinical disease activity are well controlled.

PubMed

Kawashiri, Shin-Ya; Fujikawa, Keita; Nishino, Ayako; Okada, Akitomo; Aramaki, Toshiyuki; Shimizu, Toshimasa; Umeda, Masataka; Fukui, Shoichi; Suzuki, Takahisa; Koga, Tomohiro; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Mizokami, Akinari; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Aoyagi, Kiyoshi; Maeda, Takahiro; Kawakami, Atsushi

2017-05-25

In the present study, we explored the risk factors for relapse after discontinuation of biologic disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) whose ultrasound power Doppler (PD) synovitis activity and clinical disease activity were well controlled. In this observational study in clinical practice, the inclusion criteria were based on ultrasound disease activity and clinical disease activity, set as low or remission (Disease Activity Score in 28 joints based on erythrocyte sedimentation rate <3.2). Ultrasound was performed in 22 joints of bilateral hands at discontinuation for evaluating synovitis severity and presence of bone erosion. Patients with a maximum PD score ≤1 in each joint were enrolled. Forty patients with RA were consecutively recruited (November 2010-March 2015) and discontinued bDMARD therapy. Variables at the initiation and discontinuation of bDMARD therapy that were predictive of relapse during the 12 months after discontinuation were assessed. The median patient age was 54.5 years, and the median disease duration was 3.5 years. Nineteen (47.5%) patients relapsed during the 12 months after the discontinuation of bDMARD therapy. Logistic regression analysis revealed that only the presence of bone erosion detected by ultrasound at discontinuation was predictive of relapse (OR 8.35, 95% CI 1.78-53.2, p = 0.006). No clinical characteristics or serologic biomarkers were significantly different between the relapse and nonrelapse patients. The ultrasound synovitis scores did not differ significantly between the groups. Our findings are the first evidence that ultrasound bone erosion may be a relapse risk factor after the discontinuation of bDMARD therapy in patients with RA whose PD synovitis activity and clinical disease activity are well controlled.

Remarkable evolutionary relatedness among the enzymes and proteins from the α-amylase family.

PubMed

Janeček, Štefan; Gabriško, Marek

2016-07-01

The α-amylase is a ubiquitous starch hydrolase catalyzing the cleavage of the α-1,4-glucosidic bonds in an endo-fashion. Various α-amylases originating from different taxonomic sources may differ from each other significantly in their exact substrate preference and product profile. Moreover, it also seems to be clear that at least two different amino acid sequences utilizing two different catalytic machineries have evolved to execute the same α-amylolytic specificity. The two have been classified in the Cabohydrate-Active enZyme database, the CAZy, in the glycoside hydrolase (GH) families GH13 and GH57. While the former and the larger α-amylase family GH13 evidently forms the clan GH-H with the families GH70 and GH77, the latter and the smaller α-amylase family GH57 has only been predicted to maybe define a future clan with the family GH119. Sequences and several tens of enzyme specificities found throughout all three kingdoms in many taxa provide an interesting material for evolutionarily oriented studies that have demonstrated remarkable observations. This review emphasizes just the three of them: (1) a close relatedness between the plant and archaeal α-amylases from the family GH13; (2) a common ancestry in the family GH13 of animal heavy chains of heteromeric amino acid transporter rBAT and 4F2 with the microbial α-glucosidases; and (3) the unique sequence features in the primary structures of amylomaltases from the genus Borrelia from the family GH77. Although the three examples cannot represent an exhaustive list of exceptional topics worth to be interested in, they may demonstrate the importance these enzymes possess in the overall scientific context.

Remarkable support effect on the reactivity of Pt/In2O3/MOx catalysts for methanol steam reforming

NASA Astrophysics Data System (ADS)

Liu, Xin; Men, Yong; Wang, Jinguo; He, Rong; Wang, Yuanqiang

2017-10-01

Effects of supports over Pt/In2O3/MOx catalysts with extremely low loading of Pt (1 wt%) and In2O3 loadings (3 wt%) are investigated for the hydrogen production of methanol steam reforming (MSR) in the temperature range of 250-400 °C. Under practical conditions without the pre-reduction, the 1Pt/3In2O3/CeO2 catalyst shows the highly efficient catalytic performance, achieving almost complete methanol conversion (98.7%) and very low CO selectivity of 2.6% at 325 °C. The supported Pt/In2O3 catalysts are characterized by means of Brunauer-Emmett-Teller (BET) surface area, X-ray diffraction (XRD), high-resolution transmission microscopy (HRTEM), temperature programmed reduction with hydrogen (H2-TPR), CO pulse chemisorption, temperature programmed desorption of methanol and water (CH3OH-TPD and H2O-TPD). These demonstrate that the nature of catalyst support of Pt/In2O3/MOx plays crucial roles in the Pt dispersion associated by the strong interaction among Pt, In2O3 and supporting materials and the surface redox properties at low temperature, and thus affects their capability to activate the reactants and determines the catalytic activity of methanol steam reforming. The superior 1Pt/3In2O3/CeO2 catalyst, exhibiting a remarkable reactivity and stability for 32 h on stream, demonstrates its potential for efficient hydrogen production of methanol steam reforming in mobile and de-centralized H2-fueled PEMFC systems.

Ultrasound discloses entheseal involvement in inactive and low active inflammatory bowel disease without clinical signs and symptoms of spondyloarthropathy.

PubMed

Bandinelli, Francesca; Milla, Monica; Genise, Stefania; Giovannini, Leonardo; Bagnoli, Siro; Candelieri, Antonio; Collaku, Ledio; Biagini, Silvia; Cerinic, Marco Matucci

2011-07-01

To investigate the presence of lower limb entheseal abnormalities in IBD patients without clinical signs and symptoms of SpA and their correlation with IBD clinical variables. A total of 81 IBD patients [55 Crohn's disease (CD) and 26 ulcerative colitis (UC), 43 females and 38 males, mean age 41.3 (12.4) years, BMI 24 (2)] with low active (12) and inactive (67) disease were consecutively studied with US (LOGIQ5 General Electric 10-MHz linear array transducer) of lower limb entheses and compared with 40 healthy controls matched for sex, age and BMI. Quadriceps, patellar, Achilleon and plantar fascia entheses were scored according to the 0-36 Glasgow Ultrasound Enthesitis Scoring System (GUESS) and power Doppler (PD). Correlations of GUESS and PD with IBD features [duration, type (CD/UC) and activity (disease activity index for CD/Truelove score for UC)] were investigated. The intra- and inter-reader agreements for US were estimated in all images detected in patients and controls. Of the 81 patients, 71 (92.6%) presented almost one tendon alteration with mean GUESS 5.1 (3.5): 81.5% thickness (higher than controls P < 0.05), 67.9% enthesophytosis, 27.1% bursitis and 16.1% erosions. PD was positive in 13/81 (16%) patients. In controls, US showed only enthesophytes (5%) and no PD. GUESS and PD were independent of duration, activity or type (CD/UC) of IBD. The intra- and inter-reader agreements were high (>0.9 intra-class correlation variability). US entheseal abnormalities are present in IBD patients without clinical signs and symptoms of SpA. US enthesopathy is independent of activity, duration and type of gut disease.

Objective Measurement of Clinical Competency in Surgical Education Using Electrodermal Activity.

PubMed

Quick, Jacob A; Bukoski, Alex D; Doty, Jennifer; Bennett, Bethany J; Crane, Megan; Barnes, Stephen L

Within the realm of surgical education, there is a need for objective means to determine surgical competence and resident readiness to operate independently. We propose a novel, objective method of assessing resident confidence and clinical competence based on measurement of electrodermal activity (EDA) during live surgical procedures. We hypothesized that with progressive training, EDA responses to the stress of performing surgery would exhibit decline, elucidating an objective correlate of clinical competence. EDA was measured using galvanic skin response sensors worn by residents performing laparoscopic cholecystectomy on sequential live human patients over an 8-month period. Baseline, phasic (peak) and tonic EDA responses were measured as a fractional change from baseline. University of Missouri, Columbia, Missouri, an academic tertiary care facility. Fourteen categorical general surgery residents and 5 faculty surgeons were voluntarily enrolled and participated through completion. Tonic fractional change (FC TONIC ) was highest in PGY3 residents compared with postgraduate year (PGY) 1 and 2 residents (7.199 vs. 2.100, p = 0.004, 95% CI: 8.58-1.61 and PGY4 and 5 residents (7.199 vs. 2.079, p = 0.002, 95% CI: 8.38-0.29). Phasic fractional change in EDA (FC PHASIC ) exhibited a progressive decline across resident training levels, with PGY1 and 2 residents having the highest response, and faculty displaying the lowest FC PHASIC responses. Statistical differences were seen between FC PHASIC faculty and PGY4 and 5 (3.596 vs. 6.180, p = 0.004, 95% CI: 0.80-4.36), PGY4 and 5, and PGY3 (6.180 vs. 15.998, p = 0.003, 95% CI: 3.33-16.3), as well as among all residents and faculty (13.057 vs. 3.596, p = 0.004, 95% CI: 15.8-3.1). Phasic EDA changes decrease with increasing clinical competence. For those participants with the lowest and highest levels of competence, tonic EDA changes are minimal. Tonic EDA changes follow an inverse-U shape with differing levels of clinical

Sangivamycin-Like Molecule 6 (SLM6) exhibits potent anti-multiple myeloma activity through inhibition of cyclin-dependent kinase-9 (CDK9)

PubMed Central

Dolloff, Nathan G.; Allen, Joshua E.; Dicker, David T.; Aqui, Nicole; Vogl, Dan; Malysz, Jozef; Talamo, Giampaolo; El-Deiry, Wafik S.

2012-01-01

Despite significant treatment advances over the past decade, multiple myeloma (MM) remains largely incurable. In this study we found that MM cells were remarkably sensitive to the death-inducing effects of a new class of sangivamycin-like molecules (SLMs). A panel of structurally related SLMs selectively induced apoptosis in MM cells but not other tumor or non-malignant cell lines at sub-micromolar concentrations. SLM6 was the most active compound in vivo, where it was well-tolerated and significantly inhibited growth and induced apoptosis of MM tumors. We determined that the anti-MM activity of SLM6 was mediated by direct inhibition of cyclin-dependent kinase 9 (CDK9), which resulted in transcriptional repression of oncogenes that are known to drive MM progression (c-Maf, cyclin D1, and c-Myc). Furthermore, SLM6 demonstrated superior in vivo anti-MM activity over the CDK inhibitor flavopiridol, which is currently in clinical trials for MM. These findings demonstrate that SLM6 is a novel CDK9 inhibitor with promising preclinical activity as an anti-MM agent. PMID:22964485

Clinical value of gallium-67 scintigraphy in assessment of disease activity in Wegener's granulomatosis

PubMed Central

Slart, R; Jager, P; Poot, L; Piers, D; Cohen, T; Stegeman, C

2003-01-01

Background: Diagnosis of active pulmonary and paranasal involvement in patients with Wegener's granulomatosis (WG) can be difficult. The diagnostic value of gallium-67 scintigraphy in WG is unclear. Objective: To evaluate the added diagnostic value of gallium-67 scintigraphy in patients with WG with suspected granulomatous inflammation in the paranasal and chest regions. Methods: Retrospectively, the diagnostic contribution of chest and head planar gallium scans in 40 episodes of suspected vasculitis disease activity in 28 patients with WG was evaluated. Scans were grouped into normal or increased uptake for each region. Histological proof or response to treatment was the "gold standard" for the presence of WG activity. Results: WG activity was confirmed in 8 (20%) episodes, with pulmonary locations in three, paranasal in four, and both in one (n=7 patients); all these gallium scans showed increased gallium uptake (sensitivity 100%). Gallium scans were negative for the pulmonary area in 23/36 scans (specificity 64%), and negative for paranasal activity in 13/16 scans (specificity 81%) in episodes without WG activity. Positive predictive value of WG activity for lungs and paranasal region was 24% and 63%, respectively, negative predictive value was 100% for both regions. False positive findings were caused by bacterial or viral infections. Conclusion: Gallium scans are clinically helpful as a negative scan virtually excludes active WG. Gallium scintigraphy of chest and nasal region has a high sensitivity for the detection of disease activity in WG. However, because of positive scans in cases of bacterial or viral infections, specificity was lower. PMID:12810430

Attitudes toward physical activity and exercise: comparison of memory clinic patients and their caregivers and prediction of activity levels.

PubMed

O'Connell, Megan E; Dal Bello-Haas, Vanina; Crossley, Margaret; Morgan, Debra G

2015-01-01

Regular physical activity and exercise (PA&E) reduces cognitive aging, may delay dementia onset, and for persons with dementia, may slow progression and improve quality of life. Memory clinic patients and caregivers described their PA&E and completed the Older Persons' Attitudes Toward Physical Activity and Exercise Questionnaire (OPAPAEQ). Caregivers and patients differed in their PA&E attitudes: patients were less likely to believe in the importance of PA&E for health promotion. PA&E attitudes were explored as predictors of self-reported exercise habits. Belief in the importance of high intensity exercise for health maintenance was the only variable that significantly predicted engagement in regular PA&E. Moreover, caregivers' attitudes toward high intensity exercise predicted memory patients' participation in PA&E. These findings may aid in development of exercise interventions for people with memory problems, and suggest that modification of specific attitudes toward exercise is an important component to ensure maximum participation and engagement in PA&E.

Managing diabetes at high altitude: personal experience with support from a Multidisciplinary Physical Activity and Diabetes Clinic.

PubMed

Malcolm, Gary; Rilstone, Sian; Sivasubramaniyam, Sivasujan; Jairam, Carol; Chew, Stephen; Oliver, Nick; Hill, Neil E

2017-01-01

Physical activity is important for well-being but can be challenging for people with diabetes. Data informing support of specialist activities such as climbing and high-altitude trekking are limited. A 42-year-old man with type 1 diabetes (duration 30 years) attended a Multidisciplinary Physical Activity and Diabetes Clinic planning to climb Mont Blanc during the summer and trek to Everest Base Camp in the autumn. His aims were to complete these adventures without his diabetes impacting on their success. We report the information provided that enabled him to safely facilitate his objectives, in particular, the requirement for frequent checking of blood glucose levels, the effects of altitude on insulin dose requirements, and recognition that acute mountain sickness may mimic the symptoms of hypoglycaemia and vice versa. Real-time continuous glucose monitoring was made available for his treks. The effects of high altitude on blood glucose results and glycaemic variability while treated on multiple daily injections of insulin are reported. In addition, we present a first-person account of his experience and lessons learnt from managing diabetes at high altitude. A dedicated Multidisciplinary Physical Activity and Diabetes Clinic delivering individualised, evidence-based, patient-focused advice on the effects of altitude on blood glucose levels, and provision of real-time continuous glucose monitoring enabled uneventful completion of a trek to Everest Base Camp in a person with type 1 diabetes.

[Topic on clinical anthropology in scientific activity of docent Antanas Adomaitis].

PubMed

Tutkuviene, Janina

2006-01-01

The present paper is dedicated to docent Antanas Adomaitis, anatomist and anthropologist, former member of editorial board of journal "Medicina", on the occasion of his 65th birthday and 40 years of scientific activity. First publications of Antanas Adomatis appeared in the 1960s, and now the list of his scientific publications exceeds 140 in number. The research field of docent Antanas Adomaitis is wide and covers problems from growth and development to physical status of adult people and its changes associated with a particular period. However, his most important scientific works are in the field of clinical anthropology. Antanas Adomaitis investigated growth and maturation under pathological circumstances, body composition of adult people, prevalence of obesity, growth diversity and secular trend: in 1975 he defended his thesis entitled "Physical development and sexual maturation of children with congenital heart defects" for the degree of Doctor of Medicine, later focused on growth and development of children with congenital facial anomalies, also blind and weak-sighted children. Recently docent together with the other scientists of our Department investigates growth variety of children from different towns and rural areas of Lithuania. Antanas Adomaitis collected probably most anthropological data on Lithuanians (children and adults)--this is ponderable contribution to Lithuanian auxology and clinical anthropology, valuable material for the future researches of growth and maturation, also physical status of adult people and secular trend.

Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective

PubMed Central

Tye-Din, J A; Cameron, D J S; Daveson, A J; Day, A S; Dellsperger, P; Hogan, C; Newnham, E D; Shepherd, S J; Steele, R H; Wienholt, L; Varney, M D

2015-01-01

The past decade has seen human leukocyte antigen (HLA) typing emerge as a remarkably popular test for the diagnostic work-up of coeliac disease with high patient acceptance. Although limited in its positive predictive value for coeliac disease, the strong disease association with specific HLA genes imparts exceptional negative predictive value to HLA typing, enabling a negative result to exclude coeliac disease confidently. In response to mounting evidence that the clinical use and interpretation of HLA typing often deviates from best practice, this article outlines an evidence-based approach to guide clinically appropriate use of HLA typing, and establishes a reporting template for pathology providers to improve communication of results. PMID:25827511

Effect of moderate to vigorous physical activity on long-term clinical outcomes and pain severity in fibromyalgia.

PubMed

Kaleth, Anthony S; Saha, Chandan K; Jensen, Mark P; Slaven, James E; Ang, Dennis C

2013-08-01

To evaluate the relationship between long-term maintenance of moderate to vigorous physical activity (MVPA) and clinical outcomes in fibromyalgia (FM). Patients with FM (n = 170) received individualized exercise prescriptions and completed baseline and followup physical activity assessments using the Community Health Activities Model Program for Seniors questionnaire at weeks 12, 24, and 36. The primary outcome was the change in the Fibromyalgia Impact Questionnaire-Physical Impairment (FIQ-PI) score. The secondary outcomes included improvements in overall well-being (FIQ total score), pain severity ratings, and depression. Using a threshold increase in MVPA of ≥10 metabolic equivalent hours/week above usual activities, 27 subjects (15.9%) increased and sustained (SUS-PA), 68 (40%) increased but then declined (UNSUS-PA), and 75 (44.1%) did not achieve (LO-PA) this benchmark. Compared to LO-PA subjects, both SUS-PA and UNSUS-PA subjects reported greater improvement in FIQ-PI (P < 0.01) and FIQ total score (P < 0.05). Additionally, the SUS-PA group reported greater improvement in pain severity compared to the LO-PA group (P < 0.05). However, there were no significant group differences between SUS-PA and UNSUS-PA for any primary or secondary outcome measure. Increased participation in MVPA for at least 12 weeks improved physical function and overall well-being in patients with FM. Although sustained physical activity was not associated with greater clinical benefit compared with unsustained physical activity, these findings also suggest that performing greater volumes of physical activity is not associated with worsening pain in FM. Future research is needed to determine the relationship between sustained MVPA participation and subsequent improvement in patient outcomes. Copyright © 2013 by the American College of Rheumatology.

Outcomes of active surveillance for the management of clinically localized prostate cancer in the prospective, multi-institutional Canary PASS cohort

PubMed Central

Newcomb, Lisa F.; Thompson, Ian M.; Boyer, Hilary D.; Brooks, James D.; Carroll, Peter R.; Cooperberg, Matthew R.; Dash, Atreya; Ellis, William J.; Fazli, Ladan; Feng, Ziding; Gleave, Martin E.; Kunju, Priya; Lance, Raymond S.; McKenney, Jesse K.; Meng, Maxwell V.; Nicolas, Marlo M.; Sanda, Martin G.; Simko, Jeffry; So, Alan; Tretiakova, Maria S.; Troyer, Dean A.; True, Lawrence D.; Vakar-Lopez, Funda; Virgin, Jeff; Wagner, Andrew A.; Wei, John T.; Zheng, Yingye; Nelson, Peter S.; Lin, Daniel W.

2016-01-01

Purpose Active surveillance represents a strategy to address the overtreatment of prostate cancer, yet uncertainty regarding individual patient outcomes remains a concern. We evaluated outcomes in a prospective multi-center study of active surveillance. Methods We studied 905 men in the prospective Canary Prostate cancer Active Surveillance Study (PASS) enrolled between 2008 to 2013. We collected clinical data at study entry and at pre-specified intervals and determined associations with adverse reclassification defined as increased Gleason grade or greater cancer volume on follow-up biopsy. We also evaluated the relationships of clinical parameters with pathology findings in participants who underwent surgery after a period of active surveillance. Results During a median follow-up of 28 months, 24% of participants experienced adverse reclassification, of whom 53% underwent treatment while 31% continued active surveillance. Overall, 19% of participants received treatment, 68% with adverse reclassification while 32% opted for treatment without disease reclassification. In multivariate Cox proportional hazards modeling, percent of biopsy cores with cancer, BMI, and PSA density were associated with adverse reclassification (P = 0.01, 0.04, 0.04). Of 103 participants subsequently treated by radical prostatectomy, 34% had adverse pathology, defined as primary pattern 4–5 or non-organ confined disease, including two with positive lymph nodes, with no significant relationship between risk category at diagnosis and findings at surgery (P = 0.76). Conclusion Most men remain on active surveillance at five years without adverse reclassification or adverse pathology at surgery. However, clinical factors had only modest association with disease reclassification, supporting the need for approaches that improve prediction of this outcome. PMID:26327354

The activities of a dietitian-led gastroenterology clinic using extended scope of practice.

PubMed

Ryan, Dominique; Pelly, Fiona; Purcell, Elizabeth

2016-10-21

Extending the scope of practice of allied health professionals has been a strategy adopted in the United Kingdom to address issues within the health system. Australia's health system is currently undermined by similar issues, heightening government interest in adopting the extended scope health care model. The aim of the current study was to describe the activities and outcomes of a dietitian-led gastroenterology clinic which operated under an extended scope of practice model in an outpatient gastroenterology department at a tertiary hospital in regional Queensland, Australia, and to assess patient satisfaction with the initiative. A descriptive, cross-sectional case series undertaken over 50 clinics involving 82 category 2 and 3 patients with suspected/confirmed coeliac disease or inflammatory bowel disease; low haemoglobin; gastroesophageal reflux disease, or; malnutrition. Data was analysed using Microsoft Excel 2010, and presented as descriptive statistics. Sixty out of 82 selected patients (median age 51 years) attended an initial appointment with the dietitian. Twenty-four review appointments were attended. Average waiting period for an initial appointment was 148 days (range 31-308 days). A total of 149 management strategies were provided, and 94 (63 %) of these involved the dietitian utilising extended scope of practice. The dietitian managed 47 (78 %) patients without need for gastroenterologist referral, and 25 (42 %) were discharged after dietetic management. Patients reported high levels of satisfaction with the clinic. Seventy-eight percent of category 2 and 3 patients referred to the gastroenterologist could be managed exclusively in the dietitian-led clinic. This extended scope model of care could potentially benefit the efficiency and acceptability of Australia's public health system.

Clinical outcomes and changes in venous hemodynamics after subfascial endoscopic perforating vein surgery.

PubMed

Ting, A C W; Cheng, S W K; Ho, P; Wu, L L H; Cheung, G C Y

2003-08-01

We evaluated the clinical results of subfascial endoscopic perforating vein surgery (SEPS) in patients with severe chronic venous insufficiency (CVI) (clinical class 4-6) and assessed the hemodynamic changes associated with SEPS using air plethysmography (APG). Forty-five patients with severe CVI who had undergone SEPS were evaluated. Clinical score and venous hemodynamics, as measured by APG before operation and at 1 month and 1 year after operation, were compared using the Wilcoxon signed rank test. Patient satisfaction (on a visual analogue scale of 0 to 100%) was also assessed. There were 29 men and 16 women; their mean age was 60 years (range, 37-83). Thirty-five patients (78%) had active venous ulcers; the ulcers' mean size was 7.8 +/- 11.9 cm2 and the mean duration of ulceration was 9 +/- 10 months. There were no hospital deaths. Postoperative complications were uncommon (one groin wound infection and one case of thrombophlebitis). At a mean follow-up of 15 +/- 9 months, 34 ulcers (97%) had healed. The cumulative ulcer healing was 82% at 3 months. There were five recurrent ulcers (15%). Significant improvement was seen in the clinical scores (10 +/- 3 before operation, 6 +/- 4 at 1 month, and 4 +/- 3 at 1 year after operation). The venous filling index was also significantly improved after operation; this improvement was maintained at 1-year follow-up (7.36 +/- 6.23 ml/sec before operation, 3.63 +/- 3.90 ml/sec at 1 month, and 3.14 +/- 2.06 ml/sec at 1 year). The degree of patient satisfaction was also remarkable, with 74 +/- 17% and 90 +/- 12% satisfaction at 1-month and 1-year follow-up, respectively. SEPS is a safe and effective treatment for patients with severe CVI. It leads to hemodynamic improvement, with rapid ulcer healing, and it is associated with a high degree of patient satisfaction.

Antibacterial activity of exogenous glutathione and its synergism on antibiotics sensitize carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

PubMed

Alharbe, Roaa; Almansour, Ayidh; Kwon, Dong H

2017-10-01

A major clinical impact of A. baumannii is hospital-acquired infections including ventilator-associated pneumonia. The treatment of this pathogen is often difficult due to its innate and acquired resistance to almost all commercially available antibiotics. Infections with carbapenem-associated multidrug resistant A. baumannii is the most problematic. Glutathione is a tripeptide thiol-antioxidant and antibacterial activity of exogenous glutathione was reported in some bacteria. However, clinical relevance and molecular details of the antibacterial activity of glutathione are currently unclear. Seventy clinical isolates of A. baumannii including 63 carbapenem-associated multidrug resistant isolates and a type strain A. baumannii ATCC 19606 were used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Fractional inhibitory concentration (FIC) and time-killing activity with meropenem and/or glutathione were also determined in the carbapenem-associated multidrug resistant isolates. In addition, the roles of exogenous glutathione in multidrug efflux pumps and β-lactamase production were examined. Levels of MIC and MBC were ranged from 10 to 15mM of exogenous glutathione. All tested carbapenem-associated multidrug resistant isolates were sensitized by all tested antibiotics in combination with subinhibitory concentrations of glutathione. FIC levels of glutathione with carbapenem (meropenem) were all<0.5 and the carbapenem-associated multidrug resistant isolates were killed by subinhibitory concentrations of both glutathione and meropenem at>2log10 within 12h, suggesting glutathione synergistically interacts with meropenem. The roles of multidrug efflux pumps and β-lactamase production were excluded for the glutathione-mediated antibiotic susceptibility. Overall results demonstrate that the antibacterial activity of glutathione is clinically relevant and its synergism on antibiotics sensitizes clinical isolates of A

Psychological, interpersonal, and clinical factors predicting time spent on physical activity among Mexican patients with hypertension

PubMed Central

Ybarra Sagarduy, José Luis; Camacho Mata, Dacia Yurima; Moral de la Rubia, José; Piña López, Julio Alfonso; Yunes Zárraga, José Luis Masud

2018-01-01

Background It is widely known that physical activity is the key to the optimal management and clinical control of hypertension. Purpose This research was conducted to identify factors that can predict the time spent on physical activity among Mexican adults with hypertension. Methods This cross-sectional study was conducted among 182 Mexican patients with hypertension, who completed a set of self-administered questionnaires related to personality, social support, and medical adherence and health care behaviors, body mass index, and time since the disease diagnosis. Several path analyses were performed in order to test the predictors of the study behavior. Results Lower tolerance to frustration, more tolerance to ambiguity, more effective social support, and less time since the disease diagnosis predicted more time spent on physical activity, accounting for 13.3% of the total variance. The final model shows a good fit to the sample data (pBS =0.235, χ2/gl =1.519, Jöreskog and Sörbom’s Goodness of Fit Index =0.987, adjusted modality =0.962, Bollen’s Incremental Fit Index =0.981, Bentler-Bonett Normed Fit Index =0.946, standardized root mean square residual =0.053). Conclusion The performance of physical activity in patients with hypertension depends on a complex set of interactions between personal, interpersonal, and clinical variables. Understanding how these factors interact might enhance the design of interdisciplinary intervention programs so that quality of life of patients with hypertension improves and they might be able to manage and control their disease well. PMID:29379276

Interactions of cisplatin with non-DNA targets and their influence on anticancer activity and drug toxicity: the complex world of the platinum complex.

PubMed

Mezencev, Roman

2015-01-01

Since the discovery of its anticancer activity in 1970s, cisplatin and its analogs have become widely used in clinical practice, being administered to 40-80% of patients undergoing chemotherapy for solid tumors. The fascinating story of this drug continues to evolve presently, which includes advances in our understanding of complexity of molecular mechanisms involved in its anticancer activity and drug toxicity. While genomic DNA has been generally recognized as the most critical pharmacological target of cisplatin, the results reported across multiple disciplines suggest that other targets and molecular interactions are likely involved in the anticancer mode of action, drug toxicity and resistance of cancer cells to this remarkable anticancer drug. This article reviews interactions of cisplatin with non-DNA targets, including RNAs, proteins, phospholipids and carbohydrates in the context of its pharmacological activity and drug toxicity. Some of these non-DNA targets and associated mechanisms likely act in a highly concerted manner towards the biological outcome in cisplatin-treated tumors; therefore, the understanding of complexity of cisplatin interactome may open new avenues for modulation of its clinical efficacy or for designing more efficient platinum-based anticancer drugs to reproduce the success of cisplatin in the treatment of highly curable testicular germ cell tumors in its therapeutic applications to other cancers.

[Review in the studies on tannins activity of cancer prevention and anticancer].

PubMed

Li, Haixia; Wang, Zhao; Liu, Yanze

2003-06-01

This paper reviewed the biological activities of tannins in cancer prevention and anticancer, and mainly discussed related mechanisms. The results suggest that tannins, whether total tannins or pure tannin compound, have remarkable activity in cancer prevention and anticancer. It has wealthy foreground for developing new cancer prevention agents and/or new anticancer drugs screening among tannin compounds.

A highly-active and poison-tolerant Pt12 sub-nanocluster catalyst for the reductive amination of aldehydes with amines.

PubMed

Takahashi, Masaki; Imaoka, Takane; Hongo, Yushi; Yamamoto, Kimihisa

2013-12-07

A one-atom controlled platinum sub-nanocluster (under 1 nm) was synthesized using a phenylazomethine dendrimer template. This sub-nanocluster (SNC) catalyst exhibits a remarkable catalytic activity during reductive amination compared to the standard platinum nanoparticles of 2.2 ± 0.8 nm under mild conditions and a low catalyst loading. In addition, this catalyst has a remarkable poison-tolerance to amines without adding protic acid.

Flomoxef showed excellent in vitro activity against clinically important gram-positive and gram-negative pathogens causing community- and hospital-associated infections.

PubMed

Yang, Qiwen; Zhang, Hui; Cheng, Jingwei; Xu, Zhipeng; Hou, Xin; Xu, Yingchun

2015-04-01

The objective of this study was to better understand the in vitro activity of flomoxef against clinical pathogens. A total of 545 clinical isolates, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus, Streptococcus pneumoniae, and Streptococcus pyogenes, were isolated consecutively from clinical specimens from Peking Union Medical College Hospital in 2013. MICs were determined using broth microdilution method. esbl and ampC genes were detected by polymerase chain reaction and sequencing. Flomoxef showed excellent activity against E. coli, K. pneumoniae, and P. mirabilis isolates, with susceptibility rate of 88.8%, 88.3%, and 97.7%, separately. Moreover, flomoxef exhibited great activity against extended-spectrum beta-lactamase (ESBL) producers, with MIC50/MIC90 of 0.125/(0.5-1) μg/mL. Flomoxef showed MIC50/MIC90 of 0.5/0.5 μg/mL against MSSA, 0.125/0.25 μg/mL against S. pyogenes, and 2/16 μg/mL against S. pneumoniae. In conclusion, flomoxef is one of the cephamycins showing excellent activity against ESBL-producing or ESBL-nonproducing E. coli, K. pneumoniae, and P. mirabilis and was also potent against MSSA, S. pyogenes, and S. pneumoniae. Copyright © 2015 Elsevier Inc. All rights reserved.

The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing β-Lactamases of Potential Clinical Relevance

PubMed Central

Gudeta, Dereje Dadi; Bortolaia, Valeria; Amos, Greg; Wellington, Elizabeth M. H.; Brandt, Kristian K.; Poirel, Laurent; Nielsen, Jesper Boye; Westh, Henrik

2015-01-01

The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1), and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria. PMID:26482314

Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis.

PubMed

Håkansson, I; Tisell, A; Cassel, P; Blennow, K; Zetterberg, H; Lundberg, P; Dahle, C; Vrethem, M; Ernerudh, J

2017-05-01

Improved biomarkers are needed to facilitate clinical decision-making and as surrogate endpoints in clinical trials in multiple sclerosis (MS). We assessed whether neurodegenerative and neuroinflammatory markers in cerebrospinal fluid (CSF) at initial sampling could predict disease activity during 2 years of follow-up in patients with clinically isolated syndrome (CIS) and relapsing-remitting MS. Using multiplex bead array and enzyme-linked immunosorbent assay, CXCL1, CXCL8, CXCL10, CXCL13, CCL20, CCL22, neurofilament light chain (NFL), neurofilament heavy chain, glial fibrillary acidic protein, chitinase-3-like-1, matrix metalloproteinase-9 and osteopontin were analysed in CSF from 41 patients with CIS or relapsing-remitting MS and 22 healthy controls. Disease activity (relapses, magnetic resonance imaging activity or disability worsening) in patients was recorded during 2 years of follow-up in this prospective longitudinal cohort study. In a logistic regression analysis model, NFL in CSF at baseline emerged as the best predictive marker, correctly classifying 93% of patients who showed evidence of disease activity during 2 years of follow-up and 67% of patients who did not, with an overall proportion of 85% (33 of 39 patients) correctly classified. Combining NFL with either neurofilament heavy chain or osteopontin resulted in 87% overall correctly classified patients, whereas combining NFL with a chemokine did not improve results. This study demonstrates the potential prognostic value of NFL in baseline CSF in CIS and relapsing-remitting MS and supports its use as a predictive biomarker of disease activity. © 2017 EAN.

Supporting clinical rules engine in the adjustment of medication (SCREAM): protocol of a multicentre, prospective, randomised study.

PubMed

Mestres Gonzalvo, Carlota; de Wit, Hugo A J M; van Oijen, Brigit P C; Hurkens, Kim P G M; Janknegt, Rob; Schols, Jos M G A; Mulder, Wubbo J; Verhey, Frans R; Winkens, Bjorn; van der Kuy, Paul-Hugo M

2017-01-26

In the nursing home population, it is estimated that 1 in every 3 patients is polymedicated and given their considerable frailty, these patients are especially prone to adverse drug reactions. Clinical pharmacist-led medication reviews are considered successful interventions to improve medication safety in the inpatient setting. Due to the limited available evidence concerning the benefits of medication reviews performed in the nursing home setting, we propose a study aiming to demonstrate a positive effect that a clinical decision support system, as a health care intervention, may have on the target population. The primary objective of this study is to reduce the number of patients with at least one event when using the clinical decision support system compared to the regular care. These events consist of hospital referrals, delirium, falls, and/or deaths. This study is a multicentre, prospective, randomised study with a cluster group design. The randomisation will be per main nursing home physician and stratified per ward (somatic and psychogeriatric). In the intervention group the clinical decision support system will be used to screen medication list, laboratory values and medical history in order to obtain potential clinical relevant remarks. The remarks will be sent to the main physician and feedback will be provided whether the advice was followed or not. In the control group regular care will be applied. We strongly believe that by using a clinical decision support system, medication reviews are performed in a standardised way which leads to comparable results between patients. In addition, using a clinical decision support system eliminates the time factor to perform medication reviews as the major problems related to medication, laboratory values, indications and/or established patient characteristics will be directly available. In this way, and in order to make the medication review process complete, consultation within healthcare professionals and

How GPs implement clinical guidelines in everyday clinical practice--a qualitative interview study.

PubMed

Le, Jette V; Hansen, Helle P; Riisgaard, Helle; Lykkegaard, Jesper; Nexøe, Jørgen; Bro, Flemming; Søndergaard, Jens

2015-12-01

Clinical guidelines are considered to be essential for improving quality and safety of health care. However, interventions to promote implementation of guidelines have demonstrated only partial effectiveness and the reasons for this apparent failure are not yet fully understood. To investigate how GPs implement clinical guidelines in everyday clinical practice and how implementation approaches differ between practices. Individual semi-structured open-ended interviews with seven GPs who were purposefully sampled with regard to gender, age and practice form. Interviews were recorded, transcribed verbatim and then analysed using systematic text condensation. Analysis of the interviews revealed three different approaches to the implementation of guidelines in clinical practice. In some practices the GPs prioritized time and resources on collective implementation activities and organized their everyday practice to support these activities. In other practices GPs discussed guidelines collectively but left the application up to the individual GP whilst others again saw no need for discussion or collective activities depending entirely on the individual GP's decision on whether and how to manage implementation. Approaches to implementation of clinical guidelines vary substantially between practices. Supporting activities should take this into account. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clinical review: Long-term noninvasive ventilation

PubMed Central

Robert, Dominique; Argaud, Laurent

2007-01-01

Noninvasive positive ventilation has undergone a remarkable evolution over the past decades and is assuming an important role in the management of both acute and chronic respiratory failure. Long-term ventilatory support should be considered a standard of care to treat selected patients following an intensive care unit (ICU) stay. In this setting, appropriate use of noninvasive ventilation can be expected to improve patient outcomes, reduce ICU admission, enhance patient comfort, and increase the efficiency of health care resource utilization. Current literature indicates that noninvasive ventilation improves and stabilizes the clinical course of many patients with chronic ventilatory failure. Noninvasive ventilation also permits long-term mechanical ventilation to be an acceptable option for patients who otherwise would not have been treated if tracheostomy were the only alternative. Nevertheless, these results appear to be better in patients with neuromuscular/-parietal disorders than in chronic obstructive pulmonary disease. This clinical review will address the use of noninvasive ventilation (not including continuous positive airway pressure) mainly in diseases responsible for chronic hypoventilation (that is, restrictive disorders, including neuromuscular disease and lung disease) and incidentally in others such as obstructive sleep apnea or problems of central drive. PMID:17419882

The mPED randomized controlled clinical trial: applying mobile persuasive technologies to increase physical activity in sedentary women protocol.

PubMed

Fukuoka, Yoshimi; Komatsu, Judith; Suarez, Larry; Vittinghoff, Eric; Haskell, William; Noorishad, Tina; Pham, Kristin

2011-12-14

Despite the significant health benefits of regular physical activity, approximately half of American adults, particularly women and minorities, do not meet the current physical activity recommendations. Mobile phone technologies are readily available, easily accessible and may provide a potentially powerful tool for delivering physical activity interventions. However, we need to understand how to effectively apply these mobile technologies to increase and maintain physical activity in physically inactive women. The purpose of this paper is to describe the study design and protocol of the mPED (mobile phone based physical activity education) randomized controlled clinical trial that examines the efficacy of a 3-month mobile phone and pedometer based physical activity intervention and compares two different 6-month maintenance interventions. A randomized controlled trial (RCT) with three arms; 1) PLUS (3-month mobile phone and pedometer based physical activity intervention and 6-month mobile phone diary maintenance intervention), 2) REGULAR (3-month mobile phone and pedometer based physical activity intervention and 6-month pedometer maintenance intervention), and 3) CONTROL (pedometer only, but no intervention will be conducted). A total of 192 physically inactive women who meet all inclusion criteria and successfully complete a 3-week run-in will be randomized into one of the three groups. The mobile phone serves as a means of delivering the physical activity intervention, setting individualized weekly physical activity goals, and providing self-monitoring (activity diary), immediate feedback and social support. The mobile phone also functions as a tool for communication and real-time data capture. The primary outcome is objectively measured physical activity. If efficacy of the intervention with a mobile phone is demonstrated, the results of this RCT will be able to provide new insights for current behavioral sciences and mHealth. ClinicalTrials.gov#:NCTO1280812.