A New Observation Technique Applied to Early/Fast VLF Scattering Events

NASA Astrophysics Data System (ADS)

Kotovsky, D. A.; Moore, R. C.

2012-12-01

Early/fast very low frequency (VLF, 3-30 kHz) events are understood to result from ionospheric conductivity changes associated with lightning. Early/fast amplitude and phase perturbations have been observed coincidentally with various optical observations of transient luminous events (TLEs), including elves, sprites, and sprite halos, each of which can have temporal characteristics consistent with those of early/fast VLF events. It is yet unresolved, however, whether a specific type of TLE is directly related to the ionospheric conductivity changes responsible for the typical early/fast event. In this paper, we present spread spectrum VLF scattering observations of early/fast events. The spread spectrum analysis technique determines the amplitude and phase of a subionospherically propagating VLF signal as a function of time during the early/fast event and as a function of frequency across the 200 Hz bandwidth of the VLF transmission. VLF scattering observations, each identified with causative lightning logged by the National Lightning Detection Network (NLDN), are compared with the predictions of the Long-Wave Propagation Capability (LWPC) code, a three-dimensional earth-ionosphere waveguide propagation and scattering model. Theoretical predictions for VLF scattering from ionization changes associated with elves are compared with those associated with sprite halos, and each are compared with experimental observations. Results indicate that the observed frequency dependence of VLF scattering during early/fast events results from the combination of scattering source properties and Earth-ionosphere waveguide propagation effects. Observations are more consistent with the modeled amplitude perturbations associated with sprite halos than those with elves.

Insecure Attachment and Eating Pathology in Early Adolescence: Role of Emotion Regulation

ERIC Educational Resources Information Center

van Durme, Kim; Braet, Caroline; Goossens, Lien

2015-01-01

The present study investigated whether associations exist between attachment dimensions toward mother and different forms of eating pathology (EP) in a group of early adolescent boys and girls, and whether these associations were mediated by maladaptive emotion regulation (ER) strategies. Developmentally appropriate self-report questionnaires were…

Operational early warning platform for extreme meteorological events

NASA Astrophysics Data System (ADS)

Mühr, Bernhard; Kunz, Michael

2015-04-01

Operational early warning platform for extreme meteorological events Most natural disasters are related to extreme weather events (e.g. typhoons); weather conditions, however, are also highly relevant for humanitarian and disaster relief operations during and after other natural disaster like earthquakes. The internet service "Wettergefahren-Frühwarnung" (WF) provides various information on extreme weather events, especially when these events are associated with a high potential for large damage. The main focus of the platform is on Central Europe, but major events are also monitored worldwide on a daily routine. WF provides high-resolution forecast maps for many weather parameters which allow detailed and reliable predictions about weather conditions during the next days in the affected areas. The WF service became operational in February 2004 and is part of the Center for Disaster Management and Risk Reduction Technology (CEDIM) since 2007. At the end of 2011, CEDIM embarked a new type of interdisciplinary disaster research termed as forensic disaster analysis (FDA) in near real time. In case of an imminent extreme weather event WF plays an important role in CEDIM's FDA group. It provides early and precise information which are always available and updated several times during a day and gives advice and assists with articles and reports on extreme events.

A metabolic switch toward lipid use in glycolytic muscle is an early pathologic event in a mouse model of amyotrophic lateral sclerosis

PubMed Central

Palamiuc, Lavinia; Schlagowski, Anna; Ngo, Shyuan T; Vernay, Aurelia; Dirrig-Grosch, Sylvie; Henriques, Alexandre; Boutillier, Anne-Laurence; Zoll, Joffrey; Echaniz-Laguna, Andoni; Loeffler, Jean-Philippe; René, Frédérique

2015-01-01

Amyotrophic lateral sclerosis (ALS) is the most common fatal motor neuron disease in adults. Numerous studies indicate that ALS is a systemic disease that affects whole body physiology and metabolic homeostasis. Using a mouse model of the disease (SOD1G86R), we investigated muscle physiology and motor behavior with respect to muscle metabolic capacity. We found that at 65 days of age, an age described as asymptomatic, SOD1G86R mice presented with improved endurance capacity associated with an early inhibition in the capacity for glycolytic muscle to use glucose as a source of energy and a switch in fuel preference toward lipids. Indeed, in glycolytic muscles we showed progressive induction of pyruvate dehydrogenase kinase 4 expression. Phosphofructokinase 1 was inhibited, and the expression of lipid handling molecules was increased. This mechanism represents a chronic pathologic alteration in muscle metabolism that is exacerbated with disease progression. Further, inhibition of pyruvate dehydrogenase kinase 4 activity with dichloroacetate delayed symptom onset while improving mitochondrial dysfunction and ameliorating muscle denervation. In this study, we provide the first molecular basis for the particular sensitivity of glycolytic muscles to ALS pathology. PMID:25820275

Videothoracoscopy in the diagnosis of intrathoracic pathology: early experience.

PubMed Central

Waller, D. A.; Hasan, A.; Forty, J.; Morritt, G. N.

1994-01-01

We report our experience using the new technique of videothoracoscopy in the diagnosis of intrathoracic pathology. In the last 12 months, 40 patients (24 male; 16 female) have undergone investigation by this method. Lung biopsy has been performed in 17 patients, pleural biopsy in 20 patients and mediastinal biopsy in three patients. The majority had been referred after other investigations had been inconclusive. All biopsies were diagnostic except one mediastinal biopsy. This early experience suggests that videothoracoscopic biopsy is a well-tolerated technique with high diagnostic yield. PMID:8154806

Normative development of the Child Behavior Checklist Dysregulation Profile from early childhood to adolescence: Associations with personality pathology.

PubMed

Deutz, Marike H F; Vossen, Helen G M; De Haan, Amaranta D; Deković, Maja; Van Baar, Anneloes L; Prinzie, Peter

2018-05-01

The Dysregulation Profile (DP) is a broad indicator of concurrent affective, behavioral, and cognitive dysregulation, often measured with the anxious/depressed, aggressive behavior, and attention problems syndrome scales of the Child Behavior Checklist. Despite an expanding body of research on the DP, knowledge of the normative developmental course of the DP from early childhood to adolescence is lacking. Furthermore, although we know that the DP longitudinally predicts personality pathology, no research yet has examined whether next to the DP in early childhood, the rate of change of the DP across development predicts personality pathology. Therefore, using cohort-sequential latent growth modeling in a population-based sample (N = 668), we examined the normative developmental course of mother-reported DP from ages 4 to 17 years and its associations with a wide range of adolescent-reported personality pathology dimensions 3 years later. The results showed that the DP follows a nonlinear developmental course with a peak in early adolescence. The initial level of the DP at age 4 and, to a lesser extent, the rate of change in the DP predicted a range of personality pathology dimensions in late adolescence. The findings suggest that the DP is a broad developmental precursor of personality pathology in late adolescence.

Early Warning and Early Action during the 2015-16 El Nino Event

NASA Astrophysics Data System (ADS)

Robertson, A. W.; Goddard, L. M.

2016-12-01

Strong El Niño events have a marked impact on regional climate worldwide through their influence on large-scale atmospheric circulation. As a result, seasonal climate forecasts show greater skill during El Niño events, which provide communities, governments and humanitarian agencies greater ability to plan and prepare. The scientific community has advanced considerably in the quality and content of information provided about El Niño and its impacts. As a result, society has become better aware of and engaged with this information. This talk will present some details on how we navigate the fine line between expectations and probabilistic forecasts, and how this information was used during the 2015-16 El Niño event. Examples are drawn from the health sector and food security community. Specific attention will be given to the importance of problem-focus and data availability in the appropriate tailoring of climate information for Early Warning/Early Action.

Pathological implications of cell cycle re-entry in Alzheimer disease.

PubMed

Bonda, David J; Lee, Hyun-pil; Kudo, Wataru; Zhu, Xiongwei; Smith, Mark A; Lee, Hyoung-gon

2010-06-29

The complex neurodegeneration underlying Alzheimer disease (AD), although incompletely understood, is characterised by an aberrant re-entry into the cell cycle in neurons. Pathological evidence, in the form of cell cycle markers and regulatory proteins, suggests that cell cycle re-entry is an early event in AD, which precedes the formation of amyloid-beta plaques and neurofibrillary tangles (NFTs). Although the exact mechanisms that induce and mediate these cell cycle events in AD are not clear, significant advances have been made in further understanding the pathological role of cell cycle re-entry in AD. Importantly, recent studies indicate that cell cycle re-entry is not a consequence, but rather a cause, of neurodegeneration, suggesting that targeting of cell cycle re-entry may provide an opportunity for therapeutic intervention. Moreover, multiple inducers of cell cycle re-entry and their interactions in AD have been proposed. Here, we review the most recent advances in understanding the pathological implications of cell cycle re-entry in AD.

Investigations into Retinal Pathology in the Early Stages of a Mouse Model of Alzheimer’s Disease

PubMed Central

Chidlow, Glyn; Wood, John P.M.; Manavis, Jim; Finnie, John; Casson, Robert J.

2016-01-01

There is increasing recognition that visual performance is impaired in early stages of Alzheimer’s disease (AD); however, no consensus exists as to the mechanisms underlying this visual dysfunction, in particular regarding the timing, nature, and extent of retinal versus cortical pathology. If retinal pathology presents sufficiently early, it offers great potential as a source of novel biomarkers for disease diagnosis. The current project utilized an array of immunochemical and molecular tools to perform a characterization of retinal pathology in the early stages of disease progression using a well-validated mouse model of AD (APPSWE/PS1ΔE9). Analytical endpoints included examination of aberrant amyloid and tau in the retina, quantification of any neuronal degeneration, delineation of cellular stress responses of neurons and particularly glial cells, and investigation of oxidative stress. Brain, eyes, and optic nerves were taken from transgenic and wild-type mice of 3 to 12 months of age and processed for immunohistochemistry, qPCR, or western immunoblotting. The results revealed robust expression of the human APP transgene in the retinas of transgenic mice, but a lack of identifiable retinal pathology during the period when amyloid deposits were dramatically escalating in the brain. We were unable to demonstrate the presence of amyloid plaques, dystrophic neurites, neuronal loss, macro- or micro-gliosis, aberrant cell cycle re-entry, oxidative stress, tau hyperphosphorylation, or upregulations of proinflammatory cytokines or stress signaling molecules in the retina. The overall results do not support the hypothesis that detectable retinal pathology occurs concurrently with escalating amyloid deposition in the brains of APPSWE/PS1ΔE9 mice. PMID:28035930

Impact of COX2 genotype, ER status and body constitution on risk of early events in different treatment groups of breast cancer patients.

PubMed

Markkula, Andrea; Simonsson, Maria; Rosendahl, Ann H; Gaber, Alexander; Ingvar, Christian; Rose, Carsten; Jernström, Helena

2014-10-15

The COX2 rs5277 (306G>C) polymorphism has been associated with inflammation-associated cancers. In breast cancer, tumor COX-2 expression has been associated with increased estrogen levels in estrogen receptor (ER)-positive and activated Akt-pathway in ER-negative tumors. Our study investigated the impact of COX2 genotypes on early breast cancer events and treatment response in relation to tumor ER status and body constitution. In Sweden, between 2002 and 2008, 634 primary breast cancer patients, aged 25-99 years, were included. Disease-free survival was assessed for 570 rs5277-genotyped patients. Body measurements and questionnaires were obtained preoperatively. Clinical data, patient- and tumor-characteristics were obtained from questionnaires, patients' charts, population registries and pathology reports. Minor allele(C) frequency was 16.1%. Genotype was not linked to COX-2 tumor expression. Median follow-up was 5.1 years. G/G genotype was not associated with early events in patients with ER-positive tumors, adjusted HR 0.77 (0.46-1.29), but conferred an over 4-fold increased risk in patients with ER-negative tumors, adjusted HR 4.41 (1.21-16.02)(p(interaction) = 0.015). Chemotherapy-treated G/G-carriers with a breast volume ≥ 850 ml had an increased risk of early events irrespective of ER status, adjusted HR 8.99 (1.14-70.89). Endocrine-treated C-allele carriers with ER-positive tumors and a breast volume ≥ 850 ml had increased risk of early events, adjusted HR 2.30 (1.12-4.75). COX2 genotype, body constitution and ER status had a combined effect on the risk of early events and treatment response. The high risk for early events in certain subgroups of patients suggests that COX2 genotype in combination with body measurements may identify patients in need of more personalized treatment. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

[On "early pathologic anatomy" and "anatomy of medical structure": continuity or point of epistemological rupture?].

PubMed

Lellouch, Alain

2006-06-01

The aim of this paper is to analyse the technical, conceptual and institutional changes from which, through macroscopic pathology, a new medical science (microscopic pathology) emerged. The "early" pathology was mainly implemented by the Ecole de Paris, at the beginning of the 19th century. After 1850, histo-pathology emerged, in German university institutes (which were separate buildings from the wards and from the dissecting rooms of the hospitals). The birth of histo-pathology is also linked with technical improvements in mass manufactured microscopes, with better techniques for fixing and staining histological samples and lastly, in (1848) withVirchow's cellular theory. Among French doctors, only one, the very famous physician Jean-Martin Charcot (1825-1893) was aware of these dramatic changes. Charcot wrote many texts which are testimonies of an epistemological rupture between two very different types of medicine, the old French "médecine d'hôpital" and the new "lab medicine", developed in German speaking countries and based on the microscope.

Social anxiety and negative early life events in university students.

PubMed

Binelli, Cynthia; Ortiz, Ana; Muñiz, Armando; Gelabert, Estel; Ferraz, Liliana; S Filho, Alaor; Crippa, José Alexandre S; Nardi, Antonio E; Subirà, Susana; Martín-Santos, Rocío

2012-06-01

There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i) the loss of someone close, (ii) emotional abuse, (iii) physical abuse, (iv) family violence, and (v) sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. Mean (SD) age was 21 (4.5), 75% female, LSAS score was 40 (DP = 22), 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03). None of the remaining stressors produced a significant increase in LSAS score (p > 0.05). University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population.

The Relationship Between Early Life Events, Parental Attachment, and Psychopathic Tendencies in Adolescent Detainees.

PubMed

Christian, Erica J; Meltzer, Christine L; Thede, Linda L; Kosson, David S

2017-04-01

Despite increasing interest in understanding psychopathic traits in youth, the role of early environmental factors in the development of psychopathic traits is not well understood. No prior studies have directly examined the relationship between early life events and psychopathic traits. We examined links between life events in the first 4 years of life and indices of the core affective and interpersonal components of psychopathy. Additionally, we examined relationships between early life events, psychopathic traits, and attachment to parents among 206 adjudicated adolescents. Results indicated that the total number of early life events was positively correlated with indices of the affective component of psychopathy. Moreover, psychopathic traits moderated the relationship between the number of early life events and later reports of attachment to parents. Findings suggest that early environmental factors could have important implications for the development of psychopathic traits and may impact attachment to parents for youth with psychopathic traits.

Method for early detection of cooling-loss events

DOEpatents

Bermudez, Sergio A.; Hamann, Hendrik; Marianno, Fernando J.

2015-06-30

A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

Method for early detection of cooling-loss events

DOEpatents

Bermudez, Sergio A.; Hamann, Hendrik F.; Marianno, Fernando J.

2015-12-22

A method of detecting cooling-loss event early is provided. The method includes defining a relative humidity limit and change threshold for a given space, measuring relative humidity in the given space, determining, with a processing unit, whether the measured relative humidity is within the defined relative humidity limit, generating a warning in an event the measured relative humidity is outside the defined relative humidity limit and determining whether a change in the measured relative humidity is less than the defined change threshold for the given space and generating an alarm in an event the change is greater than the defined change threshold.

Iron accumulation in multiple sclerosis: an early pathogenic event.

PubMed

LeVine, Steven M; Bilgen, Mehmet; Lynch, Sharon G

2013-03-01

Iron has been shown to accumulate in deep gray matter structures in many forms of multiple sclerosis (MS), but detecting its presence early in the disease course (e.g., clinically isolated syndrome [CIS]) has been less clear. Here, we review a recent study where MRI scanning at 7 T together with susceptibility mapping was performed to assess iron deposition in CIS and control subjects. Susceptibility indicative of iron deposition was found to be increased in the globus pallidus, caudate, putamen and pulvinar of CIS patients compared with controls. The findings suggest that iron deposition is a pathological change that occurs early in the development of MS. Identifying the mechanisms of iron accumulation and determining whether iron promotes pathogenesis in MS are important areas of future research.

Somatic POLE exonuclease domain mutations are early events in sporadic endometrial and colorectal carcinogenesis, determining driver mutational landscape, clonal neoantigen burden and immune response.

PubMed

Temko, Daniel; Van Gool, Inge C; Rayner, Emily; Glaire, Mark; Makino, Seiko; Brown, Matthew; Chegwidden, Laura; Palles, Claire; Depreeuw, Jeroen; Beggs, Andrew; Stathopoulou, Chaido; Mason, John; Baker, Ann-Marie; Williams, Marc; Cerundolo, Vincenzo; Rei, Margarida; Taylor, Jenny C; Schuh, Anna; Ahmed, Ahmed; Amant, Frédéric; Lambrechts, Diether; Smit, Vincent Thbm; Bosse, Tjalling; Graham, Trevor A; Church, David N; Tomlinson, Ian

2018-03-31

Genomic instability, which is a hallmark of cancer, is generally thought to occur in the middle to late stages of tumourigenesis, following the acquisition of permissive molecular aberrations such as TP53 mutation or whole genome doubling. Tumours with somatic POLE exonuclease domain mutations are notable for their extreme genomic instability (their mutation burden is among the highest in human cancer), distinct mutational signature, lymphocytic infiltrate, and excellent prognosis. To what extent these characteristics are determined by the timing of POLE mutations in oncogenesis is unknown. Here, we have shown that pathogenic POLE mutations are detectable in non-malignant precursors of endometrial and colorectal cancer. Using genome and exome sequencing, we found that multiple driver mutations in POLE-mutant cancers show the characteristic POLE mutational signature, including those in genes conventionally regarded as initiators of tumourigenesis. In POLE-mutant cancers, the proportion of monoclonal predicted neoantigens was similar to that in other cancers, but the absolute number was much greater. We also found that the prominent CD8 + T-cell infiltrate present in POLE-mutant cancers was evident in their precursor lesions. Collectively, these data indicate that somatic POLE mutations are early, quite possibly initiating, events in the endometrial and colorectal cancers in which they occur. The resulting early onset of genomic instability may account for the striking immune response and excellent prognosis of these tumours, as well as their early presentation. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Early pathology in sleep studies of patients with familial Creutzfeldt-Jakob disease.

PubMed

Givaty, Gili; Maggio, Nicola; Cohen, Oren S; Blatt, Ilan; Chapman, Joab

2016-10-01

In this study, we aimed to assess sleep function in patients with recent-onset familial Creutzfeldt-Jakob disease (fCJD). The largest cluster of fCJD patients is found in Jews of Libyan origin, linked to the prion protein gene (PRNP) E200K mutation. The high index of suspicion in these patients often leads to early diagnosis, with complaints of insomnia being a very common presenting symptom of the disease. The study included 10 fCJD patients diagnosed by clinical manifestations, magnetic resonance imaging (MRI) scan of the brain, elevated tau protein in the cerebrospinal fluid (CSF) and positive PRNP E200K mutation. Standard polysomnography was performed after a brief interview confirming the presence of sleep disturbances. All patients showed a pathological sleep pattern according to all scoring evaluation settings. The sleep stages were characterized by (i) disappearance of sleep spindles; (ii) outbursts of periodic sharp waves and shallowing of sleep consisting in increased Stage 2 and wake periods during the night, as well as decrease of slow-wave sleep and rapid eye movement (REM) sleep. Recordings of respiratory functions reported irregular breathing with central and obstructive apnea and hypopnea. The typical hypotonia occurring during the night and atonia during REM sleep were replaced by hyperactive sleep consisting of multiple jerks, movements and parasomnia (mainly talking) throughout the night. In conclusion, we report unique pathological sleep patterns in early fCJD associated with the E200K mutation. Specific respiratory disturbances and lack of atonia could possibly serve as new, early diagnostic tools in the disease. © 2016 European Sleep Research Society.

Placental pathology in early intrauterine growth restriction associated with maternal hypertension.

PubMed

Veerbeek, J H W; Nikkels, P G J; Torrance, H L; Gravesteijn, J; Post Uiterweer, E D; Derks, J B; Koenen, S V; Visser, G H A; Van Rijn, B B; Franx, A

2014-09-01

To identify key pathological characteristics of placentas from pregnancies complicated by early intrauterine growth restriction, and to examine their relations with maternal hypertensive disease and umbilical artery Doppler waveform abnormalities. Single-center retrospective cohort study of singleton pregnancies with abnormal umbilical artery Doppler flow patterns resulting in a live birth <34 weeks of a baby with a weight <10th percentile for gestational age. Umbilical artery end diastolic flow was classified as being either present or absent/reversed (AREDF). Data were stratified into intrauterine growth restriction with or without hypertensive disease and pathological characteristics were compared between these various conditions according to predefined scoring criteria. Among 164 placentas studied, we found high rates of characteristic histopathological features that were associated with intrauterine growth restriction, including infarction (>5% in 42%), chronic villitis (21%), chronic chorioamnionitis (36%), membrane necrosis (20%), elevated nucleated red blood cells (89%), increased syncytial knotting (93%), increased villous maturation (98%), fetal thrombosis (32%) and distal villous hypoplasia (35%). Chronic inflammation of fetal membranes and syncytial knotting were more common in women with concomitant hypertensive disease as compared to women with normotensive IUGR (p < 0.05). Placentas from women with umbilical artery AREDF were more likely to show increased numbers of nucleated red blood cells and distal villous hypoplasia (p < 0.05). Placentas of women with early IUGR show high rates of several histological aberrations. Further, concomitant maternal hypertension is associated with characteristic inflammatory changes and umbilical artery AREDF with signs of chronic hypoxia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Changes in pathology test ordering by early career general practitioners: a longitudinal study.

PubMed

Magin, Parker J; Tapley, Amanda; Morgan, Simon; Henderson, Kim; Holliday, Elizabeth G; Davey, Andrew R; Ball, Jean; Catzikiris, Nigel F; Mulquiney, Katie J; van Driel, Mieke L

2017-07-17

To assess the number of pathology tests ordered by general practice registrars during their first 18-24 months of clinical general practice. Longitudinal analysis of ten rounds of data collection (2010-2014) for the Registrar Clinical Encounters in Training (ReCEnT) study, an ongoing, multicentre, cohort study of general practice registrars in Australia. The principal analysis employed negative binomial regression in a generalised estimating equations framework (to account for repeated measures on registrars).Setting, participants: General practice registrars in training posts with five of 17 general practice regional training providers in five Australian states. The registrar participation rate was 96.4%. Number of pathology tests requested per consultation. The time unit for analysis was the registrar training term (the 6-month full-time equivalent component of clinical training); registrars contributed data for up to four training terms. 876 registrars contributed data for 114 584 consultations. The number of pathology tests requested increased by 11% (95% CI, 8-15%; P < 0.001) per training term. Contrary to expectations, pathology test ordering by general practice registrars increased significantly during their first 2 years of clinical practice. This causes concerns about overtesting. As established general practitioners order fewer tests than registrars, test ordering may peak during late vocational training and early career practice. Registrars need support during this difficult period in the development of their clinical practice patterns.

[Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology].

PubMed

Baliasnyĭ, M M

1991-01-01

Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness.

Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model.

PubMed

Mori, Yuki; Murakami, Masaaki; Arima, Yasunobu; Zhu, Dasong; Terayama, Yasuo; Komai, Yutaka; Nakatsuji, Yuji; Kamimura, Daisuke; Yoshioka, Yoshichika

2014-02-01

Magnetic resonance imaging (MRI) is widely employed for the diagnosis of multiple sclerosis (MS). However, sometimes, the lesions found by MRI do not correlate with the neurological impairments observed in MS patients. We recently showed autoreactive T cells accumulate in the fifth lumbar cord (L5) to pass the blood-brain barrier and cause inflammation in the central nervous system of experimental autoimmune encephalomyelitis (EAE) mice, an MS model. We here investigated this early event using ultrahigh-field MRI. T2-weighted image signals, which conform to the water content, increased in L4 and L5 during the development of EAE. At the same time, the sizes of L4 and L5 changed. Moreover, angiographic images of MRI showed branch positions of the blood vessels in the lower lumbar cords were significantly altered. Interestingly, EAE mice showed occluded and thickened vessels, particularly during the peak phase, followed by reperfusion in the remission phase. Additionally, demyelination regions of some MS patients had increased lactic acid content, suggesting the presence of ischemic events. These results suggest that inflammation-mediated alterations in the lower lumbar cord change the homeostasis of the spinal cord and demonstrate that ultrahigh-field MRI enables the detection of previously invisible pathological alterations in EAE.

Self-esteem and peer-perceived social status in early adolescence and prediction of eating pathology in young adulthood.

PubMed

Smink, Frédérique R E; van Hoeken, Daphne; Dijkstra, Jan Kornelis; Deen, Mathijs; Oldehinkel, Albertine J; Hoek, Hans W

2018-04-27

Self-esteem is implied as a factor in the development of eating disorders. In adolescence peers have an increasing influence. Support for the role of self-esteem in eating disorders is ambiguous and little is known about the influence of social status as judged by others. The present study investigates whether self-esteem and peer status in early adolescence are associated with eating pathology in young adulthood. This study is part of TRAILS, a longitudinal cohort study on mental health and social development from preadolescence into adulthood. At age 11, participants completed the Self-Perception Profile for Children, assessing global self-esteem and self-perceptions regarding social acceptance, physical appearance, and academic competence. At age 13, peer status among classmates was assessed regarding likeability, physical attractiveness, academic performance, and popularity in a subsample of 1,007 participants. The Eating Disorder Diagnostic Scale was administered at age 22. The present study included peer-nominated participants with completed measures of self-perception at age 11 and eating pathology at age 22 (N = 732; 57.8% female). In a combined model, self-perceived physical attractiveness at age 11 and peer popularity at age 13 were inversely correlated with eating pathology at 22 years, while likeability by peers at age 13 was positively related to eating pathology. Both self-perceptions and peer status in early adolescence are significant predictors of eating pathology in young adults. Specific measures of self-esteem and peer-perceived status may be more relevant to the prediction of eating pathology than a global measure of self-esteem. © 2018 The Authors International Journal of Eating Disorders Published by Wiley Periodicals, Inc.

Wedelolactone mitigates UVB induced oxidative stress, inflammation and early tumor promotion events in murine skin: plausible role of NFkB pathway.

PubMed

Ali, Farrah; Khan, Bilal Azhar; Sultana, Sarwat

2016-09-05

UVB (Ultra-violet B) radiation is one of the major etiological factors in various dermal pathology viz. dermatitis, actinic folliculitis, solar urticaria, psoriasis and cancer among many others. UVB causes toxic manifestation in tissues by inciting inflammatory and tumor promoting events. We have designed this study to assess the anti-inflammatory and anti-tumor promotion effect of Wedelolactone (WDL) a specific IKK inhibitor. Results indicate significant restoration of anti-oxidative enzymes due to WDL treatments. We also found that WDL was effective in mitigating inflammatory markers consisting of MPO (myeloperoxidase), Mast cells trafficking, Langerhans cells suppression and COX 2 expression up regulation due to UVB exposure. We also deduce that WDL presented a promising intervention in attenuating early tumor promotion events caused by UVB exposure as indicated by the results of ODC (Ornithine Decarboxylase), Thymidine assay, Vimentin and VEGF (Vascular-endothelial growth factor) expression. This study was able to provide substantial cues for the therapeutic ability of Wedelolactone against inflammatory and tumor promoting events in murine skin depicting plausible role of NFkB pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

In vivo characterization of cortical and white matter neuroaxonal pathology in early multiple sclerosis.

PubMed

Granberg, Tobias; Fan, Qiuyun; Treaba, Constantina Andrada; Ouellette, Russell; Herranz, Elena; Mangeat, Gabriel; Louapre, Céline; Cohen-Adad, Julien; Klawiter, Eric C; Sloane, Jacob A; Mainero, Caterina

2017-11-01

Neuroaxonal pathology is a main determinant of disease progression in multiple sclerosis; however, its underlying pathophysiological mechanisms, including its link to inflammatory demyelination and temporal occurrence in the disease course are still unknown. We used ultra-high field (7 T), ultra-high gradient strength diffusion and T1/T2-weighted myelin-sensitive magnetic resonance imaging to characterize microstructural changes in myelin and neuroaxonal integrity in the cortex and white matter in early stage multiple sclerosis, their distribution in lesional and normal-appearing tissue, and their correlations with neurological disability. Twenty-six early stage multiple sclerosis subjects (disease duration ≤5 years) and 24 age-matched healthy controls underwent 7 T T2*-weighted imaging for cortical lesion segmentation and 3 T T1/T2-weighted myelin-sensitive imaging and neurite orientation dispersion and density imaging for assessing microstructural myelin, axonal and dendrite integrity in lesional and normal-appearing tissue of the cortex and the white matter. Conventional mean diffusivity and fractional anisotropy metrics were also assessed for comparison. Cortical lesions were identified in 92% of early multiple sclerosis subjects and they were characterized by lower intracellular volume fraction (P = 0.015 by paired t-test), lower myelin-sensitive contrast (P = 0.030 by related-samples Wilcoxon signed-rank test) and higher mean diffusivity (P = 0.022 by related-samples Wilcoxon signed-rank test) relative to the contralateral normal-appearing cortex. Similar findings were observed in white matter lesions relative to normal-appearing white matter (all P < 0.001), accompanied by an increased orientation dispersion (P < 0.001 by paired t-test) and lower fractional anisotropy (P < 0.001 by related-samples Wilcoxon signed-rank test) suggestive of less coherent underlying fibre orientation. Additionally, the normal-appearing white matter in multiple sclerosis

ERP-based detection of brain pathology in rat models for preclinical Alzheimer's disease

NASA Astrophysics Data System (ADS)

Nouriziabari, Seyed Berdia

Early pathological features of Alzheimer's disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.

Pathology in Greece.

PubMed

Sakellariou, S; Patsouris, E

2015-11-01

Pathology is the field of medicine that studies diseases. Ancient Greece hosted some of the earliest societies that laid the structural foundations of pathology. Initially, knowledge was based on observations but later on the key elements of pathology were established based on the dissection of animals and the autopsy of human cadavers. Christianized Greece under Ottoman rule (1453-1821) was not conducive to the development of pathology. After liberation, however, a series of events took place that paved the way for the establishment and further development of the specialty. The appointment in 1849 of two Professors of Pathology at the Medical School of Athens for didactical purposes proved to be the most important step in fostering the field of pathology in modern Greece. Presently in Greece there are seven university departments and 74 pathology laboratories in public hospitals, employing 415 specialized pathologists and 90 residents. The First Department of Pathology at the Medical School of Athens University is the oldest (1849) and largest in Greece, encompassing most pathology subspecialties.

Correlation of placental pathology and perinatal outcomes with Hemoglobin A1c in early pregnancy in gravidas with pregestational diabetes mellitus.

PubMed

Starikov, Roman S; Inman, Kyle; Has, Phinnara; Iqbal, Sara N; Coviello, Elizabeth; He, Mai

2017-04-01

Data on the correlation among Hemoglobin A1c (HbA1c), placental pathology, and perinatal outcome in the pregestational diabetic population is severely lacking. We believe that this knowledge will enhance the management of pregnancies complicated by pregestational diabetes. We hypothesize that placental pathology correlates with glycemic control at an early gestational age. This is a retrospective cohort study conducted from 2003 to 2011 at a large tertiary care center. Women included had a singleton gestation, preexisting diabetes mellitus, and information about delivery and placental pathology available for review. Placental pathology and perinatal outcomes were compared across three groups of patients with differing HbA1c levels (<6.5%, 6.5-8.4%, and ≥8.5%). 293 placentas were examined. HbA1c was measured at a mean of 9.5week gestation. Median HbA1c was 7.5%, interquartile range 6.5%-8.9%. 23% of the cohort had HbA1c <6.5%, 41.9% between 6.5% and 8.4%, and 34.8% > 8.5%. BMI varied significantly by group (35.4 vs. 34.4 vs. 32.0 respectively, P = 0.04). Individual placental lesions did not vary with HbA1c levels. The incidence of acute chorioamnionitis differed significantly in the type 1 population and "distal villous hypoplasia" varied in the type 2 population. The results show that HbA1c values in early pregnancy are poor predictors of future placental pathologies. As a result, HbA1c values obtained during early gestation (which reflect the level of glycemic control over an extended period of time) do not correlate with any particular placental pathology, despite reflecting the potential for placental insults secondary to pre-gestational diabetes. Copyright © 2017. Published by Elsevier Ltd.

Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence.

PubMed

Humphreys, Kathryn L; Watts, Emily L; Dennis, Emily L; King, Lucy S; Thompson, Paul M; Gotlib, Ian H

2018-05-21

Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98 years (M = 11.38, SD = 1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5 years or after age 6 years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions

PubMed Central

Hendrickx, Debbie A. E.; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G.; van Eden, Corbert G.; Hol, Elly M.; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion. PMID:29312322

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions.

PubMed

Hendrickx, Debbie A E; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G; van Eden, Corbert G; Hol, Elly M; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1 , and ANO4 . Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16 , and OLR1 , and lipid uptake, such as CHIT1, GPNMB , and CCL18 . Except CCL18 , these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.

HannaH phase III randomised study: Association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up.

PubMed

Jackisch, Christian; Hegg, Roberto; Stroyakovskiy, Daniil; Ahn, Jin-Seok; Melichar, Bohuslav; Chen, Shin-Cheh; Kim, Sung-Bae; Lichinitser, Mikhail; Starosławska, Elżbieta; Kunz, Georg; Falcon, Silvia; Chen, Shou-Tung; Crepelle-Fléchais, Aulde; Heinzmann, Dominik; Shing, Mona; Pivot, Xavier

2016-07-01

In the phase III, open-label, randomised HannaH study, fixed-dose neoadjuvant-adjuvant subcutaneous trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer was non-inferior to standard weight-based intravenous infusion in terms of serum trough concentration and pathological complete response (pCR). Evidence suggests that pCR, particularly total pCR (tpCR), is likely to predict clinical benefit. We report associations between tpCR and event-free survival (EFS) from HannaH (the largest population from a single study of patients presenting with newly diagnosed HER2-positive breast cancer treated with neoadjuvant-adjuvant trastuzumab to date) plus long-term efficacy and safety. Eligible patients received four cycles of neoadjuvant docetaxel followed by four cycles of fluorouracil/epirubicin/cyclophosphamide administered concurrently with 3-weekly subcutaneous (600 mg fixed dose) or intravenous trastuzumab (8 mg/kg loading, 6 mg/kg maintenance doses). Post-surgery, patients received adjuvant trastuzumab as randomised to complete 1 year of standard treatment. In exploratory analyses, we used Cox regression to assess associations between tpCR and EFS. EFS rates per subgroup were estimated using the Kaplan-Meier method. Three-year EFS rates were 76% for subcutaneous and 73% for intravenous trastuzumab (unstratified hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.69-1.30; intention-to-treat population). Three-year overall survival rates were 92% for subcutaneous and 90% for intravenous trastuzumab (unstratified HR 0.76, 95% CI 0.44-1.32). tpCR was associated with a reduced risk of an EFS event: subcutaneous arm HR 0.38 (95% CI 0.22-0.65); intravenous arm HR 0.32 (95% CI 0.18-0.60). Results were similar for subgroups, including oestrogen receptor status. The few additional adverse events occurring during treatment-free follow-up were balanced between arms. Long-term efficacy supports the established non-inferiority of

Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

PubMed

Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

2014-10-13

Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (<1 hr) P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

Progressive Pathological Changes in Neurochemical Profile of the Hippocampus and Early Changes in the Olfactory Bulbs of Tau Transgenic Mice (rTg4510).

PubMed

Kim, Jieun; Choi, In-Young; Duff, Karen E; Lee, Phil

2017-06-01

Tauopathies such as Alzheimer's disease and frontotemporal lobe degeneration (FTLD-tau) dementia, characterized by pathologic aggregation of the microtubule-associated tau protein and formation of neurofibrillary tangles, have been linked to neurodegeneration and cognitive decline. The early detection of cerebral abnormalities and the identification of biological contributors to the continuous pathologic processes of neurodegeneration in tauopathies critically hinge on sensitive and reliable measures of biomarkers in the living brain. In this study, we measured alterations in a number of key neurochemicals associated with tauopathy-induced neurodegeneration in the hippocampus and the olfactory bulbs of a transgenic mouse model of FTLD-tauopathy, line rTg4510, using in vivo 1 H magnetic resonance spectroscopy at 9.4 T. The rTg4510 line develops tauopathy at a young age (4-5 months), reaching a severe stage by 8-12 months of age. Longitudinal measurement of neurochemical concentrations in the hippocampus of mice from 5 to 12 months of age showed significant progressive changes with distinctive disease staging patterns including N-acetylaspartate, myo-inositol, γ-aminobutyric acid, glutathione and glutamine. The accompanying hippocampal volume loss measured using magnetic resonance imaging showed significant correlation (p < 0.01) with neurochemical measurements. Neurochemical alterations in the olfactory bulbs were more pronounced than those in the hippocampus in rTg4510 mice. These results demonstrate progressive neuropathology in the mouse model and provide potential biomarkers of early neuropathological events and effective noninvasive monitoring of the disease progression and treatment efficacy, which can be easily translated to clinical studies.

The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome.

PubMed

Cadena, Anthony M; Flynn, JoAnne L; Fortune, Sarah M

2016-04-05

Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease. Copyright © 2016 Cadena et al.

Discordance in pathology report after central pathology review: Implications for breast cancer adjuvant treatment.

PubMed

Orlando, Laura; Viale, Giuseppe; Bria, Emilio; Lutrino, Eufemia Stefania; Sperduti, Isabella; Carbognin, Luisa; Schiavone, Paola; Quaranta, Annamaria; Fedele, Palma; Caliolo, Chiara; Calvani, Nicola; Criscuolo, Mario; Cinieri, Saverio

2016-12-01

Pathological predictive factors are the most important markers when selecting early breast cancer adjuvant therapy. In randomized clinical trials the variability in pathology report after central pathology review is noteworthy. We evaluated the discordance rate (DR) and inter-rater agreement between local and central histopathological report and the clinical implication on treatment decision. A retrospective analysis was conducted in a series of consecutive early breast cancer tumors diagnosed by local pathologists and subsequently reviewed at the Pathology Division of European Institute of Oncology. The inter-rater agreement (k) between local and central pathology was calculated for Ki-67, grading, hormone receptors (ER/PgR) and HER2/neu. The Bland-Altman plots were derived to determine discrepancies in Ki-67, ER and PgR. DR was calculated for ER/PgR and HER2. From 2007 to 2013, 187 pathology specimens from 10 Cancer Centers were reviewed. Substantial agreement was observed for ER (k0.612; 95% CI, 0538-0.686), PgR (k0.659; 95% CI, 0580-0.737), Ki-67 (k0.609; 95% CI, 0.534-0.684) and grading (k0.669; 95% CI, 0.569-0.769). Moderate agreement was found for HER2 (k0.546; 95% CI, 0444-0.649). DR was 9.5% (negativity to positivity) and 31.7% (positivity to negativity) for HER2 and 26.2% (negativity to positivity) and 12.5% (positivity to negativity) for ER/PgR. According to changes in Her2 and ER/PgR status, 23 (12.2%) and 33 (17.6%) systemic prescription were respectively modified. In our retrospective analysis, central pathological review has a significant impact in the decision-making process in early breast cancer, as shown in clinical trials. Further studies are warranted to confirm these provocative results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Early Alzheimer's disease-type pathology in the frontal cortex of wild mountain gorillas (Gorilla beringei beringei).

PubMed

Perez, Sylvia E; Sherwood, Chet C; Cranfield, Michael R; Erwin, Joseph M; Mudakikwa, Antoine; Hof, Patrick R; Mufson, Elliott J

2016-03-01

Amyloid beta (Aβ) and tau pathology have been described in the brains of captive aged great apes, but the natural progression of these age-related pathologies from wild great apes, including the gorilla, is unknown. In our previous study of Western lowland gorillas (Gorilla gorilla gorilla) who were housed in American Zoos and Aquariums-accredited facilities, we found an age-related increase in Aβ-positive plaques and vasculature, tau-positive astrocytes, oligodendrocyte coiled bodies, and neuritic clusters in the neocortex as well as hippocampus in older animals. Here, we demonstrate that aged wild mountain gorillas (Gorilla beringei beringei), who spent their entire lives in their natural habitat, also display an age-related increase in amyloid precursor protein (APP) and/or Aβ-immunoreactive blood vessels and plaques, but very limited tau pathology, in the frontal cortex. These results indicate that Aβ and tau lesions are age-related events that occur in the brain of gorillas living in captivity and in the wild. Copyright © 2016 Elsevier Inc. All rights reserved.

Early/fast VLF events produced by the quiescent heating of the lower ionosphere by thunderstorms

NASA Astrophysics Data System (ADS)

Kabirzadeh, R.; Marshall, R. A.; Inan, U. S.

2017-06-01

Large and easily distinguishable perturbations of the VLF transmitter signals due to interactions with thundercloud-driven ionospheric modifications have been observed and studied for about three decades. These events are called "early/fast VLF" or "early VLF" events due to their immediate detection (˜20 ms) after the causative lightning flash on the ground and the fast rise time of the perturbed signal. Despite many years of study, the physical mechanisms responsible for these perturbations are still under investigation. Modifications of the sustained heating level of the ionosphere due to a lightning flash has been previously proposed as the causative mechanism of early/fast VLF events. The perturbations predicted by this mechanism, however, have been much smaller than experimental observations of 0.2-1 dB or higher. In this study, by using an improved 3-D thundercloud electrostatic upward coupling model which uses a realistic geomagnetic field, we find that the sustained heating model can predict perturbations that are consistent with reported experimental observations. Modifications in the quiescent heating of the lower ionosphere by thundercloud fields by individual lightning flashes may thus account for some observations of early/fast VLF events.

Persistence of carbon release events through the peak of early Eocene global warmth

NASA Astrophysics Data System (ADS)

Kirtland Turner, Sandra; Sexton, Philip F.; Charles, Christopher D.; Norris, Richard D.

2014-10-01

The Early Eocene Climatic Optimum (53-50 million years ago) was preceded by approximately six million years of progressive global warming. This warming was punctuated by a series of rapid hyperthermal warming events triggered by the release of greenhouse gases. Over these six million years, the carbon isotope record suggests that the events became more frequent but smaller in magnitude. This pattern has been suggested to reflect a thermodynamic threshold for carbon release that was more easily crossed as global temperature rose, combined with a decrease in the size of carbon reservoirs during extremely warm conditions. Here we present a continuous, 4.25-million-year-long record of the stable isotope composition of carbonate sediments from the equatorial Atlantic, spanning the peak of early Eocene global warmth. A composite of this and pre-existing records shows that the carbon isotope excursions that identify the hyperthermals exhibit continuity in magnitude and frequency throughout the approximately 10-million-year period covering the onset, peak and termination of the Early Eocene Climate Optimum. We suggest that the carbon cycle processes behind these events, excluding the largest event, the Palaeocene-Eocene Thermal Maximum (about 56 million years ago), were not exceptional. Instead, we argue that the hyperthermals may reflect orbital forcing of the carbon cycle analogous to the mechanisms proposed to operate in the cooler Oligocene and Miocene.

Ophthalmic Vascular Events after Primary Unilateral Intra-arterial Chemotherapy for Retinoblastoma in Early and Recent Eras.

PubMed

Dalvin, Lauren A; Ancona-Lezama, David; Lucio-Alvarez, J Antonio; Masoomian, Babak; Jabbour, Pascal; Shields, Carol L

2018-06-16

To assess risk factors for ophthalmic vascular events after intra-arterial chemotherapy (IAC) for retinoblastoma. Retrospective cohort study. Patients who received unilateral IAC as primary treatment for retinoblastoma from January 1, 2009, to November 30, 2017, at a single center. Records were reviewed for patient demographics, tumor features, IAC parameters, and treatment-related vascular events in the early IAC era (2009-2011) compared with the recent era (2012-2017) using the t test and Fisher exact test. Change in event rates over time was assessed using Poisson regression analysis, with Spearman's rho used to test correlation. Rate of IAC-induced ophthalmic vascular events. There were 243 chemotherapy infusions in 76 eyes of 76 patients, divided into early (22 eyes, 57 infusions) and recent (54 eyes, 186 infusions) eras. Intra-arterial chemotherapy consisted of melphalan (243 infusions), topotecan (124 infusions), and carboplatin (9 infusions). A comparison (early vs. recent era) revealed fewer mean number of infusions (2.6 vs. 3.4, P = 0.02) with similar mean patient age and presenting tumor features. Event rates decreased over time (P < 0.01), with fewer ophthalmic vascular events (early era vs. recent era) in the recent era (59% vs. 9% per eye, 23% vs. 3% per infusion, P < 0.01), including peripheral retinal nonperfusion (5% vs. 2% per eye, P = 0.50), vitreous hemorrhage (9% vs. 2%, P = 0.20), subretinal hemorrhage (0% vs. 2%, P = 0.99), branch retinal vein occlusion (5% vs. 0%, P = 0.29), choroidal ischemia (14% vs. 4%, P = 0.14), and ophthalmic artery spasm/occlusion (27% vs. 0%, P < 0.01). Events did not correlate to patient age (P = 0.75), tumor diameter (P = 0.32), tumor thickness (P = 0.59), or cumulative dosage of melphalan (P = 0.13) or topotecan (P = 0.59). There were no IAC-induced vascular events in 72 infusions of 21 consecutively treated eyes in 2016 to 2017. Ophthalmic vascular events after IAC have decreased from the early era

Consequences of Serotonin Transporter Genotype and Early Adversity on Behavioral Profile – Pathology or Adaptation?

PubMed Central

Heiming, Rebecca S.; Sachser, Norbert

2010-01-01

This review focuses on how behavioral profile is shaped by early adversity in individuals with varying serotonin transporter (5-HTT) genotype. In a recent study on 5-HTT knockout mice Heiming et al. (2009) simulated a ‘dangerous environment‘ by confronting pregnant and lactating females with odor cues of unfamiliar males, indicating the risk of infant killing. Growing up in a dangerous environment induced increased anxiety-related behavior and decreased exploratory locomotion in the offspring, the effects being most pronounced in mice lacking 5-HTT expression. We argue that these alterations in behavioral profile represent adaptive maternal effects that help the individuals to cope with adversity. In principle, such effects of adversity on behavioral profile should not automatically be regarded as pathological. Rather and in accordance with modern evolutionary theory they may represent adaptations, although individuals with 5-HTT genotype induced susceptibility to adversity may be at risk of developing pathologies. PMID:21151780

Envy's pathology: Historical contexts

PubMed Central

Minou, Lina

2017-01-01

This article is concerned with the physicality of envy primarily in early –modern, but also in eighteenth-century health contexts. The discussion brings together descriptions of the effects of envy on the body of the envier, mainly from works of physiology and health preservation, but also from literary and spiritual writings. These depictions of envy are studied beyond their symbolism and with a view to establish whether they are meaningful according to the medical theories of the time in which they occur. The discussion begins by acknowledging the status of envy as a ‘disease’ and looks to the specific ways in which the discourse of envy conveys this sense. I find that in the early modern discourse envy is always pathological, that is, it is experienced as disease and signifies disease in general and several diseases in particular. Moreover, envy is uniquely placed to convey pathology on account of its being connected to inherently pathogenic elements of the humoural theory. Specifically, envy is physiologically connected to melancholy, and the way it is presented comes close to attributes assigned to black bile. In addition, envy realizes pathology, the occurrence of disease in the body, by impairing the vital process of digestion and thus depriving the person from proper nourishment and sustenance. The analysis further considers how this impairment of the body fits with the physiological manifestation of envy as ‘corrosion’ and ‘consumption’. Finding commonalities with other maladies mediated by these physiological signs the article concludes by considering the function of pathology in the conception of early modern envy. PMID:28748219

Sex differences of dental pathology in early modern samurai and commoners at Kokura in Japan.

PubMed

Oyamada, Joichi; Kitagawa, Yoshikazu; Hara, Masahito; Sakamoto, Junya; Matsushita, Takayuki; Tsurumoto, Toshiyuki; Manabe, Yoshitaka

2017-07-01

So-called "Ohaguro", teeth blackening, in the married females was a general custom regardless of class in the early modern period. As a result, Ohaguro was thought to have enhanced the acid resistance of tooth substance and tightened gingiva and prevented tooth morbidity due to periodontal disease. For investigation into the influence of Ohaguro, the skeletal remains of early modern samurai and commoners at Kokura were examined for differences in the dental pathology based on sex. Though females from archeological sites have significantly more carious teeth and antemortem tooth loss (AMTL) than males in the previous studies, the prevalence of caries and AMTL in males was higher than in females among the early modern samurai and commoners in Kokura. The efficacies of Ohaguro may influence the good dental health of females. On the other hand, as females were considered inferior to males under the feudal system in Japan, males, including children, might tend to consume more nutritious foods compared to females. However, those foods are certainly not better with regard to dental health, since those foods are more highly cariogenic. These factors may have caused higher caries and AMTL prevalence among males compared to females in early modern Kokura.

Early axonal damage and progressive myelin pathology define the kinetics of CNS histopathology in a mouse model of multiple sclerosis.

PubMed

Recks, Mascha S; Stormanns, Eva R; Bader, Jonas; Arnhold, Stefan; Addicks, Klaus; Kuerten, Stefanie

2013-10-01

Studies of MS histopathology are largely dependent on suitable animal models. While light microscopic analysis gives an overview of tissue pathology, it falls short in evaluating detailed changes in nerve fiber morphology. The ultrastructural data presented here and obtained from studies of myelin oligodendrocyte glycoprotein (MOG):35-55-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice delineate that axonal damage and myelin pathology follow different kinetics in the disease course. While myelin pathology accumulated with disease progression, axonal damage coincided with the initial clinical disease symptoms and remained stable over time. This pattern applied both to irreversible axolysis and early axonal pathology. Notably, these histopathological patterns were reflected by the normal-appearing white matter (NAWM), suggesting that the NAWM is also in an active neurodegenerative state. The data underline the need for neuroprotection in MS and suggest the MOG model as a highly valuable tool for the assessment of different therapeutic strategies. Copyright © 2013 Elsevier Inc. All rights reserved.

Ki-67 expression in early prostate cancer and associated pathological lesions.

PubMed Central

Feneley, M R; Young, M P; Chinyama, C; Kirby, R S; Parkinson, M C

1996-01-01

AIM: To assess cell proliferation in early prostate cancer and associated pathological lesions. METHODS: Using the Ki-67 antibody, the cell proliferation index was measured in early stage prostatic carcinoma in 37 incidental tumours diagnosed at transurethral prostatectomy (TURP) and in 20 low volume cancers treated by radical prostatectomy. Proliferation indexes have also been measured in areas of normal peripheral zone, transition zone hyperplasia, atrophic appearing lobules, and high grade prostatic intraepithelial neoplasia in the radical prostatectomy cases. RESULTS: In the TURP series the proliferation index correlated with grade and stage. Logistic regression analysis, however, showed that Gleason grade was the most reliable predictor of biopsy proven residual disease and clinical progression. In the radical series transition zone carcinoma the proliferation index was half that of peripheral zone carcinoma. The atrophic lobules also showed a high proliferation index of the same order as seen in the peripheral zone carcinoma. Normal peripheral zone showed the lowest proliferation index and in hyperplastic transition zone it was also less than the other areas. CONCLUSIONS: There is only limited support for the correlation of proliferation index with grade in early stage prostatic carcinoma. The findings do not suggest that proliferation index adds to the prognostic information given by grade and stage in pT1 disease. The significant difference in proliferation index in transition zone and peripheral zone carcinomas supports the morphological distinction of these tumour types and is consistent with differences in biological behaviour. The high proliferation index in lobules considered morphologically atrophic is reminiscent of previous observations in which carcinoma was spatially associated with atrophy. Images PMID:9038759

Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology.

PubMed

Wilson, Gabrielle R; Sim, Joe C H; McLean, Catriona; Giannandrea, Maila; Galea, Charles A; Riseley, Jessica R; Stephenson, Sarah E M; Fitzpatrick, Elizabeth; Haas, Stefan A; Pope, Kate; Hogan, Kirk J; Gregg, Ronald G; Bromhead, Catherine J; Wargowski, David S; Lawrence, Christopher H; James, Paul A; Churchyard, Andrew; Gao, Yujing; Phelan, Dean G; Gillies, Greta; Salce, Nicholas; Stanford, Lynn; Marsh, Ashley P L; Mignogna, Maria L; Hayflick, Susan J; Leventer, Richard J; Delatycki, Martin B; Mellick, George D; Kalscheuer, Vera M; D'Adamo, Patrizia; Bahlo, Melanie; Amor, David J; Lockhart, Paul J

2014-12-04

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ∼45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of α-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of α-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of α-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer

PubMed Central

Saslow, Debbie; Solomon, Diane; Lawson, Herschel W.; Killackey, Maureen; Kulasingam, Shalini; Cain, Joanna; Garcia, Francisco A. R.; Moriarty, Ann; Waxman, Alan; Wilbur, David; Wentzensen, Nicolas; Downs, Levi; Spitzer, Mark; Moscicki, Anna-Barbara; Saraiya, Mona; Franco, Eduardo L.; Stoler, Mark H.; Schiffman, Mark; Castle, Philip E.; Myers, Evan R.

2013-01-01

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. PMID:22418039

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology Screening Guidelines for the Prevention and Early Detection of Cervical Cancer

PubMed Central

Saslow, Debbie; Solomon, Diane; Lawson, Herschel W.; Killackey, Maureen; Kulasingam, Shalini; Cain, Joanna; Garcia, Francisco A. R.; Moriarty, Ann; Waxman, Alan; Wilbur, David; Wentzensen, Nicolas; Downs, Levi; Spitzer, Mark; Moscicki, Anna-Barbara; Franco, Eduardo L.; Stoler, Mark H.; Schiffman, Mark; Castle, Philip E.; Myers, Evan R.

2013-01-01

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium cosponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. PMID:22422631

[Per os early nutrition for colorectal pathology susceptible of laparoscopy-assisted surgery].

PubMed

Fernández de Bustos, A; Creus Costas, G; Pujol Gebelli, J; Virgili Casas, N; Pita Mercé, A M

2006-01-01

Current less invasive surgical techniques, the use of new analgesic and anesthetic drugs, and early mobilization ("multimodal surgical strategies") reduce the occurrence of post-surgery paralytic ileus and vomiting, making possible early nutrition by the digestive route. With these premises, a nutrition protocol was designed for its implementation in colorectal pathology susceptible of laparoscopy-assisted surgery. to assess the efficacy of this protocol that comprises 3 phases. Phase I: home preparation with 7 days duration; low-residues and insoluble fiber diet, supplemented with 400 mL of hyperproteic polymeric formula with no lactose or fiber, bowel cleansing 2 days prior to surgery and hydration with water, sugared infusions, and vegetable broth. Phase II: immediate post-surgical period with watery diet for 3 days with polymeric diet with no fiber. Phase III: semi-solid diet with no residues, nutritional formula and progressive reintroduction of food intake in four stages of varying duration according to surgery and digestive tolerance. prospective study performed at our hospital with patients from our influence area, from February 2003 to May 2004, including 25 patients, 19 men and 6 women, with mean age of 63.3 years (range = 33-79) and mean body mass index of 26.25 kg/m2 (range = 20.84-31.3), all of them suffering from colorectal pathology susceptible of laparoscopy-assisted surgery, and to which the study protocol was applied. Fourteen left hemicolectomies, 5 right hemicolectomies, 4 low anterior resections with protective colostomy, and subtotal colectomies and lateral ileostomy were done. Final diagnoses were: 3 diverticular diseases; 3 adenomas; 7 rectosigmoidal neoplasms; and 12 large bowel neoplasms in other locations. The pathology study confirmed: pT3N0 (n = 7), pT3N1 (n = 3), pT3N2 (n = 1), and pT3N1M1 (n = 1), pT1N0 (n = 4), pT1N1 (n = 2), pTis (n = 1). Twelve patients were started on adjuvant therapy of which 3 had received an initial treatment

Bruised Witness: Bernard Spilsbury and the Performance of Early Twentieth-Century English Forensic Pathology

PubMed Central

BURNEY, IAN; PEMBERTON, NEIL

2011-01-01

This article explores the status, apparatus and character of forensic pathology in the inter-war period, with a special emphasis on the ‘people’s pathologist’, Bernard Spilsbury. The broad expert and public profile of forensic pathology, of which Spilsbury was the most prominent contemporary representative, will be outlined and discussed. In so doing, close attention will be paid to the courtroom strategies by which he and other experts translated their isolated post-mortem encounters with the dead body into effective testimony. Pathologists built a high-profile practice that transfixed the popular, legal and scientific imagination, and this article also explores, through the celebrated 1925 murder trial of Norman Thorne, how Spilsbury’s courtroom performance focused critical attention on the practices of pathology itself, which threatened to destabilise the status of forensic pathology. In particular, the Thorne case raised questions about the interrelation between bruising and putrefaction as sources of interpretative anxiety. Here, the question of practice is vital, especially in understanding how Spilsbury’s findings clashed with those of rival pathologists whose autopsies centred on a corpse that had undergone further putrefactive changes and that had thereby mutated as an evidentiary object. Examining how pathologists dealt with interpretative problems raised by the instability of their core investigative object enables an analysis of the ways in which pathological investigation of homicide was inflected with a series of conceptual, professional and cultural difficulties stemming in significant ways from the materiality of the corpse itself. This article presents early findings of a larger study of twentieth-century English homicide investigation which focuses on the interaction between two dominant forensic regimes: the first, outlined in part here, is a body-centred forensics, associated with the lone, ‘celebrity’ pathologist, his scalpel and

Bruised witness: Bernard Spilsbury and the performance of early twentieth-century English forensic pathology.

PubMed

Burney, Ian; Pemberton, Neil

2011-01-01

This article explores the status, apparatus and character of forensic pathology in the inter-war period, with a special emphasis on the 'people's pathologist', Bernard Spilsbury. The broad expert and public profile of forensic pathology, of which Spilsbury was the most prominent contemporary representative, will be outlined and discussed. In so doing, close attention will be paid to the courtroom strategies by which he and other experts translated their isolated post-mortem encounters with the dead body into effective testimony. Pathologists built a high-profile practice that transfixed the popular, legal and scientific imagination, and this article also explores, through the celebrated 1925 murder trial of Norman Thorne, how Spilsbury's courtroom performance focused critical attention on the practices of pathology itself, which threatened to destabilise the status of forensic pathology. In particular, the Thorne case raised questions about the interrelation between bruising and putrefaction as sources of interpretative anxiety. Here, the question of practice is vital, especially in understanding how Spilsbury's findings clashed with those of rival pathologists whose autopsies centred on a corpse that had undergone further putrefactive changes and that had thereby mutated as an evidentiary object. Examining how pathologists dealt with interpretative problems raised by the instability of their core investigative object enables an analysis of the ways in which pathological investigation of homicide was inflected with a series of conceptual, professional and cultural difficulties stemming in significant ways from the materiality of the corpse itself. This article presents early findings of a larger study of twentieth-century English homicide investigation which focuses on the interaction between two dominant forensic regimes: the first, outlined in part here, is a body-centred forensics, associated with the lone, 'celebrity' pathologist, his scalpel and the mortuary

Impact Constraints on Major Events in Early Mars History

NASA Technical Reports Server (NTRS)

Frey, H. V.

2004-01-01

MOLA data have revealed a large population of "Quasi-Circular Depressions" (QCDs) with little or no visible expression in image data. These likely buried impact basins have important implications for the age of the lowland crust, how that compares with original highland crust, and when and how the crustal dichotomy may have formed. The buried lowlands are of Early Noachian age, likely slightly younger than the buried highlands but older than the exposed (visible) highland surface. A depopulation of large visible basins at diameters 800 to 1300 km suggests some global scale event early in martian history, maybe related to the formation of the lowlands and/or the development of Tharsis. A suggested early disappearance of the global magnetic field can be placed within a temporal sequence of formation of the very largest impact basins. The global field appears to have disappeared at about the time the lowlands formed. It seems likely the topographic crustal dichotomy was produced very early in martian history by processes which operated very quickly. Thus there appears to have been a northern lowland throughout nearly all of martian history, predating the last of the really large impacts (Hellas, Argyre and Isidis) and their likely very significant environmental consequences.

Dose and Effect Thresholds for Early Key Events in a Mode of PPARa-Mediated Action

EPA Science Inventory

ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. T...

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed Central

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

Neighborhood Disadvantage, Stressful Life Events, and Adjustment among Mexican American Early Adolescents

ERIC Educational Resources Information Center

Roosa, Mark W.; Burrell, Ginger L.; Nair, Rajni L.; Coxe, Stefany; Tein, Jenn-Yun; Knight, George P.

2010-01-01

This study examined a stress process model in which stressful life events and association with delinquent peers mediated the relationship of neighborhood disadvantage to Mexican American early adolescents' mental health. The authors also proposed that child gender, child generation, and neighborhood informal social control would moderate the…

Early Life Conditions, Adverse Life Events, and Chewing Ability at Middle and Later Adulthood

PubMed Central

Watt, Richard G.; Tsakos, Georgios

2014-01-01

Objectives. We sought to determine the extent to which early life conditions and adverse life events impact chewing ability in middle and later adulthood. Methods. Secondary analyses were conducted based on data from waves 2 and 3 of the Survey of Health, Ageing, and Retirement in Europe (SHARE), collected in the years 2006 to 2009 and encompassing information on current chewing ability and the life history of persons aged 50 years or older from 13 European countries. Logistic regression models were estimated with sequential inclusion of explanatory variables representing living conditions in childhood and adverse life events. Results. After controlling for current determinants of chewing ability at age 50 years or older, certain childhood and later life course socioeconomic, behavioral, and cognitive factors became evident as correlates of chewing ability at age 50 years or older. Specifically, childhood financial hardship was identified as an early life predictor of chewing ability at age 50 years or older (odds ratio = 1.58; 95% confidence interval = 1.22, 2.06). Conclusions. Findings suggest a potential enduring impact of early life conditions and adverse life events on oral health in middle and later adulthood and are relevant for public health decision-makers who design strategies for optimal oral health. PMID:24625140

Environmental change during the Late Berriasian - Early Valanginian: a prelude to the late Early Valanginian carbon-isotope event?

NASA Astrophysics Data System (ADS)

Morales, Chloé; Schnyder, Johann; Spangenberg, Jorge; Adatte, Thierry; Westermann, Stephane; Föllmi, Karl

2010-05-01

The Valanginian period is well known for a positive excursion in marine and terrestrial δ13C records, which has been interpreted as the consequence of a major perturbation in the global carbon cycle (Lini et al., 1992; Erba et al., 2004). In contrast to the positive δ13C excursions of the Early Aptian and latest Cenomanian, marine organic-rich sediments have only been recognized from a few localities (van de Schootbrugge et al., 2003; Reboulet et al., 2003; Gröcke et al., 2005; Westermann et al., in press). The δ13C excursion began in the late Early Valanginian (campylotoxus ammonite zone) and gradually ended during the Late Valanginian. It is associated with a phase of widespread carbonate-platform drowning on the shelf (Föllmi et al., 1994) and a decline in calcareous nannofossils in the pelagic realm (Erba et al., 2004). As a triggering mechanism, numerous authors invoke the formation of the Parañà-Etendeka flood basalt. The correlation of this episode with the Valanginian δ13C event depends, however, on the absolute ages attributed to the Valanginian stage. The recent geological timescale by Ogg et al. (2008) shows that the major eruptional phase occurred during the Late Valanginian. This may imply that the late Early Valanginian δ13C event resulted from a combination of different factors. Important paleoenvironmental change occurred already in the latest Berriasian and earliest Valanginian, prior to the positive δ13C excursion. An increase in nutrient input near the onset of the δ13C excursion (campylotoxus ammonite zone), which may be considered as a trigger of the carbon cycle perturbation, has been identified in different studies, (Hennig, 2003; Duchamp-Alphonse et al., 2007; Bornemann & Mutterlose, 2008). Heterozoan faunal associations became dominant since the Early Valanginian on the northern Tethyan Helvetic platform and may indicate the beginning of sea-water eutrophication (Föllmi et al., 2007). Clay assemblages in the Tethys and Western

[Adolescent pathological gambling].

PubMed

Petit, A; Karila, L; Lejoyeux, M

2015-05-01

Although experts have long thought that the problems of gambling involved only adults, recent studies tend to show that teenagers are also affected. The objective of this paper is to show the characteristics of pathological gambling in adolescents. This review focuses on the clinical features, prevalence, psychopathology, prevention and treatment of this disorder. A review of the medical literature was conducted, using PubMed, using the following keywords alone or combined: pathological gambling, dependence, addiction and adolescents. We selected 12 English articles from 1997 to 2014. Recent work estimate that between 4 and 8% of adolescents suffer from problem gambling, and the prevalence of pathological gambling is 2-4 times higher in adolescents than in adults. The term adolescent pathological gambler starts early around the age of 10-12 years, with a quick change of status from casual to that of problem gambler and player. Complications appear quickly and comorbidities are common. There is no curative pharmacological treatment approved by health authorities. Pathological gambling among adolescents has grown significantly in recent years and should be promptly taken care of. Further studies must be performed to improve our understanding of this problem among adolescents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The onset of childhood amnesia in childhood: A prospective investigation of the course and determinants of forgetting of early-life events

PubMed Central

Bauer, Patricia J.; Larkina, Marina

2013-01-01

The present research was an examination of the onset of childhood amnesia and how it relates to maternal narrative style, an important determinant of autobiographical memory development. Children and their mothers discussed unique events when the children were 3 years of age. Different subgroups of children were tested for recall of the events at ages 5, 6, 7, 8, and 9 years. At the later session, they were interviewed by an experimenter about the events discussed 2 to 6 years previously with their mothers (early-life events). Children ages 5, 6, and 7 remembered 60% or more of the early-life events. In contrast, children ages 8 and 9 years remembered fewer than 40% of the early-life events. Overall maternal narrative style predicted children's contributions to mother-child conversations at age 3 years; it did not have cross-lagged relations to memory for early-life events at ages 5 to 9 years. Maternal deflections of the conversational turn to the child predicted the amount of information children later reported about the early-life events. The findings have implications for our understanding of the onset of childhood amnesia and the achievement of an adult-like distribution of memories in the school years. They highlight the importance of forgetting processes in explanations of the amnesia. PMID:24236647

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

PubMed Central

Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L’Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal

2015-01-01

Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development. PMID:25621497

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease.

PubMed

Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L'Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal

2015-03-02

Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development.

Characterization of Early Pathological Tau Conformations and Phosphorylation in Chronic Traumatic Encephalopathy

PubMed Central

Kanaan, Nicholas M.; Cox, Kristine; Alvarez, Victor E.; Stein, Thor D.; Poncil, Sharra; McKee, Ann C.

2016-01-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that develops after repetitive head injury. Several lines of evidence in other tauopathies suggest that tau oligomer formation induces neurotoxicity and that tau oligomer-mediated neurotoxicity involves induction of axonal dysfunction through exposure of an N-terminal motif in tau, the phosphatase-activating domain (PAD). Additionally, phosphorylation at serine 422 in tau occurs early and correlates with cognitive decline in patients with Alzheimer disease (AD). We performed immunohistochemistry and immunofluorescence on fixed brain sections and biochemical analysis of fresh brain extracts to characterize the presence of PAD-exposed tau (TNT1 antibody), tau oligomers (TOC1 antibody), tau phosphorylated at S422 (pS422 antibody), and tau truncated at D421 (TauC3 antibody) in the brains of 9-11 cases with CTE and cases of nondemented aged controls and AD (Braak VI) (n = 6, each). All 3 early tau markers (ie, TNT1, TOC1, and pS422) were present in CTE and displayed extensive colocalization in perivascular tau lesions that are considered diagnostic for CTE. Notably, the TauC3 epitope, which is abundant in AD, was relatively sparse in CTE. Together, these results provide the first description of PAD exposure, TOC1 reactive oligomers, phosphorylation of S422, and TauC3 truncation in the tau pathology of CTE. PMID:26671985

Abnormal Mitochondrial Dynamics and Synaptic Degeneration as Early Events in Alzheimer’s Disease: Implications to Mitochondria-Targeted Antioxidant Therapeutics

PubMed Central

Reddy, P. Hemachandra; Tripathy, Raghav; Troung, Quang; Thirumala, Karuna; Reddy, Tejaswini P.; Anekonda, Vishwanath; Shirendeb, Ulziibat P.; Calkins, Marcus J.; Reddy, Arubala P.; Mao, Peizhong; Manczak, Maria

2011-01-01

Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer’s disease (AD) progression. Loss of synapses and synaptic damage are the best correlate of cognitive deficits found in AD patients. Recent research on amyloid bet (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed that reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. PMID:22037588

How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2006

2006-01-01

Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic…

A Further Extension of the Tahiti-Darwin SOI, Early ENSO Events and Darwin Pressure.

NASA Astrophysics Data System (ADS)

Allan, Robert J.; Nicholls, Neville; Jones, Phil D.; Butterworth, Ian J.

1991-07-01

An extension of the Tahiti minus Darwin Southern Oscillation Index (SOI) from 1882 back to 1876 is reported following the recovery of early Darwin mean sea-level pressure data spanning the period 1865-81. As a result, we are able to compare, for the first time, the major 1877-78 and 1982-83 ENSO events on the basis of this commonly used index. Early Darwin and Jakarta data are also examined in terms of a measure of the Australian response to documented El Niño and/or ENSO events in 1866, 1868, 1871, 1873, 1874 and 1875.The SOI during the 1877-78 ENSO event has a similar temporal response to that in 1982-83, but the index is slightly weaker than in the recent event. Examination of documentary evidence confirms the severity of the drought conditions that affected the Australian continent during the 1877-78 ENSO, and shows that this response is in line with the wider Indo-Pacific impacts reported in the literature. Earlier El Niño phases in 1868 and 1873 are not resolved distinctly in either the Darwin or Jakarta pressure data. This appears to illustrate that El Niño event histories do not always indicate wider ENSO influences in the Indo-Pacific basin, particularly during weak to moderate phases.

Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain

PubMed Central

Maphis, Nicole; Xu, Guixiang; Kokiko-Cochran, Olga N.; Jiang, Shanya; Cardona, Astrid; Ransohoff, Richard M.; Lamb, Bruce T.

2015-01-01

Pathological aggregation of tau is a hallmark of Alzheimer’s disease and related tauopathies. We have previously shown that the deficiency of the microglial fractalkine receptor (CX3CR1) led to the acceleration of tau pathology and memory impairment in an hTau mouse model of tauopathy. Here, we show that microglia drive tau pathology in a cell-autonomous manner. First, tau hyperphosphorylation and aggregation occur as early as 2 months of age in hTauCx3cr1−/− mice. Second, CD45+ microglial activation correlates with the spatial memory deficit and spread of tau pathology in the anatomically connected regions of the hippocampus. Third, adoptive transfer of purified microglia derived from hTauCx3cr1−/− mice induces tau hyperphosphorylation within the brains of non-transgenic recipient mice. Finally, inclusion of interleukin 1 receptor antagonist (Kineret®) in the adoptive transfer inoculum significantly reduces microglia-induced tau pathology. Together, our results suggest that reactive microglia are sufficient to drive tau pathology and correlate with the spread of pathological tau in the brain. PMID:25833819

Early event related fields during visually evoked pain anticipation.

PubMed

Gopalakrishnan, Raghavan; Burgess, Richard C; Plow, Ela B; Floden, Darlene P; Machado, Andre G

2016-03-01

Pain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. Here, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3 s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. We found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. The findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. These measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Newcomers in paediatric GI pathology: childhood enteropathies including very early onset monogenic IBD.

PubMed

Ensari, Arzu; Kelsen, Judith; Russo, Pierre

2018-01-01

Childhood enteropathies are a group of diseases causing severe chronic (>2-3 weeks) diarrhoea often starting in the first week of life with the potential for fatal complications for the affected infant. Early identification and accurate classification of childhood enteropathies are, therefore, crucial for making treatment decisions to prevent life-threatening complications. Childhood enteropathies are classified into four groups based on the underlying pathology: (i) conditions related to defective digestion, absorption and transport of nutrients and electrolytes; (ii) disorders related to enterocyte differentiation and polarization; (iii) defects of enteroendocrine cell differentiation; and (iv) disorders associated with defective modulation of intestinal immune response. While the intestinal mucosa is usually normal in enteropathies related to congenital transport or enzyme deficiencies, the intestinal biopsy in other disorders may reveal a wide range of abnormalities varying from normal villous architecture to villous atrophy and/or inflammation, or features specific to the underlying disorder including epithelial abnormalities, lipid vacuolization in the enterocytes, absence of plasma cells, lymphangiectasia, microorganisms, and mucosal eosinophilic or histiocytic infiltration. This review intends to provide an update on small intestinal biopsy findings in childhood enteropathies, the "newcomers", including very early onset monogenic inflammatory bowel disease (IBD), in particular, for the practicing pathologist.

Atmospheric pCO2 reconstructed across five early Eocene global warming events

NASA Astrophysics Data System (ADS)

Cui, Ying; Schubert, Brian A.

2017-11-01

Multiple short-lived global warming events, known as hyperthermals, occurred during the early Eocene (56-52 Ma). Five of these events - the Paleocene-Eocene Thermal Maximum (PETM or ETM1), H1 (or ETM2), H2, I1, and I2 - are marked by a carbon isotope excursion (CIE) within both marine and terrestrial sediments. The magnitude of CIE, which is a function of the amount and isotopic composition of carbon added to the ocean-atmosphere system, varies significantly between marine versus terrestrial substrates. Here we use the increase in carbon isotope fractionation by C3 land plants in response to increased pCO2 to reconcile this difference and reconstruct a range of background pCO2 and peak pCO2 for each CIE, provided two potential carbon sources: methane hydrate destabilization and permafrost-thawing/organic matter oxidation. Although the uncertainty on each pCO2 estimate using this approach is low (e.g., median uncertainty = + 23% / - 18%), this work highlights the potential for significant systematic bias in the pCO2 estimate resulting from sampling resolution, substrate type, diagenesis, and environmental change. Careful consideration of each of these factors is required especially when applying this approach to a single marine-terrestrial CIE pair. Given these limitations, we provide an upper estimate for background early Eocene pCO2 of 463 +248/-131 ppmv (methane hydrate scenario) to 806 +127/-104 ppmv (permafrost-thawing/organic matter oxidation scenario). These results, which represent the first pCO2 proxy estimates directly tied to the Eocene hyperthermals, demonstrate that early Eocene warmth was supported by background pCO2 less than ∼3.5× preindustrial levels and that pCO2 > 1000 ppmv may have occurred only briefly, during hyperthermal events.

The Existence of Primary Age-Related Tauopathy Suggests that not all the Cases with Early Braak Stages of Neurofibrillary Pathology are Alzheimer's Disease.

PubMed

Giaccone, Giorgio

2015-01-01

The distinction between Alzheimer's disease (AD) and Primary Age-Related Tauopathy (PART) is a hotly debated issue. As most lines of evidence support the tenet that tau pathology occurs downstream of amyloid-β deposition, it seems reasonable to consider PART as a separate disease process not necessarily related to Aβ and hence AD. Following this view, the early stages of neurofibrillary pathology may not always be the forerunner of diffuse neurofibrillary changes and AD. The ongoing debate further enhances the need for greater caution against any future predictions using tau cerebrospinal fluid and imaging biomarkers.

Dose and Effect Thresholds for Early Key Events in a Mode of ...

EPA Pesticide Factsheets

ABSTRACT Strategies for predicting adverse health outcomes of environmental chemicals are centered on early key events in toxicity pathways. However, quantitative relationships between early molecular changes in a given pathway and later health effects are often poorly defined. The goal of this study was to evaluate short-term key event indicators using qualitative and quantitative methods in an established pathway of mouse liver tumorigenesis mediated by peroxisome proliferator-activated receptor-alpha (PPARα). Male B6C3F1 mice were exposed for 7 days to di(2-ethylhexyl) phthalate (DEHP), di-n-octyl phthalate (DNOP), and n-butyl benzyl phthalate (BBP), which vary in PPARα activity and liver tumorigenicity. Each phthalate increased expression of select PPARα target genes at 7 days, while only DEHP significantly increased liver cell proliferation labeling index (LI). Transcriptional benchmark dose (BMDT) estimates for dose-related genomic markers stratified phthalates according to hypothetical tumorigenic potencies, unlike BMDs for non-genomic endpoints (liver weights or proliferation). The 7-day BMDT values for Acot1 as a surrogate measure for PPARα activation were 29, 370, and 676 mg/kg-d for DEHP, DNOP, and BBP, respectively, distinguishing DEHP (liver tumor BMD of 35 mg/kg-d) from non-tumorigenic DNOP and BBP. Effect thresholds were generated using linear regression of DEHP effects at 7 days and 2-year tumor incidence values to anchor early response molec

Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial.

PubMed

Thomas, Jeremy St John; Provenzano, Elena; Hiller, Louise; Dunn, Janet; Blenkinsop, Clare; Grybowicz, Louise; Vallier, Anne-Laure; Gounaris, Ioannis; Abraham, Jean; Hughes-Davies, Luke; McAdam, Karen; Chan, Stephen; Ahmad, Rizvana; Hickish, Tamas; Houston, Stephen; Rea, Daniel; Caldas, Carlos; Bartlett, John Ms; Cameron, David Allan; Hayward, Richard Laurence; Earl, Helena Margaret

2017-08-01

The ARTemis Trial tested standard neoadjuvant chemotherapy±bevacizumab in the treatment of HER2-negative early breast cancer. We compare data from central pathology review with report review and also the reporting behavior of the two central pathologists. Eight hundred women with HER2-negative early invasive breast cancer were recruited. Response to chemotherapy was assessed from local pathology reports for pathological complete response in breast and axillary lymph nodes. Sections from the original core biopsy and surgical excision were centrally reviewed by one of two trial pathologists blinded to the local pathology reports. Pathologists recorded response to chemotherapy descriptively and also calculated residual cancer burden. 10% of cases were double-reported to compare the central pathologists' reporting behavior. Full sample retrieval was obtained for 681 of the 781 patients (87%) who underwent surgery within the trial and were evaluable for pathological complete response. Four hundred and eighty-three (71%) were assessed by JSJT, and 198 (29%) were assessed by EP. Residual cancer burden calculations were possible in 587/681 (86%) of the centrally reviewed patients, as 94/681 (14%) had positive sentinel nodes removed before neoadjuvant chemotherapy invalidating residual cancer burden scoring. Good concordance was found between the two pathologists for residual cancer burden classes within the 65-patient quality assurance exercise (kappa 0.63 (95% CI: 0.57-0.69)). Similar results were obtained for the between-treatment arm comparison both from the report review and the central pathology review. For pathological complete response, report review was as good as central pathology review but for minimal residual disease, report review overestimated the extent of residual disease. In the ARTemis Trial central pathology review added little in the determination of pathological complete response but had a role in evaluating low levels of residual disease. Calculation

Constraints on early events in Martian history as derived from the cratering record

NASA Technical Reports Server (NTRS)

Barlow, Nadine G.

1990-01-01

Constrains on early events in Martian history are derived using the planet's cratering record. Variations in the shapes of the crater size-frequency distribution curves are interpreted as indicative of the size-frequency distribution of the production populations, thus providing information about the age of the unit relative to the end of the heavy bombardment period. Results from the analysis of craters superposed on heavily cratered units across the Martian surface provide constraints on the hemispheric dichotomy and the early erosional conditions on Mars.

[MODEL ESTABLISHMENT, MRI AND PATHOLOGICAL FEATURES OF EARLY STEROID-INDUCED AVASCULAR NECROSIS OF FEMORAL HEAD IN RABBIT].

PubMed

Zhang, Liyan; Sun, Xin; Tian, Dan; Xu, Rui; Lei, Hao; Al, Jinhui; Zhao, Bo; Chen, Jiying; Chai, Wei; Ma, Shoucheng; Liu, Weijia; Shen, Siyuan

2015-10-01

To establish an rabbit model of early steroid-induced avascular necrosis of the femoral head (SANFH) and evaluate its validity with MRI and pathological examination. Twenty 6-month-old rabbits (weighing, 2-3 kg) were randomly divided into 2 groups (control group and model group), 10 rabbits in each group. Dexamethasone sodium phosphate solution (10 mg/kg) was injected into bilateral gluteus in model group, and the same amount of saline was injected in control group, every 3 days for 14 times. General observation was done after modelling. Osteonecrosis was verified by pathological observation and MRI findings at 6 weeks. After 6 weeks, rabbits did not show obvious changes in control group; increased hair removal, decreased food intake, and slight limp were observed in model group. The MRI results showed normal shape of the bilateral femoral head and no abnormal signals in control group; irregular shape of the bilateral femoral head and a slice of irregular abnormal signals were observed, and necrosis and cystolization of the subchondral bone and sparse changes of trabecular bone were shown in model group. General observation from coronal section of femoral head showed smooth red cartilage surface in control group; on the contrary, the cartilage surface of the femoral head became dull, thin even visible hemorrhage under articular cartilage and necrosis of the femoral head were observed. The histopathological examination indicated that trabecular bone of the femoral head in control group was massive, thick, and close and osteocytes in the bone lacunae had normal shapes. The osseous trabecular became thinner and broken; karyopyknosis of osteocytes and bone empty lacunae could be obviously seen in model. group. The rates of empty lacunae were 8.0% ± 0.5% in control group and 49.0% ± 0.3% in model group, showing significant difference (t = 21.940, P = 0.000). Establishing a model of early SANFH through injecting short-term, shock, and high dose of dexamethasone, and it

Negative affective spillover from daily events predicts early response to cognitive therapy for depression.

PubMed

Cohen, Lawrence H; Gunthert, Kathleen C; Butler, Andrew C; Parrish, Brendt P; Wenze, Susan J; Beck, Judith S

2008-12-01

This study evaluated the predictive role of depressed outpatients' (N = 62) affective reactivity to daily stressors in their rates of improvement in cognitive therapy (CT). For 1 week before treatment, patients completed nightly electronic diaries that assessed daily stressors and negative affect (NA). The authors used multilevel modeling to compute each patient's within-day relationship between daily stressors and daily NA (within-day reactivity), as well as the relationship between daily stressors and next-day NA (next-day reactivity; affective spillover). In growth model analyses, the authors evaluated the predictive role of patients' NA reactivity in their early (Sessions 1-4) and late (Sessions 5-12) response to CT. Within-day NA reactivity did not predict early or late response to CT. However, next-day reactivity predicted early response to CT, such that patients who had greater NA spillover in response to negative events had a slower rate of symptom change during the first 4 sessions. Affective spillover did not influence later response to CT. The findings suggest that depressed patients who have difficulty bouncing back the next day from their NA reactions to a relative increase in daily negative events will respond less quickly to the early sessions of CT.

The early Toarcian anoxic event: what the beginning and the end of the story are?

NASA Astrophysics Data System (ADS)

Mattioli, Emanuela; Plancq, Julien; Raucsik, Béla

2010-05-01

The early Toarcian anoxic event: what the beginning and the end of the story are? E. Mattioli (1), J. Plancq (1), and B. Rauksik (2) (1) UMR 5125 PEPS, CNRS, France; Université Lyon 1, Campus de la DOUA, Bâtiment Géode, 69622 Villeurbanne Cedex, France (emanuela.mattioli@univ-lyon1.fr) (2) Department of Earth and Environmental Sciences, University of Pannonia, Veszprém, Hungary The early Toarcian anoxic event (T-OAE) and the associated biotic crisis have received much attention in the last decade. However, the events forewarning the crisis as well as its aftermath are still poorly known. The T-OAE coincides with a prominent carbon isotope negative excursion (T-CIE) that is preceded by an excursion of similar intensity at the Pliensbachian-Toarcian boundary (Hesselbo et al., 2007). The onset of T-CIE occurred some 700 kyr later than the end of the Boundary-CIE (Suan et al., 2008a). This succession of events demonstrates that the T-OAE was a complex suite of environmental perturbations. In this work, we focused on calcareous nannofossil assemblages occurring in the Peniche section (Portugal) during the Boundary-CIE with the aim to understand if calcifying plankton reacted in a similar/different way to the two CIEs. Also, two sections and one borehole located along a W-E transect, along the NW-Tethyan shelf (in the Yorkshire coast, in the E Paris Basin, and in Mecsek Basin, respectively), were investigated to assess which way calcareous nannoplankton recovered after the crisis, and if the recovery was a synchronous event. The production by nannoplankton collapsed during the T-CIE, as demonstrated by the lowest absolute abundance of nannofossils measured in Peniche and other studied sites (Mattioli et al., 2008). Besides this nannofossil abundance decrease, also the size of the incertae sedis Schizosphaerella test was drastically reduced (Suan et al., 2008b). If a similar size decrease is also recorded during the Boundary-CIE, calcareous nannofossil abundances are

Early events governing memory CD8+ T-cell differentiation.

PubMed

Obar, Joshua J; Lefrançois, Leo

2010-08-01

Understanding the regulation of the CD8(+) T-cell response and how protective memory cells are generated has been intensely studied. It is now appreciated that a naive CD8(+) T cell requires at least three signals to mount an effective immune response: (i) TCR triggering, (ii) co-stimulation and (iii) inflammatory cytokines. Only recently have we begun to understand the molecular integration of those signals and how early events regulate the fate decisions of the responding CD8(+) T cells. This review will discuss the recent findings about both the extracellular and intracellular factors that regulate the destiny of responding CD8(+) T cells.

[Influence of early childhood stress exposure and traumatic life events on pain perception].

PubMed

Tesarz, J; Gerhardt, A; Eich, W

2018-06-05

Adult pain perception is influenced substantially by interactions between mind, body, and social environment during early life. Early stress exposure and traumatic life events induce powerful psychophysical stress reactions that exert multiple neurofunctional processes. This has significant implications for pain perception and pain processing. As part of this review, the complex relationships between traumatic stress experiences and associated psychobiological mechanisms of chronic pain will be discussed. Based on selected studies, psychophysiological findings are presented and possible underlying mechanisms are discussed. The article concludes with a discussion of potential implications for treatment.

Early changes in physical tree characteristics during an oak decline event in the Ozark highlands

Treesearch

Martin A. Spetich

2006-01-01

An oak decline event is severely affecting up to 120 000 ha in the Ozark National Forest of Arkansas. Results of early changes in physical tree characteristics during that event are presented. In the fall and winter of 1999 and 2000, we established research plots on a site that would become a center of severe oak decline. In August 2000, standing trees > 14 cm in...

Marine ecosystem resilience during extreme deoxygenation: the Early Jurassic oceanic anoxic event.

PubMed

Caswell, Bryony A; Frid, Christopher L J

2017-01-01

Global warming during the Early Jurassic, and associated widespread ocean deoxygenation, was comparable in scale with the changes projected for the next century. This study quantifies the impact of severe global environmental change on the biological traits of marine communities that define the ecological roles and functions they deliver. We document centennial-millennial variability in the biological trait composition of Early Jurassic (Toarcian) seafloor communities and examine how this changed during the event using biological traits analysis. Environmental changes preceding the global oceanic anoxic event (OAE) produced an ecological shift leading to stressed benthic palaeocommunities with reduced resilience to the subsequent OAE. Changes in traits and ecological succession coincided with major environmental changes; and were of similar nature and magnitude to those in severely deoxygenated benthic communities today despite the very different timescales. Changes in community composition were linked to local redox conditions whereas changes in populations of opportunists were driven by primary productivity. Throughout most of the OAE substitutions by tolerant taxa conserved the trait composition and hence functioning, but periods of severe deoxygenation caused benthic defaunation that would have resulted in functional collapse. Following the OAE recovery was slow probably because the global nature of the event restricted opportunities for recruitment from outside the basin. Our findings suggest that future systems undergoing deoxygenation may initially show functional resilience, but severe global deoxygenation will impact traits and ecosystem functioning and, by limiting the species pool, will slow recovery rates.

Validation of a Molecular and Pathological Model for Five-Year Mortality Risk in Patients with Early Stage Lung Adenocarcinoma

PubMed Central

Bueno, Raphael; Hughes, Elisha; Wagner, Susanne; Gutin, Alexander S.; Lanchbury, Jerry S.; Zheng, Yifan; Archer, Michael A.; Gustafson, Corinne; Jones, Joshua T.; Rushton, Kristen; Saam, Jennifer; Kim, Edward; Barberis, Massimo; Wistuba, Ignacio; Wenstrup, Richard J.; Wallace, William A.; Harrison, David J.

2015-01-01

Introduction: The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Methods: Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. Results: The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7). Conclusions: This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality. PMID:25396679

Early events in copper-ion catalyzed oxidation of α-synuclein.

PubMed

Tiwari, Manish K; Leinisch, Fabian; Sahin, Cagla; Møller, Ian Max; Otzen, Daniel E; Davies, Michael J; Bjerrum, Morten J

2018-04-22

Previous studies on metal-ion catalyzed oxidation of α-synuclein oxidation have mostly used conditions that result in extensive modification precluding an understanding of the early events in this process. In this study, we have examined time-dependent oxidative events related to α-synuclein modification using six different molar ratios of Cu 2+ /H 2 O 2 /protein and Cu 2+ /H 2 O 2 /ascorbate/protein resulting in mild to moderate extents of oxidation. For a Cu 2+ /H 2 O 2 /protein molar ratio of 2.3:7.8:1 only low levels of carbonyls were detected (0.078 carbonyls per protein), whereas a molar ratio of 4.7:15.6:1 gave 0.22 carbonyls per α-synuclein within 15 min. With the latter conditions, rapid conversion of 3 out of 4 methionines (Met) to methionine sulfoxide, and 2 out of 4 tyrosines (Tyr) were converted to products including inter- and intra-molecular dityrosine cross-links and protein oligomers, as determined by SDS-PAGE and Western blot analysis. Limited histidine (His) modification was observed. The rapid formation of dityrosine cross-links was confirmed by fluorescence and mass-spectrometry. These data indicate that Met and Tyr oxidation are early events in Cu 2+ /H 2 O 2 -mediated damage, with carbonyl formation being a minor process. With the Cu 2+ /H 2 O 2 /ascorbate system, rapid protein carbonyl formation was detected with the first 5 min, but after this time point, little additional carbonyl formation was detected. With this system, lower levels of Met and Tyr oxidation were detected (2 Met and 1 Tyr modified with a Cu 2+ /H 2 O 2 /ascorbate/protein ratio of 2.3:7.8:7.8:1), but greater His oxidation. Only low levels of intra- dityrosine cross-links and no inter- dityrosine oligomers were detected under these conditions, suggesting that ascorbate limits Cu 2+ /H 2 O 2 -induced α-synuclein modification. Copyright © 2018. Published by Elsevier Inc.

Detection of rain events in radiological early warning networks with spectro-dosimetric systems

NASA Astrophysics Data System (ADS)

Dąbrowski, R.; Dombrowski, H.; Kessler, P.; Röttger, A.; Neumaier, S.

2017-10-01

Short-term pronounced increases of the ambient dose equivalent rate, due to rainfall are a well-known phenomenon. Increases in the same order of magnitude or even below may also be caused by a nuclear or radiological event, i.e. by artificial radiation. Hence, it is important to be able to identify natural rain events in dosimetric early warning networks and to distinguish them from radiological events. Novel spectrometric systems based on scintillators may be used to differentiate between the two scenarios, because the measured gamma spectra provide significant nuclide-specific information. This paper describes three simple, automatic methods to check whether an dot H*(10) increase is caused by a rain event or by artificial radiation. These methods were applied to measurements of three spectrometric systems based on CeBr3, LaBr3 and SrI2 scintillation crystals, investigated and tested for their practicability at a free-field reference site of PTB.

Eating pathology in adolescents with celiac disease.

PubMed

Karwautz, Andreas; Wagner, Gudrun; Berger, Gabriele; Sinnreich, Ursula; Grylli, Vasileia; Huber, Wolf-Dietrich

2008-01-01

Celiac disease (CD), treated by a gluten-free diet, may represent a nonspecific trigger for the development of eating pathology, particularly in adolescence. The authors sought to perform a systematic study on eating pathology in CD. CD patients were assessed for eating disorders by questionnaire, and body mass index was recorded. There was a higher rate of eating pathology in CD patients than would be expected, especially, a higher rate of bulimia nervosa. This subgroup reported more noncompliance with the gluten-free diet and had higher scores on most eating-related questionnaires. In most cases, diagnosis of CD preceded the onset of eating pathology. The authors recommend asking early-adolescent CD patients whether they are also dieting for aesthetic reasons.

Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early- versus later-onset.

PubMed

Black, Donald W; Shaw, Martha; Coryell, William; Crowe, Raymond; McCormick, Brett; Allen, Jeff

2015-07-01

Pathological gambling (PG) is a prevalent and impairing public health problem. In this study we assessed age at onset in men and women with PG and compared the demographic and clinical picture of early- vs. later-onset individuals. We also compared age at onset in PG subjects and their first-degree relatives with PG. Subjects with DSM-IV PG were recruited during the conduct of two non-treatment clinical studies. Subjects were evaluated with structured interviews and validated questionnaires. Early-onset was defined as PG starting prior to age 33years. Age at onset of PG in the 255 subjects ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an earlier onset than women. 84% of all subjects with PG had developed the disorder by age 50years. Early-onset subjects were more likely to be male, to prefer action games, and to have substance use disorders, antisocial personality disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and social anxiety disorder. Later-onset was more common in women and was associated with a preference for slots and a history of sexual abuse. Age at onset of PG is bimodal and differs for men and women. Early-onset PG and later-onset PG have important demographic and clinical differences. The implications of the findings are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

The Nun Study: risk factors for pathology and clinical-pathologic correlations.

PubMed

Mortimer, James A

2012-07-01

The Nun Study was the first cohort study to enroll and follow a large, well-defined population that included demented and non-demented participants, all of whom agreed to donate their brains for research. The inclusion of systematic neuropathologic analysis in this study has resulted in a greater understanding of the role of Alzheimer and vascular pathology in the expression of memory deficits and dementia and has provided data showing that biomarkers for the pathology may be evident many decades earlier in adult life. Findings related to neuropathology in this study have included the following: (1) Although clinical outcomes were strongly correlated with Alzheimer neuropathology, about one-third of the participants fulfilling criteria for neuropathologic Alzheimer's disease (AD) were not demented at the time of death. (2) Brain infarcts by themselves had little effect on cognitive status, but played an important role in increasing the risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was strongly correlated with Braak neurofibrillary stage even in participants with normal cognitive function. (4) A linguistic characteristic of essays written in early adult life, idea density, had a strong association with not only clinical outcomes in late life, but the severity of Alzheimer neuropathology as well. (5) The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but not vascular pathology.

Negative events and their potential risk of precipitating pathological forms of dental anxiety.

PubMed

Oosterink, F M D; de Jongh, A; Aartman, I H A

2009-05-01

The purpose of the present study was to assess which types of experiences are most closely associated with pathological forms of dental anxiety. Data came from a sample of dental patients (n=1462). Pathological dental anxiety was operationalized in two ways: (1) a score of > or =36 on the Short form of the Dental Anxiety Inventory (S-DAI; high dental anxiety, HDA), or (2) fulfilling the screening criteria of specific phobia (DSM-IV-TR; dental phobia, DP). A wide variety of dental experiences appeared to be significantly related with both HDA and DP, while general traumatic experiences were not. No differences were found between women and men. Retrospective accounts of dental experiences involving helplessness were most strongly associated with having HDA [OR=8.2] and positive screens of DP [OR=16.2]. The results suggest that disruptive emotional and interoceptive reactions during dental treatment (particularly helplessness) have the greatest potential risk of precipitating pathological forms of dental anxiety.

Disrupted sensory gating in pathological gambling.

PubMed

Stojanov, Wendy; Karayanidis, Frini; Johnston, Patrick; Bailey, Andrew; Carr, Vaughan; Schall, Ulrich

2003-08-15

Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.

Occurrence of early adverse events after vaccination against influenza at a Brazilian reference center.

PubMed

Lopes, Marta Heloísa; Mascheretti, Melissa; Franco, Marilia Miranda; Vasconcelos, Ricardo; Gutierrez, Eliana Battaggia

2008-02-01

Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. Local adverse events were reported by 32.5% and systemic effects by 26.4% of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05). There was no statistically significant difference in the occurrence of fever. The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers.

Not Just the 8.2 event: Dynamic Early Holocene Climate in Arctic Canada

NASA Astrophysics Data System (ADS)

Axford, Y.; Briner, J. P.; Miller, G. H.; Francis, D. R.

2006-12-01

Temperature reconstructions from a lake in the eastern Canadian Arctic indicate that peak warmth in the early Holocene was interrupted by two abrupt, short-lived temperature reversals at ~9.l and ~8.5 ka. Summer temperatures at Lake CF8, Baffin Island (~500 km west of Greenland) are inferred from subfossil midge (Chironomidae) assemblages. Our results indicate that the site, like others on Baffin Island, experienced exceptionally warm summers (almost 5°C warmer than present) through much of the early Holocene, presumably in response to enhanced summer insolation. After 1000 years of very warm, stable climate, warmth was interrupted by two discrete cold reversals at ~9.1 and ~8.5 ka, during which multiple cold-stenothermous midge taxa appeared in the lake and summer temperatures dropped more than 3°C. These two clearly-defined reversals, well beyond the range of background variability, were of similar amplitude and duration, and were separated by several centuries of near-peak warmth. The only Holocene events of comparable amplitude at this site are the rapid onset of Holocene warmth, and the more gradual Neoglacial cooling after 8 ka. Abrupt cooling events over the Baffin region are consistent with model simulations of the impacts of freshwater outbursts into the Labrador Sea, such as the Lake Agassiz outburst flood that occurred ~8.4 ka. That there are two discrete events recorded at this site indicates that the "8.2 event" was not uniquely significant in this region; rather, the period between approximately ~9.2 and 8 ka was characterized by repeated climate fluctuations forced by multiple outburst floods or other mechanisms. Thus global correlations among paleoclimate records need not assume that climate perturbations during this time period necessarily correlate with the draining of Lake Agassiz or the 8.2 ka cooling in central Greenland.

The role of parent, teacher, and peer events in maintaining depressive symptoms during early adolescence.

PubMed

Herres, Joanna; Kobak, Roger

2015-02-01

Negative interpersonal events have been consistently identified as both antecedents and sequalae of adolescent depressive symptoms. However, little is known about the relative contributions of specific domains of interpersonal events (parents, peers or teachers) to the maintenance of depressive symptoms during early adolescence or whether a lack of positive interpersonal interactions plays a direct role in maintaining depressive symptoms. Further, few studies have examined whether positive interpersonal events moderate associations between negative events and adolescents' depressive symptoms. This study combined stress generation and exposure models to evaluate the contribution of daily events to the maintenance of depressive symptoms in a sample of 132 adolescents (53 % female) followed from ages 13 to 15. Daily phone diaries collected at age 14 assessed adolescents' negative and positive interactions with parents, teachers, and peers in a sample of adolescents from economically disadvantaged families. Negative peer events uniquely accounted for the maintenance of depressive symptoms over the 2 years period. Results did not differ by gender; however, positive parent events buffered the effects of negative parent events for females but not for males. Findings highlight the significance of peer relationships during a period of vulnerability for depressive symptoms.

New Early Jurassic Tetrapod Assemblages Constrain Triassic-Jurassic Tetrapod Extinction Event

NASA Astrophysics Data System (ADS)

Olsen, P. E.; Shubin, N. H.; Anders, M. H.

1987-08-01

The discovery of the first definitively correlated earliest Jurassic (200 million years before present) tetrapod assemblage (Fundy basin, Newark Supergroup, Nova Scotia) allows reevaluation of the duration of the Triassic-Jurassic tetrapod extinction event. Present are tritheledont and mammal-like reptiles, prosauropod, theropod, and ornithischian dinosaurs, protosuchian and sphenosuchian crocodylomorphs, sphenodontids, and hybodont, semionotid, and palaeonisciform fishes. All of the families are known from Late Triassic and Jurassic strata from elsewhere; however, pollen and spore, radiometric, and geochemical correlation indicate an early Hettangian age for these assemblages. Because all ``typical Triassic'' forms are absent from these assemblages, most Triassic-Jurassic tetrapod extinctions occurred before this time and without the introduction of new families. As was previously suggested by studies of marine invertebrates, this pattern is consistent with a global extinction event at the Triassic-Jurassic boundary. The Manicouagan impact structure of Quebec provides dates broadly compatible with the Triassic-Jurassic boundary and, following the impact theory of mass extinctions, may be implicated in the cause.

Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging.

PubMed

Ben-Zvi, Anat; Miller, Elizabeth A; Morimoto, Richard I

2009-09-01

Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

Early Intravascular Events are Associated with Development of ARDS.

PubMed

Abdulnour, Raja-Elie E; Gunderson, Tina; Barkas, Ioanna; Timmons, Jack Y; Barnig, Cindy; Gong, Michelle; Kor, Daryl J; Gajic, Ognjen; Talmor, Daniel; Carter, Rickey E; Levy, Bruce D

2018-05-21

The acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies. To determine select peripheral blood lipid mediator and leukocyte responses in patients at-risk for ARDS. Patients at risk for ARDS were randomized as part of a multicenter, double-blind clinical trial of aspirin versus placebo (LIPS-A; NCT01504867). Plasma thromboxane B2 (TxB2), 15-epi-LXA4 (aspirin-triggered lipoxin A4, ATL), and peripheral blood leukocyte number and activation were determined upon enrollment and after treatment with either aspirin or placebo. Thirty-three of 367 subjects (9.0%) developed ARDS after randomization. Baseline ATL levels, total monocyte counts, intermediate monocyte (IntMo) counts, and Mo-PA were associated with the development of ARDS. Peripheral blood neutrophil count and monocyte-platelet aggregates significantly decreased over time. Of note, 9 subjects developed ARDS after randomization yet prior to study drug initiation, including 7 subjects assigned to aspirin treatment. Subjects without ARDS at the time of first dose demonstrated a lower incidence of ARDS with aspirin treatment. Compared with placebo, aspirin significantly decreased TxB2 and increased the ATL/TxB2 ratio. Biomarkers of intravascular monocyte activation in at-risk patients were associated with development of ARDS. The potential clinical benefit of early aspirin for prevention of ARDS remains uncertain. Together, results of the biochemical and immunological analyses provide a window into the early pathogenesis of human ARDS, and represent potential vascular biomarkers of ARDS risk.

Early events of citrus greening (Huanglongbing) disease development at the ultrastructural level.

PubMed

Folimonova, Svetlana Y; Achor, Diann S

2010-09-01

Citrus greening (Huanglongbing [HLB]) is one of the most destructive diseases of citrus worldwide. The causal agent of HLB in Florida is thought to be 'Candidatus Liberibacter asiaticus'. Understanding of the early events in HLB infection is critical for the development of effective measures to control the disease. In this work, we conducted cytopathological studies by following the development of the disease in citrus trees graft inoculated with 'Ca. L. asiaticus'-containing material under greenhouse conditions to examine the correlation between ultrastructural changes and symptom production, with the main objective of characterizing the early events of infection. Based on our observations, one of the first degenerative changes induced upon invasion of the pathogen appears to be swelling of middle lamella between cell walls surrounding sieve elements. This anatomical aberration was often observed in samples from newly growing flushes in inoculated sweet orange and grapefruit trees at the early "presymptomatic" stage of HLB infection. Development of symptoms and their progression correlated with an increasing degree of microscopic aberrations. Remarkably, the ability to observe the bacterium in the infected tissue also correlated with the degree of the disease progression. Large numbers of bacterial cells were found in phloem sieve tubes in tissue samples from presymptomatic young flushes. In contrast, we did not observe the bacteria in highly symptomatic leaf samples, suggesting a possibility that, at more advanced stages of the disease, a major proportion of 'Ca. L. asiaticus' is present in a nonviable state. We trust that observations reported here advance our understanding of how 'Ca. L. asiaticus' causes disease. Furthermore, they may be an important aid in answering a question: when and where within an infected tree the tissue serves as a better inoculum source for acquisition and transmission of the bacterium by its psyllid vector.

Early maritime economy and El Nino events at Quebrada Tacahuay, Peru

USGS Publications Warehouse

Keefer, D.K.; DeFrance, Susan D.; Moseley, M.E.; Richardson, J. B.; Satterlee, D.R.; Day-Lewis, A.

1998-01-01

The archaeological site of Quebrada Tacahuay, Peru, dates to 12,700 to 12,500 calibrated years before the present (10,770 to 10,530 carbon-14 years before the present). It contains some of the oldest evidence of maritime- based economic activity in the New World. Recovered materials include a hearth, lithic cutting tools and flakes, and abundant processed marine fauna, primarily seabirds and fish. Sediments below and above the occupation layer were probably generated by El Nino events, indicating that El Nino was active during the Pleistocene as well as during the early and middle Holocene.

Which early life events or current environmental and lifestyle factors influence lung function in adolescents? - results from the GINIplus & LISAplus studies.

PubMed

Luzak, Agnes; Fuertes, Elaine; Flexeder, Claudia; Standl, Marie; von Berg, Andrea; Berdel, Dietrich; Koletzko, Sibylle; Heinrich, Joachim; Nowak, Dennis; Schulz, Holger

2017-07-12

Various factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of early life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds. Best subset selection was performed for linear regression models to investigate associations between 21 diverse early life events and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF 25-75 )) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis. A higher peak weight velocity and early lung infections were the early life events prevalently associated with airflow limitation and FEF 25-75 . Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (≤23.7%). The variance explained by early life events was comparatively low (median: 4.8%; range: 0.2-22.4%), but these events were consistently negatively associated with airway function. Although the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate early life and current factors that should be considered in studies on lung health among adolescents.

Pathological analysis of the Candida albicans-infected tongue tissues of a murine oral candidiasis model in the early infection stage.

PubMed

Okada, Masashi; Hisajima, Tatsuya; Ishibashi, Hiroko; Miyasaka, Takahiro; Abe, Shigeru; Satoh, Tazuko

2013-04-01

The early pathological process of Candida infection and immunological responses in tongues of the mice with experimental oral candidiasis was analysed. CD-1 mice, pretreated by prednisolone were orally inoculated with Candida albicans. Symptoms were monitored by measuring the area of white tongue coating and number of viable Candida cells in oral cavity. The histopathological analysis was carried by PAS-stain and immunofluorescent staining. IL-4, IL-12p70, IFN-γ, TNF-α in recovered from the homogenates of the tongues were measured by ELISA. The fungus invaded the tongue surface of the mice and white patches developed within 24h after inoculation. Histopathological examination indicated the presence of local acute inflammation in superficial tissues of tongues covered by mycelium of C. albicans. Pathological exacerbation was observed from 24 to 48 h after the inoculation and from then the symptoms of oral candidiasis appeared to move into the recovery phase. Inflammatory cells mainly consisting of neutrophils was accumulated and located under the lesions covered by Candida-hyphae. An increase in IL-12p70 and IFN-γ in tongue homogenates was observed at 48 h after inoculation. The worst condition in the pathological process in experimental oral candidiasis was found 48 h after C. albicans inoculation. When the surface of the Candida-inoculated tongues was covered with Candida-hyphae, a dense accumulation of neutrophils was observed under the lesions and homogenates of the tongues contained increased levels of IL-12p70 and IFN-γ. These suggested that local pathological condition of Candida-infected tongues may be affected by neutrophils accumulation and increased levels of some cytokines. Copyright © 2012 Elsevier Ltd. All rights reserved.

Early classification of pathological heartbeats on wireless body sensor nodes.

PubMed

Braojos, Rubén; Beretta, Ivan; Ansaloni, Giovanni; Atienza, David

2014-11-27

Smart Wireless Body Sensor Nodes (WBSNs) are a novel class of unobtrusive, battery-powered devices allowing the continuous monitoring and real-time interpretation of a subject's bio-signals, such as the electrocardiogram (ECG). These low-power platforms, while able to perform advanced signal processing to extract information on heart conditions, are usually constrained in terms of computational power and transmission bandwidth. It is therefore essential to identify in the early stages which parts of an ECG are critical for the diagnosis and, only in these cases, activate on demand more detailed and computationally intensive analysis algorithms. In this work, we present a comprehensive framework for real-time automatic classification of normal and abnormal heartbeats, targeting embedded and resource-constrained WBSNs. In particular, we provide a comparative analysis of different strategies to reduce the heartbeat representation dimensionality, and therefore the required computational effort. We then combine these techniques with a neuro-fuzzy classification strategy, which effectively discerns normal and pathological heartbeats with a minimal run time and memory overhead. We prove that, by performing a detailed analysis only on the heartbeats that our classifier identifies as abnormal, a WBSN system can drastically reduce its overall energy consumption. Finally, we assess the choice of neuro-fuzzy classification by comparing its performance and workload with respect to other state-of-the-art strategies. Experimental results using the MIT-BIH Arrhythmia database show energy savings of as much as 60% in the signal processing stage, and 63% in the subsequent wireless transmission, when a neuro-fuzzy classification structure is employed, coupled with a dimensionality reduction technique based on random projections.

Early Classification of Pathological Heartbeats on Wireless Body Sensor Nodes

PubMed Central

Braojos, Rubén; Beretta, Ivan; Ansaloni, Giovanni; Atienza, David

2014-01-01

Smart Wireless Body Sensor Nodes (WBSNs) are a novel class of unobtrusive, battery-powered devices allowing the continuous monitoring and real-time interpretation of a subject's bio-signals, such as the electrocardiogram (ECG). These low-power platforms, while able to perform advanced signal processing to extract information on heart conditions, are usually constrained in terms of computational power and transmission bandwidth. It is therefore essential to identify in the early stages which parts of an ECG are critical for the diagnosis and, only in these cases, activate on demand more detailed and computationally intensive analysis algorithms. In this work, we present a comprehensive framework for real-time automatic classification of normal and abnormal heartbeats, targeting embedded and resource-constrained WBSNs. In particular, we provide a comparative analysis of different strategies to reduce the heartbeat representation dimensionality, and therefore the required computational effort. We then combine these techniques with a neuro-fuzzy classification strategy, which effectively discerns normal and pathological heartbeats with a minimal run time and memory overhead. We prove that, by performing a detailed analysis only on the heartbeats that our classifier identifies as abnormal, a WBSN system can drastically reduce its overall energy consumption. Finally, we assess the choice of neuro-fuzzy classification by comparing its performance and workload with respect to other state-of-the-art strategies. Experimental results using the MIT-BIH Arrhythmia database show energy savings of as much as 60% in the signal processing stage, and 63% in the subsequent wireless transmission, when a neuro-fuzzy classification structure is employed, coupled with a dimensionality reduction technique based on random projections. PMID:25436654

Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology.

PubMed

Radde, Rebecca; Bolmont, Tristan; Kaeser, Stephan A; Coomaraswamy, Janaky; Lindau, Dennis; Stoltze, Lars; Calhoun, Michael E; Jäggi, Fabienne; Wolburg, Hartwig; Gengler, Simon; Haass, Christian; Ghetti, Bernardino; Czech, Christian; Hölscher, Christian; Mathews, Paul M; Jucker, Mathias

2006-09-01

We have generated a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1 mice). Cerebral amyloidosis starts at 6-8 weeks and the ratio of human amyloid (A)beta42 to Abeta40 is 1.5 and 5 in pre-depositing and amyloid-depositing mice, respectively. Consistent with this ratio, extensive congophilic parenchymal amyloid but minimal amyloid angiopathy is observed. Amyloid-associated pathologies include dystrophic synaptic boutons, hyperphosphorylated tau-positive neuritic structures and robust gliosis, with neocortical microglia number increasing threefold from 1 to 8 months of age. Global neocortical neuron loss is not apparent up to 8 months of age, but local neuron loss in the dentate gyrus is observed. Because of the early onset of amyloid lesions, the defined genetic background of the model and the facile breeding characteristics, APPPS1 mice are well suited for studying therapeutic strategies and the pathomechanism of amyloidosis by cross-breeding to other genetically engineered mouse models.

Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology

PubMed Central

Radde, Rebecca; Bolmont, Tristan; Kaeser, Stephan A; Coomaraswamy, Janaky; Lindau, Dennis; Stoltze, Lars; Calhoun, Michael E; Jäggi, Fabienne; Wolburg, Hartwig; Gengler, Simon; Haass, Christian; Ghetti, Bernardino; Czech, Christian; Hölscher, Christian; Mathews, Paul M; Jucker, Mathias

2006-01-01

We have generated a novel transgenic mouse model on a C57BL/6J genetic background that coexpresses KM670/671NL mutated amyloid precursor protein and L166P mutated presenilin 1 under the control of a neuron-specific Thy1 promoter element (APPPS1 mice). Cerebral amyloidosis starts at 6–8 weeks and the ratio of human amyloid (A)β42 to Aβ40 is 1.5 and 5 in pre-depositing and amyloid-depositing mice, respectively. Consistent with this ratio, extensive congophilic parenchymal amyloid but minimal amyloid angiopathy is observed. Amyloid-associated pathologies include dystrophic synaptic boutons, hyperphosphorylated tau-positive neuritic structures and robust gliosis, with neocortical microglia number increasing threefold from 1 to 8 months of age. Global neocortical neuron loss is not apparent up to 8 months of age, but local neuron loss in the dentate gyrus is observed. Because of the early onset of amyloid lesions, the defined genetic background of the model and the facile breeding characteristics, APPPS1 mice are well suited for studying therapeutic strategies and the pathomechanism of amyloidosis by cross-breeding to other genetically engineered mouse models. PMID:16906128

Guiding principles and clinical applications for speech-language pathology practice in early intervention.

PubMed

Paul, Diane; Roth, Froma P

2011-07-01

This article describes guiding principles in early intervention (EI) and demonstrates how speech-language pathologists (SLPs) can apply these principles to best serve infants and toddlers with communication and related problems and their families. Four principles guide the implementation of speech-language pathology services. EI services are services that are (a) family centered and culturally and linguistically responsive; (b) developmentally supportive, promoting children's participation in their natural environments; (c) comprehensive, coordinated, and team based; and (d) based on the highest quality evidence available. Actual clinical scenarios are presented to illustrate each principle. The four principles provide a framework for the wide range of roles and responsibilities assumed by SLPs in EI: (a) screening/evaluation/assessment, (b) goal setting and intervention, (c) consultation with and education for team members, (d) service coordination, (e) transition planning, and (f) advocacy. It is critical that families of infants and toddlers who are at risk for, or who have been diagnosed with, communication disorders receive all necessary services and supports. EI services should be tailored to the individual and the changing needs, preferences, and priorities of each family. The earlier services are provided, the more likely is the child's chance to develop effective communication.

Risk of Pathologic Upgrading or Locally Advanced Disease in Early Prostate Cancer Patients Based on Biopsy Gleason Score and PSA: A Population-Based Study of Modern Patients

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

Caster, Joseph M.; Falchook, Aaron D.; Hendrix, Laura H.

Purpose: Radiation oncologists rely on available clinical information (biopsy Gleason score and prostate-specific antigen [PSA]) to determine the optimal treatment regimen for each prostate cancer patient. Existing published nomograms correlating clinical to pathologic extent of disease were based on patients treated in the 1980s and 1990s at select academic institutions. We used the Surveillance, Epidemiology, and End Results (SEER) database to examine pathologic outcomes (Gleason score and cancer stage) in early prostate cancer patients based on biopsy Gleason score and PSA concentration. Methods and Materials: This analysis included 25,858 patients whose cancer was diagnosed between 2010 and 2011, with biopsymore » Gleason scores of 6 to 7 and clinical stage T1 to T2 disease, who underwent radical prostatectomy. In subgroups based on biopsy Gleason score and PSA level, we report the proportion of patients with pathologically advanced disease (positive surgical margin or pT3-T4 disease) or whose Gleason score was upgraded. Logistic regression was used to examine factors associated with pathologic outcomes. Results: For patients with biopsy Gleason score 6 cancers, 84% of those with PSA <10 ng/mL had surgical T2 disease with negative margins; this decreased to 61% in patients with PSA of 20 to 29.9 ng/mL. Gleason score upgrading was seen in 43% (PSA: <10 ng/mL) to 61% (PSA: 20-29.9 ng/mL) of biopsy Gleason 6 patients. Patients with biopsy Gleason 7 cancers had a one-third (Gleason 3 + 4; PSA: <10 ng/mL) to two-thirds (Gleason 4 + 3; PSA: 20-29.9 ng/mL) probability of having pathologically advanced disease. Gleason score upgrading was seen in 11% to 19% of patients with biopsy Gleason 4 + 3 cancers. Multivariable analysis showed that higher PSA and older age were associated with Gleason score upgrading and pathologically advanced disease. Conclusions: This is the first population-based study to examine pathologic extent of disease and pathologic

Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

PubMed Central

Grégoire, Laurent; Caparos, Serge; Leblanc, Carole-Anne; Brisson, Benoit; Blanchette, Isabelle

2018-01-01

This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD) and no abuse participants. We focused particularly on an early wave (C1/P1), the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms) of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD) suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology. PMID:29379428

Divergent response of the neritic carbonate factory to environmental changes during the Early Bajocian Event

NASA Astrophysics Data System (ADS)

Bodin, Stephane; Hönig, Martin; Krencker, Francois-Nicolas; Danisch, Jan; Kabiri, Lahcen

2017-04-01

The Early Bajocian witnessed a global environmental perturbation, characterized by faunal and floral turnovers and a positive carbon isotope excursion. In Italy, this environmental perturbation coincided with an eutrophication event and a carbonate crisis, but this has so far not been adequately reported from other settings, leaving doubt about the extent and nature of these phenomena. Here, we are reporting on an extensive neritic carbonate factory demise that occurs in the upper Lower Bajocian of the Central High Atlas of Morocco, more precisely in the upper Propinquans - lower Humphriesianum Zones. This demise coincided with the acme of the global carbon isotope perturbation, recorded by a 3‰ positive carbon isotope excursion in the bulk organic matter of Morocco. Recovery of the neritic carbonate system occurs during the Early to Late Bajocian transition. The duration of the neritic carbonate factory demise was therefore in the order of 1 Myr. Furthermore, we observe that the Lower Bajocian of Morocco is relatively enriched in arenitic siliciclastic deposits, suggesting increased weathering and nutrient levels along the northwestern margin of Africa during the Early Bajocian. However, comparison with neighboring European basins highlights the non-uniqueness and different timing of the response of shallow-water carbonates to the Early Bajocian environmental perturbations, as some regions present no sign of carbonate factory crisis. Hence, we postulate that local factors were important in mediating the response of neritic carbonate factories to this global environmental perturbation. We notably highlight the role of large Early Bajocian sea-level fluctuation as a trigger for carbonate factory change and demise in Morocco. Indeed, in the Central High Atlas Basin, transgressive intervals are seeing the development of a mud-dominated carbonate factory whereas regressive intervals are associated with grain-dominated carbonate factory. We speculate that the

An Ultra-High Field Study of Cerebellar Pathology in Early Relapsing-Remitting Multiple Sclerosis Using MP2RAGE.

PubMed

Fartaria, Mário João; OʼBrien, Kieran; Şorega, Alexandra; Bonnier, Guillaume; Roche, Alexis; Falkovskiy, Pavel; Krueger, Gunnar; Kober, Tobias; Bach Cuadra, Meritxell; Granziera, Cristina

2017-05-01

The aim of this study was to study focal cerebellar pathology in early stages of multiple sclerosis (MS) using ultra-high-field magnetization-prepared 2 inversion-contrast rapid gradient-echo (7T MP2RAGE). Twenty early-stage relapsing-remitting MS patients underwent an MP2RAGE acquisition at 7 T magnetic resonance imaging (MRI) (images acquired at 2 different resolutions: 0.58 × 0.58 × 0.58 mm, 7T_0.58, and 0.75 × 0.75 × 0.90 mm, 7T_0.75) and 3 T MRI (1.0 × 1.0 × 1.2 mm, 3T_1.0). Total cerebellar lesion load and volume and mean cerebellar lesion volume were compared across images using a Wilcoxon signed-rank test. Mean T1 relaxation times in lesions and normal-appearing tissue as well as contrast-to-noise ratio (CNR) measurements were also compared using a Wilcoxon signed-rank test. A multivariate analysis was applied to assess the contribution of MRI metrics to clinical performance in MS patients. Both 7T_0.58 and 7T_0.75 MP2RAGE showed significantly higher lesion load compared with 3T_1.0 MP2RAGE (P < 0.001). Plaques that were judged as leukocortical in 7T_0.75 and 3T_1.0 MP2RAGEs were instead identified as WM lesions in 7T_0.58 MP2RAGE. Cortical lesion CNR was significantly higher in MP2RAGEs at 7 T than at 3 T. Total lesion load as well as total and mean lesion volume obtained at both 7 T and 3 T MP2RAGE significantly predicted attention (P < 0.05, adjusted R = 0.5), verbal fluency (P < 0.01, adjusted R = 0.6), and motor performance (P = 0.01, adjusted R = 0.7). This study demonstrates the value of 7 T MP2RAGE to study the cerebellum in early MS patients. 7T_0.58 MP2RAGE provides a more accurate anatomical description of white and gray matter pathology compared with 7T_0.75 and 3T_1.0 MP2RAGE, likely due to the improved spatial resolution, lower partial volume effects, and higher CNR.

Forensic Pathology Education in Pathology Residency

PubMed Central

Ross, Wayne K.; Domen, Ronald E.

2017-01-01

Forensic pathology is a fundamental part of anatomic pathology training during pathology residency. However, the lack of information on forensic teaching suggests the highly variable nature of forensic education. A survey of pathology residency program directors was performed to determine key aspects of their respective forensic rotations and curriculum. A total of 38.3% of programs from across the country responded, and the survey results show 5.6% don’t require a forensic pathology rotation. In those that do, most forensic pathology rotations are 4 weeks long, are done at a medical examiner’s office, and require set prerequisites. A total of 21.1% of responding programs have residents who are not receiving documented evaluations for this rotation. While 39.6% of programs have a defined forensics curriculum, as many as 15% do not. Furthermore, nearly 43% of programs place no limit on counting forensic autopsies when applying for pathology board examinations. Our survey confirmed the inconsistent nature of forensic pathology training in resident education. Additionally, our curriculum was reorganized to create a more robust educational experience. A pre- and post-forensic lecture quiz and Resident In-Service Examination scores were analyzed to determine our curriculum’s impact and effectiveness. Analysis of our pre- and post-lecture quiz showed an improved overall average as well as an increase in Resident In-Service Examination scores, indicating improved general forensic pathology knowledge. Using this knowledge, along with changes in our curriculum, we generated a number of recommendations for improving forensic pathology education in pathology residency. PMID:28913415

Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia

PubMed Central

Jansen, Willemijn J.; Ossenkoppele, Rik; Knol, Dirk L.; Tijms, Betty M.; Scheltens, Philip; Verhey, Frans R. J.; Visser, Pieter Jelle

2015-01-01

IMPORTANCE Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies. OBJECTIVE To use individual participant data meta-analysis to estimate the prevalence of amyloid pathology as measured with biomarkers in participants with normal cognition, subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). DATA SOURCES Relevant biomarker studies identified by searching studies published before April 2015 using the MEDLINE and Web of Science databases and through personal communication with investigators. STUDY SELECTION Studies were included if they provided individual participant data for participants without dementia and used an a priori defined cutoff for amyloid positivity. DATA EXTRACTION AND SYNTHESIS Individual records were provided for 2914 participants with normal cognition, 697 with SCI, and 3972 with MCI aged 18 to 100 years from 55 studies. MAIN OUTCOMES AND MEASURES Prevalence of amyloid pathology on positron emission tomography or in cerebrospinal fluid according to AD risk factors (age, apolipoprotein E [APOE] genotype, sex, and education) estimated by generalized estimating equations. RESULTS The prevalence of amyloid pathology increased from age 50 to 90 years from 10% (95% CI, 8%-13%) to 44% (95% CI, 37%-51%) among participants with normal cognition; from 12% (95% CI, 8%-18%) to 43% (95% CI, 32%-55%) among patients with SCI; and from 27% (95% CI, 23%-32%) to 71% (95% CI, 66%-76%) among patients with MCI. APOE-ε4 carriers had 2 to 3 times higher prevalence estimates than noncarriers. The age at which 15% of the participants with normal cognition were amyloid positive was approximately 40 years for APOEε4ε4 carriers, 50 years for ε2ε4 carriers, 55 years for ε3ε4 carriers, 65 years for ε3ε3 carriers, and

Modeling Tool for Decision Support during Early Days of an Anthrax Event.

PubMed

Rainisch, Gabriel; Meltzer, Martin I; Shadomy, Sean; Bower, William A; Hupert, Nathaniel

2017-01-01

Health officials lack field-implementable tools for forecasting the effects that a large-scale release of Bacillus anthracis spores would have on public health and hospitals. We created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examined the consequences of intervention choices. With only 3 days of case counts, the model can predict final attack sizes for simulated Sverdlovsk-like events (1979 USSR) with sufficient accuracy for decision making and confirms the value of early postexposure prophylaxis initiation. According to a baseline scenario, hospital treatment volume peaks 15 days after exposure, deaths peak earlier (day 5), and recovery peaks later (day 23). This tool gives public health, hospital, and emergency planners scenario-specific information for developing quantitative response plans for this threat.

Pathological Narcissism and Interpersonal Behavior in Daily Life

PubMed Central

Roche, Michael J.; Pincus, Aaron L.; Conroy, David E.; Hyde, Amanda L.; Ram, Nilam

2014-01-01

The Cognitive-Affective Processing System (CAPS) has been proposed as a useful meta-framework for integrating contextual differences in situations with individual differences in personality pathology. In this article, we evaluated the potential of combining the CAPS meta-framework and contemporary interpersonal theory to investigate how individual differences in pathological narcissism influenced interpersonal functioning in daily life. University students (N = 184) completed event-contingent reports about interpersonal interactions across a 7-day diary study. Using multilevel regression models, we found that combinations of narcissistic expression (grandiosity, vulnerability) were associated with different interpersonal behavior patterns reflective of interpersonal dysfunction. These results are among the first to empirically demonstrate the usefulness of the CAPS model to conceptualize personality pathology through the patterning of if-then interpersonal processes. PMID:23205698

Digital Imaging and Communications in Medicine Whole Slide Imaging Connectathon at Digital Pathology Association Pathology Visions 2017.

PubMed

Clunie, David; Hosseinzadeh, Dan; Wintell, Mikael; De Mena, David; Lajara, Nieves; Garcia-Rojo, Marcial; Bueno, Gloria; Saligrama, Kiran; Stearrett, Aaron; Toomey, David; Abels, Esther; Apeldoorn, Frank Van; Langevin, Stephane; Nichols, Sean; Schmid, Joachim; Horchner, Uwe; Beckwith, Bruce; Parwani, Anil; Pantanowitz, Liron

2018-01-01

As digital pathology systems for clinical diagnostic work applications become mainstream, interoperability between these systems from different vendors becomes critical. For the first time, multiple digital pathology vendors have publicly revealed the use of the digital imaging and communications in medicine (DICOM) standard file format and network protocol to communicate between separate whole slide acquisition, storage, and viewing components. Note the use of DICOM for clinical diagnostic applications is still to be validated in the United States. The successful demonstration shows that the DICOM standard is fundamentally sound, though many lessons were learned. These lessons will be incorporated as incremental improvements in the standard, provide more detailed profiles to constrain variation for specific use cases, and offer educational material for implementers. Future Connectathon events will expand the scope to include more devices and vendors, as well as more ambitious use cases including laboratory information system integration and annotation for image analysis, as well as more geographic diversity. Users should request DICOM features in all purchases and contracts. It is anticipated that the growth of DICOM-compliant manufacturers will likely also ease DICOM for pathology becoming a recognized standard and as such the regulatory pathway for digital pathology products.

In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology

PubMed Central

Caso, Francesca; Mandelli, Maria Luisa; Henry, Maya; Gesierich, Benno; Bettcher, Brianne M.; Ogar, Jennifer; Filippi, Massimo; Comi, Giancarlo; Magnani, Giuseppe; Sidhu, Manu; Trojanowski, John Q.; Huang, Eric J.; Grinberg, Lea T.; Miller, Bruce L.; Dronkers, Nina; Seeley, William W.

2014-01-01

Objective: To identify early cognitive and neuroimaging features of sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by frontotemporal lobar degeneration (FTLD) subtypes. Methods: We prospectively collected clinical, neuroimaging, and neuropathologic data in 11 patients with sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n = 9) or FTLD–transactive response DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed patterns of cognitive and gray matter (GM) and white matter (WM) atrophy at presentation in the whole group and in each pathologic subtype separately. We also considered longitudinal clinical data. Results: At first evaluation, regardless of pathologic FTLD subtype, apraxia of speech (AOS) was the most common cognitive feature and atrophy involved the left posterior frontal lobe. Each pathologic subtype showed few distinctive features. At presentation, patients with nfvPPA-tau presented with mild to moderate AOS, mixed dysarthria with prominent hypokinetic features, clear agrammatism, and atrophy in the GM of the left posterior frontal regions and in left frontal WM. While speech and language deficits were prominent early, within 3 years of symptom onset, all patients with nfvPPA-tau developed significant extrapyramidal motor signs. At presentation, patients with nfvPPA-TDP had severe AOS, dysarthria with spastic features, mild agrammatism, and atrophy in left posterior frontal GM only. Selective mutism occurred early, when general neurologic examination only showed mild decrease in finger dexterity in the right hand. Conclusions: Clinical features in sporadic nfvPPA caused by FTLD subtypes relate to neurodegeneration of GM and WM in frontal motor speech and language networks. We propose that early WM atrophy in nfvPPA is suggestive of FTLD-tau pathology while early selective GM loss might be indicative of FTLD-TDP. PMID:24353332

Computational analysis identifies putative prognostic biomarkers of pathological scarring in skin wounds.

PubMed

Nagaraja, Sridevi; Chen, Lin; DiPietro, Luisa A; Reifman, Jaques; Mitrophanov, Alexander Y

2018-02-20

Pathological scarring in wounds is a prevalent clinical outcome with limited prognostic options. The objective of this study was to investigate whether cellular signaling proteins could be used as prognostic biomarkers of pathological scarring in traumatic skin wounds. We used our previously developed and validated computational model of injury-initiated wound healing to simulate the time courses for platelets, 6 cell types, and 21 proteins involved in the inflammatory and proliferative phases of wound healing. Next, we analysed thousands of simulated wound-healing scenarios to identify those that resulted in pathological (i.e., excessive) scarring. Then, we identified candidate proteins that were elevated (or decreased) at the early stages of wound healing in those simulations and could therefore serve as predictive biomarkers of pathological scarring outcomes. Finally, we performed logistic regression analysis and calculated the area under the receiver operating characteristic curve to quantitatively assess the predictive accuracy of the model-identified putative biomarkers. We identified three proteins (interleukin-10, tissue inhibitor of matrix metalloproteinase-1, and fibronectin) whose levels were elevated in pathological scars as early as 2 weeks post-wounding and could predict a pathological scarring outcome occurring 40 days after wounding with 80% accuracy. Our method for predicting putative prognostic wound-outcome biomarkers may serve as an effective means to guide the identification of proteins predictive of pathological scarring.

The role of impact events play in redistributing and sequestering water on Early Mars

NASA Astrophysics Data System (ADS)

Osinski, G.; Tornabene, L. L.

2017-12-01

Impact cratering is one of the most fundamental geological process in the Solar System. Several workers have considered the effect that impact events may have had on the climate of Early Mars. The proposed effects range from impact-induced precipitation to the production of runaway stable climates to the impact delivery of climatically active gases. The role of impact events in forming hydrated minerals has been touched upon but remains debated. In this contribution, we focus on the role that impact events may have played in redistributing and sequestering water on Early Mars; a record that may still be preserved in the Noachian crust. It has been previously proposed that the sequestration of significant quantities of water may have occurred within various hydrated minerals, in particular clays, in the martian crust. There is undoubtedly no single origin for clay-bearing rocks on Mars and the purpose of this contribution is not to review all the possible formation mechanisms. What we do propose, however, is that it is theoretically possible for impact events to create all known occurrences of clays on Mars. We show that clays can form within and around impact craters in two main ways: through the solid-state devitrification of hydrous impact melts and/or impact-generated hydrothermal alteration. Neither of these mechanisms requires a warmer or wetter climate scenario on Early Mars. Notwithstanding the original origin of clays, any clays may be widely redistributed over the Martian surface in the ejecta deposits of large impact craters. However, ejecta deposits are much more complex than commonly thought, with evidence in many instances for two different types of ejecta deposits around martian craters. The first is a ballistic ejecta layer that is low-shock, melt-poor and low-temperature; it will likely not induce the formation of new clays through the mechanisms described above, but could redistribute pre-impact clays over 100's and 1000's of km over the martian

Pathological and Molecular Evaluation of Pancreatic Neoplasms

PubMed Central

Rishi, Arvind; Goggins, Michael; Wood, Laura D.; Hruban, Ralph H.

2015-01-01

Pancreatic neoplasms are morphologically and genetically heterogeneous and include wide variety of neoplasms ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings in new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from their molecular and genetic perspective. All of the major tumor types that arise in the pancreas have been sequenced, and a new classification that incorporates molecular findings together with pathological findings is now possible (Table 1). This classification has significant implications for our understanding of why tumors aggregate in some families, for the development of early detection tests, and for the development of personalized therapies for patients with established cancers. Here we describe this new classification using the framework of the standard histological classification. PMID:25726050

Clinico-pathological features of kidney disease in diabetic cases.

PubMed

Furuichi, Kengo; Shimizu, Miho; Okada, Hirokazu; Narita, Ichiei; Wada, Takashi

2018-03-21

Diabetic kidney disease is the major cause of end-stage kidney disease in developed countries. However, the onset of kidney disorder and the progression pattern of kidney dysfunction and proteinuria greatly vary cases by cases. Therefore, risk classification with clinical data and pathological findings is important. Recent clinico-pathological study with kidney biopsy samples from diabetic patients revealed that pathological changes of diabetic nephropathy are characteristic and have special impacts on prognosis in each clinical stage. Moreover, comparison of the clinico-pathological findings of diabetic nephropathy with hypertensive nephrosclerosis revealed that there are few differences in their pathological findings in cases with low albuminuria and preserved estimated glomerular filtration rate (eGFR). Because it is so difficult to clearly distinguish pure kidney lesions caused by diabetes and kidney lesions due to effects other than diabetes, it is vital that these overlapped pathological findings be confirmed on kidney biopsy in cases of early stage diabetes. Further research is warranted regarding the pathogenesis of diabetic nephropathy and indication of kidney biopsy in diabetic cases.

Pathological Gambling among Italian Nursing Students.

PubMed

Cicolini, Giancarlo; Della Pelle, Carlo; Simonetti, Valentina; Comparcini, Dania; Sepede, Gianna; Cipollone, Francesco

2018-04-01

To investigate the role of psychiatric dimensions, behavioral or substance addictions and demographical variables as determinants of pathological gambling among nursing students. Multicenter cross-sectional study. From June to October 2015 a survey was carried out among Italian Nursing students. Data were collected using a six-section tool. Nursing students who completed the survey numbered 1083, 902 (83.3%) had some problems with gambling and 29 (2.7%) showed pathological gambling. Percentage of pathological gambling was significantly associate with illicit drug/alcohol use (65.5%; p=0.001) and with male gender (58.6%) comparing to student nurse with non-pathological gambling (20%) and those with some problem (24.2%). Significant main effect was observed for IAT score (Beta=0.119, t=3.28, p=0.001): higher IAT scores were associated with higher SOGS scores. Italian nursing students have some problems with gambling and pathological gambling problem, and males are those who have more problems. Results might be useful for faculties of health professionals to identify students at risk in an early stage, to direct prevention tailored interventions. Nursing faculties should be aware of the prevalence of Gambling among students. Prevention interventions should be planned to minimize the risk of gambling behavior in the future nurses' health care workers. Copyright © 2017 Elsevier Inc. All rights reserved.

Irregularities in Early Seismic Rupture Propagation for Large Events in a Crustal Earthquake Model

NASA Astrophysics Data System (ADS)

Lapusta, N.; Rice, J. R.; Rice, J. R.

2001-12-01

We study early seismic propagation of model earthquakes in a 2-D model of a vertical strike-slip fault with depth-variable rate and state friction properties. Our model earthquakes are obtained in fully dynamic simulations of sequences of instabilities on a fault subjected to realistically slow tectonic loading (Lapusta et al., JGR, 2000). This work is motivated by results of Ellsworth and Beroza (Science, 1995), who observe that for many earthquakes, far-field velocity seismograms during initial stages of dynamic rupture propagation have irregular fluctuations which constitute a "seismic nucleation phase". In our simulations, we find that such irregularities in velocity seismograms can be caused by two factors: (1) rupture propagation over regions of stress concentrations and (2) partial arrest of rupture in neighboring creeping regions. As rupture approaches a region of stress concentration, it sees increasing background stress and its moment acceleration (to which velocity seismographs in the far field are proportional) increases. After the peak in stress concentration, the rupture sees decreasing background stress and moment acceleration decreases. Hence a fluctuation in moment acceleration is created. If rupture starts sufficiently far from a creeping region, then partial arrest of rupture in the creeping region causes a decrease in moment acceleration. As the other parts of rupture continue to develop, moment acceleration then starts to grow again, and a fluctuation again results. Other factors may cause the irregularities in moment acceleration, e.g., phenomena such as branching and/or intermittent rupture propagation (Poliakov et al., submitted to JGR, 2001) which we have not studied here. Regions of stress concentration are created in our model by arrest of previous smaller events as well as by interactions with creeping regions. One such region is deep in the fault zone, and is caused by the temperature-induced transition from seismogenic to creeping

Temporal lobe epilepsy: analysis of patients with dual pathology.

PubMed

Salanova, V; Markand, O; Worth, R

2004-02-01

To determine the frequency and types of dual pathology in patients with temporal lobe epilepsy (TLE) and to analyze the clinical manifestations and surgical outcome. A total of 240 patients with TLE underwent temporal resections following a comprehensive pre-surgical evaluation. Thirty-seven (15.4%) of these had hippocampal sclerosis (HS) or temporal lobe gliosis in association with another lesion (dual pathology). Eighteen of 37 patients with dual pathology had heterotopia of the temporal lobe, nine had cortical dysplasia, four had cavernous angiomas or arteriovenous malformations, one had a dysembryoplastic neuroepithelial tumor, one had a contusion and four patients had cerebral infarctions in childhood. 68.5% had abnormal head magnetic resonance imagings, 91.3% had abnormal positron emission tomography scans, and 96% had abnormal ictal SPECT. The intracarotid amobarbital procedure (IAP) showed impaired memory of the epileptogenic side in 72% of the patients. Twenty patients had left and 17 had right-sided en bloc temporal resections, including the lesion and mesial temporal structures. Twenty-six (70.2%) became seizure-free, eight (21.6%) had rare seizures, two (5.4%) had worthwhile seizure reduction and one (2.7%) had no improvement (range of follow-up 1-16 years, mean = 7.4 years). 15.4% had dual pathology. The dual pathology was almost exclusively seen in patients whose lesions were congenital, or occurred early in life, suggesting that the hippocampus is more vulnerable and more readily develops HS in early childhood. Resections, including the lateral and mesial temporal structures led to a favorable outcome with no mortality and little morbidity.

Gait changes precede overt arthritis and strongly correlate with symptoms and histopathological events in pristane-induced arthritis

PubMed Central

2010-01-01

Introduction Pristane-induced arthritis (PIA) in the rat has been described as an animal model of inflammatory arthritis which exhibits features similar to rheumatoid arthritis in humans, such as a chronic, destructive, and symmetrical involvement of peripheral joints. However, so far little is known about the earliest inflammatory events and their influence on locomotor behaviour during the course of PIA. To investigate this issue a detailed analysis of the pathologic changes occurring during the prodromal and early stages of PIA was performed. Methods Arthritis was induced in DA.rats by injection of 150 μl 2,6,10,4-tetramethyl-pentadecane (pristane) at the base of the tail and changes in locomotor behaviour of the affected paws were monitored using the CatWalk quantitative gait analysis system. The pathologic events occurring in the joints of pristane-injected animals were studied before onset, at onset, and during acute phase of arthritis by histological methods. Results Gait analysis revealed that changes in locomotion such as reduced paw print areas and stance phase time are already apparent before the onset of clinically discernible arthritis symptoms (erythema, paw swelling) and correlate with PIA scores. In agreement with these findings, inflammatory tenosynovitis could be observed by histology already before the onset of erythema and swelling of the respective paws. In the most heavily affected rats also irregularities in step sequence patterns occurred A kinetic analysis of clinical and histological findings demonstrated that gait changes precede the pathological changes occurring during the acute phase of pristane-induced arthritis. Conclusions Gait analysis allows for pinpointing the initial inflammatory changes in experimental arthritis models such as pristane-induced arthritis. Analysis of early clinically relevant symptoms in arthritis models may facilitate the search for novel therapeutics to interfere with pain, inflammation and joint destruction

Pathology Competencies for Medical Education and Educational Cases.

PubMed

Knollmann-Ritschel, Barbara E C; Regula, Donald P; Borowitz, Michael J; Conran, Richard; Prystowsky, Michael B

2017-01-01

Current medical school curricula predominantly facilitate early integration of basic science principles into clinical practice to strengthen diagnostic skills and the ability to make treatment decisions. In addition, they promote life-long learning and understanding of the principles of medical practice. The Pathology Competencies for Medical Education (PCME) were developed in response to a call to action by pathology course directors nationwide to teach medical students pathology principles necessary for the practice of medicine. The PCME are divided into three competencies: 1) Disease Mechanisms and Processes, 2) Organ System Pathology, and 3) Diagnostic Medicine and Therapeutic Pathology. Each of these competencies is broad and contains multiple learning goals with more specific learning objectives. The original competencies were designed to be a living document, meaning that they will be revised and updated periodically, and have undergone their first revision with this publication. The development of teaching cases, which have a classic case-based design, for the learning objectives is the next step in providing educational content that is peer-reviewed and readily accessible for pathology course directors, medical educators, and medical students. Application of the PCME and cases promotes a minimum standard of exposure of the undifferentiated medical student to pathophysiologic principles. The publication of the PCME and the educational cases will create a current educational resource and repository published through Academic Pathology .

Digital Imaging and Communications in Medicine Whole Slide Imaging Connectathon at Digital Pathology Association Pathology Visions 2017

PubMed Central

Clunie, David; Hosseinzadeh, Dan; Wintell, Mikael; De Mena, David; Lajara, Nieves; Garcia-Rojo, Marcial; Bueno, Gloria; Saligrama, Kiran; Stearrett, Aaron; Toomey, David; Abels, Esther; Apeldoorn, Frank Van; Langevin, Stephane; Nichols, Sean; Schmid, Joachim; Horchner, Uwe; Beckwith, Bruce; Parwani, Anil; Pantanowitz, Liron

2018-01-01

As digital pathology systems for clinical diagnostic work applications become mainstream, interoperability between these systems from different vendors becomes critical. For the first time, multiple digital pathology vendors have publicly revealed the use of the digital imaging and communications in medicine (DICOM) standard file format and network protocol to communicate between separate whole slide acquisition, storage, and viewing components. Note the use of DICOM for clinical diagnostic applications is still to be validated in the United States. The successful demonstration shows that the DICOM standard is fundamentally sound, though many lessons were learned. These lessons will be incorporated as incremental improvements in the standard, provide more detailed profiles to constrain variation for specific use cases, and offer educational material for implementers. Future Connectathon events will expand the scope to include more devices and vendors, as well as more ambitious use cases including laboratory information system integration and annotation for image analysis, as well as more geographic diversity. Users should request DICOM features in all purchases and contracts. It is anticipated that the growth of DICOM-compliant manufacturers will likely also ease DICOM for pathology becoming a recognized standard and as such the regulatory pathway for digital pathology products. PMID:29619278

Preserving the Past: An Early Interview Improves Delayed Event Memory in Children With Intellectual Disabilities

PubMed Central

Brown, Deirdre A; Lewis, Charlie N; Lamb, Michael E

2015-01-01

The influence of an early interview on children's (N = 194) later recall of an experienced event was examined in children with mild and moderate intellectual disabilities (CWID; 7–12 years) and typically developing (TD) children matched for chronological (7–12 years) or mental (4–9 years) age. Children previously interviewed were more informative, more accurate, and less suggestible. CWID (mild) recalled as much information as TD mental age matches, and were as accurate as TD chronological age matches. CWID (moderate) recalled less than TD mental age matches but were as accurate. Interviewers should elicit CWID's recall as early as possible and consider developmental level and severity of impairments when evaluating eyewitness testimony. PMID:25876042

Advanced glycation end products (AGEs) in oral pathology.

PubMed

Ilea, Aranka; Băbţan, Anida M; Boşca, Bianca A; Crişan, Maria; Petrescu, Nausica B; Collino, Massimo; Sainz, Rosa M; Gerlach, Jared Q; Câmpian, Radu Septimiu

2018-05-18

Maillard advanced glycation end products (AGEs) are connected with high dry temperature food processing, color and flavor modification of food products. Oral cavity pathology is strongly influenced by dietary intake. The aim of the present paper is to update current data regarding the sources and metabolism of AGEs, their impact on oral cavity tissues, to discuss and suggest new approaches for the early diagnosis and efficient treatment of AGEs-related oral pathology. This paper is a narrative review of the studies discussing AGEs and mainly the dietary AGEs (dAGEs) sources, metabolism, linkage to general diseases, and specifically the oral cavity pathology. The authors used "PUBMED" and MeSH for the finding of English written and published articles concerning AGEs. There were used the next keywords association: "advanced glycation end products- AGEs" AND "Maillard products", "AGEs" AND "diet-related disease, "AGEs" AND "salivary biosensor", "AGEs" AND "metabolic syndrome AGEs", "AGEs" AND "oral pathology", "AGEs" AND "dentin AGEs" OR "periodontal AGEs", "AGEs" AND "diagnosis and monitoring". The authors used free full-text articles to determine the etiology and physiopathology of AGEs, their association with general diseases and oral cavity disease, assessment methods used in biofluids and tissues, AGEs prevention and treatment approaches. Articles concerning AGEs etiology, metabolism and effect in the human body and specific implication in oral pathology were selected. There were no exclusion criteria in what concerns the study design. Studies in other language than English and articles abstracts were excluded. Criteria of inclusion were free full-text articles written in English. Equally human and animal model studies were included. Regarding the date of publication, all subjects concerning glycation products after 1953 (first published article) were included. Evidence show that AGEs are responsible for inducing low intensity chronic inflammation and thereby

Tumor necrosis factor-α inhibitor treatment and the risk of incident cardiovascular events in patients with early rheumatoid arthritis: a nested case-control study.

PubMed

Desai, Rishi J; Rao, Jaya K; Hansen, Richard A; Fang, Gang; Maciejewski, Matthew; Farley, Joel

2014-11-01

To compare the risk of cardiovascular (CV) events between use of tumor necrosis factor-α inhibitors (TNFi) and nonbiologic disease-modifying antirheumatic drugs (DMARD) in patients with early rheumatoid arthritis (RA). A nested case-control study was conducted using data from Truven's MarketScan commercial and Medicare claims database for patients with early RA who started treatment with either a TNFi or a nonbiologic DMARD between January 1, 2008, and December 31, 2010. Date of CV event diagnosis for cases was defined as the event date, and 12 age-matched and sex-matched controls were sampled using incidence density sampling. Drug exposure was defined into the following mutually exclusive categories hierarchically: (1) current use of TNFi (with or without nonbiologics), (2) past use of TNFi (with or without nonbiologics), (3) current use of nonbiologics only, and (4) past use of nonbiologics only. Current use was defined as any use in the period 90 days prior to the event date. Conditional logistic regression models were used to derive incidence rate ratios (IRR). From the cohort of patients with early RA, 279 cases of incident CV events and 3348 matched controls were identified. The adjusted risk of CV events was not significantly different between current TNFi users and current nonbiologic users (IRR 0.92, 95% CI 0.59-1.44). However, past users of nonbiologics showed significantly higher risk compared to current nonbiologic users (IRR 1.47, 95% CI 1.04-2.08). No differences in the CV risk were found between current TNFi and current nonbiologic DMARD treatment in patients with early RA.

Neuronopathic Lysosomal Storage Diseases: Clinical and Pathologic Findings

ERIC Educational Resources Information Center

Prada, Carlos E.; Grabowski, Gregory A.

2013-01-01

Background: The lysosomal--autophagocytic system diseases (LASDs) affect multiple body systems including the central nervous system (CNS). The progressive CNS pathology has its onset at different ages, leading to neurodegeneration and early death. Methods: Literature review provided insight into the current clinical neurological findings,…

Pathology Dynamics Predict Spinal Cord Injury Therapeutic Success

PubMed Central

Mitchell, Cassie S.

2008-01-01

Abstract Secondary injury, the complex cascade of cellular events following spinal cord injury (SCI), is a major source of post-insult neuron death. Experimental work has focused on the details of individual factors or mechanisms that contribute to secondary injury, but little is known about the interactions among factors leading to the overall pathology dynamics that underlie its propagation. Prior hypotheses suggest that the pathology is dominated by interactions, with therapeutic success lying in combinations of neuroprotective treatments. In this study, we provide the first comprehensive, system-level characterization of the entire secondary injury process using a novel relational model methodology that aggregates the findings of ~250 experimental studies. Our quantitative examination of the overall pathology dynamics suggests that, while the pathology is initially dominated by “fire-like,” rate-dependent interactions, it quickly switches to a “flood-like,” accumulation-dependent process with contributing factors being largely independent. Our evaluation of ~20,000 potential single and combinatorial treatments indicates this flood-like pathology results in few highly influential factors at clinically realistic treatment time frames, with multi-factor treatments being merely additive rather than synergistic in reducing neuron death. Our findings give new fundamental insight into the understanding of the secondary injury pathology as a whole, provide direction for alternative therapeutic strategies, and suggest that ultimate success in treating SCI lies in the pursuit of pathology dynamics in addition to individually involved factors. PMID:19125684

Computational Pathology

PubMed Central

Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

2016-01-01

Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

Multi-model data fusion to improve an early warning system for hypo-/hyperglycemic events.

PubMed

Botwey, Ransford Henry; Daskalaki, Elena; Diem, Peter; Mougiakakou, Stavroula G

2014-01-01

Correct predictions of future blood glucose levels in individuals with Type 1 Diabetes (T1D) can be used to provide early warning of upcoming hypo-/hyperglycemic events and thus to improve the patient's safety. To increase prediction accuracy and efficiency, various approaches have been proposed which combine multiple predictors to produce superior results compared to single predictors. Three methods for model fusion are presented and comparatively assessed. Data from 23 T1D subjects under sensor-augmented pump (SAP) therapy were used in two adaptive data-driven models (an autoregressive model with output correction - cARX, and a recurrent neural network - RNN). Data fusion techniques based on i) Dempster-Shafer Evidential Theory (DST), ii) Genetic Algorithms (GA), and iii) Genetic Programming (GP) were used to merge the complimentary performances of the prediction models. The fused output is used in a warning algorithm to issue alarms of upcoming hypo-/hyperglycemic events. The fusion schemes showed improved performance with lower root mean square errors, lower time lags, and higher correlation. In the warning algorithm, median daily false alarms (DFA) of 0.25%, and 100% correct alarms (CA) were obtained for both event types. The detection times (DT) before occurrence of events were 13.0 and 12.1 min respectively for hypo-/hyperglycemic events. Compared to the cARX and RNN models, and a linear fusion of the two, the proposed fusion schemes represents a significant improvement.

Potential of Breastmilk Analysis to Inform Early Events in Breast Carcinogenesis: Rationale and Considerations

PubMed Central

Murphy, Jeanne; Sherman, Mark E.; Browne, Eva P.; Caballero, Ana I.; Punska, Elizabeth C.; Pfeiffer, Ruth M.; Yang, Hannah P.; Lee, Maxwell; Yang, Howard; Gierach, Gretchen L.; Arcaro, Kathleen F.

2016-01-01

This review summarizes methods related to the study of human breastmilk in etiologic and biomarkers research. Despite the importance of reproductive factors in breast carcinogenesis, factors that act early in life are difficult to study because young women rarely require breast imaging or biopsy, and analysis of critical circulating factors (e.g. hormones) is often complicated by the requirement to accurately account for menstrual cycle date. Accordingly, novel approaches are needed to understand how events such as pregnancy, breastfeeding, weaning, and post-weaning breast remodeling influence breast cancer risk. Analysis of breastmilk offers opportunities to understand mechanisms related to carcinogenesis in the breast, and to identify risk markers that may inform efforts to identify high-risk women early in the carcinogenic process. In addition, analysis of breastmilk could have value in early detection or diagnosis of breast cancer. In this article we describe the potential for using breastmilk to characterize the microenvironment of the lactating breast with the goal of advancing research on risk assessment, prevention, and detection of breast cancer. PMID:27107568

Relation of Cardiac Complications in the Early Phase of Community-Acquired Pneumonia to Long-Term Mortality and Cardiovascular Events.

PubMed

Cangemi, Roberto; Calvieri, Camilla; Falcone, Marco; Bucci, Tommaso; Bertazzoni, Giuliano; Scarpellini, Maria G; Barillà, Francesco; Taliani, Gloria; Violi, Francesco

2015-08-15

Community-acquired pneumonia (CAP) is complicated by cardiac events in the early phase of the disease. Aim of this study was to assess if these intrahospital cardiac complications may account for overall mortality and cardiovascular events occurring during a long-term follow-up. Three hundred one consecutive patients admitted to the University-Hospital, Policlinico Umberto I, with community-acquired pneumonia were prospectively recruited and followed up for a median of 17.4 months. Primary end point was the occurrence of death for any cause, and secondary end point was the occurrence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction [MI], and stroke). During the intrahospital stay, 55 patients (18%) experienced a cardiac complication. Of these, 32 had an MI (29 non-ST-elevation MI and 3 ST-elevation MI) and 30 had a new episode of atrial fibrillation (7 nonmutually exclusive events). During the follow-up, 89 patients died (51% of patients with an intrahospital cardiac complication and 26% of patients without, p <0.001) and 73 experienced a cardiovascular event (47% of patients with and 19% of patients without an intrahospital cardiac complication, p <0.001). A Cox regression analysis showed that intrahospital cardiac complications, age, and Pneumonia Severity Index were significantly associated with overall mortality, whereas intrahospital cardiac complications, age, hypertension, and diabetes were significantly associated with cardiovascular events during the follow-up. In conclusion, this prospective study shows that intrahospital cardiac complications in the early phase of pneumonia are associated with an enhanced risk of death and cardiovascular events during long-term follow-up. Copyright © 2015 Elsevier Inc. All rights reserved.

Early Experience after Developing a Pathology Laboratory in Malawi, with Emphasis on Cancer Diagnoses

PubMed Central

Horner, Marie-Josephe; Shores, Carol G.; Alide, Noor; Kamiza, Steve; Kampani, Coxcilly; Chimzimu, Fred; Fedoriw, Yuri; Dittmer, Dirk P.; Hosseinipour, Mina C.; Hoffman, Irving F.

2013-01-01

Background Despite increasing cancer burden in Malawi, pathology services are limited. We describe operations during the first 20 months of a new pathology laboratory in Lilongwe, with emphasis on cancer diagnoses. Methods and Findings We performed a cross-sectional study of specimens from the Kamuzu Central Hospital pathology laboratory between July 1, 2011 and February 28, 2013. Patient and specimen characteristics, and final diagnoses are summarized. Diagnoses were categorized as malignant, premalignant, infectious, other pathology, normal or benign, or nondiagnostic. Patient characteristics associated with premalignancy and malignancy were assessed using logistic regression. Of 2772 specimens, 2758 (99%) with a recorded final diagnosis were included, drawn from 2639 unique patients. Mean age was 38 years and 63% were female. Of those with documented HIV status, 51% had unknown status, and 36% with known status were infected. Histologic specimens comprised 91% of cases, and cytologic specimens 9%. Malignant diagnoses were most common overall (n = 861, 31%). Among cancers, cervical cancer was most common (n = 117, 14%), followed by lymphoma (n = 91, 11%), esophageal cancer (n = 86, 10%), sarcoma excluding Kaposi sarcoma (n = 75, 9%), and breast cancer (n = 61, 7%). HIV status was known for 95 (11%) of malignancies, with HIV prevalence ranging from 9% for breast cancer to 81% for cervical cancer. Increasing age was consistently associated with malignancy [bivariable odds ratio 1.24 per decade increase (95% CI 1.19–1.29) among 2685 patients with known age; multivariable odds ratio 1.33 per decade increase (95% CI 1.14–1.56) among 317 patients with known age, gender, and HIV status], while HIV infection and gender were not. Conclusions Despite selection and referral bias inherent in these data, a new pathology laboratory in Lilongwe has created a robust platform for cancer care and research. Strategies to effectively capture clinical

Perfusion alterations converge with patterns of pathological spread in transactive response DNA-binding protein 43 proteinopathies.

PubMed

Ferraro, Pilar M; Jester, Charles; Olm, Christopher A; Placek, Katerina; Agosta, Federica; Elman, Lauren; McCluskey, Leo; Irwin, David J; Detre, John A; Filippi, Massimo; Grossman, Murray; McMillan, Corey T

2018-04-17

Amyotrophic lateral sclerosis (ALS) and the behavioral variant of frontotemporal dementia (bvFTD) commonly share the presence of transactive response DNA-binding protein 43 (TDP-43) inclusions. Structural magnetic resonance imaging studies demonstrated evidence for TDP-43 pathology spread, but while structural imaging usually reveals overt neuronal loss, perfusion imaging may detect more subtle neural activity alterations. We evaluated perfusion as an early marker for incipient pathology-associated brain alterations in TDP-43 proteinopathies. Cortical thickness (CT) and perfusion measurements were obtained in ALS (N = 18), pathologically and/or genetically confirmed bvFTD-TDP (N = 12), and healthy controls (N = 33). bvFTD showed reduced frontotemporal CT, hypoperfusion encompassing orbitofrontal and temporal cortices, and hyperperfusion in motor and occipital regions. ALS did not show reduced CT, but exhibited hypoperfusion in motor and temporal regions, and hyperperfusion in frontal and occipital cortices. Frontotemporal hypoperfusion and reduced CT correlated with cognitive and behavioral impairments as investigated using Mini-Mental State Examination and Philadelphia Brief Assessment of Cognition in bvFTD, and hypoperfusion in motor regions correlated with motor disability as measured by the ALS Functional Rating Scale-Revised in ALS. Hypoperfusion marked early pathologically involved regions, while hyperperfusion characterized regions of late pathological involvement. Distinct perfusion patterns may provide early markers of pathology distribution in TDP-43 proteinopathies. Copyright © 2018 Elsevier Inc. All rights reserved.

Approximate entropy analysis of event-related potentials in patients with early vascular dementia.

PubMed

Xu, Jin; Sheng, Hengsong; Lou, Wutao; Zhao, Songzhen

2012-06-01

This study investigated differences in event-related potential (ERP) parameters among early vascular dementia (VD) patients, healthy elder controls (ECs), and young controls (YCs). A visual "oddball" color identification task was performed while individuals' electroencephalograms (EEGs) were recorded. Approximate entropy (ApEn), a nonlinear measure, along with P300 latencies and amplitudes were used to analyze ERP data and compare these three groups. The patients with VD showed more complex ERP waveforms and higher ApEn values than did ECs while performing the visual task. It was further found that patients with VD showed reduced P300 amplitudes and increased latencies. The results indicate that patients with VD have fewer attention resources to devote to processing stimuli, lower speed of stimulus classification, and lower synchrony in their cortical activity during the response period. We suggest that ApEn, as a measure of ERP complexity, is a promising marker for early diagnosis of VD.

The Impact and Functional Outcomes of Achilles Tendon Pathology in National Basketball Association Players

PubMed Central

Amin, Nirav H; McCullough, Kirk C; Mills, Gavin L; Jones, Morgan H; Cerynik, Douglas L; Rosneck, James; Parker, Richard D

2017-01-01

Achilles tendon rupture within professional athletes has been shown to lead to devastating consequences regarding return to athletic performance. Not only can this devastating injury affect performance for the remainder of player's career, it frequently becomes a career-ending event. Considering these significant risks associated with complete rupture, the purpose of this study was to evaluate NBA players with a spectrum of reported Achilles tendon pathology, from tendinopathy (insertional and non-insertional) to complete rupture. Between the 1988-1989 and 2010-2011 NBA seasons, we identified 43 cases of Achilles tendon pathology treated non-operatively. A control group was matched for the players able to return to play with the following parameters: age, position played, number of seasons played in the league, and similarly rated career performance statistics. Considering the medical staff, trainers and facilities available to a professional athlete, a “weekend warrior” should be counseled that even in optimal conditions, 14% of NBA players were unable to return to function/play after Achilles tendinopathy, and that those who were able to return did so at a decreased level of performance. In conclusion, players with Achilles tendinopathy have a better chance to return if they are younger in age and early in their professional career. Furthermore, the association between Achilles pathology and decline in player performance is an important message to convey to coaching staff and team management to allow properly informed decisions when these conditions arise. PMID:29082269

The Impact and Functional Outcomes of Achilles Tendon Pathology in National Basketball Association Players.

PubMed

Amin, Nirav H; McCullough, Kirk C; Mills, Gavin L; Jones, Morgan H; Cerynik, Douglas L; Rosneck, James; Parker, Richard D

2016-09-01

Achilles tendon rupture within professional athletes has been shown to lead to devastating consequences regarding return to athletic performance. Not only can this devastating injury affect performance for the remainder of player's career, it frequently becomes a career-ending event. Considering these significant risks associated with complete rupture, the purpose of this study was to evaluate NBA players with a spectrum of reported Achilles tendon pathology, from tendinopathy (insertional and non-insertional) to complete rupture. Between the 1988-1989 and 2010-2011 NBA seasons, we identified 43 cases of Achilles tendon pathology treated non-operatively. A control group was matched for the players able to return to play with the following parameters: age, position played, number of seasons played in the league, and similarly rated career performance statistics. Considering the medical staff, trainers and facilities available to a professional athlete, a "weekend warrior" should be counseled that even in optimal conditions, 14% of NBA players were unable to return to function/play after Achilles tendinopathy, and that those who were able to return did so at a decreased level of performance. In conclusion, players with Achilles tendinopathy have a better chance to return if they are younger in age and early in their professional career. Furthermore, the association between Achilles pathology and decline in player performance is an important message to convey to coaching staff and team management to allow properly informed decisions when these conditions arise.

Performance of Earthquake Early Warning Systems during the Major Events of the 2016-2017 Central Italy Seismic Sequence.

NASA Astrophysics Data System (ADS)

Festa, G.; Picozzi, M.; Alessandro, C.; Colombelli, S.; Cattaneo, M.; Chiaraluce, L.; Elia, L.; Martino, C.; Marzorati, S.; Supino, M.; Zollo, A.

2017-12-01

Earthquake early warning systems (EEWS) are systems nowadays contributing to the seismic risk mitigation actions, both in terms of losses and societal resilience, by issuing an alert promptly after the earthquake origin and before the ground shaking impacts the targets to be protected. EEWS systems can be grouped in two main classes: network based and stand-alone systems. Network based EEWS make use of dense seismic networks surrounding the fault (e.g. Near Fault Observatory; NFO) generating the event. The rapid processing of the P-wave early portion allows for the location and magnitude estimation of the event then used to predict the shaking through ground motion prediction equations. Stand-alone systems instead analyze the early P-wave signal to predict the ground shaking carried by the late S or surface waves, through empirically calibrated scaling relationships, at the recording site itself. We compared the network-based (PRESTo, PRobabilistic and Evolutionary early warning SysTem, www.prestoews.org, Satriano et al., 2011) and the stand-alone (SAVE, on-Site-Alert-leVEl, Caruso et al., 2017) systems, by analyzing their performance during the 2016-2017 Central Italy sequence. We analyzed 9 earthquakes having magnitude 5.0 < M < 6.5 at about 200 stations located within 200 km from the epicentral area, including stations of The Altotiberina NFO (TABOO). Performances are evaluated in terms of rate of success of ground shaking intensity prediction and available lead-time, i.e. the time available for security actions. PRESTo also evaluated the accuracy of location and magnitude. Both systems well predict the ground shaking nearby the event source, with a success rate around 90% within the potential damage zone. The lead-time is significantly larger for the network based system, increasing to more than 10s at 40 km from the event epicentre. The stand-alone system better performs in the near-source region showing a positive albeit small lead-time (<3s). Far away from

Predicting adverse obstetric outcome after early pregnancy events and complications: a review.

PubMed

van Oppenraaij, R H F; Jauniaux, E; Christiansen, O B; Horcajadas, J A; Farquharson, R G; Exalto, N

2009-01-01

BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited or small uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care.

Curriculum Guidelines for Pathology and Oral Pathology.

ERIC Educational Resources Information Center

Journal of Dental Education, 1985

1985-01-01

Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

Pathology of cloaca anomalies with case correlation.

PubMed

Gupta, Anita; Bischoff, Andrea

2016-04-01

During the fourth week of human embryo development, a transient common channel known as a cloaca is formed from which three cavities with three external orifices arises. Cloaca anomalies occur when there is failure of separation of the rectum, vagina, and urethra channel resulting in a single drain into the perineum. In our previous institutional studies, Runck et al. compared human and mouse cloaca development and found early mis-patterning of the embryonic cloaca deranged hedgehog and bone morphogenetic proteins (BMP) signaling. Also, our group reported the embryological correlation of the epithelial and stromal histology found in step sections of the common channel in 14 cloaca malformations in humans. In this review, we present the pathology of a 4-year-old female with a cloaca and VACTERL complex, and summarize our current knowledge of cloaca pathology. Furthermore, we suggest that careful pathological examination of cloaca specimens in conjunction with surgical orientation may result in a better understanding of the etiology of this condition. Published by Elsevier Inc.

Transgenic Mice Overexpressing Amyloid Precursor Protein Exhibit Early Metabolic Deficits and a Pathologically Low Leptin State Associated with Hypothalamic Dysfunction in Arcuate Neuropeptide Y Neurons

PubMed Central

Ishii, Makoto; Wang, Gang; Racchumi, Gianfranco; Dyke, Jonathan P.

2014-01-01

Weight loss is a prominent early feature of Alzheimer's disease (AD) that often precedes the cognitive decline and clinical diagnosis. While the exact pathogenesis of AD remains unclear, accumulation of amyloid-β (Aβ) derived from the amyloid precursor protein (APP) in the brain is thought to lead to the neuronal dysfunction and death underlying the dementia. In this study, we examined whether transgenic mice overexpressing the Swedish mutation of APP (Tg2576), recapitulating selected features of AD, have hypothalamic leptin signaling dysfunction leading to early body weight deficits. We found that 3-month-old Tg2576 mice, before amyloid plaque formation, exhibit decreased weight with markedly decreased adiposity, low plasma leptin levels, and increased energy expenditure without alterations in feeding behavior. The expression of the orexigenic neuropeptide Y (NPY) in the hypothalamus to the low leptin state was abnormal at basal and fasting conditions. In addition, arcuate NPY neurons exhibited abnormal electrophysiological responses to leptin in Tg2576 hypothalamic slices or wild-type slices treated with Aβ. Finally, the metabolic deficits worsened as Tg2576 mice aged and amyloid burden increased in the brain. These results indicate that excess Aβ can potentially disrupt hypothalamic arcuate NPY neurons leading to weight loss and a pathologically low leptin state early in the disease process that progressively worsens as the amyloid burden increases. Collectively, these findings suggest that weight loss is an intrinsic pathological feature of Aβ accumulation and identify hypothalamic leptin signaling as a previously unrecognized pathogenic site of action for Aβ. PMID:24990930

Characteristics of long recovery early VLF events observed by the North African AWESOME Network

NASA Astrophysics Data System (ADS)

Naitamor, S.; Cohen, M. B.; Cotts, B. R. T.; Ghalila, H.; Alabdoadaim, M. A.; Graf, K.

2013-08-01

Lightning strokes are capable of initiating disturbances in the lower ionosphere, whose recoveries persist for many minutes. These events are remotely sensed via monitoring subionospherically propagating very low frequency (VLF) transmitter signals, which are perturbed as they pass through the region above the lightning stroke. In this paper we describe the properties and characteristics of the early VLF signal perturbations, which exhibit long recovery times using subionospheric VLF transmitter data from three identical receivers located at Algiers (Algeria), Tunis (Tunisia), and Sebha (Libya). The results indicate that the observation of long recovery events depends strongly on the modal structure of the signal electromagnetic field and the distance from the disturbed region and the receiver or transmitter locations. Comparison of simultaneously collected data at the three sites indicates that the role of the causative lightning stroke properties (e.g., peak current and polarity), or that of transient luminous events may be much less important. The dominant parameter which determines the duration of the recovery time and amplitude appears to be the modal structure of the subionospheric VLF probe signal at the ionospheric disturbance, where scattering occurs, and the subsequent modal structure that propagates to the receiver location.

EFFECT OF ARSENICALS ON THE EXPRESSION OF CELL CYCLE PROTEINS AND EARLY SIGNALING EVENTS IN PRIMARY HUMAN KERATINOCYTES.

EPA Science Inventory

Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes.

Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711.

Environmental exposure to arsenic is a m...

Career Paths of Pathology Informatics Fellowship Alumni.

PubMed

Rudolf, Joseph W; Garcia, Christopher A; Hanna, Matthew G; Williams, Christopher L; Balis, Ulysses G; Pantanowitz, Liron; Tuthill, J Mark; Gilbertson, John R

2018-01-01

preparation for their careers. We believe flexible training pathways combining informatics and clinical training may help to alleviate the burden. We highlight the importance of in-house Pathology Informatics fellowships in promoting interest in informatics among residents. We also observe the many important leadership roles in academia, large community health systems, and industry available to early career alumni and believe this reflects a strong market for formally trained informaticians. We hope this analysis will be useful as we continue to develop the informatics fellowships to meet the future needs of our trainees and discipline.

Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.

PubMed

Schwartz, G G; Olsson, A G; Ezekowitz, M D; Ganz, P; Oliver, M F; Waters, D; Zeiher, A; Chaitman, B R; Leslie, S; Stern, T

2001-04-04

Patients experience the highest rate of death and recurrent ischemic events during the early period after an acute coronary syndrome, but it is not known whether early initiation of treatment with a statin can reduce the occurrence of these early events. To determine whether treatment with atorvastatin, 80 mg/d, initiated 24 to 96 hours after an acute coronary syndrome, reduces death and nonfatal ischemic events. A randomized, double-blind trial conducted from May 1997 to September 1999, with follow-up through 16 weeks at 122 clinical centers in Europe, North America, South Africa, and Australasia. A total of 3086 adults aged 18 years or older with unstable angina or non-Q-wave acute myocardial infarction. Patients were stratified by center and randomly assigned to receive treatment with atorvastatin (80 mg/d) or matching placebo between 24 and 96 hours after hospital admission. Primary end point event defined as death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency rehospitalization. A primary end point event occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group (relative risk [RR], 0.84; 95% confidence interval [CI], 0.70-1.00; P =.048). There were no significant differences in risk of death, nonfatal myocardial infarction, or cardiac arrest between the atorvastatin group and the placebo group, although the atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency rehospitalization (6.2% vs 8.4%; RR, 0.74; 95% CI, 0.57-0.95; P =.02). Likewise, there were no significant differences between the atorvastatin group and the placebo group in the incidence of secondary outcomes of coronary revascularization procedures, worsening heart failure, or worsening angina, although there were fewer strokes in the atorvastatin group than in the placebo group (12

Middle Devonian to Early Carboniferous event stratigraphy of Devils Gate and Northern Antelope Range sections, Nevada, U.S.A

USGS Publications Warehouse

Sandberg, C.A.; Morrow, J.R.; Poole, F.G.; Ziegler, W.

2003-01-01

The classic type section of the Devils Gate Limestone at Devils Gate Pass is situated on the eastern slope of a proto-Antler forebulge that resulted from convergence of the west side of the North American continent with an ocean plate. The original Late Devonian forebulge, the site of which is now located between Devils Gate Pass and the Northern Antelope Range, separated the continental-rise to deep-slope Woodruff basin on the west from the backbulge Pilot basin on the east. Two connections between these basins are recorded by deeper water siltstone beds at Devils Gate; the older one is the lower tongue of the Woodruff Formation, which forms the basal unit of the upper member of the type Devils Gate, and the upper one is the overlying, thin lower member of the Pilot Shale. The forebulge and the backbulge Pilot basin originated during the middle Frasnian (early Late Devonian) Early hassi Zone, shortly following the Alamo Impact within the punctata Zone in southern Nevada. Evidence of this impact is recorded by coeval and reworked shocked quartz grains in the Northern Antelope Range and possibly by a unique bypass-channel or megatsunami-uprush sandy diamictite within carbonate-platform rocks of the lower member of the type Devils Gate Limestone. Besides the Alamo Impact and three regional events, two other important global events are recorded in the Devils Gate section. The semichatovae eustatic rise, the maximum Late Devonian flooding event, coincides with the sharp lithogenetic change at the discordant boundary above the lower member of the Devils Gate Limestone. Most significantly, the Devils Gate section contains the thickest and most complete rock record in North America across the late Frasnian linguiformis Zone mass extinction event. Excellent exposures include not only the extinction shale, but also a younger. Early triangularis Zone tsunamite breccia, produced by global collapse of carbonate platforms during a shallowing event that continued into the next

Endometrium and steroids, a pathologic overview.

PubMed

Plaza-Parrochia, Francisca; Romero, Carmen; Valladares, Luis; Vega, Margarita

2017-10-01

Normal endometrial function requires of cell proliferation and differentiation; therefore, disturbances in these processes could lead to pathological entities such as hyperplasia and endometrial adenocarcinoma, where cell proliferation is increased. The development of these pathologies is highly related to alterations in the levels and/or action of sexual steroids. In the present review, it has been analyzed how steroids, particularly estrogens, androgens and progestagens are involved in the etiopathogenesis of hyperplasia and endometrial endometrioid adenocarcinoma. The emphasis is given on pathological and pharmacological conditions that are presented as risk factors for endometrial pathologies, such as obesity, polycystic ovarian syndrome and hormone replacement postmenopausal women therapy, among others. Steroids alterations may promote changes at molecular level that enhance the development of hyperplasia and endometrioid cancer. In fact, there are solid data that indicate that estrogens stimulate cell-proliferation in this tissue; meanwhile, progestagens are able to stop cell proliferation and to increase differentiation. Nevertheless, the role of androgens is less clear, since there is contradictory information. It is most likely that the major contribution of steroids to the development of cell proliferation pathologies in endometria would be in early stages, where there is a high sensitivity to these molecules. This phenomenon is present even in stages previous to the occurrence of hyperplasia, like in the condition of polycystic ovarian syndrome, where the endometria have a greater sensitivity to steroids and high expression of cell cycle molecules. These abnormalities would contribute to the pathogenesis of hyperplasia and then in the progression to endometrioid adenocarcinoma. Copyright © 2017. Published by Elsevier Inc.

Age-related differences in event-related potentials for early visual processing of emotional faces.

PubMed

Hilimire, Matthew R; Mienaltowski, Andrew; Blanchard-Fields, Fredda; Corballis, Paul M

2014-07-01

With advancing age, processing resources are shifted away from negative emotional stimuli and toward positive ones. Here, we explored this 'positivity effect' using event-related potentials (ERPs). Participants identified the presence or absence of a visual probe that appeared over photographs of emotional faces. The ERPs elicited by the onsets of angry, sad, happy and neutral faces were recorded. We examined the frontocentral emotional positivity (FcEP), which is defined as a positive deflection in the waveforms elicited by emotional expressions relative to neutral faces early on in the time course of the ERP. The FcEP is thought to reflect enhanced early processing of emotional expressions. The results show that within the first 130 ms young adults show an FcEP to negative emotional expressions, whereas older adults show an FcEP to positive emotional expressions. These findings provide additional evidence that the age-related positivity effect in emotion processing can be traced to automatic processes that are evident very early in the processing of emotional facial expressions. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Early Events Leading to the Host Protective Th2 Immune Response to an Intestinal Nematode Parasite

DTIC Science & Technology

2005-01-01

expansion, eosinophilia , and IL-4 production (51;52). Similar down regulations of Th2 associated cytokines were observed using monoclonal antibodies...1. Kightlinger,L.K., Seed,J.R., and Kightlinger,M.B., The epidemiology of Ascaris lumbricoides, Trichuris trichiura, and hookworm in children in...Copyright Statement The author hereby certifies that the use of any copyrighted material in the thesis manuscript entitled: “Early Events

Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

PubMed Central

Berghella, Libera; Ferraro, Elisabetta

2012-01-01

Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

Evidence of resilience to past climate change in Southwest Asia: Early farming communities and the 9.2 and 8.2 ka events

NASA Astrophysics Data System (ADS)

Flohr, Pascal; Fleitmann, Dominik; Matthews, Roger; Matthews, Wendy; Black, Stuart

2016-03-01

Climate change is often cited as a major factor in social change. The so-called 8.2 ka event was one of the most pronounced and abrupt Holocene cold and arid events. The 9.2 ka event was similar, albeit of a smaller magnitude. Both events affected the Northern Hemisphere climate and caused cooling and aridification in Southwest Asia. Yet, the impacts of the 8.2 and 9.2 ka events on early farming communities in this region are not well understood. Current hypotheses for an effect of the 8.2 ka event vary from large-scale site abandonment and migration (including the Neolithisation of Europe) to continuation of occupation and local adaptation, while impacts of the 9.2 ka have not previously been systematically studied. In this paper, we present a thorough assessment of available, quality-checked radiocarbon (14C) dates for sites from Southwest Asia covering the time interval between 9500 and 7500 cal BP, which we interpret in combination with archaeological evidence. In this way, the synchronicity between changes observed in the archaeological record and the rapid climate events is tested. It is shown that there is no evidence for a simultaneous and widespread collapse, large-scale site abandonment, or migration at the time of the events. However, there are indications for local adaptation. We conclude that early farming communities were resilient to the abrupt, severe climate changes at 9250 and 8200 cal BP.

A catastrophic event in Lake Geneva region during the Early Bronze Age?

NASA Astrophysics Data System (ADS)

Kremer, Katrina; Yrro, Blé; Marillier, François; Hilbe, Michael; Corboud, Pierre; Rachoud-Schneider, Anne-Marie; Girardclos, Stéphanie

2013-04-01

Similarly to steep oceanic continental margins, lake slopes can collapse, producing large sublacustrine landslides and tsunamis. Lake sediments are excellent natural archives of such mass movements and their study allows the reconstructions of these prehistoric events, such as the 563 AD large tsunami over Lake Geneva (Kremer et al, 2012). In Lake Geneva, more than 100 km of high-resolution seismic reflection profiles reveal the late Holocene sedimentation history. The seismic record shows a succession of five large lens-shaped seismic units (A to I), characterized by transparent/chaotic seismic facies with irregular lower boundaries, and interpreted as mass-movement deposits. These units are interbedded with parallel, continuous and strong amplitude reflections, interpreted as the 'background' lake sediments. The oldest dated mass movement (Unit D) covers a surface of 22 km2 in the deep basin, near the city of Lausanne. This deposit has an estimated minimum volume of 0.18 km3 and thus was very likely tsunamigenic (Kremer et al, 2012). A 12-m-long sediment core confirms the seismic interpretation of the mass movement unit and shows that the uppermost 3 m of Unit D are characterized by deformed hemipelagic sediments topped by a 5 cm thick turbidite. This deposit can be classified as a slump whose scar can be interpreted in the seismic data and visualized by multibeam bathymetry. This slump of Lausanne was likely triggered by an earthquake but a spontaneous slope collapse cannot be excluded (Girardclos et al, 2007). Radiocarbon dating of plant macro-remains reveals that the unit D happened during Early Bronze Age. Three other mass wasting deposits occurred during the same time period and may have been triggered during the same event, either by a single earthquake or by a tsunami generated by the slump of Lausanne. Although the exact trigger mechanism of the all these mass-wasting deposits remains unknown, a tsunami likely generated by this event may have affected the

Membrane remodeling, an early event in benzo[alpha]pyrene-induced apoptosis

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

Tekpli, Xavier; Rissel, Mary; Huc, Laurence

2010-02-15

Benzo[alpha]pyrene (B[alpha]P) often serves as a model for mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Our previous work suggested a role of membrane fluidity in B[alpha]P-induced apoptotic process. In this study, we report that B[alpha]P modifies the composition of cholesterol-rich microdomains (lipid rafts) in rat liver F258 epithelial cells. The cellular distribution of the ganglioside-GM1 was markedly changed following B[alpha]P exposure. B[alpha]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[alpha]P-induced depletion of cholesterol in lipid rafts was linked to a reduced expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). Aryl hydrocarbon receptor (AhR) and B[alpha]P-related H{submore » 2}O{sub 2} formation were involved in the reduced expression of HMG-CoA reductase and in the remodeling of membrane microdomains. The B[alpha]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[alpha]P altered the composition of plasma membrane microstructures through AhR and H{sub 2}O{sub 2} dependent-regulation of lipid biosynthesis. In F258 cells, the B[alpha]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization.« less

Inhibition of Akt/mTOR/p70S6K Signaling Activity With Huangkui Capsule Alleviates the Early Glomerular Pathological Changes in Diabetic Nephropathy.

PubMed

Wu, Wei; Hu, Wei; Han, Wen-Bei; Liu, Ying-Lu; Tu, Yue; Yang, Hai-Ming; Fang, Qi-Jun; Zhou, Mo-Yi; Wan, Zi-Yue; Tang, Ren-Mao; Tang, Hai-Tao; Wan, Yi-Gang

2018-01-01

Huangkui capsule (HKC), a Chinese modern patent medicine extracted from Abelmoschus manihot (L.) medic, has been widely applied to clinical therapy in the early diabetic nephropathy (DN) patients. However, it remains elusive whether HKC can ameliorate the inchoate glomerular injuries in hyperglycemia. Recently the activation of phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of rapamycin (mTOR) signaling and its downstream regulator, 70-kDa ribosomal protein S6 kinase (p70S6K), play important roles in the early glomerular pathological changes of DN including glomerular hypertrophy, glomerular basement membrane (GBM) thickening and mild mesangial expansion. This study thereby aimed to clarify therapeutic effects of HKC during the initial phase of DN and its underlying mechanisms. Fifteen rats were randomly divided into 3 groups: the normal group, the model group and the HKC group. The early DN model rats were induced by unilateral nephrectomy combined with intraperitoneal injection of streptozotocin, and administered with either HKC suspension or vehicle after modeling and for a period of 4 weeks. Changes in the incipient glomerular lesions-related parameters in urine and blood were analyzed. Kidneys were isolated for histomorphometry, immunohistochemistry, immunofluorescence and Western blotting (WB) at sacrifice. In vitro , murine mesangial cells (MCs) were used to investigate inhibitory actions of hyperoside (HYP), a bioactive component of HKC, on cellular hypertrophy-associated signaling pathway by WB, compared with rapamycin (RAP). For the early DN model rats, HKC ameliorated micro-urinary albumin, body weight and serum albumin, but had no significant effects on renal function and liver enzymes; HKC improved renal shape, kidney weight and kidney hypertrophy index; HKC attenuated glomerular hypertrophy, GBM thickening and mild mesangial expansion; HKC inhibited the phosphorylation of Akt, mTOR and p70S6K, and the protein over

Disrupted Intrinsic Networks Link Amyloid-β Pathology and Impaired Cognition in Prodromal Alzheimer's Disease.

PubMed

Koch, Kathrin; Myers, Nicholas E; Göttler, Jens; Pasquini, Lorenzo; Grimmer, Timo; Förster, Stefan; Manoliu, Andrei; Neitzel, Julia; Kurz, Alexander; Förstl, Hans; Riedl, Valentin; Wohlschläger, Afra M; Drzezga, Alexander; Sorg, Christian

2015-12-01

Amyloid-β pathology (Aβ) and impaired cognition characterize Alzheimer's disease (AD); however, neural mechanisms that link Aβ-pathology with impaired cognition are incompletely understood. Large-scale intrinsic connectivity networks (ICNs) are potential candidates for this link: Aβ-pathology affects specific networks in early AD, these networks show disrupted connectivity, and they process specific cognitive functions impaired in AD, like memory or attention. We hypothesized that, in AD, regional changes of ICNs, which persist across rest- and cognitive task-states, might link Aβ-pathology with impaired cognition via impaired intrinsic connectivity. Pittsburgh compound B (PiB)-positron emission tomography reflecting in vivo Aβ-pathology, resting-state fMRI, task-fMRI, and cognitive testing were used in patients with prodromal AD and healthy controls. In patients, default mode network's (DMN) functional connectivity (FC) was reduced in the medial parietal cortex during rest relative to healthy controls, relatively increased in the same region during an attention-demanding task, and associated with patients' cognitive impairment. Local PiB-uptake correlated negatively with DMN connectivity. Importantly, corresponding results were found for the right lateral parietal region of an attentional network. Finally, structural equation modeling confirmed a direct influence of DMN resting-state FC on the association between Aβ-pathology and cognitive impairment. Data provide evidence that disrupted intrinsic network connectivity links Aβ-pathology with cognitive impairment in early AD. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Coping with a life event in bipolar disorder: ambulatory measurement, signalling and early treatment.

PubMed

Knapen, Stefan E; Riemersma-van der Lek, Rixt F; Haarman, Bartholomeus C M; Schoevers, Robert A

2016-10-13

Disruption of the biological rhythm in patients with bipolar disorder is a known risk factor for a switch in mood. This case study describes how modern techniques using ambulatory assessment of sleep parameters can help in signalling a mood switch and start early treatment. We studied a 40-year-old woman with bipolar disorder experiencing a life event while wearing an actigraph to measure sleep-wake parameters. The night after the life event the woman had sleep later and shorter sleep duration. Adequate response of both the woman and the treating psychiatrist resulted in two normal nights with the use of 1 mg lorazepam, possibly preventing further mood disturbances. Ambulatory assessment of the biological rhythm can function as an add-on to regular signalling plans for prevention of episodes in patients with bipolar disorder. More research should be conducted to validate clinical applicability, proper protocols and to understand underlying mechanisms. 2016 BMJ Publishing Group Ltd.

Breast cancer and psychosocial factors: early stressful life events, social support, and well-being.

PubMed

Ginzburg, Karni; Wrensch, Margaret; Rice, Terri; Farren, Georgianna; Spiegel, David

2008-01-01

The allostasis theory postulates that stress causes the body to activate physiologic systems in order to maintain stability. The authors sought to examine the relationship between earlier stress and later development of breast cancer (BC). Authors correlated discrete and interactive relationships of stressful life events, social support, and well-being during childhood and adolescence with the occurrence of BC in adulthood among 300 women with primary BC and 305 matched control subjects. BC patients and control subjects reported similar childhood experiences. Yet, although childhood stressful life events were associated with reports of less family support and well being among the controls, those in the BC group who experienced high stress in early childhood actually expressed higher levels of family support and well-being than did those who had experienced lower levels of stress. These findings may reflect a tendency toward a repressive coping style among the BC group, which may be either a risk factor for the disease or a result of having it.

Pathology Gross Photography: The Beginning of Digital Pathology.

PubMed

Rampy, B Alan; Glassy, Eric F

2015-06-01

The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale. Copyright © 2015 Elsevier Inc. All rights reserved.

Pathology effects at radiation doses below those causing increased mortality

NASA Technical Reports Server (NTRS)

Carnes, Bruce A.; Gavrilova, Natalia; Grahn, Douglas

2002-01-01

Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.

Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics

PubMed Central

Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

2016-01-01

Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae–Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. PMID:27604225

Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice

PubMed Central

Nemmar, Abderrahim; Hemeiri, Ahmed Al; Hammadi, Naser Al; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Elwasila, Mohamed; Ali, Badreldin H; Adeghate, Ernest

2015-01-01

Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored “moasel” tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are

Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice.

PubMed

Nemmar, Abderrahim; Al Hemeiri, Ahmed; Al Hammadi, Naser; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Elwasila, Mohamed; Ali, Badreldin H; Adeghate, Ernest

2015-03-01

Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored "moasel" tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are early

Early Holocene hydroclimate of Baffin Bay: Understanding the interplay between abrupt climate change events and ice sheet fluctuations

NASA Astrophysics Data System (ADS)

Corcoran, M. C.; Thomas, E. K.; Castañeda, I. S.; Briner, J. P.

2017-12-01

Understanding the causes of ice sheet fluctuations resulting in sea level rise is essential in today's warming climate. In high-latitude ice-sheet-proximal environments such as Baffin Bay, studying both the cause and the rate of ice sheet variability during past abrupt climate change events aids in predictions. Past climate reconstructions are used to understand ice sheet responses to changes in temperature and precipitation. The 9,300 and 8,200 yr BP events are examples of abrupt climate change events in the Baffin Bay region during which there were multiple re-advances of the Greenland and Laurentide ice sheets. High-resolution (decadal-scale) hydroclimate variability near the ice sheet margins during these abrupt climate change events is still unknown. We will generate a decadal-scale record of early Holocene temperature and precipitation using leaf wax hydrogen isotopes, δ2Hwax, from a lake sediment archive on Baffin Island, western Baffin Bay, to better understand abrupt climate change in this region. Shifts in temperature and moisture source result in changes in environmental water δ2H, which in turn is reflected in δ2Hwax, allowing for past hydroclimate to be determined from these compound-specific isotopes. The combination of terrestrial and aquatic δ2Hwax is used to determine soil evaporation and is ultimately used to reconstruct moisture variability. We will compare our results with a previous analysis of δ2Hwax and branched glycerol dialkyl glycerol tetraethers, a temperature and pH proxy, in lake sediment from western Greenland, eastern Baffin Bay, which indicates that cool and dry climate occurred in response to freshwater forcing events in the Labrador Sea. Reconstructing and comparing records on both the western and eastern sides of Baffin Bay during the early Holocene will allow for a spatial understanding of temperature and moisture balance changes during abrupt climate events, aiding in ice sheet modeling and predictions of future sea level

A Microstructurally Inspired Damage Model for Early Venous Thrombus

PubMed Central

Rausch, Manuel K.; Humphrey, Jay D.

2015-01-01

Accumulative damage may be an important contributor to many cases of thrombotic disease progression. Thus, a complete understanding of the pathological role of thrombus requires an understanding of its mechanics and in particular mechanical consequences of damage. In the current study, we introduce a novel microstructurally inspired constitutive model for thrombus that considers a non-uniform distribution of microstructural fibers at various crimp levels and employs one of the distribution parameters to incorporate stretch-driven damage on the microscopic level. To demonstrate its ability to represent the mechanical behavior of thrombus, including a recently reported Mullins type damage phenomenon, we fit our model to uniaxial tensile test data of early venous thrombus. Our model shows an agreement with these data comparable to previous models for damage in elastomers with the added advantages of a microstructural basis and fewer model parameters. We submit that our novel approach marks another important step toward modeling the evolving mechanics of intraluminal thrombus, specifically its damage, and hope it will aid in the study of physiological and pathological thrombotic events. PMID:26523784

Comparison of voice-automated transcription and human transcription in generating pathology reports.

PubMed

Al-Aynati, Maamoun M; Chorneyko, Katherine A

2003-06-01

Software that can convert spoken words into written text has been available since the early 1980s. Early continuous speech systems were developed in 1994, with the latest commercially available editions having a claimed accuracy of up to 98% of speech recognition at natural speech rates. To evaluate the efficacy of one commercially available voice-recognition software system with pathology vocabulary in generating pathology reports and to compare this with human transcription. To draw cost analysis conclusions regarding human versus computer-based transcription. Two hundred six routine pathology reports from the surgical pathology material handled at St Joseph's Healthcare, Hamilton, Ontario, were generated simultaneously using computer-based transcription and human transcription. The following hardware and software were used: a desktop 450-MHz Intel Pentium III processor with 192 MB of RAM, a speech-quality sound card (Sound Blaster), noise-canceling headset microphone, and IBM ViaVoice Pro version 8 with pathology vocabulary support (Voice Automated, Huntington Beach, Calif). The cost of the hardware and software used was approximately Can 2250 dollars. A total of 23 458 words were transcribed using both methods with a mean of 114 words per report. The mean accuracy rate was 93.6% (range, 87.4%-96%) using the computer software, compared to a mean accuracy of 99.6% (range, 99.4%-99.8%) for human transcription (P <.001). Time needed to edit documents by the primary evaluator (M.A.) using the computer was on average twice that needed for editing the documents produced by human transcriptionists (range, 1.4-3.5 times). The extra time needed to edit documents was 67 minutes per week (13 minutes per day). Computer-based continuous speech-recognition systems in pathology can be successfully used in pathology practice even during the handling of gross pathology specimens. The relatively low accuracy rate of this voice-recognition software with resultant increased editing

Preparing Speech Language Pathology Students to Work in Early Childhood

ERIC Educational Resources Information Center

Barton, Erin E.; Moore, Heather W.; Squires, Jane K.

2012-01-01

The shortage of highly qualified speech language pathologists (SLPs) with specialized training in early intervention and early childhood special education (EI/ECSE) is a pressing issue facing the field and dramatically impacts young children's social and academic success. SLP personnel preparation programs focused on training specialists in…

A Systematic Review of Early Warning Systems' Effects on Nurses' Clinical Performance and Adverse Events Among Deteriorating Ward Patients.

PubMed

Lee, Ju-Ry; Kim, Eun-Mi; Kim, Sun-Aee; Oh, Eui Geum

2018-04-25

Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses' clinical performance and patients' adverse events. This review aimed to determine the ability of EWSs to improve nurses' clinical performance and prevent adverse events among deteriorating ward patients. The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses' clinical performance (vital sign monitoring and rapid response team notification) and patients' adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission). The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses' clinical performance, based on their frequency of documenting vital signs that were related to the patient's clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death. It seems that EWSs can improve nurses' clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.

Speech-language pathology teletherapy in rural and remote educational settings: Decreasing service inequities.

PubMed

Fairweather, Glenn Craig; Lincoln, Michelle Ann; Ramsden, Robyn

2016-12-01

The objectives of this study were to investigate the efficacy of a speech-language pathology teletherapy program for children attending schools and early childcare settings in rural New South Wales, Australia, and their parents' views on the program's feasibility and acceptability. Nineteen children received speech-language pathology sessions delivered via Adobe Connect®, Facetime © or Skype © web-conferencing software. During semi-structured interviews, parents (n = 5) described factors that promoted or threatened the program's feasibility and acceptability. Participation in a speech-language pathology teletherapy program using low-bandwidth videoconferencing improved the speech and language skills of children in both early childhood settings and primary school. Emergent themes related to (a) practicality and convenience, (b) learning, (c) difficulties and (d) communication. Treatment outcome data and parental reports verified that the teletherapy service delivery was feasible and acceptable. However, it was also evident that regular discussion and communication between the various stakeholders involved in teletherapy programs may promote increased parental engagement and acceptability.

Parental Substance Abuse As an Early Traumatic Event. Preliminary Findings on Neuropsychological and Personality Functioning in Young Drug Addicts Exposed to Drugs Early

PubMed Central

Parolin, Micol; Simonelli, Alessandra; Mapelli, Daniela; Sacco, Marianna; Cristofalo, Patrizia

2016-01-01

Parental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic events. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequelae at the neuro-behavioral level. Second, parents' addiction often entails a childrearing environment characterized by poor parenting skills, disadvantaged contexts and adverse childhood experiences (ACEs), leading to dysfunctional outcomes. Young adults born from/raised by parents with drug problems and diagnosed with a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of early exposure to drugs as a traumatic event, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs early in their family context. The research involved three groups, each consisting of 15 young adults (aged 18–24): a group of inpatients diagnosed with SUDs and exposed to drugs early, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterized by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions (EF); personality disorders were also common but did not differentiate them from non-exposed youth with SUDs. Alternative multi-focused prevention and

Evaluation of Epidemic Intelligence Systems Integrated in the Early Alerting and Reporting Project for the Detection of A/H5N1 Influenza Events

PubMed Central

Barboza, Philippe; Vaillant, Laetitia; Mawudeku, Abla; Nelson, Noele P.; Hartley, David M.; Madoff, Lawrence C.; Linge, Jens P.; Collier, Nigel; Brownstein, John S.; Yangarber, Roman; Astagneau, Pascal; on behalf of the Early Alerting, Reporting Project of the Global Health Security Initiative

2013-01-01

The objective of Web-based expert epidemic intelligence systems is to detect health threats. The Global Health Security Initiative (GHSI) Early Alerting and Reporting (EAR) project was launched to assess the feasibility and opportunity for pooling epidemic intelligence data from seven expert systems. EAR participants completed a qualitative survey to document epidemic intelligence strategies and to assess perceptions regarding the systems performance. Timeliness and sensitivity were rated highly illustrating the value of the systems for epidemic intelligence. Weaknesses identified included representativeness, completeness and flexibility. These findings were corroborated by the quantitative analysis performed on signals potentially related to influenza A/H5N1 events occurring in March 2010. For the six systems for which this information was available, the detection rate ranged from 31% to 38%, and increased to 72% when considering the virtual combined system. The effective positive predictive values ranged from 3% to 24% and F1-scores ranged from 6% to 27%. System sensitivity ranged from 38% to 72%. An average difference of 23% was observed between the sensitivities calculated for human cases and epizootics, underlining the difficulties in developing an efficient algorithm for a single pathology. However, the sensitivity increased to 93% when the virtual combined system was considered, clearly illustrating complementarities between individual systems. The average delay between the detection of A/H5N1 events by the systems and their official reporting by WHO or OIE was 10.2 days (95% CI: 6.7–13.8). This work illustrates the diversity in implemented epidemic intelligence activities, differences in system's designs, and the potential added values and opportunities for synergy between systems, between users and between systems and users. PMID:23472077

Evaluation of epidemic intelligence systems integrated in the early alerting and reporting project for the detection of A/H5N1 influenza events.

PubMed

Barboza, Philippe; Vaillant, Laetitia; Mawudeku, Abla; Nelson, Noele P; Hartley, David M; Madoff, Lawrence C; Linge, Jens P; Collier, Nigel; Brownstein, John S; Yangarber, Roman; Astagneau, Pascal

2013-01-01

The objective of Web-based expert epidemic intelligence systems is to detect health threats. The Global Health Security Initiative (GHSI) Early Alerting and Reporting (EAR) project was launched to assess the feasibility and opportunity for pooling epidemic intelligence data from seven expert systems. EAR participants completed a qualitative survey to document epidemic intelligence strategies and to assess perceptions regarding the systems performance. Timeliness and sensitivity were rated highly illustrating the value of the systems for epidemic intelligence. Weaknesses identified included representativeness, completeness and flexibility. These findings were corroborated by the quantitative analysis performed on signals potentially related to influenza A/H5N1 events occurring in March 2010. For the six systems for which this information was available, the detection rate ranged from 31% to 38%, and increased to 72% when considering the virtual combined system. The effective positive predictive values ranged from 3% to 24% and F1-scores ranged from 6% to 27%. System sensitivity ranged from 38% to 72%. An average difference of 23% was observed between the sensitivities calculated for human cases and epizootics, underlining the difficulties in developing an efficient algorithm for a single pathology. However, the sensitivity increased to 93% when the virtual combined system was considered, clearly illustrating complementarities between individual systems. The average delay between the detection of A/H5N1 events by the systems and their official reporting by WHO or OIE was 10.2 days (95% CI: 6.7-13.8). This work illustrates the diversity in implemented epidemic intelligence activities, differences in system's designs, and the potential added values and opportunities for synergy between systems, between users and between systems and users.

An Alternative Explanation for "Step-Like" Early VLF Event

NASA Astrophysics Data System (ADS)

Moore, R. C.

2016-12-01

A newly-deployed array of VLF receivers along the East Coast of the United States is ideally suited for detecting VLF scattering from lightning-induced disturbances to the lower ionosphere. The array was deployed in May 2016, and one VLF receiver was deployed only 20 km from the NAA transmitter (24.0 kHz) in Cutler, Maine. The phase of the NAA signal at this closest site varies significantly with time, due simply to the impedance match of the transmitter varying with time. Additionally, both the amplitude and phase exhibit periods of rapid shifts that could possibly explain at least some "step-like" VLF scattering events. Here, we distinguish between "step-like" VLF scattering events and other events in that "step-like" events are typically not closely associated with a detected causative lightning flash and also tend to exhibit little or no recovery to ambient conditions after the event onset. We present an analysis of VLF observations from the East Coast array that demonstrates interesting examples of step-like VLF events far from the transmitter that are associated with step-like events very close to the transmitter. We conclude that step-like VLF events should be treated with caution, unless definitively associated with a causative lightning flash and/or detected using observations of multiple transmitter signals.

Precortical phase of Alzheimer’s disease (AD)-related tau cytoskeletal pathology

PubMed Central

Stratmann, Katharina; Heinsen, Helmut; Korf, Horst-Werner; Del Turco, Domenico; Ghebremedhin, Estifanos; Seidel, Kay; Bouzrou, Mohamed; Grinberg, Lea T.; Bohl, Jürgen; Wharton, Stephen B; den Dunnen, Wilfred; Rüb, Udo

2015-01-01

Alzheimer’s disease (AD) represents the most frequent progressive neuropsychiatric disorder worldwide leading to dementia and accounts for 60 to 70% of demented individuals. In view of the early appearance of neuronal deposits of the hyperphosphorylated cytoskeletal protein tau in the transentorhinal and entorhinal regions of the allocortex (i.e. in Braak and Braak AD stage I in the evolution of the AD-related cortical tau cytoskeletal pathology) it has been believed for a long time that these allocortical regions represent the first brain targets of the AD-related tau cytoskeletal pathology. However, recent pathoanatomical studies suggested that the subcortical brain nuclei that send efferent projections to the transentorhinal and entorhinal regions may also comprise AD-related cytoskeletal changes already at very early Braak and Braak AD stages. In order to corroborate these initial results we systematically investigated the presence and extent of the AD-related cytoskeletal pathology in serial thick tissue sections through all the subcortical nuclei known to send efferent projections to these vulnerable allocortical regions of three individuals with Braak and Braak AD stage 0 and fourteen individuals with Braak and Braak AD stage I by means of immunostainings with the anti-tau antibody AT8. These investigations revealed consistent AT8 immunoreactive neuronal tau cytoskeletal pathology in a subset of these subcortical nuclei (i.e. medial septal nucleus, nuclei of the vertical and horizontal limbs of the diagonal band of Broca, basal nucleus of Meynert; claustrum; hypothalamic ventromedial, tuberomamillary and supramamillary nuclei, perifornical region and lateral area; thalamic central medial, laterodorsal, subparafascicular, and central lateral nuclei, medial pulvinar and limitans-suprageniculate complex; peripeduncular nucleus, dopaminergic substantia nigra and ventral tegmental area, periaqueductal gray, midbrain and pontine dorsal raphe nuclei, locus

Early neurovascular dysfunction in a transgenic rat model of Alzheimer's disease.

PubMed

Joo, Illsung L; Lai, Aaron Y; Bazzigaluppi, Paolo; Koletar, Margaret M; Dorr, Adrienne; Brown, Mary E; Thomason, Lynsie A M; Sled, John G; McLaurin, JoAnne; Stefanovic, Bojana

2017-04-12

Alzheimer's disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans.

Defective mitochondrial dynamics is an early event in skeletal muscle of an amyotrophic lateral sclerosis mouse model.

PubMed

Luo, Guo; Yi, Jianxun; Ma, Changling; Xiao, Yajuan; Yi, Frank; Yu, Tian; Zhou, Jingsong

2013-01-01

Mitochondria are dynamic organelles that constantly undergo fusion and fission to maintain their normal functionality. Impairment of mitochondrial dynamics is implicated in various neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is an adult-onset neuromuscular degenerative disorder characterized by motor neuron death and muscle atrophy. ALS onset and progression clearly involve motor neuron degeneration but accumulating evidence suggests primary muscle pathology may also be involved. Here, we examined mitochondrial dynamics in live skeletal muscle of an ALS mouse model (G93A) harboring a superoxide dismutase mutation (SOD1(G93A)). Using confocal microscopy combined with overexpression of mitochondria-targeted photoactivatable fluorescent proteins, we discovered abnormal mitochondrial dynamics in skeletal muscle of young G93A mice before disease onset. We further demonstrated that similar abnormalities in mitochondrial dynamics were induced by overexpression of mutant SOD1(G93A) in skeletal muscle of normal mice, indicating the SOD1 mutation drives ALS-like muscle pathology in the absence of motor neuron degeneration. Mutant SOD1(G93A) forms aggregates inside muscle mitochondria and leads to fragmentation of the mitochondrial network as well as mitochondrial depolarization. Partial depolarization of mitochondrial membrane potential in normal muscle by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) caused abnormalities in mitochondrial dynamics similar to that in the SOD1(G93A) model muscle. A specific mitochondrial fission inhibitor (Mdivi-1) reversed the SOD1(G93A) action on mitochondrial dynamics, indicating SOD1(G93A) likely promotes mitochondrial fission process. Our results suggest that accumulation of mutant SOD1(G93A) inside mitochondria, depolarization of mitochondrial membrane potential and abnormal mitochondrial dynamics are causally linked and cause intrinsic muscle pathology, which occurs early in the course of ALS and may

The effect of a Lean quality improvement implementation program on surgical pathology specimen accessioning and gross preparation error frequency.

PubMed

Smith, Maxwell L; Wilkerson, Trent; Grzybicki, Dana M; Raab, Stephen S

2012-09-01

Few reports have documented the effectiveness of Lean quality improvement in changing anatomic pathology patient safety. We used Lean methods of education; hoshin kanri goal setting and culture change; kaizen events; observation of work activities, hand-offs, and pathways; A3-problem solving, metric development, and measurement; and frontline work redesign in the accessioning and gross examination areas of an anatomic pathology laboratory. We compared the pre- and post-Lean implementation proportion of near-miss events and changes made in specific work processes. In the implementation phase, we documented 29 individual A3-root cause analyses. The pre- and postimplementation proportions of process- and operator-dependent near-miss events were 5.5 and 1.8 (P < .002) and 0.6 and 0.6, respectively. We conclude that through culture change and implementation of specific work process changes, Lean implementation may improve pathology patient safety.

Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.

PubMed

Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

2016-11-01

Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The ECVP/ESVP summer school in veterinary pathology: high-standard, structured training for young veterinary pathologists.

PubMed

Kipar, Anja; Aleksandersen, Mona; Benazzi, Cinzia; Hodge, Thomas; Sukura, Antti; Wyers, Monique

2007-01-01

This article describes the ECVP/ESVP Summer School in Veterinary Pathology, a new annual two-week European training facility established by the European College of Veterinary Pathologists (ECVP) in collaboration with the European Society of Veterinary Pathology (ESVP). The aim of the Summer Schools is to provide Europe-wide, harmonized, top-standard theoretical and practical post-graduate training for veterinarians specializing in veterinary pathology. In particular, it aims to support trainees in veterinary pathology in their individual preparation for the ECVP certifying examination. Ultimately, it aims to provide young pathologists with the skills and knowledge necessary to participate in international, high-quality research and the tools for applying international standards to their own research and for independent study for the ECVP certifying examination, even if they do not work in comparable academic environments and do not have the same level of local support and training. The ECVP/ESVP Summer Schools take place in European countries, with local organization from a university department of veterinary pathology. Each event comprises modules provided by internationally recognized specialists in their specific fields of expertise on different organ systems, diseases of specific species, specific techniques, and specific topics relevant to pathology, forming a cycle of four events to cover all major topics. Every two years a mock exam is organized as a tool to monitor individual progress in preparing for the ECVP certifying examination.

Modeling Temporal Processes in Early Spacecraft Design: Application of Discrete-Event Simulations for Darpa's F6 Program

NASA Technical Reports Server (NTRS)

Dubos, Gregory F.; Cornford, Steven

2012-01-01

While the ability to model the state of a space system over time is essential during spacecraft operations, the use of time-based simulations remains rare in preliminary design. The absence of the time dimension in most traditional early design tools can however become a hurdle when designing complex systems whose development and operations can be disrupted by various events, such as delays or failures. As the value delivered by a space system is highly affected by such events, exploring the trade space for designs that yield the maximum value calls for the explicit modeling of time.This paper discusses the use of discrete-event models to simulate spacecraft development schedule as well as operational scenarios and on-orbit resources in the presence of uncertainty. It illustrates how such simulations can be utilized to support trade studies, through the example of a tool developed for DARPA's F6 program to assist the design of "fractionated spacecraft".

[Are non-clinical studies predictive of adverse events in humans?].

PubMed

Claude, N

2007-09-01

The predictibility of adverse events induced by drugs in non-clinical safety studies performed on in vitro and/or in vivo models is a key point for the safety of humans exposed to pharmaceuticals. The strength and the weakness of animal studies to predict human toxicity were assessed by an international study on the concordance of the toxicity of 150 pharmaceuticals observed in humans with that observed in experimental animals. The results showed a good correlation (70% of the adverse events in humans were detected in animal studies) and an early time to first appearance of concordant animal toxicity: 94% were first observed in studies of 1 month or less in duration. The highest incidence of overall concordance was seen in hematological and cardiovascular adverse effects and the least was seen in cutaneous and ophthalmological adverse effects. These studies, scientifically and regulatory standardized, need, in some cases to be adapted to specific problems linked to sensitive populations (young, old or with a pathology which could be worsened by the drug), or specific pharmaceuticals (produced by biotechnology). Some severe adverse events are not detected in conventional animal models (immuno-allergy, idiosyncrasy). Taken together, these elements support the value of toxicology studies to predict many human toxic events associated with pharmaceuticals. Nevertheless, a part of human toxicity is not detected by these experimental approaches, and new tools developed through progress in biology and bio-informatics should reduce this uncertainly margin.

George Henry Hepting: Pioneer Leader in Forest Pathology

Treesearch

Ellis B. Cowling; Arthur Kelman; Harry R. Powers

1999-01-01

George Henry Hepting grew up in the city environment of Brooklyn, but early in his life developed a deep love and scientific interest in forestry. He became America's most skilled scientist in the theory and practice of forest pathology. He studied how long-lived forest trees, unlike most plants, cope with the long-term changes in their biological, physical, and...

A Time Scale for Major Events in Early Mars Crustal Evolution

NASA Technical Reports Server (NTRS)

Frey, Herbert V.

2004-01-01

The population of visible and buried impact basins > 200 km diameter revealed by high resolution gridded MOLA data and the cumulative frequency curves derived for these pvide a basis for a chronology of major events in early martian history. The relative chronology can be given in terms of N(200) crater retention ages; 'absolute ages' can be assigued using the Hartmann-Neukum (H&N) model chronology. In terms of billions of H&N years, the crustal dichotomy formed by large impact basins at 4.12 +/- 0.08 BYA (N(200) = 3.0-3.2) and the global magnetic field died at about or slightly before the same time (4.15 +/- 0.08 BYA (N(200) = 3.5). In this chronology, the buried lowlands are approx. 120 my younger than the buried highlands, approx. 160 my younger than the highlands overall and approx. 340 my younger than the oldest crater retention surface we see, defined by the largest impact basins.

Early Molecular Events in Murine Gastric Epithelial Cells Mediated by Helicobacter pylori CagA.

PubMed

Banerjee, Aditi; Basu, Malini; Blanchard, Thomas G; Chintalacharuvu, Subba R; Guang, Wei; Lillehoj, Erik P; Czinn, Steven J

2016-10-01

Murine models of Helicobacter pylori infection are used to study host-pathogen interactions, but lack of severe gastritis in this model has limited its usefulness in studying pathogenesis. We compared the murine gastric epithelial cell line GSM06 to the human gastric epithelial AGS cell line to determine whether similar events occur when cultured with H. pylori. The lysates of cells infected with H. pylori isolates or an isogenic cagA-deficient mutant were assessed for translocation and phosphorylation of CagA and for activation of stress pathway kinases by immunoblot. Phosphorylated CagA was detected in both cell lines within 60 minutes. Phospho-ERK 1/2 was present within several minutes and distinctly present in GSM06 cells at 60 minutes. Similar results were obtained for phospho-JNK, although the 54 kDa phosphoprotein signal was dominant in AGS, whereas the lower molecular weight band was dominant in GSM06 cells. These results demonstrate that early events in H. pylori pathogenesis occur within mouse epithelial cells similar to human cells and therefore support the use of the mouse model for the study of acute CagA-associated host cell responses. These results also indicate that reduced disease in H. pylori-infected mice may be due to lack of the Cag PAI, or by differences in the mouse response downstream of the initial activation events. © 2016 John Wiley & Sons Ltd.

Early event-related brain potentials that reflect interest for content information in the media.

PubMed

Adachi, Shinobu; Morikawa, Koji; Nittono, Hiroshi

2012-03-28

This study investigated the relationship between event-related brain potentials (ERPs) to abridged content information in the media and the subsequent decisions to view the full content. Student volunteers participated in a task that simulated information selection on the basis of the content information. Screenshots of television clips and headlines of news articles on the Web were used as content information for the image condition and the headline condition, respectively. Following presentation of a stimulus containing content information, participants decided whether or not they would view the full content by pressing a select or a reject button. When the select button was pressed, participants were presented with a television clip or a news article. When the reject button was pressed, participants continued on to the next trial, without viewing further. In comparison with rejected stimuli, selected stimuli elicited a larger negative component, with a peak latency of ∼250 ms. The increase in the negative component was independent of the type of visual stimulus. These results suggest that interest toward content information is reflected in early-stage event-related brain potential responses.

Pathology, genetics and cytogenetics of Wilms' tumour.

PubMed

Md Zin, Reena; Murch, Ashleigh; Charles, Adrian

2011-06-01

Wilms' tumour (WT) is an embryonal cancer of childhood and is thought to be derived from embryonic kidney precursor cells. The Knudson two hit model was initially thought to occur in WT, but findings emerging from genetic and cytogenetic studies in the past two decades have implicated several genetic events. Recent techniques in genetic analysis have improved our ability to characterise changes in genes involved in WT which include WT1, CTNNB1, IGF2 and WTX. These genetic events have not only provided insight into the pathobiology of this malignancy, but the recognition of these candidate genes may offer potential targets for novel therapies. In this review, we will provide an overview of the pathological, genetic and cytogenetic characteristics of WT.

Lipid raft disarrangement as a result of neuropathological progresses: a novel strategy for early diagnosis?

PubMed

Marin, R; Rojo, J A; Fabelo, N; Fernandez, C E; Diaz, M

2013-08-15

Lipid rafts are the preferential site of numerous membrane signaling proteins which are involved in neuronal functioning and survival. These proteins are organized in multiprotein complexes, or signalosomes, in close contact with lipid classes particularly represented in lipid rafts (i.e. cholesterol, sphingolipids and saturated fatty acids), which may contribute to physiological responses leading to neuroprotection. Increasing evidence indicates that alteration of lipid composition in raft structures as a consequence of neuropathologies, such as Alzheimer's disease (AD) and Parkinson's disease (PD), causes a dramatic increase in lipid raft order. These phenomena may correlate with perturbation of signalosome activities, likely contributing to neurodegenerative progression. Interestingly, significant disruption of stable raft microenvironments has been already observed in the first stages of either AD or PD, suggesting that these alterations may represent early events in the neuropathological development. In this regard, the search for biochemical markers, such as specific metabolic products altered in the brain at the first steps of the disease, presently represents an important challenge for early diagnostic strategies. Alterations of these biomarkers may be reflected in either plasma or cerebrospinal fluid, thus representing a potential strategy to predict an accurate diagnosis. We propose that pathologically-linked lipid raft markers may be interesting candidates to be explored at this level, although it has not been studied so far to what extent alteration of different signalosome components may be reflected in peripheral fluids. In this mini-review, we will discuss on relevant aspects of lipid rafts that contribute to the modulation of neuropathological events related to AD and PD. An interesting hypothesis is that anomalies on raft biomarkers measured at peripheral fluids might mirror the lipid raft pathology observed in early stages of AD and PD. Copyright

Amplified Striatal Responses to Near-Miss Outcomes in Pathological Gamblers

PubMed Central

Sescousse, Guillaume; Janssen, Lieneke K; Hashemi, Mahur M; Timmer, Monique H M; Geurts, Dirk E M; ter Huurne, Niels P; Clark, Luke; Cools, Roshan

2016-01-01

Near-misses in gambling games are losing events that come close to a win. Near-misses were previously shown to recruit reward-related brain regions including the ventral striatum, and to invigorate gambling behavior, supposedly by fostering an illusion of control. Given that pathological gamblers are particularly vulnerable to such cognitive illusions, their persistent gambling behavior might result from an amplified striatal sensitivity to near-misses. In addition, animal studies have shown that behavioral responses to near-miss-like events are sensitive to dopamine, but this dopaminergic influence has not been tested in humans. To investigate these hypotheses, we recruited 22 pathological gamblers and 22 healthy controls who played a slot machine task delivering wins, near-misses and full-misses, inside an fMRI scanner. Each participant played the task twice, once under placebo and once under a dopamine D2 receptor antagonist (sulpiride 400 mg), in a double-blind, counter-balanced design. Participants were asked about their motivation to continue gambling throughout the task. Across all participants, near-misses elicited higher motivation to continue gambling and increased striatal responses compared with full-misses. Crucially, pathological gamblers showed amplified striatal responses to near-misses compared with controls. These group differences were not observed following win outcomes. In contrast to our hypothesis, sulpiride did not induce any reliable modulation of brain responses to near-misses. Together, our results demonstrate that pathological gamblers have amplified brain responses to near-misses, which likely contribute to their persistent gambling behavior. However, there is no evidence that these responses are influenced by dopamine. These results have implications for treatment and gambling regulation. PMID:27006113

Early events in geotropism of seedling shoots

NASA Technical Reports Server (NTRS)

Pickard, B. G.

1985-01-01

Developments during the first ten minutes of geotropic stimulation in plant seedling shoots are reviewed. Topics include induction and curvature; early processes; the relationship between auxin, electric field, calcium, and differential growth; gravity reception leading to Went-Cholodny transport; and comparison of root and shoot. Early processes reviewed are sedimentation of amyloplasts, release of ethylene, rise of electrical and auxin asymmetry, redistribution of calcium, asymmetric vascular transport, increase in tendency to deposit callose, and simulation of putative exocytotic voltage transients.

Infrared fiber optic probes for evaluation of musculoskeletal tissue pathology

NASA Astrophysics Data System (ADS)

Padalkar, Mugdha; McGoverin, Cushla; Onigbanjo, Quam; Spencer, Richard; Barbash, Scott; Kropf, Eric; Pleshko, Nancy

2014-03-01

Musculoskeletal pathology of the knee commonly occurs with aging and as a result of injury. The incidence of anterior cruciate ligament (ACL) injuries continues to increase annually, and may precede the eventual onset of osteoarthritis (OA), a debilitating and prevalent disease characterized by cartilage degeneration. Early detection of OA remains elusive, with current imaging methods lacking adequate sensitivity to detect early pathologic cartilage changes. We used mid- and near- infrared (IR) spectroscopy through arthroscopic-based fiber-optic devices to assess cartilage damage and differentiate tendon from ligament. Mid-IR spectroscopy is characterized by distinct bands and low penetration depth (< 10 μm) and near-IR spectroscopy is characterized by complex overlapping bands and greater penetration depths (< 1 cm). We have found that combined mid- and near-IR analysis greatly extends the information available through either in the analysis of soft tissues, including cartilage, ligaments and tendons. We discuss here basic science studies and the potential for translation to clinical research with novel arthroscopic probes.

[Rheumatic tendon pathologies].

PubMed

Thomas, M; Jordan, M

2014-11-01

Rheumatoid arthritis is found in approximately 2 % of the total population in Europe and the peak incidence of the disease is during the fourth and fifth decades of life. In approximately 15 % the first symptoms of the disease occur at the level of the foot and ankle. If the early stage-dependent therapy with pharmaceuticals fails isolated surgery of the tendons (e.g. tenosynovectomy) and reconstructive surgery including the tendons (e.g. tendon transfer and tendon readaptation) are performed to keep the patient mobile. The aim of this article is to give an overview of the most commonly used interventions in the reconstruction of tendons in rheumatism patients and the corresponding indications. The conservative therapy options for rheumatic foot and ankle alterations with a special emphasis on tendon pathologies have a well-established importance and are also presented. A selective literature search was carried out for therapeutic options of rheumatic tendon pathologies. If possible attempts should be made to preserve functional qualities using tenosynovectomy, tendon sutures or tendon transfer operations. If joints are already destroyed or dislocated, tendon operations should be carried out only as combined interventions with arthrodesis, endoprostheses or resection arthroplasty. The time window in which these interventions are possible should not be missed. Orthotic devices, bandages or even orthopedic shoes provide external support and splinting but do not represent a causal therapy.

Early neurovascular dysfunction in a transgenic rat model of Alzheimer’s disease

PubMed Central

Joo, Illsung L.; Lai, Aaron Y.; Bazzigaluppi, Paolo; Koletar, Margaret M.; Dorr, Adrienne; Brown, Mary E.; Thomason, Lynsie A. M.; Sled, John G.; McLaurin, JoAnne; Stefanovic, Bojana

2017-01-01

Alzheimer’s disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans. PMID:28401931

Observations on early and delayed colostomy closure.

PubMed

Tade, A O; Salami, B A; Ayoade, B A

2011-06-01

Traditional treatment of a variety of colorectal pathologies had included a diverting colostomy that was closed eight or more weeks later during a readmission. The aim of this retrospective study was to determine the outcomes of early colostomy closure and delayed colostomy closure in patients with temporary colostomies following traumatic and non-traumatic colorectal pathologies. In this study early colostomy closure was the closure of a colostomy within three weeks of its construction, while delayed colostomy closure referred to closure after 3 weeks. Complete records of the 37 adult patients who had temporary colostomy constructed and closed between Jan. 1997 December 2003 for various colorectal pathologies were studied. Fourteen patients had early colostomy closure while 23 had delayed closure. In the early colostomy closure group there were 10 men and 4 women. The mean age of the patients was 28yr with a range of 18-65yr. Colostomies were closed 9-18 days after initial colostomy construction. There was no mortality. Morbidity rate 28.6% (4 out of 14). There were two faecal fistulas (14.3%). Twenty-three patients had delayed colostomy closure 8 weeks to 18 months after initial colostomy construction. These were patients unfit for early surgery after initial colostomy construction because of carcinoma, significant weight loss, or sepsis. There was no mortality. Morbidity rate was 26.1%. There were 3 faecal fistulas (13.2%). Outcomes following early colostomy closure and delayed closure were comparable. Patients fit for surgery should have early closure whilst patients who may have compromised health should have delayed closure.

Stressful Life Events and Predictors of Post-traumatic Growth among High-Risk Early Emerging Adults.

PubMed

Arpawong, Thalida E; Rohrbach, Louise A; Milam, Joel E; Unger, Jennifer B; Land, Helen; Sun, Ping; Spruijt-Metz, Donna; Sussman, Steve

2016-01-01

Stressful life events (SLEs) may elicit positive psychosocial change among youth, referred to as Post-traumatic Growth (PTG). We assessed types of SLEs experienced, degree to which participants reported PTG, and variables predicting PTG across 24 months among a sample of high risk, ethnically diverse early emerging adults. Participants were recruited from alternative high schools ( n = 564; mean age=16.8; 65% Hispanic). Multi-level regression models were constructed to examine the impact of environmental (SLE quantity, severity) and personal factors (hedonic ability, perceived stress, developmental stage, future time orientation) on a composite score of PTG. The majority of participants reported positive changes resulted from their most life-altering SLE of the past two years. Predictors of PTG included fewer SLEs, less general stress, having a future time perspective, and greater identification with the developmental stage of Emerging Adulthood. Findings suggest intervention targets to foster positive adaptation among early emerging adults who experience frequent SLEs.

The autonomic higher order processing nuclei of the lower brain stem are among the early targets of the Alzheimer's disease-related cytoskeletal pathology.

PubMed

Rüb, U; Del Tredici, K; Schultz, C; Thal, D R; Braak, E; Braak, H

2001-06-01

The nuclei of the pontine parabrachial region (medial parabrachial nucleus, MPB; lateral parabrachial nucleus, LPB; subpeduncular nucleus, SPP) together with the intermediate zone of the medullary reticular formation (IRZ) are pivotal relay stations within central autonomic regulatory feedback systems. This study was undertaken to investigate the evolution of the Alzheimer's disease-related cytoskeletal pathology in these four sites of the lower brain stem. We examined the MPB, LPB, SPP and IRZ in 27 autopsy cases and classified the cortical Alzheimer-related cytoskeletal anomalies according to an established staging system (neurofibrillary tangle/neuropil threads [NFT/NT] stages I-VI). The lesions were visualized either with the antibody AT8, which is immunospecific for the abnormally phosphorylated form of the cytoskeletal protein tau, or with a modified Gallyas silver iodide stain. The MPB, SPB, and IRZ display cytoskeletal pathology in stage I and the LPB in stage II, whereby bothstages correspond to the preclinical phase of Alzheimer's disease (AD). In stages III-IV (incipient AD), the MPB and SPP are severely affected. In all of the stage III-IV cases, the lesions in the LPB and IRZ are well developed. In stages V and VI (clinical phase of AD), the MPB and SPP are filled with the abnormal intraneuronal material. At stages V-VI, the LPB is moderately involved and the IRZ shows severe damage. The pathogenesis of the AD-related cytoskeletal lesions in the nuclei of the pontine parabrachial region and in the IRZ conforms with the cortical NFT/NT staging sequence I-VI. In the event that the cytoskeletal pathology observed in this study impairs the function of the nerve cells involved, it is conceivable that autonomic mechanisms progressively deteriorate with advancing cortical NFT/NT stages. This relationship remains to be established, but it could provide insights into the illusive correlation between the AD-related cytoskeletal pathology and the function of

Evaluation of common elbow pathologies: a focus on physical examination.

PubMed

Laratta, Joseph; Caldwell, Jon-Michael; Lombardi, Joseph; Levine, William; Ahmad, Christopher

2017-05-01

Elbow tendinopathy accounts for the majority of elbow pathology in patients presenting to upper extremity and sports medicine surgeons. With increased participation in overhead sports in an aging population, the incidence of elbow injuries has risen. A comprehensive knowledge of elbow anatomy and biomechanical function of the elbow complex is prerequisite in the assessment of patients with elbow injuries; however, a thorough understanding of alternative and confounding pathologies is essential for accurate diagnosis. Because tendinopathy, tendonitis, and tendon tears have an anatomic basis for their pathology, a targeted history and meticulous physical examination often yields an accurate clinical diagnosis. The importance of physical examination and provocative examination maneuvers must be stressed in a technologically advanced era where clinical diagnosis is too commonly attained solely by advanced imaging modalities. A revived dedication to the physical examination may enhance our ability to correctly diagnose various pathologies about the elbow. Early and accurate clinical diagnosis is the first step in the proper initiation of treatment modalities and improvement in overall patient outcome.

Event-by-Event Simulations of Early Gluon Fields in High Energy Nuclear Collisions

NASA Astrophysics Data System (ADS)

Nickel, Matthew; Rose, Steven; Fries, Rainer

2017-09-01

Collisions of heavy ions are carried out at ultra relativistic speeds at the Relativistic Heavy Ion Collider and the Large Hadron Collider to create Quark Gluon Plasma. The earliest stages of such collisions are dominated by the dynamics of classical gluon fields. The McLerran-Venugopalan (MV) model of color glass condensate provides a model for this process. Previous research has provided an analytic solution for event averaged observables in the MV model. Using the High Performance Research Computing Center (HPRC) at Texas A&M, we have developed a C++ code to explicitly calculate the initial gluon fields and energy momentum tensor event by event using the analytic recursive solution. The code has been tested against previously known analytic results up to fourth order. We have also have been able to test the convergence of the recursive solution at high orders in time and studied the time evolution of color glass condensate.

Early Response of Mouse Joint Tissues to Noninvasive Knee Injury Suggests Treatment Targets

PubMed Central

Wu, P.; Holguin, N.; Silva, M. J.; Fu, M.; Liao, W.; Sandell, L. J.

2015-01-01

Objective Joint trauma can lead to a spectrum of acute lesions, including cartilage degradation, ligament or meniscus tears, and synovitis, all potentially associated with osteoarthritis. The goal of this study was to generate and validate a murine model of knee joint trauma following non-invasive controlled injurious compression in vivo and to investigate early molecular events. Methods The right knees of 8-week old mice were placed in a hyperflexed position and subjected to compressive joint loading at one of three peak forces (3, 6, 9 N) for 60 cycles in a single loading period and harvested at 5, 9 and 14 days post loading (n=3–5 mice for each time point and for each loading). The left knees were not loaded and served as the contralateral controls. Histological, immunohistochemical and ELISA analyses were performed to evaluate acute pathologic features in chondrocyte viability, cartilage matrix metabolism, synovial reaction, and serum COMP levels. Results Acute joint pathology was associated with increased injurious loads. All loading regimens induced chondrocyte apoptosis, cartilage matrix degradation, disruption of cartilage collagen fibril arrangement, and increased levels of serum COMP. We also observed that 6N loading induced mild synovitis by day 5 whereas at 9 N, with tearing of the anterior cruciate ligament, severe posttraumatic synovitis and ectopic cartilage formation were observed. Conclusion We have established and analyzed some early events in a murine model of knee joint trauma with different degrees of over-loading in vivo. These results suggest that immediate therapies particularly targeted to apoptosis and synovial cell proliferation could affect the acute posttraumatic reaction to potentially limit chronic consequences and osteoarthritis. PMID:24470303

Polarization-correlation investigation of biotissue multifractal structure and diagnostics of its pathological change

NASA Astrophysics Data System (ADS)

Angelsky, Oleg V.; Pishak, Vasyl P.; Ushenko, Alexander G.; Burkovets, Dimitry N.; Pishak, Olga V.

2001-05-01

The paper presents the results of polarization-correlation investigation of multifractal collagen structure of physiologically normal and pathologically changed tissues of women's reproductive sphere and of skin. The technique of polarization selection of coherent biotissues' images followed by determination of their autocorrelation functions and spectral densities is suggested. The correlation- optical criteria of early diagnostics of pathological changes' appearance of myometry (forming of the germ of fibromyoma) and of skin (psoriasis) are determined. The present paper examines the possibilities of diagnostics of pathological changes of biotissues' morphological structure by means of determining the polarizationally filtered autocorrelation functions (ACF) and corresponding spectral densities of their coherent images.

High-resolution carbonate isotopic study of the Mural Formation (Cerro Pimas section), Sonora, México: Implications for early Albian oceanic anoxic events

NASA Astrophysics Data System (ADS)

Madhavaraju, J.; Lee, Yong Il; Scott, R. W.; González-León, C. M.; Jenkyns, H. C.; Saucedo-Samaniego, J. C.; Ramasamy, S.

2018-03-01

The 420-m thick stratigraphic section of the Mural Formation that is exposed in the Cerro Pimas area of northern Sonora, Mexico, is composed of limestone lithofacies ranging from bioclastic wackestone to boundstone, whose biota is characterized by low diversity. Prominent age-diagnostic fossils are benthic foraminifera and long-ranging calcareous algae that indicate the Aptian/Albian boundary is close to the base of the Los Coyotes Member. The carbonates of this formation have negative to positive δ13C values (-4.63 to +2.6‰) and highly depleted δ18O values that range from -12.74 to -8.34‰. The absence of correlation between δ13C and δ18O values supports a primary marine origin for the δ13C values of these limestones. The carbon-isotopic curve of the Cerro Pimas stratigraphic section has well-defined δ13C segments (C8 - C15) that compare with published curves of similar age. In the lower part of the early Albian Los Coyotes Member, the presence of OAE 1b is indicated by an increase followed by a decrease in δ13C values, suggesting correlation with the Kilian Event. The middle part of the Los Coyotes Member has a significant negative carbon-isotope excursion correlated with the globally recognizable early Albian Paquier event. Moreover, another significant negative carbon-isotope shift is observed in the upper part of the Los Coyotes Member, which can be correlated with the Leenhardt Event. The occurrence of the Kilian, Paquier and Leenhardt Events (OAE 1b cluster) in the Cerro Pimas stratigraphy confirms the global nature of these early Albian disturbances of the carbon cycle.

Molecular Imaging Markers to Track Huntington's Disease Pathology.

PubMed

Wilson, Heather; De Micco, Rosa; Niccolini, Flavia; Politis, Marios

2017-01-01

Huntington's disease (HD) is a progressive, monogenic dominant neurodegenerative disorder caused by repeat expansion mutation in the huntingtin gene. The accumulation of mutant huntingtin protein, forming intranuclear inclusions, subsequently leads to degeneration of medium spiny neurons in the striatum and cortical areas. Genetic testing can identify HD gene carriers before individuals develop overt cognitive, psychiatric, and chorea symptoms. Thus, HD gene carriers can be studied in premanifest stages to understand and track the evolution of HD pathology. While advances have been made, the precise pathophysiological mechanisms underlying HD are unclear. Magnetic resonance imaging (MRI) and positron emission tomography (PET) have been employed to understand HD pathology in presymptomatic and symptomatic disease stages. PET imaging uses radioactive tracers to detect specific changes, at a molecular level, which could be used as markers of HD progression and to monitor response to therapeutic treatments for HD gene expansion carriers (HDGECs). This review focuses on available PET techniques, employed in cross-sectional and longitudinal human studies, as biomarkers for HD, and highlights future potential PET targets. PET studies have assessed changes in postsynaptic dopaminergic receptors, brain metabolism, microglial activation, and recently phosphodiesterase 10A (PDE10A) as markers to track HD progression. Alterations in PDE10A expression are the earliest biochemical change identified in HD gene carriers up to 43 years before predicted symptomatic onset. Thus, PDE10A expression could be a promising marker to track HD progression from early premanifest disease stages. Other PET targets which have been less well investigated as biomarkers include cannabinoid, adenosine, and GABA receptors. Future longitudinal studies are required to fully validate these PET biomarkers for use to track disease progression from far-onset premanifest to manifest HD stages. PET imaging

Enhanced tocopherol levels during early germination events in Chamaerops humilis var. humilis seeds.

PubMed

Siles, Laura; Alegre, Leonor; Tijero, Verónica; Munné-Bosch, Sergi

2015-10-01

Most angiosperms accumulate vitamin E in the form of tocopherols in seeds, exerting a protective antioxidant role. However, several palm trees principally accumulate tocotrienols, rather than tocopherols, in seeds, as it occurs in other monocots. To unravel the protective role of either tocopherols or tocotrienols against lipid peroxidation during seed germination in Chamaerops humilis var. humilis; seed viability, natural and induced germination capacity, seed water content, malondialdehyde levels (as an indicator of the extent of lipid peroxidation) and vitamin E levels (including both tocopherols and tocotrienols) were examined at various germination phases in a simulated, natural seed bank. At the very early stages of germination (operculum removal), malondialdehyde levels increased 2.8-fold, to decrease later up to 74%, thus indicating a transient lipid peroxidation at early stages of germination. Tocopherol levels were absent in quiescent seeds and did not increase during operculum removal, but increased later presumably dampening malondialdehyde accumulation. Thereafter, tocopherols continued increasing, while lipid peroxidation levels decreased. By contrast, tocotrienols levels remained constant or even decreased as germination progressed, showing no correlation with lipid peroxidation levels. We hypothesize that despite their high tocotrienol content, seeds synthesize tocopherols during germination to protect lipids from peroxidation events. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early life events and motor development in childhood and adolescence: a longitudinal study.

PubMed

Grace, Tegan; Bulsara, Max; Robinson, Monique; Hands, Beth

2016-05-01

Few studies have reported on early life risk factors for motor development outcomes past childhood. Antenatal, perinatal and neonatal factors affecting motor development from late childhood to adolescence were explored. As sex differences in motor development have been previously reported, males and females were examined separately. Participants (n = 2868) were from the Western Australian Pregnancy Cohort Study. Obstetric and neonatal data were examined to determine factors related to motor development at 10 (n = 1622), 14 (n = 1584) and 17 (n = 1221) years. The Neuromuscular Development Index (NDI) of the McCarron Assessment of Motor Development determined offspring motor proficiency. Linear mixed models were developed to allow for changes in motor development over time. Maternal pre-eclampsia, Caesarean section and low income were negatively related to male and female motor outcomes. Lower percentage of optimal birthweight was related to a lower male NDI. Younger maternal age, smoking during early pregnancy and stress during later pregnancy were related to lower female NDIs. Events experienced during pregnancy were related to motor development into late adolescence. Males and females were influenced differently by antenatal and perinatal risk factors; this may be due to sex-specific developmental pathways. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

EARLY ONSET OF CRANIOSYNOSTOSIS IN AN APERT MOUSE MODEL REVEALS CRITICAL FEATURES OF THIS PATHOLOGY

PubMed Central

Holmes, Greg; Rothschild, Gerson; Roy, Upal Basu; Deng, Chu-Xia; Mansukhani, Alka; Basilico, Claudio

2009-01-01

Activating mutations of FGFRs1–3 cause craniosynostosis (CS), the premature fusion of cranial bones, in man and mouse. The mechanisms by which such mutations lead to CS have been variously ascribed to increased osteoblast proliferation, differentiation, and apoptosis, but it is not always clear how these disturbances relate to the process of suture fusion. We have reassessed coronal suture fusion in an Apert Fgfr2 (S252W) mouse model. We find that the critical event of CS is the early loss of basal sutural mesenchyme as the osteogenic fronts, expressing activated Fgfr2, unite to form a contiguous skeletogenic membrane. A mild increase in osteoprogenitor proliferation precedes but does not accompany this event, and apoptosis is insignificant. On the other hand, the more apical coronal suture initially forms appropriately but then undergoes fusion, albeit at a slower rate, accompanied by a significant decrease in osteoprogenitor proliferation, and increased osteoblast maturation. Apoptosis now accompanies fusion, but is restricted to bone fronts in contact with one another. We correlated these in vivo observations with the intrinsic effects of the activated Fgfr2 S252W mutation in primary osteoblasts in culture, which show an increased capacity for both proliferation and differentiation. Our studies suggest that the major determinant of Fgfr2-induced craniosynostosis is the failure to respond to signals that would halt the recruitment or the advancement of osteoprogenitor cells at the sites where sutures should normally form. PMID:19389359

Indirect Effects of Attributional Style for Positive Events on Depressive Symptoms Through Self-Esteem During Early Adolescence.

PubMed

Rueger, Sandra Yu; George, Rachel

2017-04-01

Research on adolescent depression has overwhelmingly focused on risk factors, such as stressful negative events and cognitive vulnerabilities, but much important information can be gained by focusing on protective factors. Thus, the current study aimed to broaden understanding on adolescent depression by considering the role of two positive elements as protective factors, attributional style for positive events and self-esteem, in a model of depression. The sample included 491 middle school students (52 % female; n = 249) with an age range from 12 to 15 years (M = 13.2, SD = .70). The sample was ethnically/racially diverse, with 55 % White, 22 % Hispanic, 10 % Asian American, 3 % African American, and 10 % Biracial/Other. Correlational analyses indicated significant cross-sectional and longitudinal associations between an enhancing attributional style (internal, stable, global attributions for positive events), self-esteem and depressive symptoms. Further, prospective analyses using bootstrapping methodology demonstrated significant indirect effects of an enhancing attributional style on decreases in depressive symptoms through its effects on self-esteem. These findings highlight the importance of considering attributional style for positive events as a protective factor in the developmental course of depressive symptoms during early adolescence.

Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: evidence from a new genus and species, Grimmenodon aureum

PubMed Central

Stumpf, Sebastian; Ansorge, Jörg; Pfaff, Cathrin; Kriwet, Jürgen

2017-01-01

ABSTRACT A new genus and species of pycnodontiform fishes, Grimmenodon aureum, from marginal marine, marine-brackish lower Toarcian (Harpoceras exaratum ammonite subzone) clay deposits of Grimmen in northeastern Germany is described. The single specimen represents a diagnostic left prearticular dentition characterized by unique tooth arrangement and ornamentation patterns. Grimmenodon aureum, gen. et sp. nov., is the second unambiguously identified pycnodontiform species from the Early Jurassic, in addition to Eomesodon liassicus from the early Lower Jurassic of western Europe. We also report an indeterminate pycnodontiform tooth crown from the upper Pliensbachian (Pleuroceras apyrenum ammonite subzone) of the same site. The material expands the Early Jurassic range of pycnodontiforms significantly northwards and confirms their presence before and immediately following the onset of the Toarcian Oceanic Anoxic Event (T-OAE) in the marginal marine ecosystems south of the Fennoscandian Shield. Moreover, the new records indicate that the Early Jurassic diversity of pycnodontiform fishes was greater than previously assumed and probably equaled that of the Late Triassic. Therefore, it is hypothesized that the Triassic-Jurassic mass extinction event did not affect pycnodontiform fishes significantly. Micro-computed tomography was used to study the internal anatomy of the prearticular of Grimmenodon aureum, gen. et sp. nov. Our results show that no replacement teeth were formed within the tooth-bearing bone but rather were added posteriorly to functional teeth. http://zoobank.org/urn:lsid:zoobank.org:pub:A56BDE9C-40C4-4CFA-9C2E-F5FA35A66F2 Citation for this article: Stumpf, S., J. Ansorge, C. Pfaff, and J. Kriwet. 2017. Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: Evidence from a new genus and species, Grimmenodon aureum. Journal of Vertebrate Paleontology. DOI: 10

Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: evidence from a new genus and species, Grimmenodon aureum.

PubMed

Stumpf, Sebastian; Ansorge, Jörg; Pfaff, Cathrin; Kriwet, Jürgen

2017-07-04

A new genus and species of pycnodontiform fishes, Grimmenodon aureum , from marginal marine, marine-brackish lower Toarcian ( Harpoceras exaratum ammonite subzone) clay deposits of Grimmen in northeastern Germany is described. The single specimen represents a diagnostic left prearticular dentition characterized by unique tooth arrangement and ornamentation patterns. Grimmenodon aureum , gen. et sp. nov., is the second unambiguously identified pycnodontiform species from the Early Jurassic, in addition to Eomesodon liassicus from the early Lower Jurassic of western Europe. We also report an indeterminate pycnodontiform tooth crown from the upper Pliensbachian ( Pleuroceras apyrenum ammonite subzone) of the same site. The material expands the Early Jurassic range of pycnodontiforms significantly northwards and confirms their presence before and immediately following the onset of the Toarcian Oceanic Anoxic Event (T-OAE) in the marginal marine ecosystems south of the Fennoscandian Shield. Moreover, the new records indicate that the Early Jurassic diversity of pycnodontiform fishes was greater than previously assumed and probably equaled that of the Late Triassic. Therefore, it is hypothesized that the Triassic-Jurassic mass extinction event did not affect pycnodontiform fishes significantly. Micro-computed tomography was used to study the internal anatomy of the prearticular of Grimmenodon aureum , gen. et sp. nov. Our results show that no replacement teeth were formed within the tooth-bearing bone but rather were added posteriorly to functional teeth. http://zoobank.org/urn:lsid:zoobank.org:pub:A56BDE9C-40C4-4CFA-9C2E-F5FA35A66F2 Citation for this article: Stumpf, S., J. Ansorge, C. Pfaff, and J. Kriwet. 2017. Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: Evidence from a new genus and species, Grimmenodon aureum . Journal of Vertebrate Paleontology. DOI: 10.1080/02724634.2017.1344679.

Frequency and characteristics of dual pathology in patients with lesional epilepsy.

PubMed

Cendes, F; Cook, M J; Watson, C; Andermann, F; Fish, D R; Shorvon, S D; Bergin, P; Free, S; Dubeau, F; Arnold, D L

1995-11-01

We studied 167 patients who had identifiable lesions and temporal or extratemporal partial epilepsy. Pathology included neuronal migration disorders (NMDs) (48), low-grade tumors (52), vascular malformations (34), porencephalic cysts (16), and gliotic lesions as a result of cerebral insults early in life (17). MRI volumetric studies using thin (1.5- or 3-mm) coronal images were performed in all patients and in 44 age-matched normal controls. An atrophic hippocampal formation (HF), indicating dual pathology, was present in 25 patients (15%). Abnormal HF volumes were present in those with lesions involving temporal (17%) but also extratemporal (14%) areas. Age at onset and duration of epilepsy did not influence the presence of HF atrophy. However, febrile seizures in early childhood were more frequently, although not exclusively, found in patients with hippocampal atrophy. The frequency of hippocampal atrophy in our patients with low-grade tumors (2%) and vascular lesions (9%) was low. Dual pathology was far more common in patients with NMDs (25%), porencephalic cysts (31%), and reactive gliosis (23.5%). Some structural lesions, such as NMDs, are more likely to be associated with hippocampal atrophy, independent of the distance of the lesion from the HF. In other types of lesions, such as vascular malformations, dual pathology was found when the lesion was close to the HF. A common pathogenic mechanism during pre- or perinatal development may explain the occurrence of concomitant mesial temporal sclerosis and other structural lesions because of either (1) associated developmental abnormalities or (2) predisposition to prolonged febrile convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Energy metabolic reprogramming in the hypertrophied and early stage failing heart: a multisystems approach.

PubMed

Lai, Ling; Leone, Teresa C; Keller, Mark P; Martin, Ola J; Broman, Aimee T; Nigro, Jessica; Kapoor, Kapil; Koves, Timothy R; Stevens, Robert; Ilkayeva, Olga R; Vega, Rick B; Attie, Alan D; Muoio, Deborah M; Kelly, Daniel P

2014-11-01

An unbiased systems approach was used to define energy metabolic events that occur during the pathological cardiac remodeling en route to heart failure (HF). Combined myocardial transcriptomic and metabolomic profiling were conducted in a well-defined mouse model of HF that allows comparative assessment of compensated and decompensated (HF) forms of cardiac hypertrophy because of pressure overload. The pressure overload data sets were also compared with the myocardial transcriptome and metabolome for an adaptive (physiological) form of cardiac hypertrophy because of endurance exercise training. Comparative analysis of the data sets led to the following conclusions: (1) expression of most genes involved in mitochondrial energy transduction were not significantly changed in the hypertrophied or failing heart, with the notable exception of a progressive downregulation of transcripts encoding proteins and enzymes involved in myocyte fatty acid transport and oxidation during the development of HF; (2) tissue metabolite profiles were more broadly regulated than corresponding metabolic gene regulatory changes, suggesting significant regulation at the post-transcriptional level; (3) metabolomic signatures distinguished pathological and physiological forms of cardiac hypertrophy and served as robust markers for the onset of HF; and (4) the pattern of metabolite derangements in the failing heart suggests bottlenecks of carbon substrate flux into the Krebs cycle. Mitochondrial energy metabolic derangements that occur during the early development of pressure overload-induced HF involve both transcriptional and post-transcriptional events. A subset of the myocardial metabolomic profile robustly distinguished pathological and physiological cardiac remodeling. © 2014 American Heart Association, Inc.

Safety evaluation of laninamivir octanoate hydrate through analysis of adverse events reported during early post-marketing phase vigilance.

PubMed

Nakano, Takashi; Okumura, Akihisa; Tanabe, Takuya; Niwa, Shimpei; Fukushima, Masato; Yonemochi, Rie; Eda, Hisano; Tsutsumi, Hiroyuki

2013-06-01

Abnormal behavior and delirium are common in children with influenza. While abnormal behavior and delirium are considered to be associated with influenza encephalopathy, an increased risk of such neuropsychiatric symptoms in patients receiving neuraminidase inhibitor treatment is suspected. Laninamivir octanoate hydrate, recently approved in Japan, is a long-acting neuraminidase inhibitor. It is important to establish a safety profile for laninamivir early, based on post-marketing experiences. Spontaneous safety reports collected in the early post-marketing phase vigilance were analyzed. Adverse events of interest such as abnormal behavior/delirium, dizziness/vertigo, respiratory disorders, shock/syncope, and any other serious events were intensively reviewed by the Safety Evaluation Committee. Abnormal behavior/delirium was a frequently reported event. Almost all the reported cases were considered to be due to influenza and not laninamivir. There were 32 cases of abnormal behavior/delirium that could lead to dangerous accidents, and these were observed more frequently in males and teenagers. Syncope probably related to the act of inhalation per se of laninamivir was reported during this survey. This safety review revealed that the safety profile of laninamivir for abnormal behavior/delirium and syncope was similar to that of other neuraminidase inhibitors. As stated in the labeling, teenage patients inhaling laninamivir should remain under constant parental supervision for at least 2 days and should be closely monitored for behavioral changes to prevent serious accidents associated with abnormal behavior/delirium. Furthermore, to avoid syncope because of inhalation, patients should be instructed to inhale in a relaxed sitting position.

In vivo detection of microstructural correlates of brain pathology in preclinical and early Alzheimer Disease with magnetic resonance imaging.

PubMed

Zhao, Yue; Raichle, Marcus E; Wen, Jie; Benzinger, Tammie L; Fagan, Anne M; Hassenstab, Jason; Vlassenko, Andrei G; Luo, Jie; Cairns, Nigel J; Christensen, Jon J; Morris, John C; Yablonskiy, Dmitriy A

2017-03-01

GEPCI brain tissue metrics and beta-amyloid (Aβ) burden defined by positron emission tomography (PET) - the current in vivo gold standard for detection of cortical Aβ, thus supporting GEPCI as a potential surrogate marker for Aβ imaging - a known biomarker of early AD. Remarkably, the data show significant correlations not only in the areas of high Aβ accumulation (e.g. precuneus) but also in some areas of medial temporal lobe (e.g. parahippocampal cortex), where Aβ accumulation is relatively low. We have demonstrated that GEPCI provides a new approach for the in vivo evaluation of AD-related tissue pathology in the preclinical and early symptomatic stages of AD. Since MRI is a widely available technology, the GEPCI surrogate markers of AD pathology have a potential for improving the quality of AD diagnostic, and the evaluation of new disease-modifying therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Brachial-ankle pulse wave velocity predicts decline in renal function and cardiovascular events in early stages of chronic kidney disease.

PubMed

Yoon, Hye Eun; Shin, Dong Il; Kim, Sung Jun; Koh, Eun Sil; Hwang, Hyeon Seok; Chung, Sungjin; Shin, Seok Joon

2013-01-01

In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD). Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR < 90 ml/min/1.73m(2), eGFR < 90 group; n=117) and those with eGFR ≥ 90 ml/min/1.73 m(2) (eGFR ≥ 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events. baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (β=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (β=-0.015, p=0.035). baPWV was independently associated with cardiovascular events (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ≥ 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV events in the eGFR < 90 group (area under curve=0.691, p=0.03) CONCLUSIONS: In patients with early stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular events.

Edaravone alleviates Alzheimer's disease-type pathologies and cognitive deficits.

PubMed

Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang

2015-04-21

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.

Early Spatial and Temporal Events of Human T-Lymphotropic Virus Type 1 Spread following Blood-Borne Transmission in a Rabbit Model of Infection ▿

PubMed Central

Haynes, Rashade A. H.; Zimmerman, Bevin; Millward, Laurie; Ware, Evan; Premanandan, Christopher; Yu, Lianbo; Phipps, Andrew J.; Lairmore, Michael D.

2010-01-01

Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia/lymphoma (ATL) and is associated with a variety of lymphocyte-mediated disorders. HTLV-1 transmission occurs by transmission of infected cells via breast-feeding by infected mothers, sexual intercourse, and contaminated blood products. The route of exposure and early virus replication events are believed to be key determinants of virus-associated spread, antiviral immune responses, and ultimately disease outcomes. The lack of knowledge of early events of HTLV-1 spread following blood-borne transmission of the virus in vivo hinders a more complete understanding of the immunopathogenesis of HTLV-1 infections. Herein, we have used an established animal model of HTLV-1 infection to study early spatial and temporal events of the viral infection. Twelve-week-old rabbits were injected intravenously with cell-associated HTLV-1 (ACH-transformed R49). Blood and tissues were collected at defined intervals throughout the study to test the early spread of the infection. Antibody and hematologic responses were monitored throughout the infection. HTLV-1 intracellular Tax and soluble p19 matrix were tested from ex vivo cultured lymphocytes. Proviral copy numbers were measured by real-time PCR from blood and tissue mononuclear leukocytes. Our data indicate that intravenous infection with cell-associated HTLV-1 targets lymphocytes located in both primary lymphoid and gut-associated lymphoid compartments. A transient lymphocytosis that correlated with peak virus detection parameters was observed by 1 week postinfection before returning to baseline levels. Our data support emerging evidence that HTLV-1 promotes lymphocyte proliferation preceding early viral spread in lymphoid compartments to establish and maintain persistent infection. PMID:20219918

Pathological jealousy and pathological love: Apples to apples or apples to oranges?

PubMed

Stravogiannis, Andrea Lorena da C; Kim, Hyoun S; Sophia, Eglacy C; Sanches, Cíntia; Zilberman, Monica L; Tavares, Hermano

2018-01-01

Pathological jealousy evokes emotions, thoughts, and behaviors that cause damage to social and interpersonal relationships. On the other hand, pathological love is the uncontrollable behavior of caring for a partner that results in neglecting the needs of the self. The aim of the present research was to assess the similarities and differences between the two psychopathologies of love. To this end, thirty-two individuals with pathological jealousy and 33 individuals with pathological love were compared on demographics, aspects of romantic relationship (jealousy, satisfaction, love style), psychiatric co-morbidities, personality and psychological characteristics (e.g., impulsivity). In a univariate analysis individuals with pathological jealousy were more likely to be in a current relationship and reported greater satisfaction. The avoidant attachment and the ludus love style were associated with pathological jealousy whereas the secure attachment and agape love style was associated with pathological love. Almost three-quarters (72.3%) of the sample met criteria for a current psychiatric disorder, however no differences emerged between the pathological jealousy and pathological love groups. In a binary logistic regression, relationship status and impairments in parenting significantly differentiated the groups. While both pathological jealousy and pathological love share similarities, they also present with unique differences, which may have important treatment implications. Copyright © 2017 Elsevier B.V. All rights reserved.

Two-phase computed tomography study of warthin tumor of parotid gland: differentiation from other parotid gland tumors and its pathologic explanation.

PubMed

Woo, Seung Hoon; Choi, Dae-Seob; Kim, Jin-pyeong; Park, Jung Je; Joo, Yeon Hee; Chung, Phil-Sang; Kim, Bo-Young; Ko, Young-Hyeh; Jeong, Han-Sin; Kim, Hyung-Jin

2013-01-01

The objective of this study was to define the radiological characteristics of 2-phase computed tomography (CT) of parotid gland Warthin tumors (WTs) with a pathologic basis for these findings. We prospectively enrolled 116 patients with parotid gland tumor who underwent preoperative 2-phase CT scans(scanning delays of 30 and 120 seconds). The attenuation changes and enhancement patterns were analyzed according to pathology. We also evaluated size-matched samples of WTs and pleomorphic adenoma by staining CD31, vascular endothelial growth factor-receptor 2, collagen IV, and smooth muscle actin. Computed tomography numbers in WTs were significantly higher than those in other tumors in early-phase scans and lower in delayed scans. Pathologically, CD31(+) blood vessel area was significantly higher in WTs than in pleomorphic adenomas. In addition, WTs had an extensive capillary network and many leaky blood vessels. The enhancement pattern of early fill-in and early washout is the typical finding of WTs on 2-phase CT scans, which may be attributed pathologically to abundant blood vessel and extensive capillary network.

Impaired Early Attentional Processes in Parkinson’s Disease: A High-Resolution Event-Related Potentials Study

PubMed Central

Bocquillon, Perrine; Bourriez, Jean-Louis; Palmero-Soler, Ernesto; Defebvre, Luc; Derambure, Philippe; Dujardin, Kathy

2015-01-01

Introduction The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. A previous study using the P3 component of the event-related potentials suggested that a reduced ability to resist interference could be responsible for attention disorders at early stages of Parkinson’s disease (PD), with a possible role of the dorsolateral prefrontal cortex (DLPFC). Methods Our objective was to better determine the origin of this impairment, by studying an earlier ERP component, the N2, and its subcomponents, as they reflect early inhibition processes and as they are known to have sources in the anterior cingulate cortex (ACC), which is involved together with the DLPFC in inhibition processes. Fifteen early-stage PD patients and 15 healthy controls (HCs) performed a three-stimulus visual oddball paradigm, consisting in detecting target inputs amongst standard stimuli, while resisting interference from distracter ones. A 128-channel electroencephalogram was recorded during this task and the generators of the N2 subcomponents were identified using standardized weighted low-resolution electromagnetic tomography (swLORETA). Results PD patients displayed fewer N2 generators than HCs in both the DLPFC and the ACC, for all types of stimuli. In contrast to controls, PD patients did not show any differences between their generators for different N2 subcomponents. Conclusion Our data suggest that impaired inhibition in PD results from dysfunction of the DLPFC and the ACC during the early stages of attentional processes. PMID:26135906

New developments in digital pathology: from telepathology to virtual pathology laboratory.

PubMed

Kayser, Klaus; Kayser, Gian; Radziszowski, Dominik; Oehmann, Alexander

2004-01-01

To analyse the present status and future development of computerized diagnostic pathology in terms of work-flow integrative telepathology and virtual laboratory. Telepathology has left its childhood. The technical development of telepathology is mature, in contrast to that of virtual pathology. Two kinds of virtual pathology laboratories are emerging: a) those with distributed pathologists and distributed (>=1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists working in a centralized laboratory. Both are under technical development. Telepathology can be used for e-learning and e-training in pathology, as exemplarily demonstrated on Digital Lung Pathology Pathology (www.pathology-online.org). A virtual pathology institution (mode a) accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size of images has to be limited, and usual different magnifications have to be used. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. First experiences of a virtual pathology institution group working with the iPATH server (Dr. L. Banach, Dr. G. Haroske, Dr. I. Hurwitz, Dr. K. Kayser, Dr. K.D. Kunze, Dr. M. Oberholzer,) working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalisation of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalisation is still under

The instrumental seismicity of the Barents and Kara sea region: relocated event catalog from early twentieth century to 1989

NASA Astrophysics Data System (ADS)

Morozov, Alexey Nikolaevich; Vaganova, Natalya V.; Asming, Vladimir E.; Konechnaya, Yana V.; Evtyugina, Zinaida A.

2018-05-01

We have relocated seismic events registered within the Barents and Kara sea region from early twentieth century to 1989 with a view to creating a relocated catalog. For the relocation, we collected all available seismic bulletins from the global network using data from the ISC Bulletin (International Seismological Centre), ISC-GEM project (International Seismological Centre-Global Earthquake Model), EuroSeismos project, and by Soviet seismic stations from Geophysical Survey of the Russian Academy of Sciences. The location was performed by applying a modified method of generalized beamforming. We have considered several travel time models and selected one with the best location accuracy for ground truth events. Verification of the modified method and selection of the travel time model were performed using data on four nuclear explosions that occurred in the area of the Novaya Zemlya Archipelago and in the north of the European part of Russia. The modified method and the Barents travel time model provide sufficient accuracy for event location in the region. The relocation procedure was applied to 31 of 36 seismic events registered within the Barents and Kara sea region.

An EAS event observed in the early stage of development

NASA Astrophysics Data System (ADS)

Barroso, S. L. C.; Beggio, P. C.; de Carvalho, A. O.; Chinellato, J. A.; Mariano, A.; de Oliveira, R.; Shibuya, E. H.; Brazil-Japan Collaboration of Chacaltaya Emulsion Chamber Experiment

2008-01-01

Since 1969 the experiments of Brazil-Japan Collaboration showed the occurrence of a series of events, showing a region with a high concentration of electromagnetic particles, surrounded by isolated and/or groups of showers. These events were named "halo events" or "super-families". Currently, we have more than a dozen of such events. The first of them, due to its aspect, was named "Andromeda". We present here the main characteristics of a similar halo event, named C21S087I075. It has a halo region with many high energy showers in its border. Other small energy showers spread over the central and surrounding blocks (S088, S100, S101, I074). These isolated showers, classified as of hadronic or electromagnetic origin, present a fractional energy distribution compatible with that of a Centauro candidate event (C16S087I037), reported at this symposium [S.L.C. Barroso, P.C. Beggio, J.A. Chinellato, A.O. Carvalho, A. Mariano, R. Oliveira, E.H. Shibuya, in this issue of XIV ISVHECRI]. Moreover, the lateral distribution in the halo region is similar to that observed in other 3 halo events.

Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases.

PubMed

Handley, Renee R; Reid, Suzanne J; Brauning, Rudiger; Maclean, Paul; Mears, Emily R; Fourie, Imche; Patassini, Stefano; Cooper, Garth J S; Rudiger, Skye R; McLaughlan, Clive J; Verma, Paul J; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

2017-12-26

The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin ( HTT ) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73 -line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.

Rumination mediates the relationship between peer alienation and eating pathology in young adolescent girls.

PubMed

Hilt, Lori M; Roberto, Christina A; Nolen-Hoeksema, Susan

2013-09-01

This study examined whether rumination, the tendency to passively and repeatedly dwell on negative events, mediated the relationship between peer alienation and eating disorder symptoms among adolescent girls. Participants included 101 girls (ages 10-14; 47% Hispanic, 24% African American) who completed questionnaires regarding peer relationships, symptoms of eating pathology, rumination, and depressive symptoms. Girls who reported experiencing more peer alienation reported a higher degree of pathological eating symptoms. The relationship between peer alienation and eating pathology was mediated by rumination, even after controlling for depressive symptoms. This study extends previous work indicating that rumination is a cognitive mechanism that may contribute to the development and/or maintenance of eating pathology. The findings suggest that adolescents who feel alienated by their peers might be particularly susceptible to engaging in ruminative thinking that can lead to or exacerbate eating problems.

Advances on the Understanding of the Origins of Synaptic Pathology in AD

PubMed Central

Nathalie Lacor, Pascale

2007-01-01

Although Alzheimer’s disease (AD) was first discovered a century ago, we are still facing a lack of definitive diagnosis during the patient’s lifetime and are unable to prescribe a curative treatment. However, the past 10 years have seen a “revamping” of the main hypothesis about AD pathogenesis and the hope to foresee possible treatment. AD is no longer considered an irreversible disease. A major refinement of the classic β-amyloid cascade describing amyloid fibrils as neurotoxins has been made to integrate the key scientific evidences demonstrating that the first pathological event occurring in AD early stages affects synaptic function and maintenance. A concept fully compatible with synapse loss being the best pathological correlate of AD rather than other described neuropathological hallmarks (amyloid plaques, neurofibrillary tangles or neuronal death). The notion that synaptic alterations might be reverted, thus offering a potential curability, was confirmed by immunotherapy experiments targeting β-amyloid protein in transgenic AD mice in which cognitive functions were improved despite no reduction in the amyloid plaques burden. The updated amyloid cascade now integrates the synapse failure triggered by soluble Aβ-oligomers. Still no consensus has been reached on the most toxic Aβ conformations, neither on their site of production nor on their extra- versus intra-cellular actions. Evidence shows that soluble Aβ oligomers or ADDLs bind selectively to neurons at their synaptic loci, and trigger major changes in synapse composition and morphology, which ultimately leads to dendritic spine loss. However, the exact mechanism is not yet fully understood but is suspected to involve some membrane receptor(s). PMID:19415125

Finding the signal in the noise: Could social media be utilized for early hospital notification of multiple casualty events?

PubMed Central

Moore, Sara; Wakam, Glenn; Hubbard, Alan E.; Cohen, Mitchell J.

2017-01-01

Introduction Delayed notification and lack of early information hinder timely hospital based activations in large scale multiple casualty events. We hypothesized that Twitter real-time data would produce a unique and reproducible signal within minutes of multiple casualty events and we investigated the timing of the signal compared with other hospital disaster notification mechanisms. Methods Using disaster specific search terms, all relevant tweets from the event to 7 days post-event were analyzed for 5 recent US based multiple casualty events (Boston Bombing [BB], SF Plane Crash [SF], Napa Earthquake [NE], Sandy Hook [SH], and Marysville Shooting [MV]). Quantitative and qualitative analysis of tweet utilization were compared across events. Results Over 3.8 million tweets were analyzed (SH 1.8 m, BB 1.1m, SF 430k, MV 250k, NE 205k). Peak tweets per min ranged from 209–3326. The mean followers per tweeter ranged from 3382–9992 across events. Retweets were tweeted a mean of 82–564 times per event. Tweets occurred very rapidly for all events (<2 mins) and represented 1% of the total event specific tweets in a median of 13 minutes of the first 911 calls. A 200 tweets/min threshold was reached fastest with NE (2 min), BB (7 min), and SF (18 mins). If this threshold was utilized as a signaling mechanism to place local hospitals on standby for possible large scale events, in all case studies, this signal would have preceded patient arrival. Importantly, this threshold for signaling would also have preceded traditional disaster notification mechanisms in SF, NE, and simultaneous with BB and MV. Conclusions Social media data has demonstrated that this mechanism is a powerful, predictable, and potentially important resource for optimizing disaster response. Further investigated is warranted to assess the utility of prospective signally thresholds for hospital based activation. PMID:28982201

Survival Outcomes and Effect of Early vs. Deferred cART Among HIV-Infected Patients Diagnosed at the Time of an AIDS-Defining Event: A Cohort Analysis

PubMed Central

Mussini, Cristina; Johnson, Margaret; d'Arminio Monforte, Antonella; Antinori, Andrea; Gill, M. John; Sighinolfi, Laura; Uberti-Foppa, Caterina; Borghi, Vanni; Sabin, Caroline

2011-01-01

Objectives We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). Methods Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997–2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (<30 days after AIDS event) or deferred (30–270 days after AIDS event) cART. Results The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/µL and 5.2 (4.5, 5.7) log10 copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p = 0.20). Conclusions Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting. PMID:22043301

Paleomagnetic and Geochronologic Data from Central Asia: Inferences for Early Paleozoic Tectonic Evolution and Timing of Worldwide Glacial Events

NASA Astrophysics Data System (ADS)

Gregory, L. C.; Meert, J. G.; Levashova, N.; Grice, W. C.; Gibsher, A.; Rybanin, A.

2007-12-01

The Neoproterozoic to early Paleozoic Ural-Mongol belt that runs through Central Asia is crucial for determining the enigmatic amalgamation of microcontinents that make up the Eurasian subcontinent. Two unique models have been proposed for the evolution of Ural-Mongol belt. One involves a complex assemblage of cratonic blocks that have collided and rifted apart during diachronous opening and closing of Neoproterozoic to Devonian aged ocean basins. The opposing model of Sengor and Natal"in proposes a long-standing volcanic arc system that connected Central Asian blocks with the Baltica continent. The Aktau-Mointy and Dzabkhan microcontinents in Kazakhstan and Central Mongolia make up the central section of the Ural-Mongol belt, and both contain glacial sequences characteristic of the hypothesized snowball earth event. These worldwide glaciations are currently under considerable debate, and paleomagnetic data from these microcontients are a useful contribution to the snowball controversy. We have sampled volcanic and sedimentary sequences in Central Mongolia, Kazakhstan and Kyrgyzstan for paleomagnetic and geochronologic study. U-Pb data, 13C curves and abundant fossil records place age constraints on sequences that contain glacial deposits of the hypothesized snowball earth events. Carbonates in the Zavkhan Basin in Mongolia are likely remagnetized, but fossil evidence within the sequence suggests a readjusted age control on two glacial events that were previously labeled as Sturtian and Marinoan. U-Pb ages from both Kazakhstan and Mongolian volcanic sequences imply a similar evolution history of the areas as part of the Ural-Mongol fold belt, and these ages paired with paleomagnetic and 13C records have important tectonic implications. We will present these data in order to place better constraints on the Precambrian to early Paleozoic tectonic evolution of Central Asia and the timing of glacial events recorded in the area.

Excessive Heat Events and National Security: Building Resilience based on Early Warning Systems

NASA Astrophysics Data System (ADS)

Vintzileos, A.

2017-12-01

Excessive heat events (EHE) affect security of Nations in multiple direct and indirect ways. EHE are the top cause for morbidity/mortality associated to any atmospheric extremes. Higher energy consumption used for cooling can lead to black-outs and social disorder. EHE affect the food supply chain reducing crop yield and increasing the probability of food contamination during delivery and storage. Distribution of goods during EHE can be severely disrupted due to mechanical failure of transportation equipment. EHE during athletic events e.g., marathons, may result to a high number of casualties. Finally, EHE may also affect military planning by e.g. reducing hours of exercise and by altering combat gear. Early warning systems for EHE allow for building resilience. In this paper we first define EHE as at least two consecutive heat days; a heat day is defined as a day with a maximum heat index with probability of occurrence that exceeds a certain threshold. We then use retrospective forecasts performed with a multitude of operational models and show that it is feasible to forecast EHE at forecast lead of week-2 and week-3 over the contiguous United States. We finally introduce an improved definition of EHE based on an intensity index and investigate forecast skill of the predictive system in the tropics and subtropics.

Modeling long recovery early events (LOREs) produced by lightning-induced ionization of the nighttime upper mesosphere

NASA Astrophysics Data System (ADS)

Kotovsky, D. A.; Moore, R. C.

2017-07-01

We present results of a cylindrically symmetric, coupled electrodynamic, and photochemical model which simulates diffuse ionization of the middle atmosphere induced by strong lightning discharges (peak currents >150 kA). Scattering of subionospherically propagating, very low frequency radio waves is then evaluated using the Long-Wave Propagation Capability code. Some modeled sprite halos exhibit continued electron density growth up to timescales of seconds due to O- detachment, though it is not yet clear how this might relate to the slower onset durations (>20 ms) of some early VLF events. Modeled electron density enhancements in sprite halos, capable of strong VLF scattering, can persist for long periods of time (greater than hundreds of seconds) even at lower altitudes where their recovery is initially controlled by fast attachment processes. Consequently, our modeling results indicate that both typical recovery (20 to 240 s) and long recovery (LOREs, >300 s) VLF scattering events can be explained by scattering from conductivity changes associated with sprite halos. In contrast, modeled scattered fields resulting from elve-associated conductivity changes, though exhibiting long recovery times, are too weak to sufficiently explain typical LORE observations. Theoretical scattering from structured ionization events (e.g., sprites columns and gigantic jets) is not considered in this work.

Early Corneal Cellular and Nerve Fiber Pathology in Young Patients With Type 1 Diabetes Mellitus Identified Using Corneal Confocal Microscopy.

PubMed

Szalai, Eszter; Deák, Eszter; Módis, László; Németh, Gábor; Berta, András; Nagy, Annamária; Felszeghy, Eniko; Káposzta, Rita; Malik, Rayaz A; Csutak, Adrienne

2016-03-01

The aim of this study was to quantify epithelial, stromal, and endothelial cell density, and subbasal nerve morphology in young patients with type 1 diabetes mellitus with and without diabetic retinopathy. A total of 28 young patients (mean age, 22.86 ± 9.05 years) with type 1 diabetes, with (n = 18) and without (n = 10) retinopathy, and 17 age-matched healthy control subjects (mean age, 26.53 ± 2.43 years) underwent corneal confocal microscopy (CCM). We found significantly lower epithelial (P < 0.0001) and endothelial (P = 0.001) cell densities and higher keratocyte cell density (P = 0.024) in patients with type 1 diabetes compared to controls. Significantly lower corneal nerve fiber density (P = 0.004), nerve branch density (P = 0.004), total nerve branch density (P = 0.04), and nerve fiber length (P = 0.001), and greater nerve fiber width (P = 0.04) were observed in patients with type 1 diabetes compared to control subjects. Significantly lower epithelial (P < 0.001) and endothelial (P = 0.02) cell densities, nerve branch density (P = 0.02), and nerve fiber length (P = 0.04), and significantly higher keratocyte cell density (P = 0.02) were found in patients with type 1 diabetes without retinopathy compared to control subjects. Corneal confocal microscopy identifies corneal cellular and small nerve fiber pathology in young patients with type 1 diabetes without retinopathy, which increases in severity in those with retinopathy. Corneal confocal microscopy appears to have considerable use as an imaging biomarker for early subclinical pathology in young patients with type 1 diabetes mellitus.

Early Verb Learning: How Do Children Learn How to Compare Events?

PubMed Central

Childers, Jane B.; Parrish, Rebecca; Olson, Christina V.; Burch, Clare; Fung, Gavin; McIntyre, Kevin

2015-01-01

An important problem verb learners must solve is how to extend verbs. Children could use cross-situational information to guide their extensions, however comparing events is difficult. Two studies test whether children benefit from initially seeing a pair of similar events (‘progressive alignment’) while learning new verbs, and whether this influence changes with age. In Study 1, 2 ½- and 3 ½-year-old children participated in an interactive task. Children who saw a pair of similar events and then varied events were able to extend verbs at test, differing from a control group; children who saw two pairs of varied events did not differ from the control group. In Study 2, events were presented on a monitor. Following the initial pair of events that varied by condition, a Tobii x120 eye tracker recorded 2 ½-, 3 ½- and 4 ½-year-olds’ fixations to specific elements of events (AOIs) during the second pair of events, which were the same across conditions. After seeing the pair of events that were highly similar, 2 ½-year-olds showed significantly longer fixation durations to agents and to affected objects as compared to the all varied condition. At test, 3 ½-year-olds were able to extend the verb, but only in the progressive alignment condition. These results are important because they show children’s visual attention to relevant elements in dynamic events is influenced by their prior comparison experience, and they show that young children benefit from seeing similar events as they learn to compare events to each other. PMID:27092030

Metabolic connectomics targeting brain pathology in dementia with Lewy bodies

PubMed Central

Caminiti, Silvia P; Tettamanti, Marco; Sala, Arianna; Presotto, Luca; Iannaccone, Sandro; Cappa, Stefano F; Magnani, Giuseppe

2016-01-01

Dementia with Lewy bodies is characterized by α-synuclein accumulation and degeneration of dopaminergic and cholinergic pathways. To gain an overview of brain systems affected by neurodegeneration, we characterized the [18F]FDG-PET metabolic connectivity in 42 dementia with Lewy bodies patients, as compared to 42 healthy controls, using sparse inverse covariance estimation method and graph theory. We performed whole-brain and anatomically driven analyses, targeting cholinergic and dopaminergic pathways, and the α-synuclein spreading. The first revealed substantial alterations in connectivity indexes, brain modularity, and hubs configuration. Namely, decreases in local metabolic connectivity within occipital cortex, thalamus, and cerebellum, and increases within frontal, temporal, parietal, and basal ganglia regions. There were also long-range disconnections among these brain regions, all supporting a disruption of the functional hierarchy characterizing the normal brain. The anatomically driven analysis revealed alterations within brain structures early affected by α-synuclein pathology, supporting Braak’s early pathological staging in dementia with Lewy bodies. The dopaminergic striato-cortical pathway was severely affected, as well as the cholinergic networks, with an extensive decrease in connectivity in Ch1-Ch2, Ch5-Ch6 networks, and the lateral Ch4 capsular network significantly towards the occipital cortex. These altered patterns of metabolic connectivity unveil a new in vivo scenario for dementia with Lewy bodies underlying pathology in terms of changes in whole-brain metabolic connectivity, spreading of α-synuclein, and neurotransmission impairment. PMID:27306756

GFP-Mutant Human Tau Transgenic Mice Develop Tauopathy Following CNS Injections of Alzheimer's Brain-Derived Pathological Tau or Synthetic Mutant Human Tau Fibrils

PubMed Central

Banks, Rachel A.; Kim, Bumjin; Xu, Hong; Changolkar, Lakshmi; Leight, Susan N.; Riddle, Dawn M.; Li, Chi; Brown, Hannah J.; Zhang, Bin

2017-01-01

process such as the early seeding events leading to new tau pathology have remained elusive. This study validates the use of GFP-labeled tau expressed by neurons in vivo and in vitro as models for investigating mechanisms underlying the seeded transmission of tau pathology as well as tau-focused drug discovery to identify disease-modifying therapies for AD and related tauopathies. PMID:28986461

Reflections on some early events related to behavior analysis of child development

PubMed Central

Bijou, Sidney W.

1996-01-01

A series of events related to the early application of behavioral principles to child behavior and development is described. The events began in the 1930s at Columbia University with a solicited letter from John B. Watson suggesting a master's degree thesis problem, and continued through the 1950s and 1960s at the University of Washington. Specifically, these happenings resulted in (a) research demonstrating that Skinner's laboratory method for studying nonhuman organisms could be profitably applied to the laboratory study of young normal children; (b) a demonstration that by successive approximations, a normal child can be operantly conditioned to respond to an arbitrary situation; (c) research showing that the effects of simple schedules of reinforcement obtained with nonhuman organisms could be duplicated in young normal and retarded children; (d) the demonstration that Skinner's operant laboratory method could be adapted to study young children in field situations; (e) research showing that operant principles can be successfully applied to the treatment of a young autistic boy with a serious visual handicap; (f) laboratory studies showing that mothers can be trained to treat their own young children who have behavior problems; (g) an in-home study demonstrating that a mother can treat her own child who has behavior problems; (h) a demonstration that operant principles can be applied effectively to teaching reading, writing, and arithmetic to children with retardation; and (i) publication of a book, Child Development: A Systematic and Empirical Theory, in collaboration with Donald M. Baer, by Prentice Hall in their Century Psychological Series. PMID:22478239

Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

PubMed

Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

2015-12-01

Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. © 2015 Authors; published by Portland Press Limited.

Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

PubMed Central

Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

2015-01-01

Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

Transcriptomic dose-and-time-course indicators of early key events in a cytotoxicity-mediated mode of action for rodent urinary bladder tumorigenesis

EPA Science Inventory

TRANSCRIPTOMIC DOSE- AND TIME-COURSE INDICATORS OF EARLY KEY EVENTS IN A CYTOTOXICITY-MEDIATED MODE OF ACTION FOR RODENT URINARY BLADDER TUMORIGENESISDiuron is a substituted urea compound used globally as an herbicide. Urinary bladder tumors were induced in rats after chronic die...

A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

PubMed

Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

2011-10-01

In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

“End-Stage” Neurofibrillary Tangle Pathology in Preclinical Alzheimer's Disease: Fact or Fiction?

PubMed Central

Abner, Erin L.; Kryscio, Richard J.; Schmitt, Frederick A.; SantaCruz, Karen S.; Jicha, Gregory A.; Lin, Yushun; Neltner, Janna M.; Smith, Charles D.; Van Eldik, Linda J.; Nelson, Peter T.

2011-01-01

Among individuals who were cognitively intact before death, autopsies may reveal some Alzheimer's disease-type pathology. The presence of end-stage pathology in cognitively intact persons would support the hypothesis that pathological markers are epiphenomena. We assessed advanced neurofibrillary (Braak stages V and VI) pathology focusing on nondemented individuals. Data from the National Alzheimer's Coordinating Center database (n = 4,690 included initially) and from the Nun Study (n = 526 included initially) were analyzed, with antemortem information about global cognition and careful postmortem studies available from each case. Global cognition (final Mini-Mental State Examination scores [MMSE] and clinical ‘dementia’ status) was correlated with neuropathology, including the severity of neurofibrillary pathology (Braak stages and neurofibrillary tangle counts in cerebral neocortex). Analyses support three major findings: 1. Braak stage V cases and Braak VI cases are significantly different from each other in terms of associated antemortem cognition; 2. There is an appreciable range of pathology within the category of Braak stage VI based on tangle counts such that brains with the most neurofibrillary tangles in neocortex always had profound antemortem cognitive impairment; and 3. There was no nondemented case with final MMSE score of 30 within a year of life and Braak stage VI pathology. It may be inappropriate to combine Braak stages V and VI cases, particularly in patients with early cognitive dysfunction, since the two pathological stages appear to differ dramatically in terms of both pathological severity and antemortem cognitive status. There is no documented example of truly end-stage neurofibrillary pathology coexisting with intact cognition. PMID:21471646

Updates of pathologic myopia.

PubMed

Ohno-Matsui, Kyoko; Lai, Timothy Y Y; Lai, Chi-Chun; Cheung, Chiu Ming Gemmy

2016-05-01

Complications from pathologic myopia are a major cause of visual impairment and blindness, especially in east Asia. The eyes with pathologic myopia may develop loss of the best-corrected vision due to various pathologies in the macula, peripheral retina and the optic nerve. Despite its importance, the definition of pathologic myopia has been inconsistent. The refractive error or axial length alone often does not adequately reflect the 'pathologic myopia'. Posterior staphyloma, which is a hallmark lesion of pathologic myopia, can occur also in non-highly myopic eyes. Recently a revised classification system for myopic maculopathy has been proposed to standardize the definition among epidemiological studies. In this META-PM (meta analyses of pathologic myopia) study classification, pathologic myopia was defined as the eyes having chorioretinal atrophy equal to or more severe than diffuse atrophy. In addition, the advent of new imaging technologies such as optical coherence tomography (OCT) and three dimensional magnetic resonance imaging (3D MRI) has enabled the detailed observation of various pathologies specific to pathologic myopia. New therapeutic approaches including intravitreal injections of anti-vascular endothelial growth factor agents and the advance of vitreoretinal surgeries have greatly improved the prognosis of patients with pathologic myopia. The purpose of this review article is to provide an update on topics related to the field of pathologic myopia, and to outline the remaining issues which need to be solved in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multiple-Threshold Event Detection and Other Enhancements to the Virtual Seismologist (VS) Earthquake Early Warning Algorithm

NASA Astrophysics Data System (ADS)

Fischer, M.; Caprio, M.; Cua, G. B.; Heaton, T. H.; Clinton, J. F.; Wiemer, S.

2009-12-01

The Virtual Seismologist (VS) algorithm is a Bayesian approach to earthquake early warning (EEW) being implemented by the Swiss Seismological Service at ETH Zurich. The application of Bayes’ theorem in earthquake early warning states that the most probable source estimate at any given time is a combination of contributions from a likelihood function that evolves in response to incoming data from the on-going earthquake, and selected prior information, which can include factors such as network topology, the Gutenberg-Richter relationship or previously observed seismicity. The VS algorithm was one of three EEW algorithms involved in the California Integrated Seismic Network (CISN) real-time EEW testing and performance evaluation effort. Its compelling real-time performance in California over the last three years has led to its inclusion in the new USGS-funded effort to develop key components of CISN ShakeAlert, a prototype EEW system that could potentially be implemented in California. A significant portion of VS code development was supported by the SAFER EEW project in Europe. We discuss recent enhancements to the VS EEW algorithm. We developed and continue to test a multiple-threshold event detection scheme, which uses different association / location approaches depending on the peak amplitudes associated with an incoming P pick. With this scheme, an event with sufficiently high initial amplitudes can be declared on the basis of a single station, maximizing warning times for damaging events for which EEW is most relevant. Smaller, non-damaging events, which will have lower initial amplitudes, will require more picks to be declared an event to reduce false alarms. This transforms the VS codes from a regional EEW approach reliant on traditional location estimation (and it requirement of at least 4 picks as implemented by the Binder Earthworm phase associator) to a hybrid on-site/regional approach capable of providing a continuously evolving stream of EEW

SVCT2 Expression and Function in Reactive Astrocytes Is a Common Event in Different Brain Pathologies.

PubMed

Salazar, Katterine; Martínez, Fernando; Pérez-Martín, Margarita; Cifuentes, Manuel; Trigueros, Laura; Ferrada, Luciano; Espinoza, Francisca; Saldivia, Natalia; Bertinat, Romina; Forman, Katherine; Oviedo, María José; López-Gambero, Antonio J; Bonansco, Christian; Bongarzone, Ernesto R; Nualart, Francisco

2017-09-23

Ascorbic acid (AA), the reduced form of vitamin C, acts as a neuroprotector by eliminating free radicals in the brain. Sodium/vitamin C co-transporter isoform 2 (SVCT2) mediates uptake of AA by neurons. It has been reported that SVCT2 mRNA is induced in astrocytes under ischemic damage, suggesting that its expression is enhanced in pathological conditions. However, it remains to be established if SVCT expression is altered in the presence of reactive astrogliosis generated by different brain pathologies. In the present work, we demonstrate that SVCT2 expression is increased in astrocytes present at sites of neuroinflammation induced by intracerebroventricular injection of a GFP-adenovirus or the microbial enzyme, neuraminidase. A similar result was observed at 5 and 10 days after damage in a model of traumatic injury and in the hippocampus and cerebral cortex in the in vivo kindling model of epilepsy. Furthermore, we defined that cortical astrocytes maintained in culture for long periods acquire markers of reactive gliosis and express SVCT2, in a similar way as previously observed in situ. Finally, by means of second harmonic generation and 2-photon fluorescence imaging, we analyzed brain necropsied material from patients with Alzheimer's disease (AD), which presented with an accumulation of amyloid plaques. Strikingly, although AD is characterized by focalized astrogliosis surrounding amyloid plaques, SVCT2 expression at the astroglial level was not detected. We conclude that SVCT2 is heterogeneously induced in reactive astrogliosis generated in different pathologies affecting the central nervous system (CNS).

[Theory of functional systems: postulates and principles of human body construction in health and pathology].

PubMed

Sudakov, K V

2007-01-01

It is shown that many functional systems with different level of organization harmoniously interact in healthy humans and animals. Early stress discoordinates information links of functional systems which can be easily corrected by nonpharmacological methods. Long-term and intensive stress disturbs mechanisms of self-regulation of the weakest functional systems. This converts a pathological process to a molecular tissue level. Principles of systemic functional human organization in pathology and compensation of impaired functions are considered.

Visuo-motor and cognitive procedural learning in children with basal ganglia pathology.

PubMed

Mayor-Dubois, C; Maeder, P; Zesiger, P; Roulet-Perez, E

2010-06-01

We investigated procedural learning in 18 children with basal ganglia (BG) lesions or dysfunctions of various aetiologies, using a visuo-motor learning test, the Serial Reaction Time (SRT) task, and a cognitive learning test, the Probabilistic Classification Learning (PCL) task. We compared patients with early (<1 year old, n=9), later onset (>6 years old, n=7) or progressive disorder (idiopathic dystonia, n=2). All patients showed deficits in both visuo-motor and cognitive domains, except those with idiopathic dystonia, who displayed preserved classification learning skills. Impairments seem to be independent from the age of onset of pathology. As far as we know, this study is the first to investigate motor and cognitive procedural learning in children with BG damage. Procedural impairments were documented whatever the aetiology of the BG damage/dysfunction and time of pathology onset, thus supporting the claim of very early skill learning development and lack of plasticity in case of damage. Copyright 2010 Elsevier Ltd. All rights reserved.

Novel mouse models of oculopharyngeal muscular dystrophy (OPMD) reveal early onset mitochondrial defects and suggest loss of PABPN1 may contribute to pathology.

PubMed

Vest, Katherine E; Phillips, Brittany L; Banerjee, Ayan; Apponi, Luciano H; Dammer, Eric B; Xu, Weiting; Zheng, Dinghai; Yu, Julia; Tian, Bin; Pavlath, Grace K; Corbett, Anita H

2017-09-01

Oculopharyngeal muscular dystrophy (OPMD) is a late onset disease caused by polyalanine expansion in the poly(A) binding protein nuclear 1 (PABPN1). Several mouse models have been generated to study OPMD; however, most of these models have employed transgenic overexpression of alanine-expanded PABPN1. These models do not recapitulate the OPMD patient genotype and PABPN1 overexpression could confound molecular phenotypes. We have developed a knock-in mouse model of OPMD (Pabpn1+/A17) that contains one alanine-expanded Pabpn1 allele under the control of the native promoter and one wild-type Pabpn1 allele. This mouse is the closest available genocopy of OPMD patients. We show that Pabpn1+/A17 mice have a mild myopathic phenotype in adult and aged animals. We examined early molecular and biochemical phenotypes associated with expressing native levels of A17-PABPN1 and detected shorter poly(A) tails, modest changes in poly(A) signal (PAS) usage, and evidence of mitochondrial damage in these mice. Recent studies have suggested that a loss of PABPN1 function could contribute to muscle pathology in OPMD. To investigate a loss of function model of pathology, we generated a heterozygous Pabpn1 knock-out mouse model (Pabpn1+/Δ). Like the Pabpn1+/A17 mice, Pabpn1+/Δ mice have mild histologic defects, shorter poly(A) tails, and evidence of mitochondrial damage. However, the phenotypes detected in Pabpn1+/Δ mice only partially overlap with those detected in Pabpn1+/A17 mice. These results suggest that loss of PABPN1 function could contribute to but may not completely explain the pathology detected in Pabpn1+/A17 mice. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Early Botulinum Toxin Injections in Infants With Musculoskeletal Disorders: A Systematic Review of Safety and Effectiveness.

PubMed

Bourseul, Jean-Sébastien; Molina, Anais; Lintanf, Mael; Houx, Laetitia; Chaléat-Valayer, Emmanuelle; Pons, Christelle; Brochard, Sylvain

2018-06-01

To report current evidence regarding the safety of intramuscular botulinum toxin injection (BTI) in children with orthopedic- and neurologic-related musculoskeletal disorders >2 years of age. PubMed, Cochrane Library, and ScienceDirect, Google Scholar, and Web of Science. Two reviewers independently selected studies based on predetermined inclusion criteria. Data relating to the aim were extracted. Methodologic quality was graded independently by 2 reviewers using the Physiotherapy Evidence Database scale for randomized controlled trials (RCTs) and the Downs and Black evaluation tool for non-RCTs. Level of evidence was determined using the modified Sackett scale. Data of 473 infants were analyzed. Fifty-five infants had cerebral palsy, 112 had obstetric brachial plexus palsy, 257 had clubfoot, and 44 had congenital torticollis. No studies reported any severe adverse event that could be attributed to the BTI. The rate of mild to moderate adverse events reported varied from 5% to 25%. Results regarding efficacy were preliminary, dependent on the pathology, and limited by the small number of studies and their low levels of evidence. BTI is already widely used as an early treatment for this age group. The safety profile of BTI in infants appears similar to that of older children and risks appear more related to the severity of the pathology and the location of the injections than to the toxin itself. Regarding effectiveness, other studies with higher levels of evidence should be carried out for each specific pathology. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Edaravone alleviates Alzheimer’s disease-type pathologies and cognitive deficits

PubMed Central

Jiao, Shu-Sheng; Yao, Xiu-Qing; Liu, Yu-Hui; Wang, Qing-Hua; Zeng, Fan; Lu, Jian-Jun; Liu, Jia; Zhu, Chi; Shen, Lin-Lin; Liu, Cheng-Hui; Wang, Ye-Ran; Zeng, Gui-Hua; Parikh, Ankit; Chen, Jia; Liang, Chun-Rong; Xiang, Yang; Bu, Xian-Le; Deng, Juan; Li, Jing; Xu, Juan; Zeng, Yue-Qin; Xu, Xiang; Xu, Hai-Wei; Zhong, Jin-Hua; Zhou, Hua-Dong; Zhou, Xin-Fu; Wang, Yan-Jiang

2015-01-01

Alzheimer’s disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis. PMID:25847999

Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation.

PubMed

Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars

2011-01-01

Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

Cytokine Signatures Associated With Early Onset, Active Lesions and Late Cicatricial Events of Retinochoroidal Commitment in Infants With Congenital Toxoplasmosis.

PubMed

Carneiro, Ana Carolina Aguiar Vasconcelos; Machado, Anderson Silva; Béla, Samantha Ribeiro; Costa, Julia Gatti Ladeia; Andrade, Gláucia Manzan Queiroz; Vasconcelos-Santos, Daniel Vitor; Januário, José Nélio; Coelho-Dos-Reis, Jordana Grazziela; Ferro, Eloisa Amália Vieira; Teixeira-Carvalho, Andréa; Vitor, Ricardo Wagner Almeida; Martins-Filho, Olindo Assis

2016-06-15

Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants. Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection. Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions. These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus.

PubMed

Torres, Manuel; Jimenez, Sebastian; Sanchez-Varo, Raquel; Navarro, Victoria; Trujillo-Estrada, Laura; Sanchez-Mejias, Elisabeth; Carmona, Irene; Davila, Jose Carlos; Vizuete, Marisa; Gutierrez, Antonia; Vitorica, Javier

2012-11-22

Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer's patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that dystrophies might interfere with normal intracellular proteolysis. In this work, we have investigated the progression of the hippocampal pathology and the possible implication in Abeta production in young (6 months) and aged (18 months) PS1(M146L)/APP(751sl) transgenic mice. Our data demonstrated the existence of a progressive, age-dependent, formation of axonal dystrophies, mainly located in contact with congophilic Abeta deposition, which exhibited tau and neurofilament hyperphosphorylation. This progressive pathology was paralleled with decreased expression of the motor proteins kinesin and dynein. Furthermore, we also observed an early decrease in the activity of cathepsins B and D, progressing to a deep inhibition of these lysosomal proteases at late ages. This lysosomal impairment could be responsible for the accumulation of LC3-II and ubiquitinated proteins within axonal dystrophies. We have also investigated the repercussion of these deficiencies on the APP metabolism. Our data demonstrated the existence of an increase in the amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99 fragment, intracellular Abeta in parallel with an increase in BACE and gamma-secretase activities. In vitro experiments, using APPswe transfected N2a cells, demonstrated that any imbalance on the proteolytic systems reproduced the in vivo alterations in APP metabolism. Finally, our data also demonstrated that Abeta peptides were preferentially accumulated in isolated synaptosomes. A progressive age-dependent cytoskeletal pathology along with a reduction of lysosomal and, in minor extent, proteasomal activity could be

Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus

PubMed Central

2012-01-01

Background Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer’s patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that dystrophies might interfere with normal intracellular proteolysis. In this work, we have investigated the progression of the hippocampal pathology and the possible implication in Abeta production in young (6 months) and aged (18 months) PS1(M146L)/APP(751sl) transgenic mice. Results Our data demonstrated the existence of a progressive, age-dependent, formation of axonal dystrophies, mainly located in contact with congophilic Abeta deposition, which exhibited tau and neurofilament hyperphosphorylation. This progressive pathology was paralleled with decreased expression of the motor proteins kinesin and dynein. Furthermore, we also observed an early decrease in the activity of cathepsins B and D, progressing to a deep inhibition of these lysosomal proteases at late ages. This lysosomal impairment could be responsible for the accumulation of LC3-II and ubiquitinated proteins within axonal dystrophies. We have also investigated the repercussion of these deficiencies on the APP metabolism. Our data demonstrated the existence of an increase in the amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99 fragment, intracellular Abeta in parallel with an increase in BACE and gamma-secretase activities. In vitro experiments, using APPswe transfected N2a cells, demonstrated that any imbalance on the proteolytic systems reproduced the in vivo alterations in APP metabolism. Finally, our data also demonstrated that Abeta peptides were preferentially accumulated in isolated synaptosomes. Conclusion A progressive age-dependent cytoskeletal pathology along with a reduction of lysosomal and, in minor

Social Information Processing and Cluster B Personality Pathology among Clinic-Referred Adolescents.

PubMed

Hessels, Christel; van Aken, Marcel A G; Orobio de Castro, Bram; Laceulle, Odilia M; van Voorst, Guus

2016-01-01

This study investigated relations between personality pathology and mentalizing capacities reflected in social information processing (SIP) of adolescents. 96 adolescent outpatients completed a structured interview regarding SIP. Their clinicians completed a checklist based on DSM-IV, assessing severity of personality pathology. Significant relations were found between the severity of personality pathology and SIP: the more severe the personality pathology, the higher the intensity of reported emotions, the more likely adolescents were to choose inadequate coping strategies and aggressive reactions in social situations, and the more positively they evaluated aggressive reactions. Severity of traits of antisocial (ASPD) and borderline personality disorder (BPD) had unique associations with distinctive SIP variables: ASPD being more related to inadequate coping strategies, less reflection on other's motives and aggressive responses, and BPD being more related to avoidant or prosocial responses and in particular to memories of frustrating events. This study provides evidence for difficulties in SIP among adolescents with more severe personality pathology, suggesting that the steps in the SIP model can be used to operationalize mentalizing problems. The results seem to paint a picture of ASPD and BPD having a shared background, but their own specific problems concerning SIP. © 2016 S. Karger AG, Basel.

Pathology Reports

MedlinePlus

... pathology report will include the results of these tests. For example, the pathology report may include information obtained from ... markers or indicators of a specific cancer. For example, the Philadelphia chromosome ... ( 3 ). Some tests that might be performed on a tissue sample ...

Case Report: SPECT/CT as the New Diagnostic Tool for Specific Wrist Pathology.

PubMed

Linde, Musters; Ten Broek, M; Kraan, G A

2017-01-01

Single photon emission computed tomography has been introduced as a promising new diagnostic tool in orthopaedic pathology since the early 90'. Computed tomography, the combined with SPECT, gives insight in the specific sight of wrist pathology. Literature already supports introduction of SPECT/CT in wrist pathology, but clinical application is lagging. A 40yr old patient reported first in 2004 with persisting pain after a right distal radius fracture. Several diagnostics and operative interventions were performed, all unsuccessful. Because of the persisting pain a SPECT-CT was performed which showed a cyst in the hamate bone, which was successfully enucleated. The patient was finally pain free at recent follow-up. With a QDash-score of 43 and a PRW (H) E-DLV-score of 58/150. In this case report, SPECT/CT proved a very sensitive diagnostic tool for specific pathology of the wrist. It offered precise localisation and thereby the clinically suspected diagnosis was confirmed and the patient successfully treated.

Technical Performance Scores are strongly associated with early mortality, postoperative adverse events, and intensive care unit length of stay-analysis of consecutive discharges for 2 years.

PubMed

Nathan, Meena; Karamichalis, John; Liu, Hua; Gauvreau, Kimberley; Colan, Steven; Saia, Matthew; Pigula, Frank; Fynn-Thompson, Francis; Emani, Sitaram; Baird, Christopher; Mayer, John E; del Nido, Pedro J

2014-01-01

Previous work in our institution has indicated that the Technical Performance Score (TPS) is highly associated with early outcomes in select subsets of procedures and age groups. We hypothesized that the TPS could predict early outcomes in a wide range of diagnoses and age groups. Consecutive patients discharged from January 2011 to March 2013 were prospectively evaluated. The TPS was assigned according to the discharge echocardiographic findings and the need for reinterventions in the anatomic area of interest. Case complexity was determined using Risk Adjustment for Congenital Heart Surgery (RACHS-1) categories. Early mortality and postoperative adverse events were recorded. Relationships between the TPS and outcomes were assessed after adjusting for the baseline patient characteristics. The median age of the 1926 patients was 1.8 years (range, 0 days to 68 years). Bypass was used in 1740 (90%); 322 (17%) were neonates, 520 (27%) infants, 873 (45%) children, 211 (11%) adults. TPS was class 1 (optimal) in 956 (50%), class 2 (adequate) in 584 (30%), and class 3 (inadequate) in 226 (12%); 160 patients (8%) could not be scored. A total of 51 early deaths (2.6%) and 111 adverse events (5.7%) occurred. On univariate analysis, age, RACHS-1 category, and TPS were significantly associated with mortality and the occurrence of adverse events. On multivariate modeling, class 3 (inadequate) TPS was strongly associated with mortality (odds ratio, 16.9; 95% confidence interval, 6.7-42.9; P < .001), adverse events (odds ratio, 6.9; 95% confidence interval, 4.1-11.6; P < .001), and postoperative intensive care unit length of stay (coefficient, 2.3; 95% confidence interval, 2.0-2.6; P < .001) after adjusting for other covariates. The TPS is strongly associated with early outcomes across a wide range of ages and disease complexity and can serve as important tool for self-assessment and quality improvement. Copyright © 2014 The American Association for Thoracic Surgery

The relation between dimensions of normal and pathological personality and childhood maltreatment in incarcerated boys.

PubMed

Nederlof, E; Van der Ham, J M; Dingemans, P M J A; Oei, T I

2010-12-01

The relation between subtypes of maltreatment and dimensions of personality and personality pathology was investigated in a representative sample of 142 incarcerated Dutch male juveniles. Normal personality dimensions were assessed with the Big Five Inventory, the Dimensional Assessment of Personality Pathology-Basic Questionnaire for Adolescents was used to measure pathological personality dimensions, and the Childhood Trauma Questionnaire was used to assess childhood maltreatment. The five maltreatment subtypes were found to be differentially and uniquely related to the normal and pathological personality dimensions in juvenile delinquents. The association between the abusive subtypes and Emotional Dysregulation depended on the co-occurrence of neglect. It was concluded that subtypes of maltreatment are distinctively related to dimensions of personality and personality pathology, possibly due to specific gene-environment interactions. Further research on this interplay is needed to be able to recognize genetic vulnerability. Early identification of children at risk could aid to limit the long-term consequences of maltreatment.

High resolution chronology of late Cretaceous-early Tertiary events determined from 21,000 yr orbital-climatic cycles in marine sediments

NASA Technical Reports Server (NTRS)

Herbert, Timothy D.; Dhondt, Steven

1988-01-01

A number of South Atlantic sites cored by the Deep Sea Drilling Project (DSDP) recovered late Cretaceous and early Tertiary sediments with alternating light-dark, high-low carbonate content. The sedimentary oscillations were turned into time series by digitizing color photographs of core segments at a resolution of about 5 points/cm. Spectral analysis of these records indicates prominent periodicity at 25 to 35 cm in the Cretaceous intervals, and about 15 cm in the early Tertiary sediments. The absolute period of the cycles that is determined from paleomagnetic calibration at two sites is 20,000 to 25,000 yr, and almost certainly corresponds to the period of the earth's precessional cycle. These sequences therefore contain an internal chronometer to measure events across the K/T extinction boundary at this scale of resolution. The orbital metronome was used to address several related questions: the position of the K/T boundary within magnetic chron 29R, the fluxes of biogenic and detrital material to the deep sea immediately before and after the K/T event, the duration of the Sr anomaly, and the level of background climatic variability in the latest Cretaceous time. The carbonate/color cycles that were analyzed contain primary records of ocean carbonate productivity and chemistry, as evidenced by bioturbational mixing of adjacent beds and the weak lithification of the rhythmic sequences. It was concluded that sedimentary sequences that contain orbital cyclicity are capable of providing resolution of dramatic events in earth history with much greater precision than obtainable through radiometric methods. The data show no evidence for a gradual climatic deterioration prior to the K/T extinction event, and argue for a geologically rapid revolution at this horizon.

A Suggested Molecular Pathology Curriculum for Residents: A Report of the Association for Molecular Pathology.

PubMed

Aisner, Dara L; Berry, Anna; Dawson, D Brian; Hayden, Randall T; Joseph, Loren; Hill, Charles E

2016-03-01

Molecular pathology is an essential element of pathology training. As more molecular tests have become available, there is an increasing need for pathology trainees to receive a strong foundation in molecular pathology. Appointed by the Training and Education Committee of the Association for Molecular Pathology, the Molecular Curriculum Task Force has developed a suggested curriculum in molecular pathology for residents. The foundations of molecular pathology are presented as a series of goals and objectives that residency programs can use to develop their educational programs. As pathologists continue to expand their roles to include regular clinical consultations in the realm of molecular testing, a strong foundation in molecular pathology and genomic medicine has become essential to the practice of pathology. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Sprites and Early ionospheric VLF perturbations

NASA Astrophysics Data System (ADS)

Haldoupis, Christos; Amvrosiadi, Nino; Cotts, Ben; van der Velde, Oscar; Chanrion, Olivier; Neubert, Torsten

2010-05-01

Past studies have shown a correlation between sprites and early VLF perturbations, but the reported correlation varies widely from ~ 50% to 100%. The present study resolves these large discrepancies by analyzing several case studies of sprite and narrowband VLF observations, in which multiple transmitter-receiver VLF links with great circle paths (GCPs) passing near a sprite-producing thunderstorm were available. In this setup, the multiple links act in a complementary way that makes the detection of early VLF perturbations much more probable compared to a single VLF link that can miss several of them, a fact that was overlooked in past studies. The evidence shows that sprites are accompanied by early VLF perturbations in a one-to-one correspondence. This implies that the sprite generation mechanism may cause also sub-ionospheric conductivity disturbances that produce early VLF events. However, the one-to-one "sprite to early" event relationship, if viewed conversely as "early to sprite", appears not to be always reciprocal. This is because the number of early events detected in some cases was considerably larger than the number of sprites. Since the great majority of the early events not accompanied by sprites was caused by positive cloud to ground (+CG) lightning discharges, it is possible that sprites or sprite halos were concurrently present in these events as well but were missed by the sprite-watch detection system. In order for this option to be resolved we need more studies using highly sensitive optical systems capable of detecting weaker sprites, sprite halos and elves.

Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice

PubMed Central

Hogan, Chad H.; Oldenburg, Darby G.; Kara, Mehmet

2018-01-01

Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host. PMID:29390024

Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice.

PubMed

Van Skike, Nick D; Minkah, Nana K; Hogan, Chad H; Wu, Gary; Benziger, Peter T; Oldenburg, Darby G; Kara, Mehmet; Kim-Holzapfel, Deborah M; White, Douglas W; Tibbetts, Scott A; French, Jarrod B; Krug, Laurie T

2018-02-01

Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host.

Event-by-event gluon multiplicity, energy density, and eccentricities in ultrarelativistic heavy-ion collisions

NASA Astrophysics Data System (ADS)

Schenke, Björn; Tribedy, Prithwish; Venugopalan, Raju

2012-09-01

The event-by-event multiplicity distribution, the energy densities and energy density weighted eccentricity moments ɛn (up to n=6) at early times in heavy-ion collisions at both the BNL Relativistic Heavy Ion Collider (RHIC) (s=200GeV) and the CERN Large Hardron Collider (LHC) (s=2.76TeV) are computed in the IP-Glasma model. This framework combines the impact parameter dependent saturation model (IP-Sat) for nucleon parton distributions (constrained by HERA deeply inelastic scattering data) with an event-by-event classical Yang-Mills description of early-time gluon fields in heavy-ion collisions. The model produces multiplicity distributions that are convolutions of negative binomial distributions without further assumptions or parameters. In the limit of large dense systems, the n-particle gluon distribution predicted by the Glasma-flux tube model is demonstrated to be nonperturbatively robust. In the general case, the effect of additional geometrical fluctuations is quantified. The eccentricity moments are compared to the MC-KLN model; a noteworthy feature is that fluctuation dominated odd moments are consistently larger than in the MC-KLN model.

Seismology-based early identification of dam-formation landquake events.

PubMed

Chao, Wei-An; Zhao, Li; Chen, Su-Chin; Wu, Yih-Min; Chen, Chi-Hsuan; Huang, Hsin-Hua

2016-01-12

Flooding resulting from the bursting of dams formed by landquake events such as rock avalanches, landslides and debris flows can lead to serious bank erosion and inundation of populated areas near rivers. Seismic waves can be generated by landquake events which can be described as time-dependent forces (unloading/reloading cycles) acting on the Earth. In this study, we conduct inversions of long-period (LP, period ≥20 s) waveforms for the landquake force histories (LFHs) of ten events, which provide quantitative characterization of the initiation, propagation and termination stages of the slope failures. When the results obtained from LP waveforms are analyzed together with high-frequency (HF, 1-3 Hz) seismic signals, we find a relatively strong late-arriving seismic phase (dubbed Dam-forming phase or D-phase) recorded clearly in the HF waveforms at the closest stations, which potentially marks the time when the collapsed masses sliding into river and perhaps even impacting the topographic barrier on the opposite bank. Consequently, our approach to analyzing the LP and HF waveforms developed in this study has a high potential for identifying five dam-forming landquake events (DFLEs) in near real-time using broadband seismic records, which can provide timely warnings of the impending floods to downstream residents.

Early Alzheimer's Disease Neuropathology Detected by Proton MR Spectroscopy

PubMed Central

Murray, Melissa E.; Przybelski, Scott A.; Lesnick, Timothy G.; Liesinger, Amanda M.; Spychalla, Anthony; Zhang, Bing; Gunter, Jeffrey L.; Parisi, Joseph E.; Boeve, Bradley F.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Dickson, Dennis W.

2014-01-01

Proton magnetic resonance spectroscopy (1H-MRS) is sensitive to early neurodegenerative processes associated with Alzheimer's disease (AD). Although 1H-MRS metabolite ratios of N-acetyl aspartate (NAA)/creatine (Cr), NAA/myoinositol (mI), and mI/Cr measured in the posterior cingulate gyrus reveal evidence of disease progression in AD, pathologic underpinnings of the 1H-MRS metabolite changes in AD are unknown. Pathologically diagnosed human cases ranging from no likelihood to high likelihood AD (n = 41, 16 females and 25 males) who underwent antemortem 1H-MRS of the posterior cingulate gyrus at 3 tesla were included in this study. Immunohistochemical evaluation was performed on the posterior cingulate gyrus using antibodies to synaptic vesicles, hyperphosphorylated tau (pTau), neurofibrillary tangle conformational-epitope (cNFT), amyloid-β, astrocytes, and microglia. The slides were digitally analyzed using Aperio software, which allows neuropathologic quantification in the posterior cingulate gray matter. MRS and pathology associations were adjusted for time from scan to death. Significant associations across AD and control subjects were found between reduced synaptic immunoreactivity and both NAA/Cr and NAA/mI in the posterior cingulate gyrus. Higher pTau burden was associated with lower NAA/Cr and NAA/mI. Higher amyloid-β burden was associated with elevated mI/Cr and lower NAA/mI ratios, but not with NAA/Cr. 1H-MRS metabolite levels reveal early neurodegenerative changes associated with AD pathology. Our findings support the hypothesis that a decrease in NAA/Cr is associated with loss of synapses and early pTau pathology, but not with amyloid-β or later accumulation of cNFT pathology in the posterior cingulate gyrus. In addition, elevation of mI/Cr is associated with the occurrence of amyloid-β plaques in AD. PMID:25471565

Microgravity Effects on the Early Events of Biological Nitrogen Fixation in Medicago Truncatula: Results from the SyNRGE Experiment

NASA Technical Reports Server (NTRS)

Stutte, Gary W.; Roberts, Michael

2012-01-01

SyNRGE (Symbiotic Nodulation in a Reduced Gravity Environment) was a sortie mission on STS-135 in the Biological Research in Canisters (BRIC) hardware to study the effect of microgravity on a plant-microbe symbiosis resulting in biological nitrogen fixation. Medicago truncatula, a model species for th legume family, was inoculated with its bacterial symbiont, Sinorhizobium meliloti, to observe early biomolecular events associated with infection and nodulation in Petri Dish Fixation Units (PDFU's).

Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology

PubMed Central

Roulis, Manolis; Armaka, Maria; Manoloukos, Menelaos; Apostolaki, Maria; Kollias, George

2011-01-01

TNF plays a crucial role in the pathogenesis of Crohn disease. Dysregulated TNF production in mice that bear the genetic deletion of the TNF AU-rich regulatory elements (ARE) (TnfΔARE/+ mice) results in TNF receptor I (TNFRI)-dependent spontaneous Crohn-like pathology. Current concepts consider intestinal epithelial cell (IEC) responses to TNF to be critical for intestinal pathology, but the potential contribution of IEC-derived TNF in disease pathogenesis has not been addressed. In this study we examined whether IEC are sufficient as cellular targets or sources of TNF in the development of intestinal pathology. Using IEC-specific reactivation of a hypomorphic TnfΔAREneo allele in mice, we show that selective chronic overproduction of TNF by IEC suffices to cause full development of Crohn-like pathology. Epithelial TNF overexpression leads to early activation of the underlying intestinal myofibroblast, a cell type previously identified as a sufficient target of TNF for disease development in the TnfΔARE model. By contrast, restricted TNFRI expression on IEC although sufficient to confer IEC apoptosis after acute exogenous TNF administration, fails to induce pathology following chronic specific targeting of IEC by endogenous TNF in TnfΔARE/+ mice. Our results argue against IEC being early and sufficient responders to chronic TNF-mediated pathogenic signals and suggest that proinflammatory aberrations leading to chronic TNF production by IEC may initiate pathology in Crohn disease. PMID:21402942

Pathologic diagnosis of central centrifugal cicatricial alopecia on horizontal sections.

PubMed

Miteva, Mariya; Tosti, Antonella

2014-11-01

The pathologic findings in Central Centrifugal Cicatricial Alopecia (CCCA) have not been studied systematically in horizontal sections. Our objective was to establish the pathologic features, and their frequency in horizontal sections of scalp biopsies obtained from patients with clinically and histologically proven CCCA. Serial horizontal sections of 51 cases were evaluated retrospectively. All biopsies were assessed at 4 levels and at least on 24 horizontal sections. The most common pathologic findings were follicular miniaturization (81% of the cases); premature desquamation of the inner root sheath (96%), focal preservation of the sebaceous glands (94%), which in most of these cases appeared as surrounding "in a hug" an intact vellus follicle; compound follicular structures with perifollicular fibrosis and/or inflammation (89%), lamellar hyperkeratosis/parakeratosis in the hair canal (79%), absent or mild inflammation (77%), and naked hair shafts (68%). Horizontal sections are useful in CCCA to identify early or focal disease and to provide the clinician with better information on the presence of follicular miniaturization, inflammation, and scarring, which can be used to tailor the treatment to the individual patient.

Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease.

PubMed

Jack, Clifford R; Lowe, Val J; Weigand, Stephen D; Wiste, Heather J; Senjem, Matthew L; Knopman, David S; Shiung, Maria M; Gunter, Jeffrey L; Boeve, Bradley F; Kemp, Bradley J; Weiner, Michael; Petersen, Ronald C

2009-05-01

The purpose of this study was to use serial imaging to gain insight into the sequence of pathologic events in Alzheimer's disease, and the clinical features associated with this sequence. We measured change in amyloid deposition over time using serial (11)C Pittsburgh compound B (PIB) positron emission tomography and progression of neurodegeneration using serial structural magnetic resonance imaging. We studied 21 healthy cognitively normal subjects, 32 with amnestic mild cognitive impairment and 8 with Alzheimer's disease. Subjects were drawn from two sources--ongoing longitudinal registries at Mayo Clinic, and the Alzheimer's disease Neuroimaging Initiative (ADNI). All subjects underwent clinical assessments, MRI and PIB studies at two time points, approximately one year apart. PIB retention was quantified in global cortical to cerebellar ratio units and brain atrophy in units of cm(3) by measuring ventricular expansion. The annual change in global PIB retention did not differ by clinical group (P = 0.90), and although small (median 0.042 ratio units/year overall) was greater than zero among all subjects (P < 0.001). Ventricular expansion rates differed by clinical group (P < 0.001) and increased in the following order: cognitively normal (1.3 cm(3)/year) < amnestic mild cognitive impairment (2.5 cm(3)/year) < Alzheimer's disease (7.7 cm(3)/year). Among all subjects there was no correlation between PIB change and concurrent change on CDR-SB (r = -0.01, P = 0.97) but some evidence of a weak correlation with MMSE (r =-0.22, P = 0.09). In contrast, greater rates of ventricular expansion were clearly correlated with worsening concurrent change on CDR-SB (r = 0.42, P < 0.01) and MMSE (r =-0.52, P < 0.01). Our data are consistent with a model of typical late onset Alzheimer's disease that has two main features: (i) dissociation between the rate of amyloid deposition and the rate of neurodegeneration late in life, with amyloid deposition proceeding at a constant slow

Clinical, pathological and sonographic characteristics of unexpected gallbladder carcinoma

PubMed Central

Wang, Jin-Huan; Liu, Bo-Ji; Xu, Hui-Xiong; Sun, Li-Ping; Li, Dan-Dan; Guo, Le-Hang; Liu, Lin-Na; Xu, Xiao-Hong

2015-01-01

Objectives: To investigate the clinical, pathological, and sonographic characteristics of unexpected gallbladder carcinoma (UGC). Methods: Of 5424 patients who had undergone cholecystectomy from December 2006 to October 2013, 54 patients with primary gallbladder carcinomas confirmed by pathological diagnosis were identified. The patients were divided into two groups: diagnosed before operation (n=34) and UGC groups (n=20), of whom the clinical, pathological, and sonographic characteristics were compared. Results: No significant differences in age, gender, location of lesion, histological type, length of the gallbladder, existence of biliary sludge, and intestinal gas interference between the two groups were found (all P>0.05). The clinical symptoms, laboratory abnormalities, tumor markers, coexisting gallbladder stones, lesion size, lesion type, degree of differentiation, and tumor staging showed statistically significant differences between the two groups (all P<0.05). On ultrasound, the width of the gallbladder, gallbladder wall thickness, vascularity on color Doppler ultrasound, and bile volume in the gallbladder showed significant differences (all P<0.05). Conclusions: UGCs are commonly found at an early stage, often well-differentiated, wall thickened, and are generally accompanied with cholelithiasis. UGCs should be taken into consideration in cases with cholelithiasis or small gallbladder on ultrasound. PMID:26379911

Dual pathology: cervicofacial actinomycosis and nicorandil-induced oral ulceration.

PubMed

Cupples, H E V; McGahey, D T

2008-04-01

Oral ulceration has many causes and is a common presenting symptom in otolaryngology. This article presents an unusual case of dual pathology oral ulceration in an elderly patient. Oral malignancy was initially suspected, but the history, examination and investigation showed that the oral ulceration was caused by actinomycosis infection and by nicorandil use. Cervicofacial acinomycosis is a rare, suppurative bacterial disease in which abscesses can form in the tissues and break through the skin, creating pus-discharging lesions. Nicorandil is a potassium channel blocker used in the treatment of ischaemic heart disease. It has been recently recognised as a cause of persistent ulcerative stomatitis. This case highlights the importance of a high index of suspicion for unusual and reversible causes of oral ulceration, and of dual pathology as a cause. Such vigilance enables early recognition and treatment of potentially reversible conditions.

The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

PubMed

Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

2017-08-01

To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

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

Hong, Julian C.; Kruser, Tim J.; Gondi, Vinai

Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the causemore » of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.« less

Sports-related brain injuries: connecting pathology to diagnosis.

PubMed

Pan, James; Connolly, Ian D; Dangelmajer, Sean; Kintzing, James; Ho, Allen L; Grant, Gerald

2016-04-01

Brain injuries are becoming increasingly common in athletes and represent an important diagnostic challenge. Early detection and management of brain injuries in sports are of utmost importance in preventing chronic neurological and psychiatric decline. These types of injuries incurred during sports are referred to as mild traumatic brain injuries, which represent a heterogeneous spectrum of disease. The most dramatic manifestation of chronic mild traumatic brain injuries is termed chronic traumatic encephalopathy, which is associated with profound neuropsychiatric deficits. Because chronic traumatic encephalopathy can only be diagnosed by postmortem examination, new diagnostic methodologies are needed for early detection and amelioration of disease burden. This review examines the pathology driving changes in athletes participating in high-impact sports and how this understanding can lead to innovations in neuroimaging and biomarker discovery.

Interinstitutional review of slides for forensic pathology: types of inconsistencies.

PubMed

Ersoy, Gokhan; Akyildiz, Elif Ulker; Korkmaz, Gulay; Albek, Emre

2010-09-01

Because of the specific structure of forensic medicine in Turkey, reexamination of histopathologic specimens is a frequent practice. The aim of the present study is the assessment of microscopic diagnostic consistency in forensic pathology between different laboratories. Reports of the Council of Forensic Medicine between 2001 and 2004 were examined, and 150 cases with second pathologic examination were found. Results of histopathologic reports from peripheral laboratories were compared with those made by the Council pathologists with regard to diagnostic consistency. Consistency was assessed in 3 groups and 1 subgroup. Group 1, consistent and minor inconsistency; includes a major consistency subgroup. Group 2, major inconsistency, is the second diagnosis which is lethal; group 3, major inconsistency, is the first diagnosis which is lethal. The lung was found to be the organ with the highest frequency of diagnostic major inconsistency (group 2 and 3) and major consistency. Bronchopneumonia was the most common diagnosis. The brain had the highest frequency of intercenter diagnostic overall consistency (90.2%, group 1). Myocardial infarction was the diagnosis most frequently rejected on reevaluation (group 3). In conclusion, forensic pathology requires different experience than surgical ones. In cases of discrepancy between the anamnesis of the lethal event and pathologic findings, reevaluation of specimen is mandatory to avoid any diagnostic errors. Quality assurance systems with all include internal and external control mechanisms will improve the diagnostic reliability.

The Incidence and Predictors of Early- and Mid-Term Clinically Relevant Neurological Events After Transcatheter Aortic Valve Replacement in Real-World Patients.

PubMed

Bosmans, Johan; Bleiziffer, Sabine; Gerckens, Ulrich; Wenaweser, Peter; Brecker, Stephen; Tamburino, Corrado; Linke, Axel

2015-07-21

Transcatheter aortic valve replacement (TAVR) enables treatment of high-risk patients with symptomatic aortic stenosis without open-heart surgery; however, the benefits are mitigated by the potential for neurological events. This study sought to determine the timing and causes of clinically relevant neurological events after self-expandable TAVR. We enrolled 1,015 patients, of whom 996 underwent TAVR with a self-expandable system at 44 TAVR-experienced centers in Europe, Colombia, and Israel. Neurological events were evaluated for 3 distinct time periods: periprocedural (0 to 1 days post TAVR); early (2 to 30 days); and late (31 to 730 days). In this real-world study, neurological events were first referred to the site neurologist and then reviewed by an independent neurologist. The overall stroke rate was 1.4% through the first day post-procedure, 3.0% at 30 days, and 5.6% at 2 years. There were no significant predictors of periprocedural stroke or stroke/transient ischemic attack (TIA) combined. Significant predictors of early stroke were acute kidney injury (p = 0.03), major vascular complication (p = 0.04), and female sex (p = 0.04). For stroke/TIA combined, prior atrial fibrillation (p = 0.03) and major vascular complication (p = 0.009) were predictive. Coronary artery bypass graft surgery was the only significant predictor of late stroke (p = 0.007) or late stroke/TIA (p = 0.06). Treatment of high-risk patients with aortic stenosis using a self-expandable system was associated with a low stroke rate at short- and long-term follow-up. Multivariable predictors of clinically relevant neurological events differed on the basis of the timing after TAVR. (CoreValve Advance International Post Market Study; NCT01074658). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Computational Pathology: A Path Ahead.

PubMed

Louis, David N; Feldman, Michael; Carter, Alexis B; Dighe, Anand S; Pfeifer, John D; Bry, Lynn; Almeida, Jonas S; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E; Gilbertson, John R; Sinard, John H; Gerber, Georg K; Galli, Stephen J; Golden, Jeffrey A; Becich, Michael J

2016-01-01

We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. To define the scope and needs of computational pathology. A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and nonpathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology.

The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

PubMed

Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

2015-10-01

The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Institutional pathology consultation.

PubMed

Tsung, Jeffrey S H

2004-03-01

Sun Yat-Sen Cancer Center is the only cancer center in Taiwan. The hospital maintains a policy, and the division of oncology makes a concerted effort to obtain and review pertinent pathologic specimens in all patients who had pathologic diagnosis performed at other institution before rendering therapy. A 1-year retrospective study was undertaken to assess the frequency of discordant diagnosis of our second-opinion pathology slide review and determine its impact on patient care. Discrepancies were classified into four basic categories: A) no diagnostic disagreement; B) no diagnostic disagreement but pertinent information not included, such as tumor size, lymphovascular invasion, perineural invasion, histologic grading, margin status, extracapsular spread in metastatic lymph nodes; and C) major diagnostic disagreement, which was defined as follows; 1) change from benign to malignant, 2) change from malignant to benign, 3) a different type of neoplasm, and 4) change in N and M classification in TMN staging framework. Of 715 cases, a total of 673 (94%) showed no discrepancy. However, 35 of 673 (5.2%) cases failed to offer pertinent information (category B). Major disagreement was found in 42 16%) cases (category C). This study illustrated the fact that second pathology slide review prior to therapy can identify a small group of cases that result in a major change in their therapeutic plan. Admittedly, the review of pathology slides involves additional time and effort for both consulting and referring institutions. It can ensure quality medical care and limit medicolegal liability. As the Association of Directors of Anatomic and Surgical Pathology recommended, second pathology review should be standard practice. It is necessary that our major Pathology Association and Societies adopt a strong position on this matter to influence government or insurance company to pay for this service rendered by pathologists.

The spectral absorption coefficient at 254 nm as a real-time early warning proxy for detecting faecal pollution events at alpine karst water resources.

PubMed

Stadler, H; Klock, E; Skritek, P; Mach, R L; Zerobin, W; Farnleitner, A H

2010-01-01

Because spring water quality from alpine karst aquifers can change very rapidly during event situations, water abstraction management has to be performed in near real-time. Four summer events (2005-2008) at alpine karst springs were investigated in detail in order to evaluate the spectral absorption coefficient at 254 nm (SAC254) as a real-time early warning proxy for faecal pollution. For the investigation Low-Earth-Orbit (LEO) Satellite-based data communication between portable hydrometeorological measuring stations and an automated microbiological sampling device was used. The method for event triggered microbial sampling and analyzing was already established and described in a previous paper. Data analysis including on-line event characterisation (i.e. precipitation, discharge, turbidity, SAC254) and comprehensive E. coli determination (n>800) indicated that SAC254 is a useful early warning proxy. Irrespective of the studied event situations SAC254 always increased 3 to 6 hours earlier than the onset of faecal pollution, featuring different correlation phases. Furthermore, it seems also possible to use SAC254 as a real-time proxy parameter for estimating the extent of faecal pollution after establishing specific spring and event-type calibrations that take into consideration the variability of the occurrence and the transferability of faecal material It should be highlighted that diffuse faecal pollution from wildlife and live stock sources was responsible for spring water contamination at the investigated catchments. In this respect, the SAC254 can also provide useful information to support microbial source tracking efforts where different situations of infiltration have to be investigated.

Relationship between early and late stages of information processing: an event-related potential study

PubMed Central

Portella, Claudio; Machado, Sergio; Arias-Carrión, Oscar; Sack, Alexander T.; Silva, Julio Guilherme; Orsini, Marco; Leite, Marco Antonio Araujo; Silva, Adriana Cardoso; Nardi, Antonio E.; Cagy, Mauricio; Piedade, Roberto; Ribeiro, Pedro

2012-01-01

The brain is capable of elaborating and executing different stages of information processing. However, exactly how these stages are processed in the brain remains largely unknown. This study aimed to analyze the possible correlation between early and late stages of information processing by assessing the latency to, and amplitude of, early and late event-related potential (ERP) components, including P200, N200, premotor potential (PMP) and P300, in healthy participants in the context of a visual oddball paradigm. We found a moderate positive correlation among the latency of P200 (electrode O2), N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) and the reaction time (RT). In addition, moderate negative correlation between the amplitude of P200 and the latencies of N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) was found. Therefore, we propose that if the secondary processing of visual input (P200 latency) occurs faster, the following will also happen sooner: discrimination and classification process of this input (N200 latency), motor response processing (PMP latency), reorganization of attention and working memory update (P300 latency), and RT. N200, PMP, and P300 latencies are also anticipated when higher activation level of occipital areas involved in the secondary processing of visual input rise (P200 amplitude). PMID:23355929

NARCISSISM AND CONCERN: THE RELATIONSHIP OF SELF-OBJECT NEEDS AND NARCISSISTIC SYMPTOMS WITH HEALTHY AND PATHOLOGICAL CONCERN.

PubMed

Friedemann, Yael; Tolmacz, Rami; Doron, Yonit

2016-03-01

While concern and narcissism seem to be contradictory in nature, clinical evidence and theoretical writings on pathological forms of concern--tracing their origin to deficiencies in early relationships with primary caretakers--suggest that the actual relationship between these two characteristics might be much more complicated. We respond to a study aimed to add empirical data to the clinical and theoretical knowledge examined the relationships between self-object functions, types of narcissism and pathological concern. The findings of the study showed that pathological concern was positively associated with self-object needs and that this association was mediated by covert narcissism. Our discussion focuses on the developmental and psychodynamic sources of pathological concern, as well as its significance in the intrapersonal and interpersonal domains.

GFP-Mutant Human Tau Transgenic Mice Develop Tauopathy Following CNS Injections of Alzheimer's Brain-Derived Pathological Tau or Synthetic Mutant Human Tau Fibrils.

PubMed

Gibbons, Garrett S; Banks, Rachel A; Kim, Bumjin; Xu, Hong; Changolkar, Lakshmi; Leight, Susan N; Riddle, Dawn M; Li, Chi; Gathagan, Ronald J; Brown, Hannah J; Zhang, Bin; Trojanowski, John Q; Lee, Virginia M-Y

2017-11-22

process such as the early seeding events leading to new tau pathology have remained elusive. This study validates the use of GFP-labeled tau expressed by neurons in vivo and in vitro as models for investigating mechanisms underlying the seeded transmission of tau pathology as well as tau-focused drug discovery to identify disease-modifying therapies for AD and related tauopathies. Copyright © 2017 the authors 0270-6474/17/3711485-10$15.00/0.

Does silent reading speed in normal adult readers depend on early visual processes? evidence from event-related brain potentials.

PubMed

Korinth, Sebastian Peter; Sommer, Werner; Breznitz, Zvia

2012-01-01

Little is known about the relationship of reading speed and early visual processes in normal readers. Here we examined the association of the early P1, N170 and late N1 component in visual event-related potentials (ERPs) with silent reading speed and a number of additional cognitive skills in a sample of 52 adult German readers utilizing a Lexical Decision Task (LDT) and a Face Decision Task (FDT). Amplitudes of the N170 component in the LDT but, interestingly, also in the FDT correlated with behavioral tests measuring silent reading speed. We suggest that reading speed performance can be at least partially accounted for by the extraction of essential structural information from visual stimuli, consisting of a domain-general and a domain-specific expertise-based portion. © 2011 Elsevier Inc. All rights reserved.

Sequence of pathogenic events in cynomolgus macaques infected with aerosolized monkeypox virus.

PubMed

Tree, J A; Hall, G; Pearson, G; Rayner, E; Graham, V A; Steeds, K; Bewley, K R; Hatch, G J; Dennis, M; Taylor, I; Roberts, A D; Funnell, S G P; Vipond, J

2015-04-01

To evaluate new vaccines when human efficacy studies are not possible, the FDA's "Animal Rule" requires well-characterized models of infection. Thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques were exposed to aerosolized monkeypox virus (10(5) PFU). Clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, and 12 postchallenge. Viral DNA (vDNA) was detected in the lungs on day 2 postchallenge, and viral antigen was detected, by immunostaining, in the epithelium of bronchi, bronchioles, and alveolar walls. Lesions comprised rare foci of dysplastic and sloughed cells in respiratory bronchioles. By day 4, vDNA was detected in the throat, tonsil, and spleen, and monkeypox antigen was detected in the lung, hilar and submandibular lymph nodes, spleen, and colon. Lung lesions comprised focal epithelial necrosis and inflammation. Body temperature peaked on day 6, pox lesions appeared on the skin, and lesions, with positive immunostaining, were present in the lung, tonsil, spleen, lymph nodes, and colon. By day 8, vDNA was present in 9/13 tissues. Blood concentrations of interleukin 1ra (IL-1ra), IL-6, and gamma interferon (IFN-γ) increased markedly. By day 10, circulating IgG antibody concentrations increased, and on day 12, animals showed early signs of recovery. These results define early events occurring in an inhalational macaque monkeypox infection model, supporting its use as a surrogate model for human smallpox. Bioterrorism poses a major threat to public health, as the deliberate release of infectious agents, such smallpox or a related virus, monkeypox, would have catastrophic consequences. The development and testing of new medical countermeasures, e.g., vaccines, are thus priorities; however, tests for efficacy in humans cannot be performed because it would be unethical and

Sequence of Pathogenic Events in Cynomolgus Macaques Infected with Aerosolized Monkeypox Virus

PubMed Central

Hall, G.; Pearson, G.; Rayner, E.; Graham, V. A.; Steeds, K.; Bewley, K. R.; Hatch, G. J.; Dennis, M.; Taylor, I.; Roberts, A. D.; Funnell, S. G. P.; Vipond, J.

2015-01-01

ABSTRACT To evaluate new vaccines when human efficacy studies are not possible, the FDA's “Animal Rule” requires well-characterized models of infection. Thus, in the present study, the early pathogenic events of monkeypox infection in nonhuman primates, a surrogate for variola virus infection, were characterized. Cynomolgus macaques were exposed to aerosolized monkeypox virus (105 PFU). Clinical observations, viral loads, immune responses, and pathological changes were examined on days 2, 4, 6, 8, 10, and 12 postchallenge. Viral DNA (vDNA) was detected in the lungs on day 2 postchallenge, and viral antigen was detected, by immunostaining, in the epithelium of bronchi, bronchioles, and alveolar walls. Lesions comprised rare foci of dysplastic and sloughed cells in respiratory bronchioles. By day 4, vDNA was detected in the throat, tonsil, and spleen, and monkeypox antigen was detected in the lung, hilar and submandibular lymph nodes, spleen, and colon. Lung lesions comprised focal epithelial necrosis and inflammation. Body temperature peaked on day 6, pox lesions appeared on the skin, and lesions, with positive immunostaining, were present in the lung, tonsil, spleen, lymph nodes, and colon. By day 8, vDNA was present in 9/13 tissues. Blood concentrations of interleukin 1ra (IL-1ra), IL-6, and gamma interferon (IFN-γ) increased markedly. By day 10, circulating IgG antibody concentrations increased, and on day 12, animals showed early signs of recovery. These results define early events occurring in an inhalational macaque monkeypox infection model, supporting its use as a surrogate model for human smallpox. IMPORTANCE Bioterrorism poses a major threat to public health, as the deliberate release of infectious agents, such smallpox or a related virus, monkeypox, would have catastrophic consequences. The development and testing of new medical countermeasures, e.g., vaccines, are thus priorities; however, tests for efficacy in humans cannot be performed because it

Selective pathologies of the head and neck in children: a developmental perspective.

PubMed

Ozolek, John A

2009-09-01

The range of pathology seen in the head and neck region is truly amazing and to a large extent probably mirrors the complex signaling pathways and careful orchestration of events that occurs between the primordial germ layers during the development of this region. As is true in general for the entire discipline of pediatric pathology, the head and neck pathology within this age group is as diverse and different as its adult counterpart. Cases that come across the pediatric head and neck surgical pathology bench are more heavily weighted toward developmental and congenital lesions such as branchial cleft anomalies, thyroglossal duct cysts, ectopias, heterotopias, choristomas, and primitive tumors. Many congenital "benign" lesions can cause significant morbidity and even mortality if they compress the airway or other vital structures. Exciting investigations into the molecular embryology of craniofacial development have begun to shed light on the pathogenesis of craniofacial developmental lesions and syndromes. Much more investigation is needed, however, to intertwine aberrations in the molecular ontogeny and development of the head and neck regions to the represented pathology. This review will integrate traditional morphologic embryology with some of the recent advances in the molecular pathways of head and neck development followed by a discussion of a variety of developmental lesions finishing with tumors presumed to be derived from pluripotent/progenitor cells and tumors that show anomalous or aborted development.

Realizing Aspects by Transforming for Events

NASA Technical Reports Server (NTRS)

Filman, Robert E.; Havelund, Klaus; Clancy, Daniel (Technical Monitor)

2002-01-01

We explore the extent to which concerns can be separated in programs by program transformation with respect to the events required by these concerns. We describe our early work on developing a system to perform event-driven transformation and discuss possible applications of this approach.

Advanced imaging of tau pathology in Alzheimer Disease: New perspectives from super resolution microscopy and label-free nanoscopy.

PubMed

Schierle, Gabriele S Kaminski; Michel, Claire H; Gasparini, Laura

2016-08-01

Alzheimer's disease (AD) is the main cause of dementia in the elderly population. Over 30 million people worldwide are living with dementia and AD prevalence is projected to increase dramatically in the next two decades. In terms of neuropathology, AD is characterized by two major cerebral hallmarks: extracellular β-amyloid (Aβ) plaques and intracellular Tau inclusions, which start accumulating in the brain 15-20 years before the onset of symptoms. Within this context, the scientific community worldwide is undertaking a wide research effort to detect AD pathology at its earliest, before symptoms appear. Neuroimaging of Aβ by positron emission tomography (PET) is clinically available and is a promising modality for early detection of Aβ pathology and AD diagnosis. Substantive efforts are ongoing to develop advanced imaging techniques for early detection of Tau pathology. Here, we will briefly describe the key features of Tau pathology and its heterogeneity across various neurodegenerative diseases bearing cerebral Tau inclusions (i.e., tauopathies). We will outline the current status of research on Tau-specific PET tracers and their clinical development. Finally, we will discuss the potential application of novel super-resolution and label-free techniques for investigating Tau pathology at the experimental level and their potential application for AD diagnosis. Microsc. Res. Tech. 79:677-683, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The role of imaging in early hip OA.

PubMed

Siebelt, M; Agricola, R; Weinans, H; Kim, Y J

2014-10-01

Hip osteoarthritis (OA) is characterized by cartilage degradation, subchondral bone sclerosis and osteophyte formation. Nowadays, OA is thought to develop via different etiologies that all lead to a similar form of end stage joint degradation. One of these subtypes is related to an abnormal shaped hip joint, like acetabular dysplasia and a cam deformity. These bony abnormalities are highly predictive for development of hip OA, but they are likely to already be present from childhood. This suggests that these deformations induce OA changes in the hip, well before extensive hip degradation becomes present three to four decades later. Accurate detection and successful characterization of these early OA events might lead to better treatment options for hip OA besides nowadays available invasive joint replacement surgery. However, current diagnostic imaging techniques like radiographs or plain magnetic resonance imaging (MRI), are not sensitive enough to detect these subtle early OA changes. Nor are they able to disentangle intertwined and overlapping cascades from different OA subtypes, and neither can they predict OA progression. New and more sensitive imaging techniques might enable us to detect first OA changes on a cellular level, providing us with new opportunities for early intervention. In this respect, shape analysis using radiography, MRI, computed tomography (CT), single photon emission computed tomography (SPECT)/CT, and positron emission tomography (PET) might prove promising techniques and be more suited to detect early pathological changes in the hip joint. A broad application of these techniques might give us more understanding what can be considered physiological adaptation of the hip, or when early OA really starts. With a more clear definition of early OA, more homogenous patient populations can be selected and help with the development of new disease modifying OA interventions. Copyright © 2014 Osteoarthritis Research Society International

[Once again: theoretical pathology].

PubMed

Bleyl, U

2010-07-01

Theoretical pathology refers to the attempt to reintroduce methodical approaches from the humanities, philosophical logic and "gestalt philosophy" into medical research and pathology. Diseases, in particular disease entities and more complex polypathogenetic mechanisms of disease, have a "gestalt quality" due to the significance of their pathophysiologic coherence: they have a "gestalt". The Research group Theoretical Pathology at the Academy of Science in Heidelberg are credited with having revitalized the philosophical notion of "gestalt" for morphological and pathological diagnostics. Gestalt means interrelated schemes of pathophysiological significance in the mind of the diagnostician. In pathology, additive and associative diagnostic are simply not possible without considering the notion of synthetic entities in Kant's logic.

Myocardial Infarction. Pathological Relevance and Relationship with Coronary Risk Factors.

PubMed

Leone, Aurelio

2017-01-01

Three types of necrosis characterize MI: coagulation necrosis, typically due to a coronarogenic mechanism, coagulative myocytolysis with formation of contract bands as an effect of sympathetic nervous system and adrenergic stimulation, and colliquative myocytolysis, characterized by myocardial fiber lysis, which is a close result of hydrolytic enzyme activity deriving from the material reaching the infarct area. Although a multifactorial etiology may be identified, nevertheless coronary alterations, which are a consequence of atherosclerotic plaque formation and complications with a reduced blood flow supply to the myocardium, are the benchmark of MI. Evidence indicates a close relationship between the MI and some coronary risk factors, associated with this pathologic pattern with a different, but high rate. Precipitating events to cause acute myocardial pathology need, however, to develop an acute myocardial infarction. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The influence of deficient retro-aortic rim on technical success and early adverse events following device closure of secundum atrial septal defects: An Analysis of the IMPACT Registry®.

PubMed

O'Byrne, Michael L; Gillespie, Matthew J; Kennedy, Kevin F; Dori, Yoav; Rome, Jonathan J; Glatz, Andrew C

2017-01-01

Concern regarding aortic erosion has focused attention on the retro-aortic rim in patients undergoing device closure of atrial septal defects (ASD), but its effect on early outcomes is not well studied. A multicenter retrospective cohort study of patients undergoing device occlusion of ASD between 1/2011-10/2014 was performed, using data from the IMproving Pediatric and Adult Congenital Treatment Registry. Subjects were divided between those with retro-aortic rim <5 and ≥5 mm. Primary outcomes were technical failure and major early adverse events. Case times were measured as surrogates of technical complexity. The effect of deficient retro-aortic rim on primary outcomes was assessed using hierarchical logistic regression, adjusting for other suspected covariates and assessing whether they represent independent risk factors RESULTS: 1,564 subjects (from 77 centers) were included, with deficient retro-aortic rim present in 40%. Technical failure occurred in 91 subjects (5.8%) and a major early adverse event in 64 subjects (4.1%). Adjusting for known covariates, the presence of a deficient retro-aortic rim was not significantly associated with technical failure (OR: 1.3, 95% CI: 0.9-2.1) or major early adverse event (OR: 0.7, 95% CI: 0.4-1. 2). Total case (P = 0.01) and fluoroscopy time (P = 0.02) were greater in subjects with deficient rim, but sheath time was not significantly different (P = 0.07). Additional covariates independently associated with these outcomes were identified. Deficient retro-aortic rim was highly prevalent but not associated with increased risk of technical failure or early adverse events. Studies with longer follow-up are necessary to assess other outcomes, including device erosion. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Treatment decisions and the impact of adverse events before and during extended endocrine therapy in postmenopausal early breast cancer.

PubMed

Blok, Erik J; Kroep, Judith R; Meershoek-Klein Kranenbarg, Elma; Duijm-de Carpentier, Marjolijn; Putter, Hein; Liefers, Gerrit-Jan; Nortier, Johan W R; Rutgers, Emiel J Th; Seynaeve, Caroline M; van de Velde, Cornelis J H

2018-05-01

Extended endocrine therapy beyond 5 years for postmenopausal breast cancer has been studied within multiple phase III trials. Treatment compliance in these trials is generally poor. In this analysis, we aimed to determine factors that were associated with participation in the phase III Investigation on the Duration of Extended Adjuvant Letrozole (IDEAL) trial and with early treatment discontinuation, and how this influenced survival outcome. In the IDEAL trial, postmenopausal patients were randomised between 2.5 or 5 years of extended letrozole, after completing 5 years of endocrine therapy for hormone receptor-positive early breast cancer. A subgroup of this population participated earlier in the Tamoxifen Exemestane Adjuvant Multinational trial (5 years of exemestane or 2.5 years of tamoxifen followed by exemestane as primary adjuvant therapy) in which we explored which factors were determinative for enrolment in the IDEAL study. In the IDEAL cohort, we evaluated which factors predicted for early treatment discontinuation and the effect of early treatment discontinuation on disease-free survival (DFS). Nodal status, younger age and adjuvant chemotherapy were significantly associated with higher enrolment in the IDEAL trial. In the IDEAL cohort, adverse events (AEs), the type of primary endocrine therapy and the interval between primary and extended therapy were associated with early treatment discontinuation. Among the reported AEs, depressive feelings (56%) were most frequently associated with early treatment discontinuation. Early treatment discontinuation was not associated with worse DFS (hazard ratio [HR] = 1.02, 95% confidence interval = 0.76-1.37). In this analysis, we found that risk factors were most strongly associated enrolment in the IDEAL trial. In contrast, patient experiences were the most significant factors leading to early treatment discontinuation, with no effect on DFS. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diagnostic pathology in 2012: development of digital pathology in an open access journal

PubMed Central

2013-01-01

Abstract Herein we describe and interpret the digital world of diagnostic surgical pathology, and take the in Pathology leading Open Access Journal Diagnostic Pathology as example. Virtual slide http://www.diagnosticpathology.diagnomx.eu/vs/1944221953867351 PMID:23305209

Slow slip events in the early part of the earthquake cycle

NASA Astrophysics Data System (ADS)

Voss, Nicholas K.; Malservisi, Rocco; Dixon, Timothy H.; Protti, Marino

2017-08-01

In February 2014 a Mw = 7.0 slow slip event (SSE) took place beneath the Nicoya Peninsula, Costa Rica. This event occurred 17 months after the 5 September 2012, Mw = 7.6, earthquake and along the same subduction zone segment, during a period when significant postseismic deformation was ongoing. A second SSE occurred in the middle of 2015, 21 months after the 2014 SSE and 38 months after the earthquake. The recurrence interval for Nicoya SSEs was unchanged by the earthquake. However, the spatial distribution of slip for the 2014 event differed significantly from previous events, having only deep ( 40 km) slip, compared to previous events, which had both deep and shallow slip. The 2015 SSE marked a return to the combination of deep plus shallow slip of preearthquake SSEs. However, slip magnitude in 2015 was nearly twice as large (Mw = 7.2) as preearthquake SSEs. We employ Coulomb Failure Stress change modeling in order to explain these changes. Stress changes associated with the earthquake and afterslip were highest near the shallow portion of the megathrust, where preearthquake SSEs had significant slip. Lower stress change occurred on the deeper parts of the plate interface, perhaps explaining why the deep ( 40 km) region for SSEs remained unchanged. The large amount of shallow slip in the 2015 SSE may reflect lack of shallow slip in the prior SSE. These observations highlight the variability of aseismic strain release rates throughout the earthquake cycle.